Revealing Transient Interactions between Phosphatidylinositol-specific Phospholipase C and Phosphatidylcholine--Rich Lipid Vesicles

NASA Astrophysics Data System (ADS)

Yang, Boqian; He, Tao; Grauffel, Cédric; Reuter, Nathalie; Roberts, Mary; Gershenson, Anne

2013-03-01

Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes transiently interact with target membranes. Previous fluorescence correlation spectroscopy (FCS) experiments showed that Bacillus thuringiensis PI-PLC specifically binds to phosphatidylcholine (PC)-rich membranes and preferentially interacts with unilamellar vesicles that show larger curvature. Mutagenesis studies combined with FCS measurements of binding affinity highlighted the importance of interfacial PI-PLC tyrosines in the PC specificity. All-atom molecular dynamics simulations of PI-PLC performed in the presence of a PC membrane indicate these tyrosines are involved in specific cation-pi interactions with choline headgroups. To further understand those transient interactions between PI-PLC and PC-rich vesicles, we monitor single fluorescently labeled PI-PLC proteins as they cycle on and off surface-tethered small unilamellar vesicles using total internal reflection fluorescent microscopy. The residence times on vesicles along with vesicle size information, based on vesicle fluorescence intensity, reveal the time scales of PI-PLC membrane interactions as well as the curvature dependence. The PC specificity and the vesicle curvature dependence of this PI-PLC/membrane interaction provide insight into how the interface modulates protein-membrane interactions. This work was supported by the National Institute of General Medical Science of the National Institutes of Health (R01GM060418).

Cell-material interactions revealed via material techniques of surface patterning.

PubMed

Yao, Xiang; Peng, Rong; Ding, Jiandong

2013-10-04

Cell-material interactions constitute a key fundamental topic in biomaterials study. Various cell cues and matrix cues as well as soluble factors regulate cell behaviors on materials. These factors are coupled with each other as usual, and thus it is very difficult to unambiguously elucidate the role of each regulator. The recently developed material techniques of surface patterning afford unique ways to reveal the underlying science. This paper reviews the pertinent material techniques to fabricate patterns of microscale and nanoscale resolutions, and corresponding cell studies. Some issues are emphasized, such as cell localization on patterned surfaces of chemical contrast, and effects of cell shape, cell size, cell-cell contact, and seeding density on differentiation of stem cells. Material cues to regulate cell adhesion, cell differentiation and other cell events are further summed up. Effects of some physical properties, such as surface topography and matrix stiffness, on cell behaviors are also discussed; nanoscaled features of substrate surfaces to regulate cell fate are summarized as well. The pertinent work sheds new insight into the cell-material interactions, and is stimulating for biomaterial design in regenerative medicine, tissue engineering, and high-throughput detection, diagnosis, and drug screening. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interactive Social Neuroscience to Study Autism Spectrum Disorder

PubMed Central

Rolison, Max J.; Naples, Adam J.; McPartland, James C.

2015-01-01

Individuals with autism spectrum disorder (ASD) demonstrate difficulty with social interactions and relationships, but the neural mechanisms underlying these difficulties remain largely unknown. While social difficulties in ASD are most apparent in the context of interactions with other people, most neuroscience research investigating ASD have provided limited insight into the complex dynamics of these interactions. The development of novel, innovative “interactive social neuroscience” methods to study the brain in contexts with two interacting humans is a necessary advance for ASD research. Studies applying an interactive neuroscience approach to study two brains engaging with one another have revealed significant differences in neural processes during interaction compared to observation in brain regions that are implicated in the neuropathology of ASD. Interactive social neuroscience methods are crucial in clarifying the mechanisms underlying the social and communication deficits that characterize ASD. PMID:25745371

Interactive social neuroscience to study autism spectrum disorder.

PubMed

Rolison, Max J; Naples, Adam J; McPartland, James C

2015-03-01

Individuals with autism spectrum disorder (ASD) demonstrate difficulty with social interactions and relationships, but the neural mechanisms underlying these difficulties remain largely unknown. While social difficulties in ASD are most apparent in the context of interactions with other people, most neuroscience research investigating ASD have provided limited insight into the complex dynamics of these interactions. The development of novel, innovative "interactive social neuroscience" methods to study the brain in contexts with two interacting humans is a necessary advance for ASD research. Studies applying an interactive neuroscience approach to study two brains engaging with one another have revealed significant differences in neural processes during interaction compared to observation in brain regions that are implicated in the neuropathology of ASD. Interactive social neuroscience methods are crucial in clarifying the mechanisms underlying the social and communication deficits that characterize ASD.

Differential C3NET reveals disease networks of direct physical interactions

PubMed Central

2011-01-01

proliferation genes, which further suggests that the genes in this network may serve in the process of oncogenesis. Conclusions Our approach reveals disease specific interactions. It may help to make experimental follow-up studies more cost and time efficient by prioritizing disease relevant parts of the global gene network. PMID:21777411

Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate.

PubMed

Ryan, Eathen; Shen, Di; Wang, Xu

2016-04-01

Pleiotrophin (PTN) is a potent glycosaminoglycan-binding cytokine that is important in neural development, angiogenesis and tissue regeneration. Much of its activity is attributed to its interactions with the chondroitin sulfate (CS) proteoglycan, receptor type protein tyrosine phosphatase ζ (PTPRZ). However, there is little high resolution structural information on the interactions between PTN and CS, nor is it clear why the C-terminal tail of PTN is necessary for signaling through PTPRZ, even though it does not contribute to heparin binding. We determined the first structure of PTN and analyzed its interactions with CS. Our structure shows that PTN possesses large basic surfaces on both of its structured domains and also that residues in the hinge segment connecting the domains have significant contacts with the C-terminal domain. Our analysis of PTN-CS interactions showed that the C-terminal tail of PTN is essential for maintaining stable interactions with chondroitin sulfate A, the type of CS commonly found on PTPRZ. These results offer the first possible explanation of why truncated PTN missing the C-terminal tail is unable to signal through PTPRZ. NMR analysis of the interactions of PTN with CS revealed that the C-terminal domain and hinge of PTN make up the major CS-binding site in PTN, and that removal of the C-terminal tail weakened the affinity of the site for CSA but not for other high sulfation density CS. Coordinates of the ensemble of ten PTN structures have been deposited in RCSB under accession number 2n6f. Chemical shifts assignments and structural constraints have been deposited in BMRB under accession number 25762. © 2016 Federation of European Biochemical Societies.

Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces.

PubMed

Engin, H Billur; Kreisberg, Jason F; Carter, Hannah

2016-01-01

Recently it has been shown that cancer mutations selectively target protein-protein interactions. We hypothesized that mutations affecting distinct protein interactions involving established cancer genes could contribute to tumor heterogeneity, and that novel mechanistic insights might be gained into tumorigenesis by investigating protein interactions under positive selection in cancer. To identify protein interactions under positive selection in cancer, we mapped over 1.2 million nonsynonymous somatic cancer mutations onto 4,896 experimentally determined protein structures and analyzed their spatial distribution. In total, 20% of mutations on the surface of known cancer genes perturbed protein-protein interactions (PPIs), and this enrichment for PPI interfaces was observed for both tumor suppressors (Odds Ratio 1.28, P-value < 10(-4)) and oncogenes (Odds Ratio 1.17, P-value < 10(-3)). To study this further, we constructed a bipartite network representing structurally resolved PPIs from all available human complexes in the Protein Data Bank (2,864 proteins, 3,072 PPIs). Analysis of frequently mutated cancer genes within this network revealed that tumor-suppressors, but not oncogenes, are significantly enriched with functional mutations in homo-oligomerization regions (Odds Ratio 3.68, P-Value < 10(-8)). We present two important examples, TP53 and beta-2-microglobulin, for which the patterns of somatic mutations at interfaces provide insights into specifically perturbed biological circuits. In patients with TP53 mutations, patient survival correlated with the specific interactions that were perturbed. Moreover, we investigated mutations at the interface of protein-nucleotide interactions and observed an unexpected number of missense mutations but not silent mutations occurring within DNA and RNA binding sites. Finally, we provide a resource of 3,072 PPI interfaces ranked according to their mutation rates. Analysis of this list highlights 282 novel candidate cancer

Multitargeting by curcumin as revealed by molecular interaction studies

PubMed Central

Gupta, Subash C.; Prasad, Sahdeo; Kim, Ji Hye; Patchva, Sridevi; Webb, Lauren J.; Priyadarsini, Indira K.

2012-01-01

Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

NASA Astrophysics Data System (ADS)

Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

2016-02-01

Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

Comparative interactomics: analysis of arabidopsis 14-3-3 complexes reveals highly conserved 14-3-3 interactions between humans and plants.

PubMed

Paul, Anna-Lisa; Liu, Li; McClung, Scott; Laughner, Beth; Chen, Sixue; Ferl, Robert J

2009-04-01

As a first step in the broad characterization of plant 14-3-3 multiprotein complexes in vivo, stringent and specific antibody affinity purification was used to capture 14-3-3s together with their interacting proteins from extracts of Arabidopsis cell suspension cultures. Approximately 120 proteins were identified as potential in vivo 14-3-3 interacting proteins by mass spectrometry of the recovered complexes. Comparison of the proteins in this data set with the 14-3-3 interacting proteins from a similar study in human embryonic kidney cell cultures revealed eight interacting proteins that likely represent reasonably abundant, fundamental 14-3-3 interaction complexes that are highly conserved across all eukaryotes. The Arabidopsis 14-3-3 interaction data set was also compared to a yeast in vivo 14-3-3 interaction data set. Four 14-3-3 interacting proteins are conserved in yeast, humans, and Arabidopsis. Comparisons of the data sets based on biochemical function revealed many additional similarities in the human and Arabidopsis data sets that represent conserved functional interactions, while also leaving many proteins uniquely identified in either Arabidopsis or human cells. In particular, the Arabidopsis interaction data set is enriched for proteins involved in metabolism.

Systematic pan-cancer analysis reveals immune cell interactions in the tumor microenvironment

PubMed Central

Varn, Frederick S.; Wang, Yue; Mullins, David W.; Fiering, Steven; Cheng, Chao

2017-01-01

With the recent advent of immunotherapy, there is a critical need to understand immune cell interactions in the tumor microenvironment in both pan-cancer and tissue-specific contexts. Multi-dimensional datasets have enabled systematic approaches to dissect these interactions in large numbers of patients, furthering our understanding of the patient immune response to solid tumors. Using an integrated approach, we inferred the infiltration levels of distinct immune cell subsets in 23 tumor types from The Cancer Genome Atlas. From these quantities, we constructed a co-infiltration network, revealing interactions between cytolytic cells and myeloid cells in the tumor microenvironment. By integrating patient mutation data, we found that while mutation burden was associated with immune infiltration differences between distinct tumor types, additional factors likely explained differences between tumors originating from the same tissue. We concluded this analysis by examining the prognostic value of individual immune cell subsets as well as how co-infiltration of functionally discordant cell types associated with patient survival. In multiple tumor types, we found that the protective effect of CD8+ T cell infiltration was heavily modulated by co-infiltration of macrophages and other myeloid cell types, suggesting the involvement of myeloid-derived suppressor cells in tumor development. Our findings illustrate complex interactions between different immune cell types in the tumor microenvironment and indicate these interactions play meaningful roles in patient survival. These results demonstrate the importance of personalized immune response profiles when studying the factors underlying tumor immunogenicity and immunotherapy response. PMID:28126714

The coxsackievirus-adenovirus receptor reveals complex homophilic and heterophilic interactions on neural cells.

PubMed

Patzke, Christopher; Max, Klaas E A; Behlke, Joachim; Schreiber, Jadwiga; Schmidt, Hannes; Dorner, Armin A; Kröger, Stephan; Henning, Mechthild; Otto, Albrecht; Heinemann, Udo; Rathjen, Fritz G

2010-02-24

The coxsackievirus-adenovirus receptor (CAR) is a member of the Ig superfamily strongly expressed in the developing nervous system. Our histological investigations during development reveal an initial uniform distribution of CAR on all neural cells with a concentration on membranes that face the margins of the nervous system (e.g., the basal laminae and the ventricular side). At more advanced stages, CAR becomes downregulated and restricted to specific regions including areas rich in axonal and dendritic surfaces. To study the function of CAR on neural cells, we used the fiber knob of the adenovirus, extracellular CAR domains, blocking antibodies to CAR, as well as CAR-deficient neural cells. Blocking antibodies were found to inhibit neurite extension in retina organ and retinal explant cultures, whereas the application of the recombinant fiber knob of the adenovirus subtype Ad2 or extracellular CAR domains promoted neurite extension and adhesion to extracellular matrices. We observed a promiscuous interaction of CAR with extracellular matrix glycoproteins, which was deduced from analytical ultracentrifugation experiments, affinity chromatography, and adhesion assays. The membrane proximal Ig domain of CAR, termed D2, was found to bind to a fibronectin fragment, including the heparin-binding domain 2, which promotes neurite extension of wild type, but not of CAR-deficient neural cells. In contrast to heterophilic interactions, homophilic association of CAR involves both Ig domains, as was revealed by ultracentrifugation, chemical cross-linking, and adhesion studies. The results of these functional and binding studies are correlated to a U-shaped homodimer of the complete extracellular domains of CAR detected by x-ray crystallography.

Gene Expression Profiling of Monkeypox Virus-Infected Cells Reveals Novel Interfaces for Host-Virus Interactions

DTIC Science & Technology

2010-07-28

expression is plotted on Y -axis after normalization to mock-treated samples. Results plotted to compare calculated fold change in expression of each gene ...RESEARCH Open Access Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions Abdulnaser...suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes

Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks

PubMed Central

Ulitsky, Igor; Shamir, Ron

2007-01-01

The biological interpretation of genetic interactions is a major challenge. Recently, Kelley and Ideker proposed a method to analyze together genetic and physical networks, which explains many of the known genetic interactions as linking different pathways in the physical network. Here, we extend this method and devise novel analytic tools for interpreting genetic interactions in a physical context. Applying these tools on a large-scale Saccharomyces cerevisiae data set, our analysis reveals 140 between-pathway models that explain 3765 genetic interactions, roughly doubling those that were previously explained. Model genes tend to have short mRNA half-lives and many phosphorylation sites, suggesting that their stringent regulation is linked to pathway redundancy. We also identify ‘pivot' proteins that have many physical interactions with both pathways in our models, and show that pivots tend to be essential and highly conserved. Our analysis of models and pivots sheds light on the organization of the cellular machinery as well as on the roles of individual proteins. PMID:17437029

A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities

PubMed Central

Vizeacoumar, Franco J; Arnold, Roland; Vizeacoumar, Frederick S; Chandrashekhar, Megha; Buzina, Alla; Young, Jordan T F; Kwan, Julian H M; Sayad, Azin; Mero, Patricia; Lawo, Steffen; Tanaka, Hiromasa; Brown, Kevin R; Baryshnikova, Anastasia; Mak, Anthony B; Fedyshyn, Yaroslav; Wang, Yadong; Brito, Glauber C; Kasimer, Dahlia; Makhnevych, Taras; Ketela, Troy; Datti, Alessandro; Babu, Mohan; Emili, Andrew; Pelletier, Laurence; Wrana, Jeff; Wainberg, Zev; Kim, Philip M; Rottapel, Robert; O'Brien, Catherine A; Andrews, Brenda; Boone, Charles; Moffat, Jason

2013-01-01

Improved efforts are necessary to define the functional product of cancer mutations currently being revealed through large-scale sequencing efforts. Using genome-scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co-culture competition assays to generate a high-confidence genetic interaction network of differentially essential or differential essentiality (DiE) genes. The network uncovered examples of conserved genetic interactions, densely connected functional modules derived from comparative genomics with model systems data, functions for uncharacterized genes in the human genome and targetable vulnerabilities. Finally, we demonstrate a general applicability of DiE gene signatures in determining genetic dependencies of other non-isogenic cancer cell lines. For example, the PTEN−/− DiE genes reveal a signature that can preferentially classify PTEN-dependent genotypes across a series of non-isogenic cell lines derived from the breast, pancreas and ovarian cancers. Our reference network suggests that many cancer vulnerabilities remain to be discovered through systematic derivation of a network of differentially essential genes in an isogenic cancer cell model. PMID:24104479

Revealing the Structural Complexity of Component Interactions of Topic-Specific PCK when Planning to Teach

NASA Astrophysics Data System (ADS)

Mavhunga, Elizabeth

2018-04-01

Teaching pedagogical content knowledge (PCK) at a topic-specific level requires clarity on the content-specific nature of the components employed, as well as the specific features that bring about the desirable depth in teacher explanations. Such understanding is often hazy; yet, it influences the nature of teacher tasks and learning opportunities afforded to pre-service teachers in a teaching program. The purpose of this study was twofold: firstly, to illuminate the emerging complexity when content-specific components of PCK interact when planning to teach a chemistry topic; and secondly, to identify the kinds of teacher tasks that promote the emergence of such complexity. Data collected were content representations (CoRes) in chemical equilibrium accompanied by expanded lesson outlines from 15 pre-service teachers in their final year of study towards a first degree in teaching (B Ed). The analysis involved extraction of episodes that exhibited component interaction by using a qualitative in-depth analysis method. The results revealed the structure in which the components of PCK in a topic interact among each other to be linear, interwoven, or a combination of the two. The interwoven interactions contained multiple components that connected explanations on different aspects of a concept, all working in a complementary manner. The most sophisticated component interactions emerged from teacher tasks on descriptions of a lesson sequence and a summary of a lesson. Recommendations in this study highlight core practices for making pedagogical transformation of topic content knowledge more accessible.

An in vivo screen reveals protein-lipid interactions crucial for gating a mechanosensitive channel

PubMed Central

Iscla, Irene; Wray, Robin; Blount, Paul

2011-01-01

The bacterial mechanosensitive channel MscL is the best-studied mechanosensor, thus serving as a paradigm of how a protein senses and responds to mechanical force. Models for the transition of Escherichia coli MscL from closed to open states propose a tilting of the transmembrane domains in the plane of the membrane, suggesting dynamic protein-lipid interactions. Here, we used a rapid in vivo assay to assess the function of channels that were post-translationally modified at several different sites in a region just distal to the cytoplasmic end of the second transmembrane helix. We utilized multiple probes with various affinities for the membrane environment. The in vivo functional data, combined with site-directed mutagenesis, single-channel analyses, and tryptophan fluorescence measurements, confirmed that lipid interactions within this region are critical for MscL gating. The data suggest a model in which this region acts as an anchor for the transmembrane domain tilting during gating. Furthermore, the conservation of analogous motifs among many other channels suggests a conserved protein-lipid dynamic mechanism.—Iscla, I., Wray, R., Blount, P. An in vivo screen reveals protein-lipid interactions crucial for gating a mechanosensitive channel. PMID:21068398

Single Molecule Study of Metalloregulatory Protein-DNA Interactions

NASA Astrophysics Data System (ADS)

Sarkar, Susanta; Benitez, Jaime; Huang, Zhengxi; Wang, Qi; Chen, Peng

2007-03-01

Control of metal concentrations is essential for living body. Metalloregulatory proteins respond to metal concentrations by regulating transcriptions of metal resistance genes via protein-DNA interactions. It is thus necessary to understand interactions of metalloregulatory proteins with DNA. Ensemble measurements provide average behavior of a vast number of biomolecules. In contrast, single molecule spectroscopy can track single molecules individually and elucidate dynamics of processes of short time scales and intermediate structures not revealed by ensemble measurements. Here we present single molecule study of interactions between PbrR691, a MerR-family metalloregulatory protein and DNA. We presume that the dynamics of protein/DNA conformational changes and interactions are important for the transcription regulation and kinetics of these dynamic processes can provide useful information about the mechanisms of these metalloregulatory proteins.

Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions

DOE PAGES

Jiang, Jiansen; Chan, Henry; Cash, Darian D.; ...

2015-10-15

Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). In this paper, we report the cryo–electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunitmore » interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Finally, our findings provide structural and mechanistic insights into telomerase holoenzyme function.« less

Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Jiansen; Chan, Henry; Cash, Darian D.

Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). In this paper, we report the cryo–electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunitmore » interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Finally, our findings provide structural and mechanistic insights into telomerase holoenzyme function.« less

Reconstruction of the bifidobacterial pan-secretome reveals the network of extracellular interactions between bifidobacteria and the infant gut.

PubMed

Lugli, Gabriele Andrea; Mancino, Walter; Milani, Christian; Duranti, Sabrina; Turroni, Francesca; van Sinderen, Douwe; Ventura, Marco

2018-06-08

The repertoire of secreted proteins decoded by a microorganism represents proteins released from or associated with the cell's surface. In gut commensals, such as bifidobacteria, these proteins are perceived to be functionally relevant as they regulate the interaction with the gut environment. In the current study, we have screened the predicted proteome of over 300 bifidobacterial strains amongst the currently recognized bifidobacterial species to generate a comprehensive database encompassing bifidobacterial extracellular proteins. A glycobiome analysis of this predicted bifidobacterial secretome revealed that a correlation exists between particular bifidobacterial species and their capability to hydrolyze HMOs and intestinal glyconjugates such as mucin. Furthermore, exploration of metatranscriptomic datasets of the infant gut microbiota allowed the evaluation of the expression of bifidobacterial genes encoding extracellular proteins, represented by ABC transporter substrate-binding proteins and glycoside hydrolases enzymes involved in the degradation of human milk oligosaccharides and mucin. Overall, this study provides insights into how bifidobacteria interact with their natural yet highly complex environment, the infant gut. Importance The ecological success of bifidobacteria relies on the activity of extracellular proteins that are involved in the metabolism of nutrients and the interaction with the environment. To date, information on secreted proteins encoded by bifidobacteria are incomplete and just related to few species. In this study, we reconstructed the bifidobacterial pan-secretome, revealing extracellular proteins that modulate the interaction of bifidobacteria with their natural environment. Furthermore, a survey of secretion system between bifidobacterial genomes allowed the identification of a conserved Sec-dependent secretion machinery in all the analyzed genomes and the Tat protein translocation system in the chromosomes of 23 strains belonging

Non-visual spatial tasks reveal increased interactions with stance postural control.

PubMed

Woollacott, Marjorie; Vander Velde, Timothy

2008-05-07

The current investigation aimed to contrast the level and quality of dual-task interactions resulting from the combined performance of a challenging primary postural task and three specific, yet categorically dissociated, secondary central executive tasks. Experiments determined the extent to which modality (visual vs. auditory) and code (non-spatial vs. spatial) specific cognitive resources contributed to postural interference in young adults (n=9) in a dual-task setting. We hypothesized that the different forms of executive n-back task processing employed (visual-object, auditory-object and auditory-spatial) would display contrasting levels of interactions with tandem Romberg stance postural control, and that interactions within the spatial domain would be revealed as most vulnerable to dual-task interactions. Across all cognitive tasks employed, including auditory-object (aOBJ), auditory-spatial (aSPA), and visual-object (vOBJ) tasks, increasing n-back task complexity produced correlated increases in verbal reaction time measures. Increasing cognitive task complexity also resulted in consistent decreases in judgment accuracy. Postural performance was significantly influenced by the type of cognitive loading delivered. At comparable levels of cognitive task difficulty (n-back demands and accuracy judgments) the performance of challenging auditory-spatial tasks produced significantly greater levels of postural sway than either the auditory-object or visual-object based tasks. These results suggest that it is the employment of limited non-visual spatially based coding resources that may underlie previously observed visual dual-task interference effects with stance postural control in healthy young adults.

RNA-Seq reveals virus–virus and virus–plant interactions in nature

PubMed Central

Kamitani, Mari; Nagano, Atsushi J.; Honjo, Mie N.; Kudoh, Hiroshi

2016-01-01

Abstract As research on plant viruses has focused mainly on crop diseases, little is known about these viruses in natural environments. To understand the ecology of viruses in natural systems, comprehensive information on virus–virus and virus–host interactions is required. We applied RNA-Seq to plants from a natural population of Arabidopsis halleri subsp. gemmifera to simultaneously determine the presence/absence of all sequence-reported viruses, identify novel viruses and quantify the host transcriptome. By introducing the criteria of read number and genome coverage, we detected infections by Turnip mosaic virus (TuMV), Cucumber mosaic virus and Brassica yellows virus. Active TuMV replication was observed by ultramicroscopy. De novo assembly further identified a novel partitivirus, Arabidopsis halleri partitivirus 1. Interestingly, virus reads reached a maximum level that was equivalent to that of the host's total mRNA, although asymptomatic infection was common. AhgAGO2, a key gene in host defence systems, was upregulated in TuMV-infected plants. Multiple infection was frequent in TuMV-infected leaves, suggesting that TuMV facilitates multiple infection, probably by suppressing host RNA silencing. Revealing hidden plant–virus interactions in nature can enhance our understanding of biological interactions and may have agricultural applications. PMID:27549115

Network-based study reveals potential infection pathways of hepatitis-C leading to various diseases.

PubMed

Mukhopadhyay, Anirban; Maulik, Ujjwal

2014-01-01

Protein-protein interaction network-based study of viral pathogenesis has been gaining popularity among computational biologists in recent days. In the present study we attempt to investigate the possible pathways of hepatitis-C virus (HCV) infection by integrating the HCV-human interaction network, human protein interactome and human genetic disease association network. We have proposed quasi-biclique and quasi-clique mining algorithms to integrate these three networks to identify infection gateway host proteins and possible pathways of HCV pathogenesis leading to various diseases. Integrated study of three networks, namely HCV-human interaction network, human protein interaction network, and human proteins-disease association network reveals potential pathways of infection by the HCV that lead to various diseases including cancers. The gateway proteins have been found to be biologically coherent and have high degrees in human interactome compared to the other virus-targeted proteins. The analyses done in this study provide possible targets for more effective anti-hepatitis-C therapeutic involvement.

Network-Based Study Reveals Potential Infection Pathways of Hepatitis-C Leading to Various Diseases

PubMed Central

Mukhopadhyay, Anirban; Maulik, Ujjwal

2014-01-01

Protein-protein interaction network-based study of viral pathogenesis has been gaining popularity among computational biologists in recent days. In the present study we attempt to investigate the possible pathways of hepatitis-C virus (HCV) infection by integrating the HCV-human interaction network, human protein interactome and human genetic disease association network. We have proposed quasi-biclique and quasi-clique mining algorithms to integrate these three networks to identify infection gateway host proteins and possible pathways of HCV pathogenesis leading to various diseases. Integrated study of three networks, namely HCV-human interaction network, human protein interaction network, and human proteins-disease association network reveals potential pathways of infection by the HCV that lead to various diseases including cancers. The gateway proteins have been found to be biologically coherent and have high degrees in human interactome compared to the other virus-targeted proteins. The analyses done in this study provide possible targets for more effective anti-hepatitis-C therapeutic involvement. PMID:24743187

A Large-Scale Comparative Metagenomic Study Reveals the Functional Interactions in Six Bloom-Forming Microcystis-Epibiont Communities

PubMed Central

Li, Qi; Lin, Feibi; Yang, Chen; Wang, Juanping; Lin, Yan; Shen, Mengyuan; Park, Min S.; Li, Tao; Zhao, Jindong

2018-01-01

Cyanobacterial blooms are worldwide issues of societal concern and scientific interest. Lake Taihu and Lake Dianchi, two of the largest lakes in China, have been suffering from annual Microcystis-based blooms over the past two decades. These two eutrophic lakes differ in both nutrient load and environmental parameters, where Microcystis microbiota consisting of different Microcystis morphospecies and associated bacteria (epibionts) have dominated. We conducted a comprehensive metagenomic study that analyzed species diversity, community structure, functional components, metabolic pathways and networks to investigate functional interactions among the members of six Microcystis-epibiont communities in these two lakes. Our integrated metagenomic pipeline consisted of efficient assembly, binning, annotation, and quality assurance methods that ensured high-quality genome reconstruction. This study provides a total of 68 reconstructed genomes including six complete Microcystis genomes and 28 high quality bacterial genomes of epibionts belonging to 14 distinct taxa. This metagenomic dataset constitutes the largest reference genome catalog available for genome-centric studies of the Microcystis microbiome. Epibiont community composition appears to be dynamic rather than fixed, and the functional profiles of communities were related to the environment of origin. This study demonstrates mutualistic interactions between Microcystis and epibionts at genetic and metabolic levels. Metabolic pathway reconstruction provided evidence for functional complementation in nitrogen and sulfur cycles, fatty acid catabolism, vitamin synthesis, and aromatic compound degradation among community members. Thus, bacterial social interactions within Microcystis-epibiont communities not only shape species composition, but also stabilize the communities functional profiles. These interactions appear to play an important role in environmental adaptation of Microcystis colonies. PMID:29731741

In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

PubMed Central

Grey, Corinne; Clément, Julie A.J.; Buard, Jérôme; Leblanc, Benjamin; Gut, Ivo; Gut, Marta; Duret, Laurent

2017-01-01

In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner. Another subset reveals DSB-independent interactions between PRDM9 and genomic sites, such as the binding sites for the insulator protein CTCF. We propose that these DSB-independent sites result from interactions between hotspot-bound PRDM9 and genomic sequences located on the chromosome axis. PMID:28336543

Spectrophotometric studies on the interaction between (-)-epigallocatechin gallate and lysozyme

NASA Astrophysics Data System (ADS)

Ghosh, Kalyan Sundar; Sahoo, Bijaya Ketan; Dasgupta, Swagata

2008-02-01

Various reported antibacterial activities of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea prompted us to study its binding with lysozyme. This has been investigated by fluorescence, circular dichroism (CD) and protein-ligand docking. The binding parameters were determined using a modified Stern-Volmer equation. The thermodynamic parameters are indicative of an initial hydrophobic association. The complex is, however, held together predominantly by van der Waals interactions and hydrogen bonding. CD studies do not indicate any significant changes in the secondary structure of lysozyme. Docking studies revealed that specific interactions are observed with residues Trp 62 and Trp 63.

Theoretical and Numerical Studies of a Vortex - Interaction Problem

NASA Astrophysics Data System (ADS)

Hsu, To-Ming

The problem of vortex-airfoil interaction has received considerable interest in the helicopter industry. This phenomenon has been shown to be a major source of noise, vibration, and structural fatigue in helicopter flight. Since unsteady flow is always associated with vortex shedding and movement of free vortices, the problem of vortex-airfoil interaction also serves as a basic building block in unsteady aerodynamics. A careful study of the vortex-airfoil interaction reveals the major effects of the vortices on the generation of unsteady aerodynamic forces, especially the lift. The present work establishes three different flow models to study the vortex-airfoil interaction problem: a theoretical model, an inviscid flow model, and a viscous flow model. In the first two models, a newly developed aerodynamic force theorem has been successfully applied to identify the contributions to unsteady forces from various vortical systems in the flow field. Through viscous flow analysis, different features of laminar interaction, turbulent attached interaction, and turbulent separated interaction are examined. Along with the study of the vortex-airfoil interaction problem, several new schemes are developed for inviscid and viscous flow solutions. New formulas are derived to determine the trailing edge flow conditions, such as flow velocity and direction, in unsteady inviscid flow. A new iteration scheme that is faster for higher Reynolds number is developed for solving the viscous flow problem.

Paradoxical Expectation: Oscillatory Brain Activity Reveals Social Interaction Impairment in Schizophrenia.

PubMed

Billeke, Pablo; Armijo, Alejandra; Castillo, Daniel; López, Tamara; Zamorano, Francisco; Cosmelli, Diego; Aboitiz, Francisco

2015-09-15

People with schizophrenia show social impairments that are related to functional outcomes. We tested the hypothesis that social interaction impairments in people with schizophrenia are related to alterations in the predictions of others' behavior and explored their underlying neurobiological mechanisms. Electroencephalography was performed in 20 patients with schizophrenia and 25 well-matched control subjects. Participants played as proposers in the repeated version of the Ultimatum Game believing that they were playing with another human or with a computer. The power of oscillatory brain activity was obtained by means of the wavelet transform. We performed a trial-by-trial correlation between the oscillatory activity and the risk of the offer. Control subjects adapted their offers when playing with computers and tended to maintain their offers when playing with humans, as such revealing learning and bargaining strategies, respectively. People with schizophrenia presented the opposite pattern of behavior in both games. During the anticipation of others' responses, the power of alpha oscillations correlated with the risk of the offers made, in a different way in both games. Patients with schizophrenia presented a greater correlation in computer games than in human games; control subjects showed the opposite pattern. The alpha activity correlated with positive symptoms. Our results reveal an alteration in social interaction in patients with schizophrenia that is related to oscillatory brain activity, suggesting maladjustment of expectation when patients face social and nonsocial agents. This alteration is related to psychotic symptoms and could guide further therapies for improving social functioning in patients with schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Interactive Radio for Supporting Distance Education: An Evaluation Study.

ERIC Educational Resources Information Center

Bansal, Kiron; Chaudhary, Sohanvir S.

1999-01-01

Indira Gandhi National Open University (IGNOU) started an interactive radio project with the objective of interacting with students in their own languages and sharing experiences with them. Findings revealed that students appreciated the interactive radio sessions for helping accomplish course objectives, and that students' participation in the…

Interactivity in the Online Learning Environment: A Study of Users of the North Carolina Virtual Public School

ERIC Educational Resources Information Center

Ingerham, Laura

2012-01-01

Recent studies of online learning environments reveal the importance of interaction within the virtual environment. Abrami, Bernard, Bures, Borokhovski, and Tamim (2011) identify and study 3 types of student interactions: student-content, student-teacher, and student-student. This article builds on this classification of interactions as it…

Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms

NASA Astrophysics Data System (ADS)

Puckett, James G.; Ni, Rui; Ouellette, Nicholas T.

2015-06-01

The macroscopic emergent behavior of social animal groups is a classic example of dynamical self-organization, and is thought to arise from the local interactions between individuals. Determining these interactions from empirical data sets of real animal groups, however, is challenging. Using multicamera imaging and tracking, we studied the motion of individual flying midges in laboratory mating swarms. By performing a time-frequency analysis of the midge trajectories, we show that the midge behavior can be segmented into two distinct modes: one that is independent and composed of low-frequency maneuvers, and one that consists of higher-frequency nearly harmonic oscillations conducted in synchrony with another midge. We characterize these pairwise interactions, and make a hypothesis as to their biological function.

The experimental and theoretical QM/MM study of interaction of chloridazon herbicide with ds-DNA

NASA Astrophysics Data System (ADS)

Ahmadi, F.; Jamali, N.; Jahangard-Yekta, S.; Jafari, B.; Nouri, S.; Najafi, F.; Rahimi-Nasrabadi, M.

2011-09-01

We report a multispectroscopic, voltammetric and theoretical hybrid of QM/MM study of the interaction between double-stranded DNA containing both adenine-thymine and guanine-cytosine alternating sequences and chloridazon (CHL) herbicide. The electrochemical behavior of CHL was studied by cyclic voltammetry on HMDE, and the interaction of ds-DNA with CHL was investigated by both cathodic differential pulse voltammetry (CDPV) at a hanging mercury drop electrode (HMDE) and anodic differential pulse voltammetry (ADPV) at a glassy carbon electrode (GCE). The constant bonding of CHL-DNA complex that was obtained by UV/vis, CDPV and ADPV was 2.1 × 10 4, 5.1 × 10 4 and 2.6 × 10 4, respectively. The competition fluorescence studies revealed that the CHL quenches the fluorescence of DNA-ethidium bromide complex significantly and the apparent Stern-Volmer quenching constant has been estimated to be 1.71 × 10 4. Thermal denaturation study of DNA with CHL revealed the Δ Tm of 8.0 ± 0.2 °C. Thermodynamic parameters, i.e., enthalpy (Δ H), entropy (Δ S°), and Gibbs free energy (Δ G) were 98.45 kJ mol -1, 406.3 J mol -1 and -22.627 kJ mol -1, respectively. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G(d,p)/UFF) methodology, was also performed using Gaussian 2003 package. The results revealed that the interaction is base sequence dependent, and the CHL has more interaction with ds-DNA via the GC base sequence. The results revealed that CHL may have an interaction with ds-DNA via the intercalation mode.

Revealing protein functions based on relationships of interacting proteins and GO terms.

PubMed

Teng, Zhixia; Guo, Maozu; Liu, Xiaoyan; Tian, Zhen; Che, Kai

2017-09-20

In recent years, numerous computational methods predicted protein function based on the protein-protein interaction (PPI) network. These methods supposed that two proteins share the same function if they interact with each other. However, it is reported by recent studies that the functions of two interacting proteins may be just related. It will mislead the prediction of protein function. Therefore, there is a need for investigating the functional relationship between interacting proteins. In this paper, the functional relationship between interacting proteins is studied and a novel method, called as GoDIN, is advanced to annotate functions of interacting proteins in Gene Ontology (GO) context. It is assumed that the functional difference between interacting proteins can be expressed by semantic difference between GO term and its relatives. Thus, the method uses GO term and its relatives to annotate the interacting proteins separately according to their functional roles in the PPI network. The method is validated by a series of experiments and compared with the concerned method. The experimental results confirm the assumption and suggest that GoDIN is effective on predicting functions of protein. This study demonstrates that: (1) interacting proteins are not equal in the PPI network, and their function may be same or similar, or just related; (2) functional difference between interacting proteins can be measured by their degrees in the PPI network; (3) functional relationship between interacting proteins can be expressed by relationship between GO term and its relatives.

Augmented reality cube game for cognitive training: an interaction study.

PubMed

Boletsis, Costas; Mccallum, Simon

2014-01-01

There is the potential that cognitive activity may delay cognitive decline in people with mild cognitive impairment. Games provide both cognitive challenge and motivation for repeated use, a prerequisite for long lasting effect. Recent advances in technology introduce several new interaction methods, potentially leading to more efficient, personalized cognitive gaming experiences. In this paper, we present an Augmented Reality (AR) cognitive training game, utilizing cubes as input tools, and we test the cube interaction with a pilot study. The results of the study revealed the marker occlusion problem, and that novice AR users can adjust to the developed AR environment after a small number of sessions.

Students' Peer Interactions within a Cohort and in Host Countries during a Short-Term Study Abroad

ERIC Educational Resources Information Center

Jessup-Anger, Jody E.; Aragones, Aileen

2013-01-01

In this qualitative case study, we explored students' peer interactions within their cohort and in the host countries during a short-term study abroad. Framed by Bronfenbrenner's (1993) ecological systems theory, findings revealed that students spent considerable energy reflecting on interactions with peers. The students considered themselves…

Arpeggio: harmonic compression of ChIP-seq data reveals protein-chromatin interaction signatures

PubMed Central

Stanton, Kelly Patrick; Parisi, Fabio; Strino, Francesco; Rabin, Neta; Asp, Patrik; Kluger, Yuval

2013-01-01

Researchers generating new genome-wide data in an exploratory sequencing study can gain biological insights by comparing their data with well-annotated data sets possessing similar genomic patterns. Data compression techniques are needed for efficient comparisons of a new genomic experiment with large repositories of publicly available profiles. Furthermore, data representations that allow comparisons of genomic signals from different platforms and across species enhance our ability to leverage these large repositories. Here, we present a signal processing approach that characterizes protein–chromatin interaction patterns at length scales of several kilobases. This allows us to efficiently compare numerous chromatin-immunoprecipitation sequencing (ChIP-seq) data sets consisting of many types of DNA-binding proteins collected from a variety of cells, conditions and organisms. Importantly, these interaction patterns broadly reflect the biological properties of the binding events. To generate these profiles, termed Arpeggio profiles, we applied harmonic deconvolution techniques to the autocorrelation profiles of the ChIP-seq signals. We used 806 publicly available ChIP-seq experiments and showed that Arpeggio profiles with similar spectral densities shared biological properties. Arpeggio profiles of ChIP-seq data sets revealed characteristics that are not easily detected by standard peak finders. They also allowed us to relate sequencing data sets from different genomes, experimental platforms and protocols. Arpeggio is freely available at http://sourceforge.net/p/arpeggio/wiki/Home/. PMID:23873955

Arpeggio: harmonic compression of ChIP-seq data reveals protein-chromatin interaction signatures.

PubMed

Stanton, Kelly Patrick; Parisi, Fabio; Strino, Francesco; Rabin, Neta; Asp, Patrik; Kluger, Yuval

2013-09-01

Researchers generating new genome-wide data in an exploratory sequencing study can gain biological insights by comparing their data with well-annotated data sets possessing similar genomic patterns. Data compression techniques are needed for efficient comparisons of a new genomic experiment with large repositories of publicly available profiles. Furthermore, data representations that allow comparisons of genomic signals from different platforms and across species enhance our ability to leverage these large repositories. Here, we present a signal processing approach that characterizes protein-chromatin interaction patterns at length scales of several kilobases. This allows us to efficiently compare numerous chromatin-immunoprecipitation sequencing (ChIP-seq) data sets consisting of many types of DNA-binding proteins collected from a variety of cells, conditions and organisms. Importantly, these interaction patterns broadly reflect the biological properties of the binding events. To generate these profiles, termed Arpeggio profiles, we applied harmonic deconvolution techniques to the autocorrelation profiles of the ChIP-seq signals. We used 806 publicly available ChIP-seq experiments and showed that Arpeggio profiles with similar spectral densities shared biological properties. Arpeggio profiles of ChIP-seq data sets revealed characteristics that are not easily detected by standard peak finders. They also allowed us to relate sequencing data sets from different genomes, experimental platforms and protocols. Arpeggio is freely available at http://sourceforge.net/p/arpeggio/wiki/Home/.

Mapping of Adenovirus of serotype 3 fibre interaction to desmoglein 2 revealed a novel 'non-classical' mechanism of viral receptor engagement.

PubMed

Vassal-Stermann, Emilie; Mottet, Manon; Ducournau, Corinne; Iseni, Frédéric; Vragniau, Charles; Wang, Hongjie; Zubieta, Chloe; Lieber, André; Fender, Pascal

2018-05-30

High-affinity binding of the trimeric fibre protein to a cell surface primary receptor is a common feature shared by all adenovirus serotypes. Recently, a long elusive species B adenovirus receptor has been identified. Desmoglein 2 (DSG2) a component of desmosomal junction, has been reported to interact at high affinity with Human adenoviruses HAd3, HAd7, HAd11 and HAd14. Little is known with respect to the molecular interactions of adenovirus fibre with the DSG2 ectodomain. By using different DSG2 ectodomain constructs and biochemical and biophysical experiments, we report that the third extracellular cadherin domain (EC3) of DSG2 is critical for HAd3 fibre binding. Unexpectedly, stoichiometry studies using multi-angle laser light scattering (MALLS) and analytical ultra-centrifugation (AUC) revealed a non-classical 1:1 interaction (one DSG2 per trimeric fibre), thus differentiating 'DSG2-interacting' adenoviruses from other protein receptor interacting adenoviruses in their infection strategy.

Ecoinformatics Can Reveal Yield Gaps Associated with Crop-Pest Interactions: A Proof-of-Concept

PubMed Central

Rosenheim, Jay A.; Meisner, Matthew H.

2013-01-01

Farmers and private consultants execute a vast, decentralized data collection effort with each cropping cycle, as they gather pest density data to make real-time pest management decisions. Here we present a proof of concept for an ecoinformatics approach to pest management research, which attempts to harness these data to answer questions about pest-crop interactions. The impact of herbivory by Lygus hesperus on cotton is explored as a case study. Consultant-derived data satisfied a ‘positive control’ test for data quality by clearly resolving the expected negative relationship between L. hesperus density and retention of flower buds. The enhanced statistical power afforded by the large ecoinformatics dataset revealed an early-season window of crop sensitivity, during which L. hesperus densities as low as 1-2 per sample were associated with yield loss. In contrast, during the mid-season insecticide use by farmers was often unnecessary, as cotton compensated fully for moderate L. hesperus densities. Because the dataset emerged from the commercial production setting, it also revealed the limited degree to which farmers were willing to delay crop harvest to provide opportunities for compensatory fruiting. Observational approaches to pest management research have strengths and weaknesses that complement those of traditional, experimental approaches; combining these methods can contribute to enhanced agricultural productivity. PMID:24260408

Interaction Mindsets, Interactional Behaviors, and L2 Development: An Affective-Social-Cognitive Model

ERIC Educational Resources Information Center

Sato, Masatoshi

2017-01-01

This classroom-based study explored links among second language (L2) learners' interaction mindsets, interactional behaviors, and L2 development in the context of peer interaction. While peer interaction research has revealed that certain interactional behaviors (e.g., receiving corrective feedback and engaging in collaborative interaction) assist…

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

PubMed

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

2016-01-01

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

Andreev spectrum with high spin-orbit interactions: Revealing spin splitting and topologically protected crossings

NASA Astrophysics Data System (ADS)

Murani, A.; Chepelianskii, A.; Guéron, S.; Bouchiat, H.

2017-10-01

In order to point out experimentally accessible signatures of spin-orbit interaction, we investigate numerically the Andreev spectrum of a multichannel mesoscopic quantum wire (N) with high spin-orbit interaction coupled to superconducting electrodes (S), contrasting topological and nontopological behaviors. In the nontopological case (square lattice with Rashba interactions), we find that the Kramers degeneracy of Andreev levels is lifted by a phase difference between the S reservoirs except at multiples of π , when the normal quantum wires can host several conduction channels. The level crossings at these points invariant by time-reversal symmetry are not lifted by disorder. Whereas the dc Josephson current is insensitive to these level crossings, the high-frequency admittance (susceptibility) at finite temperature reveals these level crossings and the lifting of their degeneracy at π by a small Zeeman field. We have also investigated the hexagonal lattice with intrinsic spin-orbit interaction in the range of parameters where it is a two-dimensional topological insulator with one-dimensional helical edges protected against disorder. Nontopological superconducting contacts can induce topological superconductivity in this system characterized by zero-energy level crossing of Andreev levels. Both Josephson current and finite-frequency admittance carry then very specific signatures at low temperature of this disorder-protected Andreev level crossing at π and zero energy.

Dynamic Interactions between Bombyx mori Nucleopolyhedrovirus and Its Host Cells Revealed by Transcriptome Analysis

PubMed Central

Xue, Jian; Qiao, Nan; Zhang, Wei; Cheng, Ruo-Lin; Zhang, Xiao-Qin; Bao, Yan-Yuan; Xu, Yi-Peng; Gu, Lin-Zhu

2012-01-01

Although microarray and expressed sequence tag (EST)-based approaches have been used to profile gene expression during baculovirus infection, the response of host genes to baculovirus infection and the interaction between baculovirus and its host remain largely unknown. To determine the host response to Bombyx mori nucleopolyhedrovirus infection and the dynamic interaction between the virus and its host, eight digital gene expression libraries were examined in a Bm5 cell line before infection and at 1.5, 3, 6, 12, 24, 48, and 96 h postinfection. Gene set enrichment analysis of differentially expressed genes at each time point following infection showed that gene sets including cytoskeleton, transcription, translation, energy metabolism, iron ion metabolism, and the ubiquitin-proteasome pathway were altered after viral infection. In addition, a time course depicting protein-protein interaction networks between the baculovirus and the host were constructed and revealed that viral proteins interact with a multitude of cellular machineries, such as the proteasome, cytoskeleton, and spliceosome. Several viral proteins, including IE2, CG30, PE38, and PK-1/2, were predicted to play key roles in mediating virus-host interactions. Based on these results, we tested the role of the ubiquitin-proteasome pathway and iron ion metabolism in the viral infection cycle. Treatment with a proteasome inhibitor and deferoxamine mesylate in vitro and in vivo confirmed that these pathways regulate viral infection. Taken together, these findings provide new insights into the interaction between the baculovirus and its host and identify molecular mechanisms that can be used to block viral infection and improve baculovirus expression systems. PMID:22532689

A case-control study of rheumatoid arthritis revealed abdominal obesity and environmental risk factor interactions in northern China.

PubMed

Fu, Lingyu; Zhang, Jianming; Jin, Lei; Zhang, Yao; Cui, Saisai; Chen, Meng

2018-03-01

The aim of this study was to evaluate new and previously hypothesized environmental risk factors and their interaction with rheumatoid arthritis (RA). Four hundred patients recently diagnosed with RA and 400 controls frequency-matched by gender and birth year using Propensity Score Matching (PSM) were selected from northern China. Investigation was performed using self-reported data from interviewer-administered surveys. Associations between exposure variables and risk of RA were evaluated using multifactor non-conditional logistic regression. It showed that damp localities, draft indoor, abdominal obesity (AO), and family history of RA among first-degree relatives were independent risk factors and drinking of milk was independent protective factors for RA. Besides these risk factors, in women, infrequent delivery times, early age at menopause, and late age at menarche were also independent risk factors for RA. Both the additive model and the multiplication model suggested that there was an interaction relationship between AO and damp localities (p < .001), and only the additive model suggested that there was interaction relationship between AO and no milk drinking (p < .001) in our study population. In women, there was interaction relationship between AO and damp localities (p < .001) and between AO and age at menopause (p < .001). In northern China, damp localities, draft indoor, AO, family history of RA among first-degree relatives, and no milk drinking may be important risk factors of RA patients.

Mining for recurrent long-range interactions in RNA structures reveals embedded hierarchies in network families.

PubMed

Reinharz, Vladimir; Soulé, Antoine; Westhof, Eric; Waldispühl, Jérôme; Denise, Alain

2018-05-04

The wealth of the combinatorics of nucleotide base pairs enables RNA molecules to assemble into sophisticated interaction networks, which are used to create complex 3D substructures. These interaction networks are essential to shape the 3D architecture of the molecule, and also to provide the key elements to carry molecular functions such as protein or ligand binding. They are made of organised sets of long-range tertiary interactions which connect distinct secondary structure elements in 3D structures. Here, we present a de novo data-driven approach to extract automatically from large data sets of full RNA 3D structures the recurrent interaction networks (RINs). Our methodology enables us for the first time to detect the interaction networks connecting distinct components of the RNA structure, highlighting their diversity and conservation through non-related functional RNAs. We use a graphical model to perform pairwise comparisons of all RNA structures available and to extract RINs and modules. Our analysis yields a complete catalog of RNA 3D structures available in the Protein Data Bank and reveals the intricate hierarchical organization of the RNA interaction networks and modules. We assembled our results in an online database (http://carnaval.lri.fr) which will be regularly updated. Within the site, a tool allows users with a novel RNA structure to detect automatically whether the novel structure contains previously observed RINs.

Spatial interactions reveal inhibitory cortical networks in human amblyopia.

PubMed

Wong, Erwin H; Levi, Dennis M; McGraw, Paul V

2005-10-01

Humans with amblyopia have a well-documented loss of sensitivity for first-order, or luminance defined, visual information. Recent studies show that they also display a specific loss of sensitivity for second-order, or contrast defined, visual information; a type of image structure encoded by neurons found predominantly in visual area A18/V2. In the present study, we investigate whether amblyopia disrupts the normal architecture of spatial interactions in V2 by determining the contrast detection threshold of a second-order target in the presence of second-order flanking stimuli. Adjacent flanks facilitated second-order detectability in normal observers. However, in marked contrast, they suppressed detection in each eye of the majority of amblyopic observers. Furthermore, strabismic observers with no loss of visual acuity show a similar pattern of detection suppression. We speculate that amblyopia results in predominantly inhibitory cortical interactions between second-order neurons.

Recent Coselection in Human Populations Revealed by Protein–Protein Interaction Network

PubMed Central

Qian, Wei; Zhou, Hang; Tang, Kun

2015-01-01

Genome-wide scans for signals of natural selection in human populations have identified a large number of candidate loci that underlie local adaptations. This is surprising given the relatively short evolutionary time since the divergence of the human population. One hypothesis that has not been formally examined is whether and how the recent human evolution may have been shaped by coselection in the context of complex molecular interactome. In this study, genome-wide signals of selection were scanned in East Asians, Europeans, and Africans using 1000 Genome data, and subsequently mapped onto the protein–protein interaction (PPI) network. We found that the candidate genes of recent positive selection localized significantly closer to each other on the PPI network than expected, revealing substantial clustering of selected genes. Furthermore, gene pairs of shorter PPI network distances showed higher similarities of their recent evolutionary paths than those further apart. Last, subnetworks enriched with recent coselection signals were identified, which are substantially overrepresented in biological pathways related to signal transduction, neurogenesis, and immune function. These results provide the first genome-wide evidence for association of recent selection signals with the PPI network, shedding light on the potential mechanisms of recent coselection in the human genome. PMID:25532814

Elaborate cellulosome architecture of Acetivibrio cellulolyticus revealed by selective screening of cohesin-dockerin interactions.

PubMed

Hamberg, Yuval; Ruimy-Israeli, Vered; Dassa, Bareket; Barak, Yoav; Lamed, Raphael; Cameron, Kate; Fontes, Carlos M G A; Bayer, Edward A; Fried, Daniel B

2014-01-01

Cellulosic waste represents a significant and underutilized carbon source for the biofuel industry. Owing to the recalcitrance of crystalline cellulose to enzymatic degradation, it is necessary to design economical methods of liberating the fermentable sugars required for bioethanol production. One route towards unlocking the potential of cellulosic waste lies in a highly complex class of molecular machines, the cellulosomes. Secreted mainly by anaerobic bacteria, cellulosomes are structurally diverse, cell surface-bound protein assemblies that can contain dozens of catalytic components. The key feature of the cellulosome is its modularity, facilitated by the ultra-high affinity cohesin-dockerin interaction. Due to the enormous number of cohesin and dockerin modules found in a typical cellulolytic organism, a major bottleneck in understanding the biology of cellulosomics is the purification of each cohesin- and dockerin-containing component, prior to analyses of their interaction. As opposed to previous approaches, the present study utilized proteins contained in unpurified whole-cell extracts. This strategy was made possible due to an experimental design that allowed for the relevant proteins to be "purified" via targeted affinity interactions as a function of the binding assay. The approach thus represents a new strategy, appropriate for future medium- to high-throughput screening of whole genomes, to determine the interactions between cohesins and dockerins. We have selected the cellulosome of Acetivibrio cellulolyticus for this work due to its exceptionally complex cellulosome systems and intriguing diversity of its cellulosomal modular components. Containing 41 cohesins and 143 dockerins, A. cellulolyticus has one of the largest number of potential cohesin-dockerin interactions of any organism, and contains unusual and novel cellulosomal features. We have surveyed a representative library of cohesin and dockerin modules spanning the cellulosome's total cohesin

Bacterial discrimination by Dictyostelid amoebae reveals the complexity of ancient interspecies interactions

PubMed Central

Nasser, Waleed; Santhanam, Balaji; Miranda, Edward Roshan; Parikh, Anup; Juneja, Kavina; Rot, Gregor; Dinh, Chris; Chen, Rui; Zupan, Blaz; Shaulsky, Gad; Kuspa, Adam

2014-01-01

Background Amoebae and bacteria interact within predator/prey and host/pathogen relationships, but the general response of amoeba to bacteria is not well understood. The amoeba Dictyostelium discoideum feeds on, and is colonized by diverse bacterial species including Gram-positive [Gram(+)] and Gram-negative [Gram(−)] bacteria, two major groups of bacteria that differ in structure and macromolecular composition. Results Transcriptional profiling of D. discoideum revealed sets of genes whose expression is enriched in amoebae interacting with different species of bacteria, including sets that appear specific to amoebae interacting with Gram(+), or with Gram(−) bacteria. In a genetic screen utilizing the growth of mutant amoebae on a variety of bacteria as a phenotypic readout, we identified amoebal genes that are only required for growth on Gram(+) bacteria, including one that encodes the cell surface protein gp130, as well as several genes that are only required for growth on Gram(−) bacteria including one that encodes a putative lysozyme, AlyL. These genes are required for parts of the transcriptional response of wild-type amoebae, and this allowed their classification into potential response pathways. Conclusions We have defined genes that are critical for amoebal survival during feeding on Gram(+), or Gram(−), bacteria which we propose form part of a regulatory network that allows D. discoideum to elicit specific cellular responses to different species of bacteria in order to optimize survival. PMID:23664307

Molecular dynamics simulations revealed structural differences among WRKY domain-DNA interaction in barley (Hordeum vulgare).

PubMed

Pandey, Bharati; Grover, Abhinav; Sharma, Pradeep

2018-02-12

The WRKY transcription factors are a class of DNA-binding proteins involved in diverse plant processes play critical roles in response to abiotic and biotic stresses. Genome-wide divergence analysis of WRKY gene family in Hordeum vulgare provided a framework for molecular evolution and functional roles. So far, the crystal structure of WRKY from barley has not been resolved; moreover, knowledge of the three-dimensional structure of WRKY domain is pre-requisites for exploring the protein-DNA recognition mechanisms. Homology modelling based approach was used to generate structures for WRKY DNA binding domain (DBD) and its variants using AtWRKY1 as a template. Finally, the stability and conformational changes of the generated model in unbound and bound form was examined through atomistic molecular dynamics (MD) simulations for 100 ns time period. In this study, we investigated the comparative binding pattern of WRKY domain and its variants with W-box cis-regulatory element using molecular docking and dynamics (MD) simulations assays. The atomic insight into WRKY domain exhibited significant variation in the intermolecular hydrogen bonding pattern, leading to the structural anomalies in the variant type and differences in the DNA-binding specificities. Based on the MD analysis, residual contribution and interaction contour, wild-type WRKY (HvWRKY46) were found to interact with DNA through highly conserved heptapeptide in the pre- and post-MD simulated complexes, whereas heptapeptide interaction with DNA was missing in variants (I and II) in post-MD complexes. Consequently, through principal component analysis, wild-type WRKY was also found to be more stable by obscuring a reduced conformational space than the variant I (HvWRKY34). Lastly, high binding free energy for wild-type and variant II allowed us to conclude that wild-type WRKY-DNA complex was more stable relative to variants I. The results of our study revealed complete dynamic and structural information

Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.

PubMed

Babu, Mohan; Díaz-Mejía, J Javier; Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F; Emili, Andrew

2011-11-01

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners

PubMed Central

Strübbe, Gero; Popp, Christian; Schmidt, Alexander; Pauli, Andrea; Ringrose, Leonie; Beisel, Christian; Paro, Renato

2011-01-01

The maintenance of specific gene expression patterns during cellular proliferation is crucial for the identity of every cell type and the development of tissues in multicellular organisms. Such a cellular memory function is conveyed by the complex interplay of the Polycomb and Trithorax groups of proteins (PcG/TrxG). These proteins exert their function at the level of chromatin by establishing and maintaining repressed (PcG) and active (TrxG) chromatin domains. Past studies indicated that a core PcG protein complex is potentially associated with cell type or even cell stage-specific sets of accessory proteins. In order to better understand the dynamic aspects underlying PcG composition and function we have established an inducible version of the biotinylation tagging approach to purify Polycomb and associated factors from Drosophila embryos. This system enabled fast and efficient isolation of Polycomb containing complexes under near physiological conditions, thereby preserving substoichiometric interactions. Novel interacting proteins were identified by highly sensitive mass spectrometric analysis. We found many TrxG related proteins, suggesting a previously unrecognized extent of molecular interaction of the two counteracting chromatin regulatory protein groups. Furthermore, our analysis revealed an association of PcG protein complexes with the cohesin complex and showed that Polycomb-dependent silencing of a transgenic reporter depends on cohesin function. PMID:21415365

NMR Studies of the C-Terminus of alpha4 Reveal Possible Mechanism of Its Interaction with MID1 and Protein Phosphatase 2A

PubMed Central

Du, Haijuan; Massiah, Michael A.

2011-01-01

Alpha4 is a regulatory subunit of the protein phosphatase family of enzymes and plays an essential role in regulating the catalytic subunit of PP2A (PP2Ac) within the rapamycin-sensitive signaling pathway. Alpha4 also interacts with MID1, a microtubule-associated ubiquitin E3 ligase that appears to regulate the function of PP2A. The C-terminal region of alpha4 plays a key role in the binding interaction of PP2Ac and MID1. Here we report on the solution structure of a 45-amino acid region derived from the C-terminus of alpha4 (alpha45) that binds tightly to MID1. In aqueous solution, alpha45 has properties of an intrinsically unstructured peptide although chemical shift index and dihedral angle estimation based on chemical shifts of backbone atoms indicate the presence of a transient α-helix. Alpha45 adopts a helix-turn-helix HEAT-like structure in 1% SDS micelles, which may mimic a negatively charged surface for which alpha45 could bind. Alpha45 binds tightly to the Bbox1 domain of MID1 in aqueous solution and adopts a structure consistent with the helix-turn-helix structure observed in 1% SDS. The structure of alpha45 reveals two distinct surfaces, one that can interact with a negatively charged surface, which is present on PP2A, and one that interacts with the Bbox1 domain of MID1. PMID:22194938

Differential Anoxic Expression of Sugar-Regulated Genes Reveals Diverse Interactions between Sugar and Anaerobic Signaling Systems in Rice

PubMed Central

Lim, Mi-na; Lee, Sung-eun; Yim, Hui-kyeong; Kim, Jeong Hoe; Yoon, In Sun; Hwang, Yong-sic

2013-01-01

The interaction between the dual roles of sugar as a metabolic fuel and a regulatory molecule was unveiled by examining the changes in sugar signaling upon oxygen deprivation, which causes the drastic alteration in the cellular energy status. In our study, the expression of anaerobically induced genes is commonly responsive to sugar, either under the control of hexokinase or non-hexokinase mediated signaling cascades. Only sugar regulation via the hexokinase pathway was susceptible for O2 deficiency or energy deficit conditions evoked by uncoupler. Examination of sugar regulation of those genes under anaerobic conditions revealed the presence of multiple paths underlying anaerobic induction of gene expression in rice, subgrouped into three distinct types. The first of these, which was found in type-1 genes, involved neither sugar regulation nor additional anaerobic induction under anoxia, indicating that anoxic induction is a simple result from the release of sugar repression by O2-deficient conditions. In contrast, type-2 genes also showed no sugar regulation, albeit with enhanced expression under anoxia. Lastly, expression of type-3 genes is highly enhanced with sugar regulation sustained under anoxia. Intriguingly, the inhibition of the mitochondrial ATP synthesis can reproduce expression pattern of a specific set of anaerobically induced genes, implying that rice cells may sense O2 deprivation, partly via perception of the perturbed cellular energy status. Our study of interaction between sugar signaling and anaerobic conditions has revealed that sugar signaling and the cellular energy status are likely to communicate with each other and influence anaerobic induction of gene expression in rice. PMID:23852132

Molecular interaction of 2-mercaptobenzimidazole with catalase reveals a potentially toxic mechanism of the inhibitor.

PubMed

Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

2014-12-01

2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment possesses a potential risk to human health. In this work, the toxic interaction of MBI with the important antioxidant enzyme catalase (CAT) was investigated using spectroscopic and molecular docking methods under physiological conditions. MBI can spontaneously bind with CAT with one binding site through hydrogen bonds and van der Waals forces to form MBI-CAT complex. The molecular docking study revealed that MBI bound into the CAT interface of chains B and C, which led to some conformational and microenvironmental changes of CAT and further resulted in the inhibition of CAT activity. This present study provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme CAT. Copyright © 2014 Elsevier B.V. All rights reserved.

Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs

PubMed Central

Kinoshita, Masanao; Suzuki, Kenichi G.N.; Takada, Misa; Ano, Hikaru; Abe, Mitsuhiro; Makino, Asami; Kobayashi, Toshihide; Hirosawa, Koichiro M.; Fujiwara, Takahiro K.; Murata, Michio

2017-01-01

Sphingomyelin (SM) has been proposed to form cholesterol-dependent raft domains and sphingolipid domains in the plasma membrane (PM). How SM contributes to the formation and function of these domains remains unknown, primarily because of the scarcity of suitable fluorescent SM analogs. We developed new fluorescent SM analogs by conjugating a hydrophilic fluorophore to the SM choline headgroup without eliminating its positive charge, via a hydrophilic nonaethylene glycol linker. The new analogs behaved similarly to the native SM in terms of their partitioning behaviors in artificial liquid order-disorder phase-separated membranes and detergent-resistant PM preparations. Single fluorescent molecule tracking in the live-cell PM revealed that they indirectly interact with each other in cholesterol- and sphingosine backbone–dependent manners, and that, for ∼10–50 ms, they undergo transient colocalization-codiffusion with a glycosylphosphatidylinositol (GPI)-anchored protein, CD59 (in monomers, transient-dimer rafts, and clusters), in CD59-oligomer size–, cholesterol-, and GPI anchoring–dependent manners. These results suggest that SM continually and rapidly exchanges between CD59-associated raft domains and the bulk PM. PMID:28330937

Recent coselection in human populations revealed by protein-protein interaction network.

PubMed

Qian, Wei; Zhou, Hang; Tang, Kun

2014-12-21

Genome-wide scans for signals of natural selection in human populations have identified a large number of candidate loci that underlie local adaptations. This is surprising given the relatively short evolutionary time since the divergence of the human population. One hypothesis that has not been formally examined is whether and how the recent human evolution may have been shaped by coselection in the context of complex molecular interactome. In this study, genome-wide signals of selection were scanned in East Asians, Europeans, and Africans using 1000 Genome data, and subsequently mapped onto the protein-protein interaction (PPI) network. We found that the candidate genes of recent positive selection localized significantly closer to each other on the PPI network than expected, revealing substantial clustering of selected genes. Furthermore, gene pairs of shorter PPI network distances showed higher similarities of their recent evolutionary paths than those further apart. Last, subnetworks enriched with recent coselection signals were identified, which are substantially overrepresented in biological pathways related to signal transduction, neurogenesis, and immune function. These results provide the first genome-wide evidence for association of recent selection signals with the PPI network, shedding light on the potential mechanisms of recent coselection in the human genome. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

PubMed Central

Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J.; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F.; Emili, Andrew

2011-01-01

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. PMID:22125496

Simulated tri-trophic networks reveal complex relationships between species diversity and interaction diversity

PubMed Central

Lumpkin, Will; Hurtado, Paul J.; Dyer, Lee A.

2018-01-01

Most of earth’s biodiversity is comprised of interactions among species, yet it is unclear what causes variation in interaction diversity across space and time. We define interaction diversity as the richness and relative abundance of interactions linking species together at scales from localized, measurable webs to entire ecosystems. Large-scale patterns suggest that two basic components of interaction diversity differ substantially and predictably between different ecosystems: overall taxonomic diversity and host specificity of consumers. Understanding how these factors influence interaction diversity, and quantifying the causes and effects of variation in interaction diversity are important goals for community ecology. While previous studies have examined the effects of sampling bias and consumer specialization on determining patterns of ecological networks, these studies were restricted to two trophic levels and did not incorporate realistic variation in species diversity and consumer diet breadth. Here, we developed a food web model to generate tri-trophic ecological networks, and evaluated specific hypotheses about how the diversity of trophic interactions and species diversity are related under different scenarios of species richness, taxonomic abundance, and consumer diet breadth. We investigated the accumulation of species and interactions and found that interactions accumulate more quickly; thus, the accumulation of novel interactions may require less sampling effort than sampling species in order to get reliable estimates of either type of diversity. Mean consumer diet breadth influenced the correlation between species and interaction diversity significantly more than variation in both species richness and taxonomic abundance. However, this effect of diet breadth on interaction diversity is conditional on the number of observed interactions included in the models. The results presented here will help develop realistic predictions of the relationships

Simulated tri-trophic networks reveal complex relationships between species diversity and interaction diversity.

PubMed

Pardikes, Nicholas A; Lumpkin, Will; Hurtado, Paul J; Dyer, Lee A

2018-01-01

Most of earth's biodiversity is comprised of interactions among species, yet it is unclear what causes variation in interaction diversity across space and time. We define interaction diversity as the richness and relative abundance of interactions linking species together at scales from localized, measurable webs to entire ecosystems. Large-scale patterns suggest that two basic components of interaction diversity differ substantially and predictably between different ecosystems: overall taxonomic diversity and host specificity of consumers. Understanding how these factors influence interaction diversity, and quantifying the causes and effects of variation in interaction diversity are important goals for community ecology. While previous studies have examined the effects of sampling bias and consumer specialization on determining patterns of ecological networks, these studies were restricted to two trophic levels and did not incorporate realistic variation in species diversity and consumer diet breadth. Here, we developed a food web model to generate tri-trophic ecological networks, and evaluated specific hypotheses about how the diversity of trophic interactions and species diversity are related under different scenarios of species richness, taxonomic abundance, and consumer diet breadth. We investigated the accumulation of species and interactions and found that interactions accumulate more quickly; thus, the accumulation of novel interactions may require less sampling effort than sampling species in order to get reliable estimates of either type of diversity. Mean consumer diet breadth influenced the correlation between species and interaction diversity significantly more than variation in both species richness and taxonomic abundance. However, this effect of diet breadth on interaction diversity is conditional on the number of observed interactions included in the models. The results presented here will help develop realistic predictions of the relationships

Information theory and robotics meet to study predator-prey interactions

NASA Astrophysics Data System (ADS)

Neri, Daniele; Ruberto, Tommaso; Cord-Cruz, Gabrielle; Porfiri, Maurizio

2017-07-01

Transfer entropy holds promise to advance our understanding of animal behavior, by affording the identification of causal relationships that underlie animal interactions. A critical step toward the reliable implementation of this powerful information-theoretic concept entails the design of experiments in which causal relationships could be systematically controlled. Here, we put forward a robotics-based experimental approach to test the validity of transfer entropy in the study of predator-prey interactions. We investigate the behavioral response of zebrafish to a fear-evoking robotic stimulus, designed after the morpho-physiology of the red tiger oscar and actuated along preprogrammed trajectories. From the time series of the positions of the zebrafish and the robotic stimulus, we demonstrate that transfer entropy correctly identifies the influence of the stimulus on the focal subject. Building on this evidence, we apply transfer entropy to study the interactions between zebrafish and a live red tiger oscar. The analysis of transfer entropy reveals a change in the direction of the information flow, suggesting a mutual influence between the predator and the prey, where the predator adapts its strategy as a function of the movement of the prey, which, in turn, adjusts its escape as a function of the predator motion. Through the integration of information theory and robotics, this study posits a new approach to study predator-prey interactions in freshwater fish.

Physical and genetic-interaction density reveals functional organization and informs significance cutoffs in genome-wide screens

PubMed Central

Dittmar, John C.; Pierce, Steven; Rothstein, Rodney; Reid, Robert J. D.

2013-01-01

Genome-wide experiments often measure quantitative differences between treated and untreated cells to identify affected strains. For these studies, statistical models are typically used to determine significance cutoffs. We developed a method termed “CLIK” (Cutoff Linked to Interaction Knowledge) that overlays biological knowledge from the interactome on screen results to derive a cutoff. The method takes advantage of the fact that groups of functionally related interacting genes often respond similarly to experimental conditions and, thus, cluster in a ranked list of screen results. We applied CLIK analysis to five screens of the yeast gene disruption library and found that it defined a significance cutoff that differed from traditional statistics. Importantly, verification experiments revealed that the CLIK cutoff correlated with the position in the rank order where the rate of true positives drops off significantly. In addition, the gene sets defined by CLIK analysis often provide further biological perspectives. For example, applying CLIK analysis retrospectively to a screen for cisplatin sensitivity allowed us to identify the importance of the Hrq1 helicase in DNA crosslink repair. Furthermore, we demonstrate the utility of CLIK to determine optimal treatment conditions by analyzing genome-wide screens at multiple rapamycin concentrations. We show that CLIK is an extremely useful tool for evaluating screen quality, determining screen cutoffs, and comparing results between screens. Furthermore, because CLIK uses previously annotated interaction data to determine biologically informed cutoffs, it provides additional insights into screen results, which supplement traditional statistical approaches. PMID:23589890

Dynamic cross correlation studies of wave particle interactions in ULF phenomena

NASA Technical Reports Server (NTRS)

Mcpherron, R. L.

1979-01-01

Magnetic field observations made by satellites in the earth's magnetic field reveal a wide variety of ULF waves. These waves interact with the ambient particle populations in complex ways, causing modulation of the observed particle fluxes. This modulation is found to be a function of species, pitch angle, energy and time. The characteristics of this modulation provide information concerning the wave mode and interaction process. One important characteristic of wave-particle interactions is the phase of the particle flux modulation relative to the magnetic field variations. To display this phase as a function of time a dynamic cross spectrum program has been developed. The program produces contour maps in the frequency time plane of the cross correlation coefficient between any particle flux time series and the magnetic field vector. This program has been utilized in several studies of ULF wave-particle interactions at synchronous orbit.

Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

PubMed

Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E; Levesque, Brié; Pedersen, Stine B; Bartels, Lina; Wapenaar, Hannah; Ye, Fei; Zhang, Mingjie; Bowen, Mark E; Strømgaard, Kristian

2017-09-15

The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners. We observed complex effects on affinity. Most notably, phosphorylation at Y397 induced a significant increase in affinity for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we compared the effects of phosphorylation to phosphomimetic mutations, which revealed that phosphomimetics are ineffective substitutes for tyrosine phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD-95 interactions.

Content-Related Interactions in Self-initiated Study Groups

NASA Astrophysics Data System (ADS)

Christian, Karen; Talanquer, Vicente

2012-09-01

The central goal of the present exploratory study was to investigate the nature of the content-related interactions in study groups independently organized by college organic chemistry students. We were particularly interested in the identification of the different factors that affected the emergence of opportunities for students to co-construct understanding and engage in higher levels of cognitive processing. Our results are based on the analysis of in situ observations of 34 self-initiated study sessions involving over a 100 students in three academic semesters. The investigation revealed three major types of social regulation processes, teaching, tutoring, and co-construction in the observed study sessions. However, the extent to which students engaged in each of them varied widely from one session to another. This variability was mostly determined by the specific composition of the study groups and the nature of the study tasks in which they were engaged. Decisions about how to organize the study session, the relative content knowledge and conceptual understanding expressed by the participants, as well as the cognitive level of the problems that guided group work had a strong impact on the nature of student interactions. Nevertheless, group talk in the observed study groups was mostly focused on low-level cognitive processes. The results of our work provide insights on how to better support students' productive engagement in study groups.

Revealing the Interactional Features of Learning and Teaching Moments in Outdoor Activity

ERIC Educational Resources Information Center

Waters, Jane; Bateman, Amanda

2015-01-01

The data considered in this article was generated as part of a doctoral research study entitled: "A sociocultural consideration of child-initiated interaction with teachers in indoor and outdoor spaces" (Waters 2011) where child-initiated, teacher-child interaction in indoor and outdoor spaces were investigated. The purpose of the…

Environmental Interactions and Epistasis Are Revealed in the Proteomic Responses to Complex Stimuli

PubMed Central

Samir, Parimal; Rahul; Slaughter, James C.; Link, Andrew J.

2015-01-01

Ultimately, the genotype of a cell and its interaction with the environment determine the cell’s biochemical state. While the cell’s response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well. PMID:26247773

Revealing the role of oxidation state in interaction between nitro/amino-derived particulate matter and blood proteins

PubMed Central

Liu, Zhen; Li, Ping; Bian, Weiwei; Yu, Jingkai; Zhan, Jinhua

2016-01-01

Surface oxidation states of ultrafine particulate matter can influence the proinflammatory responses and reactive oxygen species levels in tissue. Surface active species of vehicle-emission soot can serve as electron transfer-mediators in mitochondrion. Revealing the role of surface oxidation state in particles-proteins interaction will promote the understanding on metabolism and toxicity. Here, the surface oxidation state was modeled by nitro/amino ligands on nanoparticles, the interaction with blood proteins were evaluated by capillary electrophoresis quantitatively. The nitro shown larger affinity than amino. On the other hand, the affinity to hemoglobin is 103 times larger than that to BSA. Further, molecular docking indicated the difference of binding intensity were mainly determined by hydrophobic forces and hydrogen bonds. These will deepen the quantitative understanding of protein-nanoparticles interaction from the perspective of surface chemical state. PMID:27181651

Free-energy calculations reveal the subtle differences in the interactions of DNA bases with α-hemolysin.

PubMed

Manara, Richard M A; Guy, Andrew T; Wallace, E Jayne; Khalid, Syma

2015-02-10

Next generation DNA sequencing methods that utilize protein nanopores have the potential to revolutionize this area of biotechnology. While the technique is underpinned by simple physics, the wild-type protein pores do not have all of the desired properties for efficient and accurate DNA sequencing. Much of the research efforts have focused on protein nanopores, such as α-hemolysin from Staphylococcus aureus. However, the speed of DNA translocation has historically been an issue, hampered in part by incomplete knowledge of the energetics of translocation. Here we have utilized atomistic molecular dynamics simulations of nucleotide fragments in order to calculate the potential of mean force (PMF) through α-hemolysin. Our results reveal specific regions within the pore that play a key role in the interaction with DNA. In particular, charged residues such as D127 and K131 provide stabilizing interactions with the anionic DNA and therefore are likely to reduce the speed of translocation. These regions provide rational targets for pore optimization. Furthermore, we show that the energetic contributions to the protein-DNA interactions are a complex combination of electrostatics and short-range interactions, often mediated by water molecules.

A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

PubMed

Bush, W S; McCauley, J L; DeJager, P L; Dudek, S M; Hafler, D A; Gibson, R A; Matthews, P M; Kappos, L; Naegelin, Y; Polman, C H; Hauser, S L; Oksenberg, J; Haines, J L; Ritchie, M D

2011-07-01

Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-β isoforms, PLCβ1 and PLCβ4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.

Supramolecular Interactions in Secondary Plant Cell Walls: Effect of Lignin Chemical Composition Revealed with the Molecular Theory of Solvation.

PubMed

Silveira, Rodrigo L; Stoyanov, Stanislav R; Gusarov, Sergey; Skaf, Munir S; Kovalenko, Andriy

2015-01-02

Plant biomass recalcitrance, a major obstacle to achieving sustainable production of second generation biofuels, arises mainly from the amorphous cell-wall matrix containing lignin and hemicellulose assembled into a complex supramolecular network that coats the cellulose fibrils. We employed the statistical-mechanical, 3D reference interaction site model with the Kovalenko-Hirata closure approximation (or 3D-RISM-KH molecular theory of solvation) to reveal the supramolecular interactions in this network and provide molecular-level insight into the effective lignin-lignin and lignin-hemicellulose thermodynamic interactions. We found that such interactions are hydrophobic and entropy-driven, and arise from the expelling of water from the mutual interaction surfaces. The molecular origin of these interactions is carbohydrate-π and π-π stacking forces, whose strengths are dependent on the lignin chemical composition. Methoxy substituents in the phenyl groups of lignin promote substantial entropic stabilization of the ligno-hemicellulosic matrix. Our results provide a detailed molecular view of the fundamental interactions within the secondary plant cell walls that lead to recalcitrance.

The Promise of Systems Biology Approaches for Revealing Host Pathogen Interactions in Malaria

PubMed Central

Zuck, Meghan; Austin, Laura S.; Danziger, Samuel A.; Aitchison, John D.; Kaushansky, Alexis

2017-01-01

Despite global eradication efforts over the past century, malaria remains a devastating public health burden, causing almost half a million deaths annually (WHO, 2016). A detailed understanding of the mechanisms that control malaria infection has been hindered by technical challenges of studying a complex parasite life cycle in multiple hosts. While many interventions targeting the parasite have been implemented, the complex biology of Plasmodium poses a major challenge, and must be addressed to enable eradication. New approaches for elucidating key host-parasite interactions, and predicting how the parasite will respond in a variety of biological settings, could dramatically enhance the efficacy and longevity of intervention strategies. The field of systems biology has developed methodologies and principles that are well poised to meet these challenges. In this review, we focus our attention on the Liver Stage of the Plasmodium lifecycle and issue a “call to arms” for using systems biology approaches to forge a new era in malaria research. These approaches will reveal insights into the complex interplay between host and pathogen, and could ultimately lead to novel intervention strategies that contribute to malaria eradication. PMID:29201016

A study on the interactions of amino acids with nitrogen doped graphene; docking, MD simulation, and QM/MM studies.

PubMed

Ghadari, Rahim

2016-02-14

The binding properties of twenty amino acids with nitrogen-doped graphene structures were studied using docking, MD simulation, and QM/MM methods. TDDFT studies were carried out to investigate the change in the electronic properties of the amino acids because of the presence of the solvent and nitrogen-doped graphene. The results revealed that π-π interactions between the amino acids with a benzene moiety and the surface of the graphene are the most important interactions. The observed red shifts in the TDDFT results which were related to the lower LUMO energies and higher HOMO energies are consistent with this statement.

Interactive Visualization of Dependencies

ERIC Educational Resources Information Center

Moreno, Camilo Arango; Bischof, Walter F.; Hoover, H. James

2012-01-01

We present an interactive tool for browsing course requisites as a case study of dependency visualization. This tool uses multiple interactive visualizations to allow the user to explore the dependencies between courses. A usability study revealed that the proposed browser provides significant advantages over traditional methods, in terms of…

Coevolution study of mitochondria respiratory chain proteins: toward the understanding of protein--protein interaction.

PubMed

Yang, Ming; Ge, Yan; Wu, Jiayan; Xiao, Jingfa; Yu, Jun

2011-05-20

Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein--protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 × 10(-6)). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein--protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Copyright © 2011. Published by Elsevier Ltd.

Spectroscopic Study on the Interaction of 4-dimethylaminochalcones with Phospholipids

NASA Astrophysics Data System (ADS)

Tomečková, V.; Revická, M.; Sassen, A.; Veliká, B.; Stupák, M.; Perjési, P.

2014-11-01

The ultraviolet-visible and fluorescence spectroscopic properties of 4'-dimethylaminochalcone ( 1a) and its cyclic analogs 2a-4a have been studied in the presence of phospholipid vesicles (i.e., egg yolk lecithin and dipalmitoylpho sphatidylcholine), bovine serum albumin (BSA), and lipoprotein particles (i.e., bovine serum albumin plus egg yolk lecithin). The spectral results showed that compounds 1a-4a formed hydrophobic interactions with the phospholipids, lipoproteins, and BSA at the polar/nonpolar interface. Compounds 3a and 4a exhibited the strongest hydrophobic interactions of all of the compounds tested towards the phospholipids. Compound 2a gave the best fluorescent fluorophore indicating interactions with the lipids, lipoproteins, and proteins. Fluorescent microscopic imaging of breast cancer cells treated with compounds 1a-4a revealed that they could be used to stain all of the cellular components and destroy the nuclear structure. Compounds 1a-4a were found to be concentrated predominantly on the surfaces of the liposomes and lipoproteins.

Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

NASA Astrophysics Data System (ADS)

Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

2014-01-01

Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

A proteomic analysis reveals the interaction of GluK1 ionotropic kainate receptor subunits with Go proteins.

PubMed

Rutkowska-Wlodarczyk, Izabela; Aller, M Isabel; Valbuena, Sergio; Bologna, Jean-Charles; Prézeau, Laurent; Lerma, Juan

2015-04-01

Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved. Here we performed a proteomic analysis to define proteins that interact with the C-terminal domain of GluK1 and we identified a variety of proteins with many different functions, including a Go α subunit. These interactions were verified through distinct in vitro and in vivo assays, and the activation of the Go protein by GluK1 was validated in bioluminescence resonance energy transfer experiments, while the specificity of this association was confirmed in GluK1-deficient mice. These data reveal components of the KAR interactome, and they show that GluK1 and Go proteins are natural partners, accounting for the metabotropic effects of KARs. Copyright © 2015 the authors 0270-6474/15/355171-09$15.00/0.

A study of social interaction and teamwork in reformed physics laboratories

NASA Astrophysics Data System (ADS)

Gresser, Paul W.

It is widely accepted that, for many students, learning can be accomplished most effectively through social interaction with peers, and there have been many successes in using the group environment to improve learning in a variety of classroom settings. What is not well understood, however, are the dynamics of student groups, specifically how the students collectively apprehend the subject matter and share the mental workload. This research examines recent developments of theoretical tools for describing the cognitive states of individual students: associational patterns such as epistemic games and cultural structures such as epistemological framing. Observing small group interaction in authentic classroom situations (labs, tutorials, problem solving) suggests that these tools could be effective in describing these interactions. Though conventional wisdom tells us that groups may succeed where individuals fail, there are many reasons why group work may also run into difficulties, such as a lack or imbalance of knowledge, an inappropriate mix of learning styles, or a destructive power arrangement. This research explores whether or not inconsistent epistemological framing among group members can also be a cause of group failure. Case studies of group interaction in the laboratory reveal evidence of successful groups employing common framing, and unsuccessful groups failing from lack of a shared frame. This study was conducted in a large introductory algebra-based physics course at the University of Maryland, College Park, in a laboratory designed specifically to foster increased student interaction and cooperation. Videotape studies of this environment reveal that productive lab groups coordinate their efforts through a number of locally coherent knowledge-building activities, which are described through the framework of epistemic games. The existence of these epistemic games makes it possible for many students to participate in cognitive activities without a

Sunitinib: from charge-density studies to interaction with proteins.

PubMed

Malińska, Maura; Jarzembska, Katarzyna N; Goral, Anna M; Kutner, Andrzej; Woźniak, Krzysztof; Dominiak, Paulina M

2014-05-01

Protein kinases are targets for the treatment of a number of diseases. Sunitinib malate is a type I inhibitor of tyrosine kinases and was approved as a drug in 2006. This contribution constitutes the first comprehensive analysis of the crystal structures of sunitinib malate and of complexes of sunitinib with a series of protein kinases. The high-resolution single-crystal X-ray measurement and aspherical atom databank approach served as a basis for reconstruction of the charge-density distribution of sunitinib and its protein complexes. Hirshfeld surface and topological analyses revealed a similar interaction pattern in the sunitinib malate crystal structure to that in the protein binding pockets. Sunitinib forms nine preserved bond paths corresponding to hydrogen bonds and also to the C-H···O and C-H···π contacts common to the VEGRF2, CDK2, G2, KIT and IT kinases. In general, sunitinib interacts with the studied proteins with a similar electrostatic interaction energy and can adjust its conformation to fit the binding pocket in such a way as to enhance the electrostatic interactions, e.g. hydrogen bonds in ligand-kinase complexes. Such behaviour may be responsible for the broad spectrum of action of sunitinib as a kinase inhibitor.

Studies on interaction of norbixin with DNA: Multispectroscopic and in silico analysis

NASA Astrophysics Data System (ADS)

Anantharaman, Amrita; Priya, Rajendra Rao; Hemachandran, Hridya; Sivaramakrishna, Akella; Babu, Subramanian; Siva, Ramamoorthy

2015-06-01

The interaction of food colorant norbixin with calf thymus DNA (CTDNA) was investigated through UV-Visible spectroscopy, Fourier Transform Infrared (FTIR), Circular Dichroism (CD), Nuclear Magnetic Resonance (NMR), DNA melting studies, electrophoretic analysis, histological staining technique and molecular docking studies. The results indicated that norbixin interacted with CTDNA by partial intercalation mode. The binding constant (K) of norbixin with CTDNA was calculated to be 5.08 × 105 Mol-1 L. FTIR and CD studies were coupled with 1H NMR spectra revealed that norbixin intercalates partially and binds to the groove's, phosphate group, deoxyribose sugar of DNA and also induces conformational transition of B-form to A-form DNA. Agarose gel electrophoretic and histological staining technique results further prove that, norbixin specifically binds to the DNA in the cell. Moreover, molecular docking studies on the specific binding of norbixin with CTDNA have exhibited lowest conformation energy score of -3.2. Therefore, this food colorant has the ability to interact with DNA and it could emerge as a promising class of natural DNA targeted therapeutic.

Genes involved in host-parasite interactions can be revealed by their correlated expression.

PubMed

Reid, Adam James; Berriman, Matthew

2013-02-01

Molecular interactions between a parasite and its host are key to the ability of the parasite to enter the host and persist. Our understanding of the genes and proteins involved in these interactions is limited. To better understand these processes it would be advantageous to have a range of methods to predict pairs of genes involved in such interactions. Correlated gene expression profiles can be used to identify molecular interactions within a species. Here we have extended the concept to different species, showing that genes with correlated expression are more likely to encode proteins, which directly or indirectly participate in host-parasite interaction. We go on to examine our predictions of molecular interactions between the malaria parasite and both its mammalian host and insect vector. Our approach could be applied to study any interaction between species, for example, between a host and its parasites or pathogens, but also symbiotic and commensal pairings.

Hyperspectral remote sensing and long term monitoring reveal watershed-estuary ecosystem interactions

NASA Astrophysics Data System (ADS)

Hestir, E. L.; Schoellhamer, D. H.; Santos, M. J.; Greenberg, J. A.; Morgan-King, T.; Khanna, S.; Ustin, S.

2016-02-01

Estuarine ecosystems and their biogeochemical processes are extremely vulnerable to climate and environmental changes, and are threatened by sea level rise and upstream activities such as land use/land cover and hydrological changes. Despite the recognized threat to estuaries, most aspects of how change will affect estuaries are not well understood due to the poorly resolved understanding of the complex physical, chemical and biological processes and their interactions in estuarine systems. Remote sensing technologies such as high spectral resolution optical systems enable measurements of key environmental parameters needed to establish baseline conditions and improve modeling efforts. The San Francisco Bay-Delta is a highly modified estuary system in a state of ecological crisis due to the numerous threats to its sustainability. In this study, we used a combination of hyperspectral remote sensing and long-term in situ monitoring records to investigate how water clarity has been responding to extreme climatic events, anthropogenic watershed disturbances, and submerged aquatic vegetation (SAV) invasions. From the long-term turbidity monitoring record, we found that water clarity underwent significant increasing step changes associated with sediment depletion and El Nino-extreme run-off events. Hyperspectral remote sensing data revealed that invasive submerged aquatic pant species have facultative C3 and C4-like photosynthetic pathways that give them a competitive advantage under the changing water clarity conditions of the Bay-Delta system. We postulate that this adaptation facilitated the rapid expansion of SAV following the significant step changes in increasing water clarity caused by watershed disturbances and the 1982-1983 El Nino events. Using SAV maps from hyperspectral remote sensing, we estimate that SAV-water clarity feedbacks were responsible for 20-70% of the increasing water clarity trend in the Bay-Delta. Ongoing and future developments in airborne and

Covalent Label Transfer between Peroxisomal Importomer Components Reveals Export-driven Import Interactions.

PubMed

Bhogal, Moninder S; Lanyon-Hogg, Thomas; Johnston, Katherine A; Warriner, Stuart L; Baker, Alison

2016-01-29

Peroxisomes are vital metabolic organelles found in almost all eukaryotic organisms, and they rely exclusively on import of their matrix protein content from the cytosol. In vitro import of proteins into isolated peroxisomal fractions has provided a wealth of knowledge on the import process. However, the common method of protease protection garnered no information on the import of an N-terminally truncated PEX5 (PEX5C) receptor construct or peroxisomal malate dehydrogenase 1 (pMDH1) cargo protein into sunflower peroxisomes because of high degrees of protease susceptibility or resistance, respectively. Here we present a means for analysis of in vitro import through a covalent biotin label transfer and employ this method to the import of PEX5C. Label transfer demonstrates that the PEX5C construct is monomeric under the conditions of the import assay. This technique was capable of identifying the PEX5-PEX14 interaction as the first interaction of the import process through competition experiments. Labeling of the peroxisomal protein import machinery by PEX5C demonstrated that this interaction was independent of added cargo protein, and, strikingly, the interaction between PEX5C and the import machinery was shown to be ATP-dependent. These important mechanistic insights highlight the power of label transfer in studying interactions, rather than proteins, of interest and demonstrate that this technique should be applied to future studies of peroxisomal in vitro import. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Evolution of acyl-ACP-thioesterases and β-ketoacyl-ACP-synthases revealed by protein-protein interactions.

PubMed

Beld, Joris; Blatti, Jillian L; Behnke, Craig; Mendez, Michael; Burkart, Michael D

2014-08-01

The fatty acid synthase (FAS) is a conserved primary metabolic enzyme complex capable of tolerating cross-species engineering of domains for the development of modified and overproduced fatty acids. In eukaryotes, acyl-acyl carrier protein thioesterases (TEs) off-load mature cargo from the acyl carrier protein (ACP), and plants have developed TEs for short/medium-chain fatty acids. We showed that engineering plant TEs into the green microalga Chlamydomonas reinhardtii does not result in the predicted shift in fatty acid profile. Since fatty acid biosynthesis relies on substrate recognition and protein-protein interactions between the ACP and its partner enzymes, we hypothesized that plant TEs and algal ACP do not functionally interact. Phylogenetic analysis revealed major evolutionary differences between FAS enzymes, including TEs and ketoacyl synthases (KSs), in which the former is present only in some species, whereas the latter is present in all, and has a common ancestor. In line with these results, TEs appeared to be selective towards their ACP partners whereas KSs showed promiscuous behavior across bacterial, plant and algal species. Based on phylogenetic analyses, in silico docking, in vitro mechanistic crosslinking and in vivo algal engineering, we propose that phylogeny can predict effective interactions between ACPs and partner enzymes.

Evolution of acyl-ACP-thioesterases and β-ketoacyl-ACP-synthases revealed by protein-protein interactions

PubMed Central

Beld, Joris; Blatti, Jillian L.; Behnke, Craig; Mendez, Michael; Burkart, Michael D.

2014-01-01

The fatty acid synthase (FAS) is a conserved primary metabolic enzyme complex capable of tolerating cross-species engineering of domains for the development of modified and overproduced fatty acids. In eukaryotes, acyl-acyl carrier protein thioesterases (TEs) off-load mature cargo from the acyl carrier protein (ACP), and plants have developed TEs for short/medium-chain fatty acids. We showed that engineering plant TEs into the green microalga Chlamydomonas reinhardtii does not result in the predicted shift in fatty acid profile. Since fatty acid biosynthesis relies on substrate recognition and protein-protein interactions between the ACP and its partner enzymes, we hypothesized that plant TEs and algal ACP do not functionally interact. Phylogenetic analysis revealed major evolutionary differences between FAS enzymes, including TEs and ketoacyl synthases (KSs), in which the former is present only in some species, whereas the latter is present in all, and has a common ancestor. In line with these results, TEs appeared to be selective towards their ACP partners whereas KSs showed promiscuous behavior across bacterial, plant and algal species. Based on phylogenetic analyses, in silico docking, in vitro mechanistic crosslinking and in vivo algal engineering, we propose that phylogeny can predict effective interactions between ACPs and partner enzymes. PMID:25110394

Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid.

PubMed

Asai, Shuta; Rallapalli, Ghanasyam; Piquerez, Sophie J M; Caillaud, Marie-Cécile; Furzer, Oliver J; Ishaque, Naveed; Wirthmueller, Lennart; Fabro, Georgina; Shirasu, Ken; Jones, Jonathan D G

2014-10-01

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome.

Lattice QCD studies of s-wave meson-baryon interactions

NASA Astrophysics Data System (ADS)

Ikeda, Yoichi

2011-10-01

We study the s-wave KN interactions in the isospin I = 0, 1 channels and associated exotic state Θ+ from 2+1 flavor full lattice QCD simulation for relatively heavy quark mass corresponding to mπ = 871 MeV. The s-wave KN potentials are obtained from the Bethe-Salpeter amplitudes. Potentials in both channels reveal short range repulsions: Strength of the repulsion is stronger in the I = 1 potential. The I = 0 potential is found to have attractive well at mid range. The KN scattering phase shifts are calculated and compared with the experimental data.

Neurobehavioral Integrity of Chimpanzee Newborns: Comparisons across groups and across species reveal gene-environment interaction effects

PubMed Central

Bard, Kim A.; Brent, Linda; Lester, Barry; Worobey, John; Suomi, Stephen J.

2014-01-01

The aims of this article are to describe the neurobehavioral integrity of chimpanzee newborns, to investigate how early experiences affect the neurobehavioral organization of chimpanzees, and to explore species differences by comparing chimpanzee newborns to a group of typically developing human newborns. Neurobehavioral integrity related to orientation, motor performance, arousal, and state regulation of 55 chimpanzee (raised in four different settings) and 42 human newborns was measured with the Neonatal Behavioral Assessment Scale (NBAS) a semi-structured 25-minute interactive assessment. Thirty-eight chimpanzees were tested every other day from birth, and analyses revealed significant developmental changes in 19 of 27 NBAS scores. The cross-group and cross-species comparisons were conducted at 2 and 30 days of age. Among the 4 chimpanzee groups, significant differences were found in 23 of 24 NBAS scores. Surprisingly, the cross-species comparisons revealed that the human group was distinct in only 1 of 25 NBAS scores (the human group had significantly less muscle tone than all the chimpanzee groups). The human group was indistinguishable from at least one of the chimpanzee groups in the remaining 24 of 25 NBAS scores. The results of this study support the conclusion that the interplay between genes and environment, rather than genes alone or environment alone, accounts for phenotypic expressions of newborn neurobehavioral integrity in hominids. PMID:25110465

Interactions between Skeletal Muscle Myoblasts and their Extracellular Matrix Revealed by a Serum Free Culture System.

PubMed

Chaturvedi, Vishal; Dye, Danielle E; Kinnear, Beverley F; van Kuppevelt, Toin H; Grounds, Miranda D; Coombe, Deirdre R

2015-01-01

Decellularisation of skeletal muscle provides a system to study the interactions of myoblasts with muscle extracellular matrix (ECM). This study describes the efficient decellularisation of quadriceps muscle with the retention of matrix components and the use of this matrix for myoblast proliferation and differentiation under serum free culture conditions. Three decellularisation approaches were examined; the most effective was phospholipase A2 treatment, which removed cellular material while maximizing the retention of ECM components. Decellularised muscle matrices were then solubilized and used as substrates for C2C12 mouse myoblast serum free cultures. The muscle matrix supported myoblast proliferation and differentiation equally as well as collagen and fibronectin. Immunofluorescence analyses revealed that myoblasts seeded on muscle matrix and fibronectin differentiated to form long, well-aligned myotubes, while myoblasts seeded on collagen were less organized. qPCR analyses showed a time dependent increase in genes involved in skeletal muscle differentiation and suggested that muscle-derived matrix may stimulate an increased rate of differentiation compared to collagen and fibronectin. Decellularized whole muscle three-dimensional scaffolds also supported cell adhesion and spreading, with myoblasts aligning along specific tracts of matrix proteins within the scaffolds. Thus, under serum free conditions, intact acellular muscle matrices provided cues to direct myoblast adhesion and migration. In addition, myoblasts were shown to rapidly secrete and organise their own matrix glycoproteins to create a localized ECM microenvironment. This serum free culture system has revealed that the correct muscle ECM facilitates more rapid cell organisation and differentiation than single matrix glycoprotein substrates.

Mother-infant interactions and regional brain volumes in infancy: an MRI study.

PubMed

Sethna, Vaheshta; Pote, Inês; Wang, Siying; Gudbrandsen, Maria; Blasi, Anna; McCusker, Caroline; Daly, Eileen; Perry, Emily; Adams, Kerrie P H; Kuklisova-Murgasova, Maria; Busuulwa, Paula; Lloyd-Fox, Sarah; Murray, Lynne; Johnson, Mark H; Williams, Steven C R; Murphy, Declan G M; Craig, Michael C; McAlonan, Grainne M

2017-07-01

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.

Social risky decision-making reveals gender differences in the TPJ: A hyperscanning study using functional near-infrared spectroscopy.

PubMed

Zhang, Mingming; Liu, Tao; Pelowski, Matthew; Jia, Huibin; Yu, Dongchuan

2017-12-01

Previous neuroscience studies have investigated neural correlates of risky decision-making in a single-brain frame during pseudo social (predominantly non face-to-face) contexts. To fully understand the risky decision-making behavior in more natural social interactions, the present study employed a functional near-infrared spectroscopy (fNIRS) hyperscanning technique to simultaneously measure pairs of participants' fronto-temporal activations in a face-to-face gambling card-game. The intra-brain results revealed that both those who identified as males and as females showed higher activations in their mPFC and in the inferior parts of the frontopolar area, as well as in the tempo-parietal junction (TPJ) in cases involving higher versus lower risk. This is consistent with previous findings suggesting importance of the mentalizing network in decision tasks. The fNIRS results of inter-brain neural synchronization (INS) also revealed that males and females showed increased inter-brain coherence in the mPFC and dlPFC. Females, however, uniquely showed increased inter-brain coherence in the left TPJ. This INS result suggests that males may primarily depend on non-social cognitive ability to make a risky decision in a social interaction, while females may use both social and non-social cognitive abilities. The implications are also discussed for general topics of human interaction and two-person neuroscience. Copyright © 2017 Elsevier Inc. All rights reserved.

Mutual influence between triel bond and cation-π interactions: an ab initio study

NASA Astrophysics Data System (ADS)

Esrafili, Mehdi D.; Mousavian, Parisasadat

2017-12-01

Using ab initio calculations, the cooperative and solvent effects on cation-π and B...N interactions are studied in some model ternary complexes, where these interactions coexist. The nature of the interactions and the mechanism of cooperativity are investigated by means of quantum theory of atoms in molecules (QTAIM), noncovalent interaction (NCI) index and natural bond orbital analysis. The results indicate that all cation-π and B...N binding distances in the ternary complexes are shorter than those of corresponding binary systems. The QTAIM analysis reveals that ternary complexes have higher electron density at their bond critical points relative to the corresponding binary complexes. In addition, according to the QTAIM analysis, the formation of cation-π interaction increases covalency of B...N bonds. The NCI analysis indicates that the cooperative effects in the ternary complexes make a shift in the location of the spike associated with each interaction, which can be regarded as an evidence for the reinforcement of both cation-π and B...N interactions in these systems. Solvent effects on the cooperativity of cation-π and B...N interactions are also investigated.

Reveal genes functionally associated with ACADS by a network study.

PubMed

Chen, Yulong; Su, Zhiguang

2015-09-15

Establishing a systematic network is aimed at finding essential human gene-gene/gene-disease pathway by means of network inter-connecting patterns and functional annotation analysis. In the present study, we have analyzed functional gene interactions of short-chain acyl-coenzyme A dehydrogenase gene (ACADS). ACADS plays a vital role in free fatty acid β-oxidation and regulates energy homeostasis. Modules of highly inter-connected genes in disease-specific ACADS network are derived by integrating gene function and protein interaction data. Among the 8 genes in ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with ACADS are HAHDA, HADHB, ECHS1 and ACAT1. Interestingly, the ontological aspect of genes in the ACADS network reveals that ACADS, HAHDA and HADHB play equally vital roles in fatty acid metabolism. The gene ACAT1 together with ACADS indulges in ketone metabolism. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of ACADS, HAHDA, HADHB, ECHS1 and ACAT1 not only with lipid metabolism but also with infant death syndrome, skeletal myopathy, acute hepatic encephalopathy, Reye-like syndrome, episodic ketosis, and metabolic acidosis. The current study presents a comprehensible layout of ACADS network, its functional strategies and candidate disease approach associated with ACADS network. Copyright © 2015 Elsevier B.V. All rights reserved.

The Dynamic Reactance Interaction - How Vested Interests Affect People's Experience, Behavior, and Cognition in Social Interactions.

PubMed

Steindl, Christina; Jonas, Eva

2015-01-01

In social interactions, individuals may sometimes pursue their own interests at the expense of their interaction partner. Such self-interested behaviors impose a threat to the interaction partner's freedom to act. The current article investigates this threat in the context of interdependence and reactance theory. We explore how vested interests influence reactance process stages of an advisor-client interaction. We aim to explore the interactional process that evolves. In two studies, participants took the perspective of a doctor (advisor) or a patient (client). In both studies we incorporated a vested interest. In Study 1 (N = 82) we found that in response to a vested interest of their interaction partner, patients indicated a stronger experience of reactance, more aggressive behavioral intentions, and more biased cognitions than doctors. A serial multiple mediation revealed that a vested interest engendered mistrust toward the interaction partner and this mistrust led to an emerging reactance process. Study 2 (N = 207) further demonstrated that doctors expressed their reactance in a subtle way: they revealed a classic confirmation bias when searching for additional information on their preliminary decision preference, indicating stronger defense motivation. We discuss how these findings can help us to understand how social interactions develop dynamically.

Possible interaction between baryons and dark-matter particles revealed by the first stars.

PubMed

Barkana, Rennan

2018-02-28

The cosmic radio-frequency spectrum is expected to show a strong absorption signal corresponding to the 21-centimetre-wavelength transition of atomic hydrogen around redshift 20, which arises from Lyman-α radiation from some of the earliest stars. By observing this 21-centimetre signal-either its sky-averaged spectrum or maps of its fluctuations, obtained using radio interferometers-we can obtain information about cosmic dawn, the era when the first astrophysical sources of light were formed. The recent detection of the global 21-centimetre spectrum reveals a stronger absorption than the maximum predicted by existing models, at a confidence level of 3.8 standard deviations. Here we report that this absorption can be explained by the combination of radiation from the first stars and excess cooling of the cosmic gas induced by its interaction with dark matter. Our analysis indicates that the spatial fluctuations of the 21-centimetre signal at cosmic dawn could be an order of magnitude larger than previously expected and that the dark-matter particle is no heavier than several proton masses, well below the commonly predicted mass of weakly interacting massive particles. Our analysis also confirms that dark matter is highly non-relativistic and at least moderately cold, and primordial velocities predicted by models of warm dark matter are potentially detectable. These results indicate that 21-centimetre cosmology can be used as a dark-matter probe.

Possible interaction between baryons and dark-matter particles revealed by the first stars

NASA Astrophysics Data System (ADS)

Barkana, Rennan

2018-03-01

The cosmic radio-frequency spectrum is expected to show a strong absorption signal corresponding to the 21-centimetre-wavelength transition of atomic hydrogen around redshift 20, which arises from Lyman-α radiation from some of the earliest stars. By observing this 21-centimetre signal—either its sky-averaged spectrum or maps of its fluctuations, obtained using radio interferometers—we can obtain information about cosmic dawn, the era when the first astrophysical sources of light were formed. The recent detection of the global 21-centimetre spectrum reveals a stronger absorption than the maximum predicted by existing models, at a confidence level of 3.8 standard deviations. Here we report that this absorption can be explained by the combination of radiation from the first stars and excess cooling of the cosmic gas induced by its interaction with dark matter. Our analysis indicates that the spatial fluctuations of the 21-centimetre signal at cosmic dawn could be an order of magnitude larger than previously expected and that the dark-matter particle is no heavier than several proton masses, well below the commonly predicted mass of weakly interacting massive particles. Our analysis also confirms that dark matter is highly non-relativistic and at least moderately cold, and primordial velocities predicted by models of warm dark matter are potentially detectable. These results indicate that 21-centimetre cosmology can be used as a dark-matter probe.

Syntopic frogs reveal different patterns of interaction with the landscape: A comparative landscape genetic study of Pelophylax nigromaculatus and Fejervarya limnocharis from central China.

PubMed

Garcia, Vhon Oliver S; Ivy, Catherine; Fu, Jinzhong

2017-11-01

Amphibians are often considered excellent environmental indicator species. Natural and man-made landscape features are known to form effective genetic barriers to amphibian populations; however, amphibians with different characteristics may have different species-landscape interaction patterns. We conducted a comparative landscape genetic analysis of two closely related syntopic frog species from central China, Pelophylax nigromaculatus ( PN ) and Fejervarya limnocharis ( FL ). These two species differ in several key life history traits; PN has a larger body size and larger clutch size, and reaches sexual maturity later than FL . Microsatellite DNA data were collected and analyzed using conventional ( F ST , isolation by distance (IBD), AMOVA) and recently developed (Bayesian assignment test, isolation by resistance) landscape genetic methods. As predicted, a higher level of population structure in FL ( F ST ' = 0.401) than in PN ( F ST ' = 0.354) was detected, in addition to FL displaying strong IBD patterns ( r  =   .861) unlike PN ( r  =   .073). A general north-south break in FL populations was detected, consistent with the IBD pattern, while PN exhibited clustering of northern- and southern-most populations, suggestive of altered dispersal patterns. Species-specific resistant landscape features were also identified, with roads and land cover the main cause of resistance to FL , and elevation the main influence on PN . These different species-landscape interactions can be explained mostly by their life history traits, revealing that closely related and ecologically similar species have different responses to the same landscape features. Comparative landscape genetic studies are important in detecting such differences and refining generalizations about amphibians in monitoring environmental changes.

Combined zebrafish-yeast chemical-genetic screens reveal gene-copper-nutrition interactions that modulate melanocyte pigmentation.

PubMed

Ishizaki, Hironori; Spitzer, Michaela; Wildenhain, Jan; Anastasaki, Corina; Zeng, Zhiqiang; Dolma, Sonam; Shaw, Michael; Madsen, Erik; Gitlin, Jonathan; Marais, Richard; Tyers, Mike; Patton, E Elizabeth

2010-01-01

Hypopigmentation is a feature of copper deficiency in humans, as caused by mutation of the copper (Cu(2+)) transporter ATP7A in Menkes disease, or an inability to absorb copper after gastric surgery. However, many causes of copper deficiency are unknown, and genetic polymorphisms might underlie sensitivity to suboptimal environmental copper conditions. Here, we combined phenotypic screens in zebrafish for compounds that affect copper metabolism with yeast chemical-genetic profiles to identify pathways that are sensitive to copper depletion. Yeast chemical-genetic interactions revealed that defects in intracellular trafficking pathways cause sensitivity to low-copper conditions; partial knockdown of the analogous Ap3s1 and Ap1s1 trafficking components in zebrafish sensitized developing melanocytes to hypopigmentation in low-copper environmental conditions. Because trafficking pathways are essential for copper loading into cuproproteins, our results suggest that hypomorphic alleles of trafficking components might underlie sensitivity to reduced-copper nutrient conditions. In addition, we used zebrafish-yeast screening to identify a novel target pathway in copper metabolism for the small-molecule MEK kinase inhibitor U0126. The zebrafish-yeast screening method combines the power of zebrafish as a disease model with facile genome-scale identification of chemical-genetic interactions in yeast to enable the discovery and dissection of complex multigenic interactions in disease-gene networks.

Molecular interaction of triclosan with superoxide dismutase (SOD) reveals a potentially toxic mechanism of the antimicrobial agent.

PubMed

Mi, Chenyu; Teng, Yue; Wang, Xiaofang; Yu, Hongyan; Huang, Zhenxing; Zong, Wansong; Zou, Luyi

2018-05-30

In this article, the interaction mechanism between the superoxide dismutase (SOD) and the triclosan (TCS), a kind of antimicrobial agent which is of widely application with potential effects both on environment and human health, was explored through a series of spectroscopic methods, animal experiment and the molecular docking simulation. The negative free energy change ∆G, enthalpy change (∆H = 162.21 kJmol -1 ) and entropy change (∆S = 615 Jmol -1 K -1 ) demonstrated that TCS could combine with SOD spontaneously through hydrophobic interaction to form a complex. The binding constants of K a293 and K a313 were 1.706 × 10 3 and 1.2 × 10 5 Lmol -1 , respectively. Furthermore, the interaction could also influence the skeleton structure and secondary contents of SOD. The molecular docking analysis revealed the TCS located between two subunits of SOD, and there was a hydrogen bond between TCS and the residue Asn51 of SOD, which influenced the structure of protein and resulted in a decrease of enzyme activity. This work could help understand the interaction mechanism between SOD and TCS. Moreover, it could also be used to consult for toxicity assessment of TCS at molecular level. Copyright © 2018 Elsevier Inc. All rights reserved.

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes

NASA Astrophysics Data System (ADS)

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M.; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-10-01

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti

Multiple Strategies Reveal a Bidentate Interaction between the Nipah Virus Attachment and Fusion Glycoproteins.

PubMed

Stone, Jacquelyn A; Vemulapati, Bhadra M; Bradel-Tretheway, Birgit; Aguilar, Hector C

2016-12-01

The paramyxoviral family contains many medically important viruses, including measles virus, mumps virus, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and the deadly zoonotic henipaviruses Hendra and Nipah virus (NiV). To both enter host cells and spread from cell to cell within infected hosts, the vast majority of paramyxoviruses utilize two viral envelope glycoproteins: the attachment glycoprotein (G, H, or hemagglutinin-neuraminidase [HN]) and the fusion glycoprotein (F). Binding of G/H/HN to a host cell receptor triggers structural changes in G/H/HN that in turn trigger F to undergo a series of conformational changes that result in virus-cell (viral entry) or cell-cell (syncytium formation) membrane fusion. The actual regions of G/H/HN and F that interact during the membrane fusion process remain relatively unknown though it is generally thought that the paramyxoviral G/H/HN stalk region interacts with the F head region. Studies to determine such interactive regions have relied heavily on coimmunoprecipitation approaches, whose limitations include the use of detergents and the micelle-mediated association of proteins. Here, we developed a flow-cytometric strategy capable of detecting membrane protein-protein interactions by interchangeably using the full-length form of G and a soluble form of F, or vice versa. Using both coimmunoprecipitation and flow-cytometric strategies, we found a bidentate interaction between NiV G and F, where both the stalk and head regions of NiV G interact with F. This is a new structural-biological finding for the paramyxoviruses. Additionally, our studies disclosed regions of the NiV G and F glycoproteins dispensable for the G and F interactions. Nipah virus (NiV) is a zoonotic paramyxovirus that causes high mortality rates in humans, with no approved treatment or vaccine available for human use. Viral entry into host cells relies on two viral envelope glycoproteins: the attachment (G) and fusion (F

Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?

PubMed Central

Hall, F. Scott; Perona, Maria T. G.

2012-01-01

This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that are determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms. PMID:22643448

Yeast-yeast interactions revealed by aromatic profile analysis of Sauvignon Blanc wine fermented by single or co-culture of non-Saccharomyces and Saccharomyces yeasts.

PubMed

Sadoudi, Mohand; Tourdot-Maréchal, Raphaëlle; Rousseaux, Sandrine; Steyer, Damien; Gallardo-Chacón, Joan-Josep; Ballester, Jordi; Vichi, Stefania; Guérin-Schneider, Rémi; Caixach, Josep; Alexandre, Hervé

2012-12-01

There has been increasing interest in the use of selected non-Saccharomyces yeasts in co-culture with Saccharomyces cerevisiae. The main reason is that the multistarter fermentation process is thought to simulate indigenous fermentation, thus increasing wine aroma complexity while avoiding the risks linked to natural fermentation. However, multistarter fermentation is characterised by complex and largely unknown interactions between yeasts. Consequently the resulting wine quality is rather unpredictable. In order to better understand the interactions that take place between non-Saccharomyces and Saccharomyces yeasts during alcoholic fermentation, we analysed the volatile profiles of several mono-culture and co-cultures. Candida zemplinina, Torulaspora delbrueckii and Metschnikowia pulcherrima were used to conduct fermentations either in mono-culture or in co-culture with S. cerevisiae. Up to 48 volatile compounds belonging to different chemical families were quantified. For the first time, we show that C. zemplinina is a strong producer of terpenes and lactones. We demonstrate by means of multivariate analysis that different interactions exist between the co-cultures studied. We observed a synergistic effect on aromatic compound production when M. pulcherrima was in co-culture with S. cerevisiae. However a negative interaction was observed between C. zemplinina and S. cerevisiae, which resulted in a decrease in terpene and lactone content. These interactions are independent of biomass production. The aromatic profiles of T. delbrueckii and S. cerevisiae in mono-culture and in co-culture are very close, and are biomass-dependent, reflecting a neutral interaction. This study reveals that a whole family of compounds could be altered by such interactions. These results suggest that the entire metabolic pathway is affected by these interactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

An Eye Tracking Study of High- and Low-Performing Students in Solving Interactive and Analytical Problems

ERIC Educational Resources Information Center

Hu, Yiling; Wu, Bian; Gu, Xiaoqing

2017-01-01

Test results from the Program for International Student Assessment (PISA) reveal that Shanghai students performed less well in solving interactive problems (those that require uncovering necessary information) than in solving analytical problems (those having all information disclosed at the outset). Accordingly, this study investigates…

Microscopy based studies on the interaction of bio-based silver nanoparticles with Bombyx mori Nuclear Polyhedrosis virus.

PubMed

Tamilselvan, Selvaraj; Ashokkumar, Thirunavukkarasu; Govindaraju, Kasivelu

2017-04-01

In the present investigation, silver nanoparticles (AgNPs) interactions with Bombyx mori Nuclear Polyhedrosis virus (BmNPV) were characterized using High-Resolution Scanning Electron Microscopy (HR-SEM), Energy Dispersive X-ray Analysis (EDAX), Transmission Electron Microscopy (TEM), Atomic Force Microcopy (AFM) and Confocal Microscope (CM). HR-SEM study reveals that the biosynthesized AgNPs have interacted with BmNPV and were found on the surface. TEM micrographs of normal and viral polyhedra treated with AgNPs showed that the nanoparticles were accumulated in the membrane and it was noted that some of the AgNPs successfully penetrated the membrane by reaching the capsid of BmNPV. AFM and confocal microscopy studies reveal that the disruption in the shell membrane tends to lose its stability due to exposure of AgNPs to BmNPV. Copyright © 2017 Elsevier B.V. All rights reserved.

Fish introductions reveal the temperature dependence of species interactions

PubMed Central

Hein, Catherine L.; Öhlund, Gunnar; Englund, Göran

2014-01-01

A major area of current research is to understand how climate change will impact species interactions and ultimately biodiversity. A variety of environmental conditions are rapidly changing owing to climate warming, and these conditions often affect both the strength and outcome of species interactions. We used fish distributions and replicated fish introductions to investigate environmental conditions influencing the coexistence of two fishes in Swedish lakes: brown trout (Salmo trutta) and pike (Esox lucius). A logistic regression model of brown trout and pike coexistence showed that these species coexist in large lakes (more than 4.5 km2), but not in small, warm lakes (annual air temperature more than 0.9–1.5°C). We then explored how climate change will alter coexistence by substituting climate scenarios for 2091–2100 into our model. The model predicts that brown trout will be extirpated from approximately half of the lakes where they presently coexist with pike and from nearly all 9100 lakes where pike are predicted to invade. Context dependency was critical for understanding pike–brown trout interactions, and, given the widespread occurrence of context-dependent species interactions, this aspect will probably be critical for accurately predicting climate impacts on biodiversity. PMID:24307673

Genomic maps of lincRNA occupancy reveal principles of RNA-chromatin interactions

PubMed Central

Chu, Ci; Qu, Kun; Zhong, Franklin; Artandi, Steven E.; Chang, Howard Y.

2011-01-01

SUMMARY Long intergenic noncoding RNAs (lincRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lincRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lincRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3’ end, peaking at CES sites. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lincRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome-wide. PMID:21963238

Binding of Alkali Metal Ions with 1,3,5-Tri(phenyl)benzene and 1,3,5-Tri(naphthyl)benzene: The Effect of Phenyl and Naphthyl Ring Substitution on Cation-π Interactions Revealed by DFT Study.

PubMed

Mirchi, Ali; Sizochenko, Natalia; Dinadayalane, Tandabany; Leszczynski, Jerzy

2017-11-22

The effect of substitution of phenyl and naphthyl rings to benzene was examined to elucidate the cation-π interactions involving alkali metal ions with 1,3,5-tri(phenyl)benzene (TPB) and 1,3,5-tri(naphthyl)benzene (TNB). Benzene, TPB, and four TNB isomers (with ααα, ααβ, αββ, and βββ types of fusion) and their complexes with Li + , Na + , K + , Rb + , and Cs + were optimized using DFT approach with B3LYP and M06-2X functionals in conjunction with the def2-QZVP basis set. Higher relative stability of β,β,β-TNB over α,α,α-TNB can be attributed to peri repulsion, which is defined as the nonbonding repulsive interaction between substituents in the 1- and the 8-positions on the naphthalene core. Binding energies, distances between ring centroid and the metal ions, and the distance to metal ions from the center of other six-membered rings were compared for all complexes. Our computational study reveals that the binding affinity of alkali metal cations increases significantly with the 1,3,5-trisubstitution of phenyl and naphthyl rings to benzene. The detailed computational analyses of geometries, partial charges, binding energies, and ligand organization energies reveal the possibility of favorable C-H···M + interactions when a α-naphthyl group exists in complexes of TNB structures. Like benzene-alkali metal ion complexes, the binding affinity of metal ions follows the order: Li + > Na + > K + > Rb + > Cs + for any considered 1,3,5-trisubstituted benzene systems. In case of TNB, we found that the strength of interactions increases as the fusion point changes from α to β position of naphthalene.

Effect of PDGF-B aptamer on PDGFRβ/PDGF-B interaction: Molecular dynamics study.

PubMed

Vu, Cong Quang; Rotkrua, Pichayanoot; Soontornworajit, Boonchoy; Tantirungrotechai, Yuthana

2018-06-01

PDGFRβ/PDGF-B interaction plays a role in angiogenesis, and is mandatory in wound healing and cancer treatment. It has been reported that the PDGF-B aptamer was able to bind to PDGF-B, thus regulating the angiogenesis. However, the binding interaction between the aptamer and the growth factor, including the binding sites, has not been well investigated. This study applied a molecular dynamics (MD) simulation to investigate the aptamer-growth factor interaction in the presence or absence of a receptor (PDGFRβ). Characterization of the structure of an aptamer-growth factor complex revealed binding sites from each section in the complex. Upon the complex formation, PDGF-B and its aptamer exhibited less flexibility in their molecular movement, as indicated by the minimum values of RMSD, RMSF, loop-to-loop distance, and the summation of PCA eigenvalues. Our study of residue pairwise interaction demonstrated that the binding interaction was mainly contributed by electrostatic interaction between the positively-charged amino acid and the negatively-charged phosphate backbone. The role of the PDGF-B aptamer in PDGFRβ/PDGF-B interaction was also investigated. We demonstrated that the stability of the Apt-PDGF-B complex could prevent the presence of a competitor, of PDGFRβ, interrupting the binding process. Because the aptamer was capable of binding with PDGF-B, and blocking the growth factor from the PDGFRβ, it could down regulate the consequent signaling pathway. We provide evidence that the PDGF-BB aptamer is a promising molecule for regulation of angiogenesis. The MD study provides a molecular understanding to modification of the aptamer binding interaction, which could be used in a number of medical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer.

PubMed

Gallon, Matthew; Clairfeuille, Thomas; Steinberg, Florian; Mas, Caroline; Ghai, Rajesh; Sessions, Richard B; Teasdale, Rohan D; Collins, Brett M; Cullen, Peter J

2014-09-02

The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to-plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo-1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo sorting. Crystal structures and NMR experiments reveal that an exposed β-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26. Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection. With disruption of SNX27 and retromer function linked to synaptic dysfunction and neurodegenerative disease, our work provides the first step, to our knowledge, in the molecular description of this important sorting complex, and more broadly describes a unique interaction between a PDZ domain and an arrestin-like fold.

Revealing interaction between sulfobutylether-β-cyclodextrin and reserpine by chemiluminescence and site-directed molecular docking.

PubMed

Xiong, Xunyu; Wu, Min; Zhao, Xinfeng; Song, Zhenghua

2014-09-01

The host-guest interaction between sulfobutylether-β-cyclodextrin (SBE-β-CD) and reserpine (RSP) is described using flow injection-chemiluminescence (FI-CL) and site-directed molecular docking methods. It was found that RSP could inhibit the CL intensity produced by a luminol/SBE-β-CD system. The decrease in CL intensity was logarithmic over an RSP concentration range of 0.03 to 700.0 nM, giving a regression equation of ∆I = 107.1lgCRES  + 186.1 with a detection limit of 10 pM (3σ). The CL assay was successfully applied in the determination of RSP in injection, saliva and urine samples with recoveries in the range 93.5-106.1%. Using the proposed CL model, the binding constant (KCD-R ) and the stoichiometric ratio of SBE-β-CD/RSP were calculated to be 7.4 × 10(6)  M(-1) and 1 : 1, respectively. Using molecular docking, it was confirmed that luminol binds to the small cavity of SBE-β-CD with a nonpolar interaction, while RSP targeted the larger cavity of SBE-β-CD and formed a 1 : 1 complex with hydrogen bonds. The proposed new CL method has the potential to become a powerful tool for revealing the host-guest interaction between CDs and drugs, as well as monitoring drugs with high sensitivity. Copyright © 2013 John Wiley & Sons, Ltd.

Force spectroscopy studies on protein-ligand interactions: a single protein mechanics perspective.

PubMed

Hu, Xiaotang; Li, Hongbin

2014-10-01

Protein-ligand interactions are ubiquitous and play important roles in almost every biological process. The direct elucidation of the thermodynamic, structural and functional consequences of protein-ligand interactions is thus of critical importance to decipher the mechanism underlying these biological processes. A toolbox containing a variety of powerful techniques has been developed to quantitatively study protein-ligand interactions in vitro as well as in living systems. The development of atomic force microscopy-based single molecule force spectroscopy techniques has expanded this toolbox and made it possible to directly probe the mechanical consequence of ligand binding on proteins. Many recent experiments have revealed how ligand binding affects the mechanical stability and mechanical unfolding dynamics of proteins, and provided mechanistic understanding on these effects. The enhancement effect of mechanical stability by ligand binding has been used to help tune the mechanical stability of proteins in a rational manner and develop novel functional binding assays for protein-ligand interactions. Single molecule force spectroscopy studies have started to shed new lights on the structural and functional consequence of ligand binding on proteins that bear force under their biological settings. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

PubMed Central

Starkey, Jason L.; Han, Jun; Chadha, Pooja; Marsh, Jacob A.

2014-01-01

UL16 is a tegument protein of herpes simplex virus (HSV) that is conserved among all members of the Herpesviridae, but its function is poorly understood. Previous studies revealed that UL16 is associated with capsids in the cytoplasm and interacts with the membrane protein UL11, which suggested a “bridging” function during cytoplasmic envelopment, but this conjecture has not been tested. To gain further insight, cells infected with UL16-null mutants were examined by electron microscopy. No defects in the transport of capsids to cytoplasmic membranes were observed, but the wrapping of capsids with membranes was delayed. Moreover, clusters of cytoplasmic capsids were often observed, but only near membranes, where they were wrapped to produce multiple capsids within a single envelope. Normal virion production was restored when UL16 was expressed either by complementing cells or from a novel position in the HSV genome. When the composition of the UL16-null viruses was analyzed, a reduction in the packaging of glycoprotein E (gE) was observed, which was not surprising, since it has been reported that UL16 interacts with this glycoprotein. However, levels of the tegument protein VP22 were also dramatically reduced in virions, even though this gE-binding protein has been shown not to depend on its membrane partner for packaging. Cotransfection experiments revealed that UL16 and VP22 can interact in the absence of other viral proteins. These results extend the UL16 interaction network beyond its previously identified binding partners to include VP22 and provide evidence that UL16 plays an important function at the membrane during virion production. PMID:24131716

The Dynamic Reactance Interaction – How Vested Interests Affect People’s Experience, Behavior, and Cognition in Social Interactions

PubMed Central

Steindl, Christina; Jonas, Eva

2015-01-01

In social interactions, individuals may sometimes pursue their own interests at the expense of their interaction partner. Such self-interested behaviors impose a threat to the interaction partner’s freedom to act. The current article investigates this threat in the context of interdependence and reactance theory. We explore how vested interests influence reactance process stages of an advisor–client interaction. We aim to explore the interactional process that evolves. In two studies, participants took the perspective of a doctor (advisor) or a patient (client). In both studies we incorporated a vested interest. In Study 1 (N = 82) we found that in response to a vested interest of their interaction partner, patients indicated a stronger experience of reactance, more aggressive behavioral intentions, and more biased cognitions than doctors. A serial multiple mediation revealed that a vested interest engendered mistrust toward the interaction partner and this mistrust led to an emerging reactance process. Study 2 (N = 207) further demonstrated that doctors expressed their reactance in a subtle way: they revealed a classic confirmation bias when searching for additional information on their preliminary decision preference, indicating stronger defense motivation. We discuss how these findings can help us to understand how social interactions develop dynamically. PMID:26640444

Theoretical study of the interactions of a graphene-on-Ni(111) composite with dopamine

NASA Astrophysics Data System (ADS)

Yang, Junwei; Yuan, Yanhong; Zhao, Hua

2016-03-01

The physics underlying the interactions between nanomaterials and biomolecules is largely unexplored. In this study, we modelled the interactions of a graphene-on-Ni(111) nanocomposite with dopamine, an important biomolecule with crucial physiological functions in the human brain and body, using density functional theory methods. Stable adsorption of the dopamine molecule was observed on the surface of the graphene-on-Ni(111) composite. The adsorption mechanism was revealed to involve both charge and π-π interactions between the dopamine and graphene when they are in close proximity. Simulated scanning tunnelling microscopy images of dopamine on the surface of the graphene-on-Ni(111) composite, as an application of this nanomaterial, could distinguish one side of the G2 conformation of dopamine from the other conformations as a result of their interactions. Therefore, the graphene-on-Ni(111) composite is expected to have potential as a nanomaterial for detecting single biomolecules. The findings of this study will provide a significant contribution to the fields of nanomaterials and biotechnology, including the development of highly accurate biodevices and biosensors.

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes.

PubMed

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-11-14

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.

Why study gene-environment interactions?

USDA-ARS?s Scientific Manuscript database

PURPOSE OF REVIEW: We examine the reasons for investigating gene-environment interactions and address recent reports evaluating interactions between genes and environmental modulators in relation to cardiovascular disease and its common risk factors. RECENT FINDINGS: Studies focusing on smoking, phy...

Laboratory simulation reveals significant impacts of ocean acidification on microbial community composition and host-pathogen interactions between the blood clam and Vibrio harveyi.

PubMed

Zha, Shanjie; Liu, Saixi; Su, Wenhao; Shi, Wei; Xiao, Guoqiang; Yan, Maocang; Liu, Guangxu

2017-12-01

It has been suggested that climate change may promote the outbreaks of diseases in the sea through altering the host susceptibility, the pathogen virulence, and the host-pathogen interaction. However, the impacts of ocean acidification (OA) on the pathogen components of bacterial community and the host-pathogen interaction of marine bivalves are still poorly understood. Therefore, 16S rRNA high-throughput sequencing and host-pathogen interaction analysis between blood clam (Tegillarca granosa) and Vibrio harveyi were conducted in the present study to gain a better understanding of the ecological impacts of ocean acidification. The results obtained revealed a significant impact of ocean acidification on the composition of microbial community at laboratory scale. Notably, the abundance of Vibrio, a major group of pathogens to many marine organisms, was significantly increased under ocean acidification condition. In addition, the survival rate and haemolytic activity of V. harveyi were significantly higher in the presence of haemolymph of OA treated T. granosa, indicating a compromised immunity of the clam and enhanced virulence of V. harveyi under future ocean acidification scenarios. Conclusively, the results obtained in this study suggest that future ocean acidification may increase the risk of Vibrio pathogen infection for marine bivalve species, such as blood clams. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatial proximity between the VPAC1 receptor and the amino terminus of agonist and antagonist peptides reveals distinct sites of interaction.

PubMed

Ceraudo, Emilie; Hierso, Régine; Tan, Yossan-Var; Murail, Samuel; Rouyer-Fessard, Christiane; Nicole, Pascal; Robert, Jean-Claude; Jamin, Nadège; Neumann, Jean-Michel; Robberecht, Patrick; Laburthe, Marc; Couvineau, Alain

2012-05-01

Vasoactive intestinal peptide (VIP) plays a major role in pathophysiology. Our previous studies demonstrated that the VIP sequence 6-28 interacts with the N-terminal ectodomain (N-ted) of its receptor, VPAC1. Probes for VIP and receptor antagonist PG97-269 were synthesized with a photolabile residue/Bpa at various positions and used to explore spatial proximity with VPAC1. PG97-269 probes with Bpa at position 0, 6, and 24 behaved as high-affinity receptor antagonists (K(i)=12, 9, and 7 nM, respectively). Photolabeling experiments revealed that the [Bpa(0)]-VIP probe was in physical contact with VPAC1 Q(135), while [Bpa(0)]-PG97-269 was covalently bound to G(62) residue of N-ted, indicating different binding sites. In contrast, photolabeling with [Bpa(6)]- and [Bpa(24)]-PG97-269 showed that the distal domains of PG97-269 interacted with N-ted, as we previously showed for VIP. Substitution with alanine of the K(143), T(144), and T(147) residues located in the first transmembrane domain of VPAC1 induced a loss of receptor affinity (IC(50)=1035, 874, and 2070 nM, respectively), and pharmacological studies using VIP2-28 indicated that these three residues play an important role in VPAC1 interaction with the first histidine residue of VIP. These data demonstrate that VIP and PG97-269 bind to distinct domains of VPAC1.

Non-Native Metal Ion Reveals the Role of Electrostatics in Synaptotagmin 1-Membrane Interactions.

PubMed

Katti, Sachin; Nyenhuis, Sarah B; Her, Bin; Srivastava, Atul K; Taylor, Alexander B; Hart, P John; Cafiso, David S; Igumenova, Tatyana I

2017-06-27

C2 domains are independently folded modules that often target their host proteins to anionic membranes in a Ca 2+ -dependent manner. In these cases, membrane association is triggered by Ca 2+ binding to the negatively charged loop region of the C2 domain. Here, we used a non-native metal ion, Cd 2+ , in lieu of Ca 2+ to gain insight into the contributions made by long-range Coulombic interactions and direct metal ion-lipid bridging to membrane binding. Using X-ray crystallography, NMR, Förster resonance energy transfer, and vesicle cosedimentation assays, we demonstrate that, although Cd 2+ binds to the loop region of C2A/B domains of synaptotagmin 1 with high affinity, long-range Coulombic interactions are too weak to support membrane binding of individual domains. We attribute this behavior to two factors: the stoichiometry of Cd 2+ binding to the loop regions of the C2A and C2B domains and the impaired ability of Cd 2+ to directly coordinate the lipids. In contrast, electron paramagnetic resonance experiments revealed that Cd 2+ does support membrane binding of the C2 domains in full-length synaptotagmin 1, where the high local lipid concentrations that result from membrane tethering can partially compensate for lack of a full complement of divalent metal ions and specific lipid coordination in Cd 2+ -complexed C2A/B domains. Our data suggest that long-range Coulombic interactions alone can drive the initial association of C2A/B with anionic membranes and that Ca 2+ further augments membrane binding by the formation of metal ion-lipid coordination bonds and additional Ca 2+ ion binding to the C2 domain loop regions.

The Role of Cognitive and Affective Empathy in Spouses' Support Interactions: An Observational Study

PubMed Central

Verhofstadt, Lesley; Devoldre, Inge; Buysse, Ann; Stevens, Michael; Hinnekens, Céline; Ickes, William; Davis, Mark

2016-01-01

The present study examined how support providers’ empathic dispositions (dispositional perspective taking, empathic concern, and personal distress) as well as their situational empathic reactions (interaction-based perspective taking, empathic concern, and personal distress) relate to the provision of spousal support during observed support interactions. Forty-five committed couples provided questionnaire data and participated in two ten-minute social support interactions designed to assess behaviors when partners are offering and soliciting social support. A video-review task was used to assess situational forms of perspective taking (e.g., empathic accuracy), empathic concern and personal distress. Data were analyzed by means of the multi-level Actor-Partner Interdependence Model. Results revealed that providers scoring higher on affective empathy (i.e., dispositional empathic concern), provided lower levels of negative support. In addition, for male partners, scoring higher on cognitive empathy (i.e., situational perspective taking) was related to lower levels of negative support provision. For both partners, higher scores on cognitive empathy (i.e., situational perspective taking) correlated with more instrumental support provision. Male providers scoring higher on affective empathy (i.e., situational personal distress) provided higher levels of instrumental support. Dispositional perspective taking was related to higher scores on emotional support provision for male providers. The current study furthers our insight into the empathy-support link, by revealing differential effects (a) for men and women, (b) of both cognitive and affective empathy, and (c) of dispositional as well as situational empathy, on different types of support provision. PMID:26910769

Interactions of the Human Calcitonin Fragment 9–32 with Phospholipids: A Monolayer Study

PubMed Central

Wagner, Kerstin; Van Mau, Nicole; Boichot, Sylvie; Kajava, Andrey V.; Krauss, Ulrike; Le Grimellec, Christian; Beck-Sickinger, Annette; Heitz, Frédéric

2004-01-01

Human calcitonin and its C-terminal fragment 9–32 (hCT(9–32)) administered in a spray translocate into respiratory nasal epithelium with an effect similar to intravenous injection. hCT(9–32) is an efficient carrier to transfer the green fluorescent protein into excised bovine nasal mucosa. To understand the translocation of hCT(9–32) across plasma membranes, we investigated its interactions with phospholipids and its interfacial structure using model lipid monolayers. A combination of physicochemical methods was applied including surface tension measurements on adsorbed and spread monolayers at the air-water interface, Fourier transform infrared, circular dichroism, and atomic force microscopy on Langmuir-Blodgett monolayers. The results disclose that hCT(9–32) preferentially interacts with negatively charged phospholipids and does not insert spontaneously into lipid monolayers. This supports a nonreceptor-mediated endocytic internalization pathway as previously suggested. Structural studies revealed a random coil conformation of hCT(9–32) in solution, transforming to α-helices when the peptide is localized at lipid-free or lipid-containing air-water interfaces. Atomic force microscopy studies of monolayers of the peptide alone or mixed with dioleoylphosphatidylcholine revealed that hCT(9–32) forms filaments rolled into spirals. In contrast, when interacting with dioleoylphosphatidylglycerol, hCT(9–32) does not adopt filamentous structures. A molecular model and packing is proposed for the spiral-forming hCT(9–32). PMID:15240473

Studies of the Interaction of Influenza Virus RNA Polymerase PAN with Endonuclease Inhibitors.

PubMed

Dong, Li-Hua; Cao, Xiao-Rong

2018-06-01

Influenza virus is a major causative agent of respiratory viral infections, and RNA polymerase catalyzes its replication and transcription activities in infected cell nuclei. Since it is highly conserved in all virus strains, RNA polymerase becomes a key target of anti-influenza virus agents. Although experimental studies have revealed the good inhibitory activity of endonuclease inhibitors to RNA polymerase, the mechanism is still unclear. In this study, the docking and molecular dynamics simulations have been performed to explore the interaction of three kinds of endonuclease inhibitors with the subunit (PA N ) of RNA polymerase. Our calculations indicate that all these endonuclease inhibitors can bind to the binding pocket of PA N , in which the electronegative oxygen atoms of the inhibitors form a chelated structure with the two Mn 2+ cations of the active center. The most important interaction between these inhibitors and PA N is electrostatic interaction. The electron density of the chelate oxygen atoms determines the magnitude of the electrostatic energy, and the chelated structure and orientation of inhibitors depend largely on the distance between the chelate oxygen atoms.

Bathymetry data reveal glaciers vulnerable to ice-ocean interaction in Uummannaq and Vaigat glacial fjords, west Greenland

NASA Astrophysics Data System (ADS)

Rignot, E.; Fenty, I.; Xu, Y.; Cai, C.; Velicogna, I.; Cofaigh, C. Ó.; Dowdeswell, J. A.; Weinrebe, W.; Catania, G.; Duncan, D.

2016-03-01

Marine-terminating glaciers play a critical role in controlling Greenland's ice sheet mass balance. Their frontal margins interact vigorously with the ocean, but our understanding of this interaction is limited, in part, by a lack of bathymetry data. Here we present a multibeam echo sounding survey of 14 glacial fjords in the Uummannaq and Vaigat fjords, west Greenland, which extends from the continental shelf to the glacier fronts. The data reveal valleys with shallow sills, overdeepenings (>1300 m) from glacial erosion, and seafloor depths 100-1000 m deeper than in existing charts. Where fjords are deep enough, we detect the pervasive presence of warm, salty Atlantic Water (AW) (>2.5°C) with high melt potential, but we also find numerous glaciers grounded on shallow (<200 m) sills, standing in cold (<1°C) waters in otherwise deep fjords, i.e., with reduced melt potential. Bathymetric observations extending to the glacier fronts are critical to understand the glacier evolution.

Interactions With Robots: The Truths We Reveal About Ourselves.

PubMed

Broadbent, Elizabeth

2017-01-03

In movies, robots are often extremely humanlike. Although these robots are not yet reality, robots are currently being used in healthcare, education, and business. Robots provide benefits such as relieving loneliness and enabling communication. Engineers are trying to build robots that look and behave like humans and thus need comprehensive knowledge not only of technology but also of human cognition, emotion, and behavior. This need is driving engineers to study human behavior toward other humans and toward robots, leading to greater understanding of how humans think, feel, and behave in these contexts, including our tendencies for mindless social behaviors, anthropomorphism, uncanny feelings toward robots, and the formation of emotional attachments. However, in considering the increased use of robots, many people have concerns about deception, privacy, job loss, safety, and the loss of human relationships. Human-robot interaction is a fascinating field and one in which psychologists have much to contribute, both to the development of robots and to the study of human behavior.

Spectroscopic studies of the interaction mechanisms between mono-caffeoylquinic acids and transferrin

NASA Astrophysics Data System (ADS)

Guan, Yanqing; Dong, Jing; Chen, Shizhong; Liu, Meixian; Wang, Daidong; Zhang, Xiaotian; Wang, Hong; Lin, Zongtao

2017-06-01

Transferrin (Tf) is an important protein responsible for circulating and transporting iron into cytoplasm. Tf can be taken into cells through endocytosis mediated by Tf receptor, which usually overexpresses in cancer cells. The Tf-Tf receptor pathway opens a possible avenue for novel targeted cancer therapy by utilizing Tf-binding active compounds. Among which, anti-cancer active caffeoylquinic acids (CQAs) were recently found to be promising Tf-binders by our group. For better understanding the anti-cancer activities of CQAs, it is important to unveil the binding mechanisms between CQAs and Tf. In this study, the fluorescence quenching, surface plasmon resonance (SPR), circular dichroism (CD) and molecular docking were used to investigate the interactions between CQA and Tf. The results showed that the calculated apparent association constants of interactions between 1-, 3-, 4- and 5-CQA and Tf at 298 K were 7.97 × 105 M- 1, 4.36 × 107 M- 1, 6.58 × 105 M- 1 and 4.42 × 106 M- 1, respectively. The thermodynamic parameters indicated that the interaction between 1-, 3-, 5-CQA and Tf is due to H-bonding, and electrostatic interactions were likely involved in the binding of 4-CQA and Tf. The CD results indicated that bindings of 1-CQA, 4-CQA and 5-CQA with Tf resulted in more stretched β-turn and random coil translated from β-sheet. In contrast, 3-CQA led to more stable a-helix conformation. Molecular docking studies of CQAs with Tf further displayed that CQAs were able to interact with residues near Fe3 + binding site. The spectroscopic studies revealed the action mechanisms, thermodynamics and interacting forces between CQAs and Tf, and thus are helpful for future design and discovery of Tf-binders for targeted cancer therapy applying Tf-Tf receptor pathway.

Using a contextualized sensemaking model for interaction design: A case study of tumor contouring.

PubMed

Aselmaa, Anet; van Herk, Marcel; Laprie, Anne; Nestle, Ursula; Götz, Irina; Wiedenmann, Nicole; Schimek-Jasch, Tanja; Picaud, Francois; Syrykh, Charlotte; Cagetti, Leonel V; Jolnerovski, Maria; Song, Yu; Goossens, Richard H M

2017-01-01

Sensemaking theories help designers understand the cognitive processes of a user when he/she performs a complicated task. This paper introduces a two-step approach of incorporating sensemaking support within the design of health information systems by: (1) modeling the sensemaking process of physicians while performing a task, and (2) identifying software interaction design requirements that support sensemaking based on this model. The two-step approach is presented based on a case study of the tumor contouring clinical task for radiotherapy planning. In the first step of the approach, a contextualized sensemaking model was developed to describe the sensemaking process based on the goal, the workflow and the context of the task. In the second step, based on a research software prototype, an experiment was conducted where three contouring tasks were performed by eight physicians respectively. Four types of navigation interactions and five types of interaction sequence patterns were identified by analyzing the gathered interaction log data from those twenty-four cases. Further in-depth study on each of the navigation interactions and interaction sequence patterns in relation to the contextualized sensemaking model revealed five main areas for design improvements to increase sensemaking support. Outcomes of the case study indicate that the proposed two-step approach was beneficial for gaining a deeper understanding of the sensemaking process during the task, as well as for identifying design requirements for better sensemaking support. Copyright © 2016. Published by Elsevier Inc.

Simple analytical model reveals the functional role of embodied sensorimotor interaction in hexapod gaits

PubMed Central

Aoi, Shinya; Nachstedt, Timo; Manoonpong, Poramate; Wörgötter, Florentin; Matsuno, Fumitoshi

2018-01-01

Insects have various gaits with specific characteristics and can change their gaits smoothly in accordance with their speed. These gaits emerge from the embodied sensorimotor interactions that occur between the insect’s neural control and body dynamic systems through sensory feedback. Sensory feedback plays a critical role in coordinated movements such as locomotion, particularly in stick insects. While many previously developed insect models can generate different insect gaits, the functional role of embodied sensorimotor interactions in the interlimb coordination of insects remains unclear because of their complexity. In this study, we propose a simple physical model that is amenable to mathematical analysis to explain the functional role of these interactions clearly. We focus on a foot contact sensory feedback called phase resetting, which regulates leg retraction timing based on touchdown information. First, we used a hexapod robot to determine whether the distributed decoupled oscillators used for legs with the sensory feedback generate insect-like gaits through embodied sensorimotor interactions. The robot generated two different gaits and one had similar characteristics to insect gaits. Next, we proposed the simple model as a minimal model that allowed us to analyze and explain the gait mechanism through the embodied sensorimotor interactions. The simple model consists of a rigid body with massless springs acting as legs, where the legs are controlled using oscillator phases with phase resetting, and the governed equations are reduced such that they can be explained using only the oscillator phases with some approximations. This simplicity leads to analytical solutions for the hexapod gaits via perturbation analysis, despite the complexity of the embodied sensorimotor interactions. This is the first study to provide an analytical model for insect gaits under these interaction conditions. Our results clarified how this specific foot contact sensory

A rice gid1 suppressor mutant reveals that gibberellin is not always required for interaction between its receptor, GID1, and DELLA proteins.

PubMed

Yamamoto, Yuko; Hirai, Takaaki; Yamamoto, Eiji; Kawamura, Mayuko; Sato, Tomomi; Kitano, Hidemi; Matsuoka, Makoto; Ueguchi-Tanaka, Miyako

2010-11-01

To investigate gibberellin (GA) signaling using the rice (Oryza sativa) GA receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) mutant gid1-8, we isolated a suppressor mutant, Suppressor of gid1-1 (Sgd-1). Sgd-1 is an intragenic mutant containing the original gid1-8 mutation (L45F) and an additional amino acid substitution (P99S) in the loop region. GID1(P99S) interacts with the rice DELLA protein SLENDER RICE1 (SLR1), even in the absence of GA. Substitution of the 99th Pro with other amino acids revealed that substitution with Ala (P99A) caused the highest level of GA-independent interaction. Physicochemical analysis using surface plasmon resonance revealed that GID1(P99A) has smaller K(a) (association) and K(d) (dissociation) values for GA(4) than does wild-type GID1. This suggests that the GID1(P99A) lid is at least partially closed, resulting in both GA-independent and GA-hypersensitive interactions with SLR1. One of the three Arabidopsis thaliana GID1s, At GID1b, can also interact with DELLA proteins in the absence of GA, so we investigated whether GA-independent interaction of At GID1b depends on a mechanism similar to that of rice GID1(P99A). Substitution of the loop region or a few amino acids of At GID1b with those of At GID1a diminished its GA-independent interaction with GAI while maintaining the GA-dependent interaction. Soybean (Glycine max) and Brassica napus also have GID1s similar to At GID1b, indicating that these unique GID1s occur in various dicots and may have important functions in these plants.

Social patterns revealed through random matrix theory

NASA Astrophysics Data System (ADS)

Sarkar, Camellia; Jalan, Sarika

2014-11-01

Despite the tremendous advancements in the field of network theory, very few studies have taken weights in the interactions into consideration that emerge naturally in all real-world systems. Using random matrix analysis of a weighted social network, we demonstrate the profound impact of weights in interactions on emerging structural properties. The analysis reveals that randomness existing in particular time frame affects the decisions of individuals rendering them more freedom of choice in situations of financial security. While the structural organization of networks remains the same throughout all datasets, random matrix theory provides insight into the interaction pattern of individuals of the society in situations of crisis. It has also been contemplated that individual accountability in terms of weighted interactions remains as a key to success unless segregation of tasks comes into play.

Revealing the sequence of interactions of PuroA peptide with Candida albicans cells by live-cell imaging

NASA Astrophysics Data System (ADS)

Shagaghi, Nadin; Bhave, Mrinal; Palombo, Enzo A.; Clayton, Andrew H. A.

2017-03-01

To determine the mechanism(s) of action of antimicrobial peptides (AMPs) it is desirable to provide details of their interaction kinetics with cellular, sub-cellular and molecular targets. The synthetic peptide, PuroA, displays potent antimicrobial activities which have been attributed to peptide-induced membrane destabilization, or intracellular mechanisms of action (DNA-binding) or both. We used time-lapse fluorescence microscopy and fluorescence lifetime imaging microscopy (FLIM) to directly monitor the localization and interaction kinetics of a FITC- PuroA peptide on single Candida albicans cells in real time. Our results reveal the sequence of events leading to cell death. Within 1 minute, FITC-PuroA was observed to interact with SYTO-labelled nucleic acids, resulting in a noticeable quenching in the fluorescence lifetime of the peptide label at the nucleus of yeast cells, and cell-cycle arrest. A propidium iodide (PI) influx assay confirmed that peptide translocation itself did not disrupt the cell membrane integrity; however, PI entry occurred 25-45 minutes later, which correlated with an increase in fractional fluorescence of pores and an overall loss of cell size. Our results clarify that membrane disruption appears to be the mechanism by which the C. albicans cells are killed and this occurs after FITC-PuroA translocation and binding to intracellular targets.

Preparation of water soluble L-arginine capped CdSe/ZnS QDs and their interaction with synthetic DNA: Picosecond-resolved FRET study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giri, Anupam; Goswami, Nirmal; Lemmens, Peter

2012-08-15

Graphical abstract: Förster resonance energy transfer (FRET) studies on the interaction of water soluble arginine-capped CdSe/ZnS QDs with ethidium bromide (EB) labeled synthetic dodecamer DNA. Highlights: ► We have solubilized CdSe/ZnS QD in water replacing their TOPO ligand by L-arginine. ► We have studied arginine@QD–DNA interaction using FRET technique. ► Arginine@QDs act as energy donor and ethidium bromide-DNA acts as energy acceptor. ► We have applied a kinetic model to understand the kinetics of energy transfer. ► Circular dichroism studies revealed negligible perturbation in the DNA B-form in the arg@QD-DNA complex. -- Abstract: We have exchanged TOPO (trioctylphosphine oxide) ligandmore » of CdSe/ZnS core/shell quantum dots (QDs) with an amino acid L-arginine (Arg) at the toluene/water interface and eventually rendered the QDs from toluene to aqueous phase. We have studied the interaction of the water soluble Arg-capped QDs (energy donor) with ethidium (EB) labeled synthetic dodecamer DNA (energy acceptor) using picoseconds resolved Förster resonance energy transfer (FRET) technique. Furthermore, we have applied a model developed by M. Tachiya to understand the kinetics of energy transfer and the distribution of acceptor (EB-DNA) molecules around the donor QDs. Circular dichroism (CD) studies revealed a negligible perturbation in the native B-form structure of the DNA upon interaction with Arg-capped QDs. The melting and the rehybridization pathways of the DNA attached to the QDs have been monitored by the CD which reveals hydrogen bonding is the associative mechanism for interaction between Arg-capped QDs and DNA.« less

Spectroscopic and thermodynamic studies on ferulic acid - Alpha-2-macroglobulin interaction

NASA Astrophysics Data System (ADS)

Rehman, Ahmed Abdur; Sarwar, Tarique; Arif, Hussain; Ali, Syed Saqib; Ahsan, Haseeb; Tabish, Mohammad; Khan, Fahim Halim

2017-09-01

Ferulic acid is a major phenolic acid found in numerous plant species in conjugated form. It binds to enzymes and oligomeric proteins and modifies their structure and function. This study was designed to examine the interaction of ferulic acid, an active ingredient of some important medicines, with α2M, a key serum proteinase, under physiological conditions. The mechanism of interaction was studied by spectroscopic techniques such as, UV-visible absorption, fluorescence spectroscopy, circular dichroism along with isothermal titration calorimetry. Fluorescence quenching of α2M by ferulic acid demonstrated the formation of α2M-ferulic acid complex by static quenching mechanism. Binding parameters calculated by Stern-Volmer method showed that ferulic acid binds to α2M with moderate affinity of the order of ∼104 M-1. The thermodynamic signatures reveal that binding was enthalpy driven and hydrogen bonding played a major role in ferulic acid-α2M binding. CD spectra analysis suggests very little conformational changes in α2M on ferulic acid binding.

Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography

PubMed Central

Han, Shen; Kollmer, Marius; Markx, Daniel; Claus, Stephanie; Walther, Paul; Fändrich, Marcus

2017-01-01

The deposition of amyloid fibrils as plaques is a key feature of several neurodegenerative diseases including in particular Alzheimer’s. This disease is characterized, if not provoked, by amyloid aggregates formed from Aβ peptide that deposit inside the brain or are toxic to neuronal cells. We here used scanning transmission electron microscopy (STEM) to determine the fibril network structure and interactions of Aβ fibrils within a cell culture model of Alzheimer’s disease. STEM images taken from the formed Aβ amyloid deposits revealed three main types of fibril network structures, termed amorphous meshwork, fibril bundle and amyloid star. All three were infiltrated by different types of lipid inclusions from small-sized exosome-like structures (50–100 nm diameter) to large-sized extracellular vesicles (up to 300 nm). The fibrils also presented strong interactions with the surrounding cells such that fibril bundles extended into tubular invaginations of the plasma membrane. Amyloid formation in the cell model was previously found to have an intracellular origin and we show here that it functionally destroys the integrity of the intracellular membranes as it leads to lysosomal leakage. These data provide a mechanistic link to explain why intracellular fibril formation is toxic to the cell. PMID:28240273

Classroom Interaction in Kenyan Primary Schools.

ERIC Educational Resources Information Center

Ackers, Jim; Hardman, Frank

2001-01-01

Reports on a study of classroom interaction in Kenyan primary schools. Analyzes video recordings of 102 lessons in English, mathematics, and science using systematic observation, discourse analysis, and a time-line analysis. Reveals the preponderance of teacher dominated lessons with little opportunity for student interaction. Considers…

COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study.

PubMed

Kontis, Dimitrios; Theochari, Eirini; Fryssira, Helen; Kleisas, Spyridon; Sofocleous, Christalena; Andreopoulou, Angeliki; Kalogerakou, Stamatina; Gazi, Anthia; Boniatsi, Lucia; Chaidemenos, Alexandros; Tsaltas, Eleftheria

2013-03-14

The investigation of the catechol-O-methyltransferase (COMT-[rs4680]) and methylenetetrahydrofolate reductase (MTHFR-[rs1801133]) polymorphisms' interaction might shed light into the pathogenetic mechanisms of the cognitive dysfunction in schizophrenia. In an exploratory study, we hypothesized that the MTHFR 677T allele which has been related to a hypoactive MTHFR enzyme would augment the unfavorable effects of COMT Val158 homozygosity which has been associated with COMT enzyme hyperfunction. 90 schizophrenia patients and 55 healthy volunteers were assessed on psychomotor speed, pattern and spatial recognition memory (SRM), spatial working memory (SWM), attentional flexibility and planning (Stockings of Cambridge-SOC). IQ scores in a random subgroup of patients were also measured. A significant COMT×MTHFR interaction on SWM (p=0.048) and planning (p=0.026) was revealed in both groups. Among COMT-Val/Val participants, MTHFR-C/C made more SWM errors (p=0.033) and solved fewer SOC problems (p=0.025) than MTHFR-T carriers. In patients, there was a significant COMT×MTHFR interaction on full scale IQ (p=0.035): among COMT-Met carriers, MTHFR-T carriers performed significantly worse than MTHFR-C/C (p=0.021), which was driven by a COMT×MTHFR interaction involving performance IQ (p=0.047). In conclusion, COMT and MTHFR polymorphisms interacted on cognition, suggesting that the MTHFR enzyme activity might moderate the effects of the COMT enzyme. In contrast to our initial hypothesis, the MTHFR T-allele attenuated the cognitive effects of COMT Val homozygosity. In this preliminary study, we propose that dopaminergic and intracellular methylation mechanisms could interact on cognitive deficits in schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A Protein Interaction Map of the Kalimantacin Biosynthesis Assembly Line

PubMed Central

Uytterhoeven, Birgit; Lathouwers, Thomas; Voet, Marleen; Michiels, Chris W.; Lavigne, Rob

2016-01-01

The antimicrobial secondary metabolite kalimantacin (also called batumin) is produced by a hybrid polyketide/non-ribosomal peptide system in Pseudomonas fluorescens BCCM_ID9359. In this study, the kalimantacin biosynthesis gene cluster is analyzed by yeast two-hybrid analysis, creating a protein–protein interaction map of the entire assembly line. In total, 28 potential interactions were identified, of which 13 could be confirmed further. These interactions include the dimerization of ketosynthase domains, a link between assembly line modules 9 and 10, and a specific interaction between the trans-acting enoyl reductase BatK and the carrier proteins of modules 8 and 10. These interactions reveal fundamental insight into the biosynthesis of secondary metabolites. This study is the first to reveal interactions in a complete biosynthetic pathway. Similar future studies could build a strong basis for engineering strategies in such clusters. PMID:27853452

De-novo assembly and characterization of the transcriptome of Metschnikowia fructicola reveals differences in gene expression following interaction with Penicillium digitatum and grapefruit peel

PubMed Central

2013-01-01

Background The yeast Metschnikowia fructicola is an antagonist with biological control activity against postharvest diseases of several fruits. We performed a transcriptome analysis, using RNA-Seq technology, to examine the response of M. fructicola with citrus fruit and with the postharvest pathogen, Penicillium digitatum. Results More than 26 million sequencing reads were assembled into 9,674 unigenes. Approximately 50% of the unigenes could be annotated based on homology matches in the NCBI database. Based on homology, sequences were annotated with a gene description, gene ontology (GO term), and clustered into functional groups. An analysis of differential expression when the yeast was interacting with the fruit vs. the pathogen revealed more than 250 genes with specific expression responses. In the antagonist-pathogen interaction, genes related to transmembrane, multidrug transport and to amino acid metabolism were induced. In the antagonist-fruit interaction, expression of genes involved in oxidative stress, iron homeostasis, zinc homeostasis, and lipid metabolism were induced. Patterns of gene expression in the two interactions were examined at the individual transcript level by quantitative real-time PCR analysis (RT-qPCR). Conclusion This study provides new insight into the biology of the tritrophic interactions that occur in a biocontrol system such as the use of the yeast, M. fructicola for the control of green mold on citrus caused by P. digitatum. PMID:23496978

Revealing the Coulomb interaction strength in a cuprate superconductor

DOE PAGES

Yang, S. -L.; Sobota, J. A.; He, Y.; ...

2017-12-08

Here, we study optimally doped Bi 2 Sr 2 Ca 0.92 Y 0.08 Cu 2 O 8 + δ (Bi2212) using angle-resolved two-photon photoemission spectroscopy. Three spectral features are resolved near 1.5, 2.7, and 3.6 eV above the Fermi level. By tuning the photon energy, we determine that the 2.7-eV feature arises predominantly from unoccupied states. The 1.5- and 3.6-eV features reflect unoccupied states whose spectral intensities are strongly modulated by the corresponding occupied states. These unoccupied states are thus consistent with the prediction from a cluster perturbation theory based on the single-band Hubbard model. Through this comparison, amore » Coulomb interaction strength U of 2.7 eV is extracted. Our study complements equilibrium photoemission spectroscopy and provides a direct spectroscopic measurement of the unoccupied states in cuprates. The determined Coulomb U indicates that the charge-transfer gap of optimally doped Bi2212 is 1.1 eV.« less

Experimental and Calculational Studies of the Interactions of BF3 with Fluoroethers

NASA Technical Reports Server (NTRS)

Zehe, Michael J.; Morales, Wilfredo; Ball, David W.

1998-01-01

BF3 was co-condensed with (C2H5)2O, (CF3CH2)2O and (C2F5)2O in excess argon at 15 K. Infrared spectra of the matrices showed a definite Lewis acid-base interaction between BF3 and diethyl ether; a weak but definite interaction with bis(2,2,2,-trifluorodiethyl)ether, and no observable interaction with perfluorodiethyl ether. Molecular orbital (MO) calculations complemented the experimental observations by revealing that fluorine atoms on the ethers decreased electron localization about the oxygen atom. Thus, the experimental data and MO calculations indicated a clear trend between strength of interaction with BF3 and the degree of ether F substitution. The implications of the results for commercial perfluoro ether lubricant/metal oxide surface interactions are discussed.

Study on the interactions between toxic nitroanilines and lysozyme by spectroscopic approaches and molecular modeling.

PubMed

Gu, Yunlan; Wang, Yanqing; Zhang, Hongmei

2018-05-05

Being exogenous environmental pollutants, nitroanilines (NAs) are highly toxic and have mutagenic and carcinogenic activity. Being lack of studies on interactions between NAs and lysozyme at molecular level, the binding interactions of lysozyme with o-nitroaniline (oNA), m-nitroaniline (mNA) and p-nitroaniline (pNA) were investigated by means of steady-state fluorescence, synchronous fluorescence, UV-vis absorption spectroscopy, as well as molecular modeling. The experimental results revealed that the fluorescence of lysozyme is quenched by oNA and mNA through a static quenching, while the fluorescence quenching triggered by pNA is a combined dynamic and static quenching. The number of binding sites (n) and the binding constant (K b ) corresponding thermodynamic parameters ΔH ⊖ , ΔS ⊖ , ΔG ⊖ at different temperatures were calculated. The reactions between NAs and lysozyme were spontaneous and entropy driven and the binding of NAs to lysozyme induced conformation changes of lysozyme. The difference of the position of -NO 2 group affected the binding and the binding constants K b decreased in the following pattern: K b (pNA) >K b (mNA) >K b (oNA). Molecular docking studies were performed to reveal the most favorable binding sites of NAs on lysozyme. Our recently results could offer mechanistic insights into the nature of the binding interactions between NAs and lysozyme and provide information about the toxicity risk of NAs to human health. Copyright © 2018 Elsevier B.V. All rights reserved.

[Study on the interaction of doxycycline with human serum albumin].

PubMed

Hu, Tao-Ying; Chen, Lin; Liu, Ying

2014-05-01

The present study was designed to investigate the interaction of doxycycline (DC) with human serum albumin (HSA) by the inner filter effects, displacement experiments and molecular docking methods, based on classic multi-spectroscopy. With fluorescence quenching method at 298 and 310 K, the binding constants Ka, were determined to be 2. 73 X 10(5) and 0. 74X 10(5) L mol-1, respectively, and there was one binding site between DC and HSA, indicating that the binding of DC to HSA was strong, and the quenching mechanism was a static quenching. The thermodynamic parameters (enthalpy change, AH and enthropy change, delta S) were calculated to be -83. 55 kJ mol-1 and -176. 31 J mol-1 K-1 via the Vant' Hoff equation, which indicated that the interaction of DC with HSA was driven mainly by hydrogen bonding and van der Waals forces. Based on the Föster's theory of non-radiation energy transfer, the specific binding distance between Trp-214 (acceptor) and DC (donor) was 4. 98 nm, which was similar to the result confirmed by molecular docking. Through displacement experiments, sub-domain IIA of HSA was assigned to possess the high-affinity binding site of DC. Three-dimensional fluorescence spectra indicated that the binding of DC to HSA induced the conformation change of HSA and increased the disclosure of some part of hydrophobic regions that had been buried before. The results of FTIR spectroscopy showed that DC bound to HSA led to the slight unfolding of the polypeptide chain of HSA. Furthermore, the binding details between DC and HSA were further confirmed by molecular docking methods, which revealed that DC was bound at sub-domain IIA through multiple interactions, such as hydrophobic effect, polar forces and pi-pi interactions. The experimental results provide theoretical basis and reliable data for the study of the interaction between small drug molecule and human serum albumin

Interaction of chloroquine and its analogues with heme: An isothermal titration calorimetric study.

PubMed

Bachhawat, K; Thomas, C J; Surolia, N; Surolia, A

2000-10-05

Quinoline-containing drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy. Identification of ferriprotoporphyrin IX ([Fe(III)PPIX], haematin) as the drug receptors for these antimalarials called for investigations of the binding affinity, mode of interaction, and the conditions affecting the interaction. The parameters obtained are significant in recent times with the emergence of chloroquine resistant strains of the malaria parasites. This has underlined the need to unravel the molecular mechanism of their action so as to meet the requirement of an alternative to the existing antimalarial drugs. The isothermal titration calorimetric studies on the interaction of chloroquine with haematin lead us to propose an altered mode of binding. The initial recognition is ionic in nature mediated by the propionyl group of haematin with the quaternary nitrogen on CQ. This ionic interaction induces a conformational change, such as to favour binding of subsequent CQ molecules. On the contrary, conditions emulating the cytosolic environment (pH 7.4 and 150 mM salt) reveal the hydrophobic force to be the sole contributor driving the interaction. Interaction of a carefully selected panel of quinoline antimalarial drugs with monomeric ferriprotoporphyrin IX has also been investigated at pH 5.6 mimicking the acidic environment prevalent in the food vacuoles of parasite, the center of drug activity, which are consistent with their antimalarial activity. Copyright 2000 Academic Press.

Hydrogen bonding-assisted interaction between amitriptyline hydrochloride and hemoglobin: spectroscopic and molecular dynamics studies.

PubMed

Maurya, Neha; Maurya, Jitendra Kumar; Kumari, Meena; Khan, Abbul Bashar; Dohare, Ravins; Patel, Rajan

2017-05-01

Herein, we have explored the interaction between amitriptyline hydrochloride (AMT) and hemoglobin (Hb), using steady-state and time-resolved fluorescence spectroscopy, UV-visible spectroscopy, and circular dichroism spectroscopy, in combination with molecular docking and molecular dynamic (MD) simulation methods. The steady-state fluorescence reveals the static quenching mechanism in the interaction system, which was further confirmed by UV-visible and time-resolved fluorescence spectroscopy. The binding constant, number of binding sites, and thermodynamic parameters viz. ΔG, ΔH, ΔS are also considered; result confirms that the binding of the AMT with Hb is a spontaneous process, involving hydrogen bonding and van der Waals interactions with a single binding site, as also confirmed by molecular docking study. Synchronous fluorescence, CD data, and MD simulation results contribute toward understanding the effect of AMT on Hb to interpret the conformational change in Hb upon binding in aqueous solution.

A Study of the Destruction of Spacecraft Surfaces at Contact Interactions with Microparticles of the Space Environment

NASA Astrophysics Data System (ADS)

Sidnyaev, N. I.

2018-05-01

The results of studying the high-velocity impact interactions of a particle flux of space's meteoric background with satellites have been presented. The effects that arises during the microparticle motion in the material have been described; the models of solid particle interactions with spacecraft's onboard hardware protection have been presented. The experimental and analytical dependences have been given. The basic factors have been revealed, and their effect on the erosion wear of satellite's surface has been estimated. The dependences for calculating the rectilinear (horizontal, inclined and vertical) sections of satellite's surface have been given. The presented dependences represent the results of experimental and analytical studies.

Understanding the Symbolic Capital of Intercultural Interactions: A Case Study of International Students in Australia

ERIC Educational Resources Information Center

Pham, Lien; Tran, Ly

2015-01-01

Intercultural interaction plays an important role in contributing to international students' learning and wellbeing in the host country. While research on international students' intercultural interactions reveals multifaceted aspects of personal and social factors, there is a tendency to consider language barrier and cultural differences as…

On the Rhetorical Contract in Human-Computer Interaction.

ERIC Educational Resources Information Center

Wenger, Michael J.

1991-01-01

An exploration of the rhetorical contract--i.e., the expectations for appropriate interaction--as it develops in human-computer interaction revealed that direct manipulation interfaces were more likely to establish social expectations. Study results suggest that the social nature of human-computer interactions can be examined with reference to the…

Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface.

PubMed

Jiang, Jianwen; Taylor, Alexander B; Prasad, Kondury; Ishikawa-Brush, Yumiko; Hart, P John; Lafer, Eileen M; Sousa, Rui

2003-05-20

J-domains are widespread protein interaction modules involved in recruiting and stimulating the activity of Hsp70 family chaperones. We have determined the crystal structure of the J-domain of auxilin, a protein which is involved in uncoating clathrin-coated vesicles. Comparison to the known structures of J-domains from four other proteins reveals that the auxilin J-domain is the most divergent of all J-domain structures described to date. In addition to the canonical J-domain features described previously, the auxilin J-domain contains an extra N-terminal helix and a long loop inserted between helices I and II. The latter loop extends the positively charged surface which forms the Hsc70 binding site, and is shown by directed mutagenesis and surface plasmon resonance to contain side chains important for binding to Hsc70.

Molecular spectroscopic studies on the interaction of ferulic acid with calf thymus DNA

NASA Astrophysics Data System (ADS)

Zhang, Shufang; Sun, Xuejun; Qu, Fengli; Kong, Rongmei

2013-08-01

The interaction between ferulic acid and calf thymus deoxyribonucleic acid (ctDNA) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) was investigated by UV-Vis spectroscopy, fluorescence spectroscopy, DNA melting techniques, and viscosity measurements. Results indicated that a complex of ferulic acid with ctDNA was formed with a binding constant of K290K = 7.60 × 104 L mol-1 and K310K = 4.90 × 104 L mol-1. The thermodynamic parameters enthalpy change (ΔH°), entropy change (ΔS°) and Gibbs free energy (ΔG°) were calculated to be -1.69 × 104 J mol-1, 35.36 J K-1 mol-1 and -2.79 × 104 J mol-1 at 310 K, respectively. The acting forces between ferulic acid and DNA mainly included hydrophobic interaction and hydrogen bonds. Acridine orange displacement studies revealed that ferulic acid can substitute for AO probe in the AO-DNA complex which was indicative of intercalation binding. Thermal denaturation study suggested that the interaction of ferulic acid with DNA could result in the increase of the denaturation temperature, which indicated that the stabilization of the DNA helix was increased in the presence of ferulic acid. Spectroscopic techniques together with melting techniques and viscosity determination provided evidences of intercalation mode of binding for the interaction between ferulic acid and ctDNA.

Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis.

PubMed

Collins, Ryan L; Hu, Ting; Wejse, Christian; Sirugo, Giorgio; Williams, Scott M; Moore, Jason H

2013-02-18

Identifying high-order genetics associations with non-additive (i.e. epistatic) effects in population-based studies of common human diseases is a computational challenge. Multifactor dimensionality reduction (MDR) is a machine learning method that was designed specifically for this problem. The goal of the present study was to apply MDR to mining high-order epistatic interactions in a population-based genetic study of tuberculosis (TB). The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases and 347 healthy controls from Guniea-Bissau in Africa. The ReliefF algorithm was applied first to generate a smaller set of the five most informative SNPs. MDR with 10-fold cross-validation was then applied to look at all possible combinations of two, three, four and five SNPs. The MDR model with the best testing accuracy (TA) consisted of SNPs rs2305619, rs187084, and rs11465421 (TA = 0.588) in PTX3, TLR9 and DC-Sign, respectively. A general 1000-fold permutation test of the null hypothesis of no association confirmed the statistical significance of the model (p = 0.008). An additional 1000-fold permutation test designed specifically to test the linear null hypothesis that the association effects are only additive confirmed the presence of non-additive (i.e. nonlinear) or epistatic effects (p = 0.013). An independent information-gain measure corroborated these results with a third-order epistatic interaction that was stronger than any lower-order associations. We have identified statistically significant evidence for a three-way epistatic interaction that is associated with susceptibility to TB. This interaction is stronger than any previously described one-way or two-way associations. This study highlights the importance of using machine learning methods that are designed to embrace, rather than ignore, the complexity of common diseases such as TB. We recommend future studies of the

Characterization of C-type lectins reveals an unexpectedly limited interaction between Cryptococcus neoformans spores and Dectin-1

PubMed Central

Walsh, Naomi M.; Wuthrich, Marcel; Wang, Huafeng; Klein, Bruce; Hull, Christina M.

2017-01-01

Phagocytosis by innate immune cells is an important process for protection against multiple pathologies and is particularly important for resistance to infection. However, phagocytosis has also been implicated in the progression of some diseases, including the dissemination of the human fungal pathogen, Cryptococcus neoformans. Previously, we identified Dectin-1 as a likely phagocytic receptor for C. neoformans spores through the use of soluble components in receptor-ligand blocking experiments. In this study, we used gain-of-function and loss-of-function assays with intact cells to evaluate the in vivo role of Dectin-1 and other C-type lectins in interactions with C. neoformans spores and discovered stark differences in outcome when compared with previous assays. First, we found that non-phagocytic cells expressing Dectin-1 were unable to bind spores and that highly sensitive reporter cells expressing Dectin-1 were not stimulated by spores. Second, we determined that some phagocytes from Dectin-1-/- mice interacted with spores differently than wild type (WT) cells, but the effects varied among assays and were modest overall. Third, while we detected small but statistically significant reductions in phagocytosis by primary alveolar macrophages from Dectin-1-/- mice compared to WT, we found no differences in survival between WT and Dectin-1-/- mice challenged with spores. Further analyses to assess the roles of other C-type lectins and their adapters revealed very weak stimulation of Dectin-2 reporter cells by spores and modest differences in binding and phagocytosis by Dectin-2-/- bone marrow-derived phagocytes. There were no discernable defects in binding or phagocytosis by phagocytes lacking Mannose Receptor, Mincle, Card-9, or FcRγ. Taken together, these results lead to the conclusion that Dectin-1 and other C-type lectins do not individually play a major roles in phagocytosis and innate defense by phagocytes against C. neoformans spores and highlight

Interactive effects of multiple stressors revealed by sequencing total (DNA) and active (RNA) components of experimental sediment microbial communities.

PubMed

Birrer, Simone C; Dafforn, Katherine A; Simpson, Stuart L; Kelaher, Brendan P; Potts, Jaimie; Scanes, Peter; Johnston, Emma L

2018-05-15

Coastal waterways are increasingly exposed to multiple stressors, e.g. contaminants that can be delivered via pulse or press exposures. Therefore, it is crucial that ecological impacts can be differentiated among stressors to manage ecosystem threats. We investigated microbial community development in sediments exposed to press and pulse stressors. Press exposures were created with in situ mesocosm sediments containing a range of 'metal' concentrations (sediment contaminated with multiple metal(loid)s) and organic enrichment (fertiliser), while the pulse exposure was simulated by a single dose of organic fertiliser. All treatments and exposure concentrations were crossed in a fully factorial field experiment. We used amplicon sequencing to compare the sensitivity of the 1) total (DNA) and active (RNA) component of 2) bacterial (16S rRNA) and eukaryotic (18S rRNA) communities to contaminant exposures. Overall microbial community change was greater when exposed to press than pulse stressors, with the bacterial community responding more strongly than the eukaryotes. The total bacterial community represents a more time-integrated measure of change and proved to be more sensitive to multiple stressors than the active community. Metals and organic enrichment treatments interacted such that the effect of metals was weaker when the sediment was organically enriched. Taxa-level analyses revealed that press enrichment resulted in potential functional changes, mainly involving nitrogen cycling. Furthermore, enrichment generally reduced the abundance of active eukaryotes in the sediment. As well as demonstrating interactive impacts of metals and organic enrichment, this study highlights the sensitivity of next-generation sequencing for ecosystem biomonitoring of interacting stressors and identifies opportunities for more targeted application. Copyright © 2018 Elsevier B.V. All rights reserved.

In Vitro Characterization of Thermostable CAM Rubisco Activase Reveals a Rubisco Interacting Surface Loop.

PubMed

Shivhare, Devendra; Mueller-Cajar, Oliver

2017-07-01

To maintain metabolic flux through the Calvin-Benson-Bassham cycle in higher plants, dead-end inhibited complexes of Rubisco must constantly be engaged and remodeled by the molecular chaperone Rubisco activase (Rca). In C3 plants, the thermolability of Rca is responsible for the deactivation of Rubisco and reduction of photosynthesis at moderately elevated temperatures. We reasoned that crassulacean acid metabolism (CAM) plants must possess thermostable Rca to support Calvin-Benson-Bassham cycle flux during the day when stomata are closed. A comparative biochemical characterization of rice ( Oryza sativa ) and Agave tequilana Rca isoforms demonstrated that the CAM Rca isoforms are approximately10°C more thermostable than the C3 isoforms. Agave Rca also possessed a much higher in vitro biochemical activity, even at low assay temperatures. Mixtures of rice and agave Rca form functional hetero-oligomers in vitro, but only the rice isoforms denature at nonpermissive temperatures. The high thermostability and activity of agave Rca mapped to the N-terminal 244 residues. A Glu-217-Gln amino acid substitution was found to confer high Rca activity to rice Rca Further mutational analysis suggested that Glu-217 restricts the flexibility of the α4-β4 surface loop that interacts with Rubisco via Lys-216. CAM plants thus promise to be a source of highly functional, thermostable Rca candidates for thermal fortification of crop photosynthesis. Careful characterization of their properties will likely reveal further protein-protein interaction motifs to enrich our mechanistic model of Rca function. © 2017 American Society of Plant Biologists. All Rights Reserved.

Energy Landscape of All-Atom Protein-Protein Interactions Revealed by Multiscale Enhanced Sampling

PubMed Central

Moritsugu, Kei; Terada, Tohru; Kidera, Akinori

2014-01-01

Protein-protein interactions are regulated by a subtle balance of complicated atomic interactions and solvation at the interface. To understand such an elusive phenomenon, it is necessary to thoroughly survey the large configurational space from the stable complex structure to the dissociated states using the all-atom model in explicit solvent and to delineate the energy landscape of protein-protein interactions. In this study, we carried out a multiscale enhanced sampling (MSES) simulation of the formation of a barnase-barstar complex, which is a protein complex characterized by an extraordinary tight and fast binding, to determine the energy landscape of atomistic protein-protein interactions. The MSES adopts a multicopy and multiscale scheme to enable for the enhanced sampling of the all-atom model of large proteins including explicit solvent. During the 100-ns MSES simulation of the barnase-barstar system, we observed the association-dissociation processes of the atomistic protein complex in solution several times, which contained not only the native complex structure but also fully non-native configurations. The sampled distributions suggest that a large variety of non-native states went downhill to the stable complex structure, like a fast folding on a funnel-like potential. This funnel landscape is attributed to dominant configurations in the early stage of the association process characterized by near-native orientations, which will accelerate the native inter-molecular interactions. These configurations are guided mostly by the shape complementarity between barnase and barstar, and lead to the fast formation of the final complex structure along the downhill energy landscape. PMID:25340714

Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study.

PubMed

A Santos, Jose C; Nassif, Houssam; Page, David; Muggleton, Stephen H; E Sternberg, Michael J

2012-07-11

There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP), which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. In addition to confirming literature results, ProGolem's model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners.

Hypernetworks Reveal Compound Variables That Capture Cooperative and Competitive Interactions in a Soccer Match.

PubMed

Ramos, João; Lopes, Rui J; Marques, Pedro; Araújo, Duarte

2017-01-01

The combination of sports sciences theorization and social networks analysis (SNA) has offered useful new insights for addressing team behavior. However, SNA typically represents the dynamics of team behavior during a match in dyadic interactions and in a single cumulative snapshot. This study aims to overcome these limitations by using hypernetworks to describe illustrative cases of team behavior dynamics at various other levels of analyses. Hypernetworks simultaneously access cooperative and competitive interactions between teammates and opponents across space and time during a match. Moreover, hypernetworks are not limited to dyadic relations, which are typically represented by edges in other types of networks. In a hypernetwork, n-ary relations (with n > 2) and their properties are represented with hyperedges connecting more than two players simultaneously (the so-called simplex -plural, simplices ). Simplices can capture the interactions of sets of players that may include an arbitrary number of teammates and opponents. In this qualitative study, we first used the mathematical formalisms of hypernetworks to represent a multilevel team behavior dynamics, including micro (interactions between players), meso (dynamics of a given critical event, e.g., an attack interaction), and macro (interactions between sets of players) levels. Second, we investigated different features that could potentially explain the occurrence of critical events, such as, aggregation or disaggregation of simplices relative to goal proximity. Finally, we applied hypernetworks analysis to soccer games from the English premier league (season 2010-2011) by using two-dimensional player displacement coordinates obtained with a multiple-camera match analysis system provided by STATS (formerly Prozone). Our results show that (i) at micro level the most frequently occurring simplices configuration is 1vs.1 (one attacker vs. one defender); (ii) at meso level, the dynamics of simplices

Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study

PubMed Central

Roetker, Nicholas S; Yonker, James A; Lee, Chee; Chang, Vicky; Basson, Jacob J; Roan, Carol L; Hauser, Taissa S; Hauser, Robert M

2012-01-01

Objectives Single genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene–gene (G × G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression. Design A retrospective cohort study. Setting A survey of participants in the Wisconsin Longitudinal Study. Participants A total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. Primary outcome measure Depression as determine by the Composite International Diagnostic Interview–Short-Form. Results Using a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G × G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G × G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men: GNRH1 novel SNP: (1.43 → 1.57); women: APOC3 rs2854116: (1.28 → 1.55), ACVR2B rs3749386: (1.11 → 2.17), FTO rs1421085: (1.32 → 1.65), IL6 rs1800795: (1.12 → 1.85)). Conclusions The results suggest that examining G × G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions

Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors

NASA Astrophysics Data System (ADS)

Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

2015-05-01

In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

Outrun or Outmaneuver: Predator-Prey Interactions as a Model System for Integrating Biomechanical Studies in a Broader Ecological and Evolutionary Context.

PubMed

Moore, Talia Y; Biewener, Andrew A

2015-12-01

Behavioral studies performed in natural habitats provide a context for the development of hypotheses and the design of experiments relevant both to biomechanics and to evolution. In particular, predator-prey interactions are a model system for integrative study because success or failure of predation has a direct effect on fitness and drives the evolution of specialized performance in both predator and prey. Although all predators share the goal of capturing prey, and all prey share the goal of survival, the behavior of predators and prey are diverse in nature. This article presents studies of some predator-prey interactions sharing common predation strategies that reveal general principles governing the behaviors of predator and prey, even in distantly related taxa. Studies of predator-prey interactions also reveal that maximal performance observed in a laboratory setting is not necessarily the performance that determines fitness. Thus, considering locomotion in the context of predation ecology can aid in evolutionarily relevant experimental design. Classification by strategy reveals that displaying unpredictable trajectories is a relevant anti-predator behavior in response to multiple predation strategies. A predator's perception and pursuit of prey can be affected indirectly by divergent locomotion of similar animals that share an ecosystem. Variation in speed and direction of locomotion that directly increases the unpredictability of a prey's trajectory can be increased through genetic mutation that affects locomotor patterns, musculoskeletal changes that affect maneuverability, and physical interactions between an animal and the environment. By considering the interconnectedness of ecology, physical constraints, and the evolutionary history of behavior, studies in biomechanics can be designed to inform each of these fields. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights

Experimentally reduced root-microbe interactions reveal limited plasticity in functional root traits in Acer and Quercus.

PubMed

Lee, Mei-Ho; Comas, Louise H; Callahan, Hilary S

2014-02-01

Interactions between roots and soil microbes are critical components of below-ground ecology. It is essential to quantify the magnitude of root trait variation both among and within species, including variation due to plasticity. In addition to contextualizing the magnitude of plasticity relative to differences between species, studies of plasticity can ascertain if plasticity is predictable and whether an environmental factor elicits changes in traits that are functionally advantageous. To compare functional traits and trait plasticities in fine root tissues with natural and reduced levels of colonization by microbial symbionts, trimmed and surface-sterilized root segments of 2-year-old Acer rubrum and Quercus rubra seedlings were manipulated. Segments were then replanted into satellite pots filled with control or heat-treated soil, both originally derived from a natural forest. Mycorrhizal colonization was near zero in roots grown in heat-treated soil; roots grown in control soil matched the higher colonization levels observed in unmanipulated root samples collected from field locations. Between-treatment comparisons revealed negligible plasticity for root diameter, branching intensity and nitrogen concentration across both species. Roots from treated soils had decreased tissue density (approx. 10-20 %) and increased specific root length (approx. 10-30 %). In contrast, species differences were significant and greater than treatment effects in traits other than tissue density. Interspecific trait differences were also significant in field samples, which generally resembled greenhouse samples. The combination of experimental and field approaches was useful for contextualizing trait plasticity in comparison with inter- and intra-specific trait variation. Findings that root traits are largely species dependent, with the exception of root tissue density, are discussed in the context of current literature on root trait variation, interactions with symbionts and recent

Experimentally reduced root–microbe interactions reveal limited plasticity in functional root traits in Acer and Quercus

PubMed Central

Lee, Mei-Ho; Comas, Louise H.; Callahan, Hilary S.

2014-01-01

Background and Aims Interactions between roots and soil microbes are critical components of below-ground ecology. It is essential to quantify the magnitude of root trait variation both among and within species, including variation due to plasticity. In addition to contextualizing the magnitude of plasticity relative to differences between species, studies of plasticity can ascertain if plasticity is predictable and whether an environmental factor elicits changes in traits that are functionally advantageous. Methods To compare functional traits and trait plasticities in fine root tissues with natural and reduced levels of colonization by microbial symbionts, trimmed and surface-sterilized root segments of 2-year-old Acer rubrum and Quercus rubra seedlings were manipulated. Segments were then replanted into satellite pots filled with control or heat-treated soil, both originally derived from a natural forest. Mycorrhizal colonization was near zero in roots grown in heat-treated soil; roots grown in control soil matched the higher colonization levels observed in unmanipulated root samples collected from field locations. Key Results Between-treatment comparisons revealed negligible plasticity for root diameter, branching intensity and nitrogen concentration across both species. Roots from treated soils had decreased tissue density (approx. 10–20 %) and increased specific root length (approx. 10–30 %). In contrast, species differences were significant and greater than treatment effects in traits other than tissue density. Interspecific trait differences were also significant in field samples, which generally resembled greenhouse samples. Conclusions The combination of experimental and field approaches was useful for contextualizing trait plasticity in comparison with inter- and intra-specific trait variation. Findings that root traits are largely species dependent, with the exception of root tissue density, are discussed in the context of current literature on root

Dynamics of Disagreement: Large-Scale Temporal Network Analysis Reveals Negative Interactions in Online Collaboration

NASA Astrophysics Data System (ADS)

Tsvetkova, Milena; García-Gavilanes, Ruth; Yasseri, Taha

2016-11-01

Disagreement and conflict are a fact of social life. However, negative interactions are rarely explicitly declared and recorded and this makes them hard for scientists to study. In an attempt to understand the structural and temporal features of negative interactions in the community, we use complex network methods to analyze patterns in the timing and configuration of reverts of article edits to Wikipedia. We investigate how often and how fast pairs of reverts occur compared to a null model in order to control for patterns that are natural to the content production or are due to the internal rules of Wikipedia. Our results suggest that Wikipedia editors systematically revert the same person, revert back their reverter, and come to defend a reverted editor. We further relate these interactions to the status of the involved editors. Even though the individual reverts might not necessarily be negative social interactions, our analysis points to the existence of certain patterns of negative social dynamics within the community of editors. Some of these patterns have not been previously explored and carry implications for the knowledge collection practice conducted on Wikipedia. Our method can be applied to other large-scale temporal collaboration networks to identify the existence of negative social interactions and other social processes.

Targeted studies on the interaction of nicotine and morin molecules with amyloid β-protein.

PubMed

Boopathi, Subramaniam; Kolandaivel, Ponmalai

2014-03-01

Alzheimer's disease (AD) is a neurodegenerative disorder that occurs due to progressive deposition of amyloid β-protein (Aβ) in the brain. Stable conformations of solvated Aβ₁₋₄₂ protein were predicted by molecular dynamics (MD) simulation using the OPLSAA force field. The seven residue peptide (Lys-Leu-Val-Phe-Phe-Ala-Glu) Aβ₁₆₋₂₂ associated with AD was studied and reported in this paper. Since effective therapeutic agents have not yet been studied in detail, attention has focused on the use of natural products as effective anti-aggregation compounds, targeting the Aβ₁₋₄₂ protein directly. Experimental and theoretical investigation suggests that some compounds extracted from natural products might be useful, but detailed insights into the mechanism by which they might act remains elusive. The molecules nicotine and morin are found in cigarettes and beverages. Here, we report the results of interaction studies of these compounds at each hydrophobic residue of Aβ₁₆₋₂₂ peptide using the hybrid ONIOM (B3LYP/6-31G**:UFF) method. It was found that interaction with nicotine produced higher deformation in the Aβ₁₆₋₂₂ peptide than interaction with morin. MD simulation studies revealed that interaction of the nicotine molecule with the β-sheet of Aβ₁₆₋₂₂ peptide transforms the β-sheet to an α-helical structure, which helps prohibit the aggregation of Aβ-protein.

Chitosan nanoparticles-trypsin interactions: Bio-physicochemical and molecular dynamics simulation studies.

PubMed

Salar, Safoura; Mehrnejad, Faramarz; Sajedi, Reza H; Arough, Javad Mohammadnejad

2017-10-01

Herein, we investigated the effect of the chitosan nanoparticles (CsNP) on the structure, dynamics, and activity of trypsin. The enzyme activity in complex with the nanoparticles slightly increased, which represents the interactions between the nanoparticles and the enzyme. The kinetic parameters of the enzyme, K m and k cat , increased after adding the nanoparticles, resulting in a slight increase in the catalytic efficiency (k cat /K m ). However, the effect of the nanoparticles on the kinetic stability of trypsin has not exhibited significant variations. Fluorescence spectroscopy did not show remarkable changes in the trypsin conformation in the presence of the nanoparticles. The circular dichroism (CD) spectroscopy results also revealed the secondary structure of trypsin attached to the nanoparticles slightly changed. Furthermore, we used molecular dynamics (MD) simulation to find more information about the interaction mechanisms between the nanoparticles and trypsin. The root mean square deviation (RMSD) of Cα atoms results have shown that in the presence of the nanoparticles, trypsin was stable. The simulation and the calculation of the binding free energy demonstrate that the nonpolar interactions are the most important forces for the formation of stable nanoparticle-trypsin complex. This study has explicitly elucidated that the nanoparticles have not considerable effect on the trypsin. Copyright © 2017. Published by Elsevier B.V.

Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology.

PubMed

DeBlasio, Stacy L; Chavez, Juan D; Alexander, Mariko M; Ramsey, John; Eng, Jimmy K; Mahoney, Jaclyn; Gray, Stewart M; Bruce, James E; Cilia, Michelle

2016-02-15

Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus [PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in the Luteoviridae and with unrelated viruses in the Herpesviridae and Adenoviridae. Functional analysis of three PLRV-interacting host proteins in planta using a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection-hallmarks of host-pathogen interactions-were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies. The exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used protein interaction

Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution

PubMed Central

Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J.; Golovanov, Alexander P.

2016-01-01

The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (SosCat) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of SosCat, while SosCat also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos. PMID:27412770

Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution.

PubMed

Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J; Golovanov, Alexander P

2016-07-14

The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (Sos(Cat)) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of Sos(Cat), while Sos(Cat) also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos.

A Rice gid1 Suppressor Mutant Reveals That Gibberellin Is Not Always Required for Interaction between Its Receptor, GID1, and DELLA Proteins[W][OA

PubMed Central

Yamamoto, Yuko; Hirai, Takaaki; Yamamoto, Eiji; Kawamura, Mayuko; Sato, Tomomi; Kitano, Hidemi; Matsuoka, Makoto; Ueguchi-Tanaka, Miyako

2010-01-01

To investigate gibberellin (GA) signaling using the rice (Oryza sativa) GA receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) mutant gid1-8, we isolated a suppressor mutant, Suppressor of gid1-1 (Sgd-1). Sgd-1 is an intragenic mutant containing the original gid1-8 mutation (L45F) and an additional amino acid substitution (P99S) in the loop region. GID1P99S interacts with the rice DELLA protein SLENDER RICE1 (SLR1), even in the absence of GA. Substitution of the 99th Pro with other amino acids revealed that substitution with Ala (P99A) caused the highest level of GA-independent interaction. Physicochemical analysis using surface plasmon resonance revealed that GID1P99A has smaller Ka (association) and Kd (dissociation) values for GA4 than does wild-type GID1. This suggests that the GID1P99A lid is at least partially closed, resulting in both GA-independent and GA-hypersensitive interactions with SLR1. One of the three Arabidopsis thaliana GID1s, At GID1b, can also interact with DELLA proteins in the absence of GA, so we investigated whether GA-independent interaction of At GID1b depends on a mechanism similar to that of rice GID1P99A. Substitution of the loop region or a few amino acids of At GID1b with those of At GID1a diminished its GA-independent interaction with GAI while maintaining the GA-dependent interaction. Soybean (Glycine max) and Brassica napus also have GID1s similar to At GID1b, indicating that these unique GID1s occur in various dicots and may have important functions in these plants. PMID:21098733

Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology

PubMed Central

DeBlasio, Stacy L.; Chavez, Juan D.; Alexander, Mariko M.; Ramsey, John; Eng, Jimmy K.; Mahoney, Jaclyn; Gray, Stewart M.; Bruce, James E.

2015-01-01

ABSTRACT Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus [PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in the Luteoviridae and with unrelated viruses in the Herpesviridae and Adenoviridae. Functional analysis of three PLRV-interacting host proteins in planta using a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection—hallmarks of host-pathogen interactions—were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies. IMPORTANCE The exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used

Anisotropic interaction rules in circular motions of pigeon flocks: An empirical study based on sparse Bayesian learning

NASA Astrophysics Data System (ADS)

Chen, Duxin; Xu, Bowen; Zhu, Tao; Zhou, Tao; Zhang, Hai-Tao

2017-08-01

Coordination shall be deemed to the result of interindividual interaction among natural gregarious animal groups. However, revealing the underlying interaction rules and decision-making strategies governing highly coordinated motion in bird flocks is still a long-standing challenge. Based on analysis of high spatial-temporal resolution GPS data of three pigeon flocks, we extract the hidden interaction principle by using a newly emerging machine learning method, namely the sparse Bayesian learning. It is observed that the interaction probability has an inflection point at pairwise distance of 3-4 m closer than the average maximum interindividual distance, after which it decays strictly with rising pairwise metric distances. Significantly, the density of spatial neighbor distribution is strongly anisotropic, with an evident lack of interactions along individual velocity. Thus, it is found that in small-sized bird flocks, individuals reciprocally cooperate with a variational number of neighbors in metric space and tend to interact with closer time-varying neighbors, rather than interacting with a fixed number of topological ones. Finally, extensive numerical investigation is conducted to verify both the revealed interaction and decision-making principle during circular flights of pigeon flocks.

Annonalide and derivatives: Semisynthesis, cytotoxic activities and studies on interaction of annonalide with DNA.

PubMed

Marques, Ricardo A; Gomes, Akenaton O C V; de Brito, Maria V; Dos Santos, Ana L P; da Silva, Gladyane S; de Lima, Leandro B; Nunes, Fátima M; de Mattos, Marcos C; de Oliveira, Fátima C E; do Ó Pessoa, Cláudia; de Moraes, Manoel O; de Fátima, Ângelo; Franco, Lucas L; Silva, Marina de M; Dantas, Maria Dayanne de A; Santos, Josué C C; Figueiredo, Isis M; da Silva-Júnior, Edeíldo F; de Aquino, Thiago M; de Araújo-Júnior, João X; de Oliveira, Maria C F; Leslie Gunatilaka, A A

2018-02-01

The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC 50 s below 4.0 μM, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as -28.24 kJ mol -1 , and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19). Copyright © 2018. Published by Elsevier B.V.

Scanning mutagenesis studies reveal a potential intramolecular interaction within the C-terminal half of dengue virus NS2A involved in viral RNA replication and virus assembly and secretion.

PubMed

Wu, Ren-Huang; Tsai, Ming-Han; Chao, Day-Yu; Yueh, Andrew

2015-04-01

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMSs; pTMS1 to pTMS8). NS2A has been shown to participate in RNA replication, virion assembly, and the host antiviral response. However, the role of the amino acid residues within the pTMS regions of NS2A during the virus life cycle is poorly understood. In the study described here, we explored the function of DENV NS2A by introducing a series of double or triple alanine substitutions into the C-terminal half (pTMS4 to pTMS8) of NS2A in the context of a DENV infectious clone or subgenomic replicon. Fourteen (8 within pTMS8) of 35 NS2A mutants displayed a lethal phenotype due to impairment of RNA replication by a replicon assay. Three NS2A mutants with mutations within pTMS7, the CM20, CM25, and CM27 mutants, displayed similar phenotypes, low virus yields (>100-fold reduction), wild-type-like replicon activity, and low infectious virus-like particle yields by transient trans-packaging experiments, suggesting a defect in virus assembly and secretion. The sequencing of revertant viruses derived from CM20, CM25, and CM27 mutant viruses revealed a consensus reversion mutation, leucine (L) to phenylalanine (F), at codon 181 within pTMS7. The introduction of an L181F mutation into a full-length NS2A mutant, i.e., the CM20, CM25, and CM27 constructs, completely restored wild-type infectivity. Notably, L181F also substantially rescued the other severely RNA replication-defective mutants with mutations within pTMS4, pTMS6, and pTMS8, i.e., the CM2, CM3, CM13, CM31, and CM32 mutants. In conclusion, the results revealed the essential roles of pTMS4 to pTMS8 of NS2A in RNA replication and/or virus assembly and secretion. The intramolecular interaction between pTMS7 and pTMS4, pTMS6, or pTMS8 of the NS2A protein was also implicated. The reported characterization of the C-terminal half of dengue virus NS2A is the first comprehensive mutagenesis study to investigate the function of flavivirus NS2A

Perspectives of Future Satellite Observations for Studying Aerosol-Cloud Interactions

NASA Astrophysics Data System (ADS)

Vane, D. G.; Stephens, G. L.

2008-12-01

There are many studies that examine the effects of aerosol on clouds and the consequence of these effects for climate. Much of the focus of these interactions revolve around two types of indirect effects. Using the A- Train as a resource for studying these interactions as a way of defining the requirements for future new missions, we find that the sensitivity of the cloud albedo, as observed by CERES, to aerosol varies according to these various conditions and does not simply correlate with decreased particle size as is typically assumed. It is clear that these effects require more in-depth information about cloud water path, and the occurrence and amount of precipitation and the environmental conditions in which the interactions take place. Information about the motions in clouds, the depths of clouds and more resolved microphysical details on cloud and drizzle are essential to study these effects. Perhaps more important than indirect effects on cloud albedo are the possible effects of aerosol on precipitation. There is much speculation about such influences and the A-Train observations are beginning to reveal much insight on such effects. These observations appear to suggest that the effects on shallow clouds is to delay precipitation production and reduce rainfall as has been speculated. The effects of aerosol on the precipitation falling from deep convection is less clear and more difficult to observe, although many model studies consistently suggest that the effects might be even more pronounced than on shallow convection through, among other mechanisms, the invigoration of storms via freezing of elevated water contents in updrafts. Such studies are now clearly pointing to the need to define the water contents and microphysics of hydrometeors in convective updrafts. This talk draws on these results as a way of framing the definition of the cloud-aerosol and precipitation component of the ACE mission of the decadal survey. This mission represents the follow

Interaction Studies of Withania Somnifera's Key Metabolite Withaferin A with Different Receptors Assoociated with Cardiovascular Disease.

PubMed

Ravindran, Rekha; Sharma, Nitika; Roy, Sujata; Thakur, Ashoke R; Ganesh, Subhadra; Kumar, Sriram; Devi, Jamuna; Rajkumar, Johanna

2015-01-01

Withania somnifera commonly known as Ashwagandha in India is used in many herbal formulations to treat various cardiovascular diseases. The key metabolite of this plant, Withaferin A was analyzed for its molecular mechanism through docking studies on different targets of cardiovascular disease. Six receptor proteins associated with cardiovascular disease were selected and interaction studies were performed with Withaferin A using AutoDock Vina. CORINA was used to model the small molecules and HBAT to compute the hydrogen bonding. Among the six targets, β1- adrenergic receptors, HMG-CoA and Angiotensinogen-converting enzyme showed significant interaction with Withaferin A. Pharmacophore modeling was done using PharmaGist to understand the pharmacophoric potential of Withaferin A. Clustering of Withaferin A with different existing drug molecules for cardiovascular disease was performed with ChemMine based on structural similarity and physicochemical properties. The ability of natural active component, Withaferin A to interact with different receptors associated with cardiovascular disease was elucidated with various modeling techniques. These studies conclusively revealed Withaferin A as a potent lead compound against multiple targets associated with cardiovascular disease.

Studies of Peptide-Mineral Interactions and Biosilicification

DTIC Science & Technology

2010-07-16

His). The effect of zinc oxide -binding peptides ( ZnO -BPs) on the morphology and formation of ZnO were studied using G-12 (GLHVMHKVAPPR) and EM-12...interactions with silica and zinc oxide . Detailed quantitative experimental studies together with molecular modeling studies have shown that G12 (GLHVMHKVAPPR...studies of a primitive 15. SUBJECT TERMS Peptides, zinc oxide , silica, silver, peptide-mineral interactions, computational chemistry, molecular

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup’ik) population

PubMed Central

Vaughan, Laura Kelly; Wiener, Howard W.; Aslibekyan, Stella; Allison, David B.; Havel, Peter J.; Stanhope, Kimber L.; O’Brien, Diane M.; Hopkins, Scarlett E.; Lemas, Dominick J.; Boyer, Bert B.; Tiwari, Hemant K.

2015-01-01

Objective To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup’ik people. Material and Methods We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. Results We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). Conclusions This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup’ik people. PMID:25772781

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.

PubMed

Vaughan, Laura Kelly; Wiener, Howard W; Aslibekyan, Stella; Allison, David B; Havel, Peter J; Stanhope, Kimber L; O'Brien, Diane M; Hopkins, Scarlett E; Lemas, Dominick J; Boyer, Bert B; Tiwari, Hemant K

2015-06-01

To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people. We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people. Copyright © 2015 Elsevier Inc. All rights reserved.

Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

PubMed

Sato, Trey K; Tremaine, Mary; Parreiras, Lucas S; Hebert, Alexander S; Myers, Kevin S; Higbee, Alan J; Sardi, Maria; McIlwain, Sean J; Ong, Irene M; Breuer, Rebecca J; Avanasi Narasimhan, Ragothaman; McGee, Mick A; Dickinson, Quinn; La Reau, Alex; Xie, Dan; Tian, Mingyuan; Reed, Jennifer L; Zhang, Yaoping; Coon, Joshua J; Hittinger, Chris Todd; Gasch, Audrey P; Landick, Robert

2016-10-01

The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae

PubMed Central

Tremaine, Mary; Hebert, Alexander S.; Myers, Kevin S.; Sardi, Maria; Dickinson, Quinn; Reed, Jennifer L.; Zhang, Yaoping; Coon, Joshua J.; Hittinger, Chris Todd; Gasch, Audrey P.; Landick, Robert

2016-01-01

The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism. PMID:27741250

Molecular spectroscopic studies on the interaction of ferulic acid with calf thymus DNA.

PubMed

Zhang, Shufang; Sun, Xuejun; Qu, Fengli; Kong, Rongmei

2013-08-01

The interaction between ferulic acid and calf thymus deoxyribonucleic acid (ctDNA) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) was investigated by UV-Vis spectroscopy, fluorescence spectroscopy, DNA melting techniques, and viscosity measurements. Results indicated that a complex of ferulic acid with ctDNA was formed with a binding constant of K(290K)=7.60×10(4) L mol(-1) and K(310K)=4.90×10(4) L mol(-1). The thermodynamic parameters enthalpy change (ΔH°), entropy change (ΔS°) and Gibbs free energy (ΔG°) were calculated to be -1.69×10(4) J mol(-1), 35.36 J K(-1) mol(-1) and -2.79×10(4) J mol(-1) at 310 K, respectively. The acting forces between ferulic acid and DNA mainly included hydrophobic interaction and hydrogen bonds. Acridine orange displacement studies revealed that ferulic acid can substitute for AO probe in the AO-DNA complex which was indicative of intercalation binding. Thermal denaturation study suggested that the interaction of ferulic acid with DNA could result in the increase of the denaturation temperature, which indicated that the stabilization of the DNA helix was increased in the presence of ferulic acid. Spectroscopic techniques together with melting techniques and viscosity determination provided evidences of intercalation mode of binding for the interaction between ferulic acid and ctDNA. Copyright © 2013 Elsevier B.V. All rights reserved.

A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria

PubMed Central

Hoppins, Suzanne; Collins, Sean R.; Cassidy-Stone, Ann; Hummel, Eric; DeVay, Rachel M.; Lackner, Laura L.; Westermann, Benedikt; Schuldiner, Maya

2011-01-01

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane–associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria. PMID:21987634

Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study

PubMed Central

2012-01-01

Background There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP), which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. Results The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. Conclusions In addition to confirming literature results, ProGolem’s model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners. PMID:22783946

The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity

PubMed Central

Stein, Matthias; Pilli, Manohar; Bernauer, Sabine; Habermann, Bianca H.; Zerial, Marino; Wade, Rebecca C.

2012-01-01

Background Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood. Methodology/Principal Findings Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics. Conclusions/Significance We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity. PMID:22523562

Interactions between Casein Kinase Iε (CKIε) and Two Substrates from Disparate Signaling Pathways Reveal Mechanisms for Substrate-Kinase Specificity

PubMed Central

Dahlberg, Caroline Lund; Nguyen, Elizabeth Z.; Goodlett, David; Kimelman, David

2009-01-01

Background Members of the Casein Kinase I (CKI) family of serine/threonine kinases regulate diverse biological pathways. The seven mammalian CKI isoforms contain a highly conserved kinase domain and divergent amino- and carboxy-termini. Although they share a preferred target recognition sequence and have overlapping expression patterns, individual isoforms often have specific substrates. In an effort to determine how substrates recognize differences between CKI isoforms, we have examined the interaction between CKIε and two substrates from different signaling pathways. Methodology/Principal Findings CKIε, but not CKIα, binds to and phosphorylates two proteins: Period, a transcriptional regulator of the circadian rhythms pathway, and Disheveled, an activator of the planar cell polarity pathway. We use GST-pull-down assays data to show that two key residues in CKIα's kinase domain prevent Disheveled and Period from binding. We also show that the unique C-terminus of CKIε does not determine Dishevelled's and Period's preference for CKIε nor is it essential for binding, but instead plays an auxillary role in stabilizing the interactions of CKIε with its substrates. We demonstrate that autophosphorylation of CKIε's C-terminal tail prevents substrate binding, and use mass spectrometry and chemical crosslinking to reveal how a phosphorylation-dependent interaction between the C-terminal tail and the kinase domain prevents substrate phosphorylation and binding. Conclusions/Significance The biochemical interactions between CKIε and Disheveled, Period, and its own C-terminus lead to models that explain CKIε's specificity and regulation. PMID:19274088

Genome sequencing and comparative genomics of honey bee microsporidia, Nosema apis reveal novel insights into host-parasite interactions.

PubMed

Chen, Yan ping; Pettis, Jeffery S; Zhao, Yan; Liu, Xinyue; Tallon, Luke J; Sadzewicz, Lisa D; Li, Renhua; Zheng, Huoqing; Huang, Shaokang; Zhang, Xuan; Hamilton, Michele C; Pernal, Stephen F; Melathopoulos, Andony P; Yan, Xianghe; Evans, Jay D

2013-07-05

The microsporidia parasite Nosema contributes to the steep global decline of honey bees that are critical pollinators of food crops. There are two species of Nosema that have been found to infect honey bees, Nosema apis and N. ceranae. Genome sequencing of N. apis and comparative genome analysis with N. ceranae, a fully sequenced microsporidia species, reveal novel insights into host-parasite interactions underlying the parasite infections. We applied the whole-genome shotgun sequencing approach to sequence and assemble the genome of N. apis which has an estimated size of 8.5 Mbp. We predicted 2,771 protein- coding genes and predicted the function of each putative protein using the Gene Ontology. The comparative genomic analysis led to identification of 1,356 orthologs that are conserved between the two Nosema species and genes that are unique characteristics of the individual species, thereby providing a list of virulence factors and new genetic tools for studying host-parasite interactions. We also identified a highly abundant motif in the upstream promoter regions of N. apis genes. This motif is also conserved in N. ceranae and other microsporidia species and likely plays a role in gene regulation across the microsporidia. The availability of the N. apis genome sequence is a significant addition to the rapidly expanding body of microsprodian genomic data which has been improving our understanding of eukaryotic genome diversity and evolution in a broad sense. The predicted virulent genes and transcriptional regulatory elements are potential targets for innovative therapeutics to break down the life cycle of the parasite.

HIV-malaria interactions in North-East India: A prospective cohort study

PubMed Central

Mohapatra, Pradhyumn K.; Pachuau, Elsa; Kumar, Chandra; Borkakoty, Biswajit; Zomawia, Eric; Singh, Achouba; Walia, Kamini; Arora, Rashmi; Mahanta, Jagdish; Subbarao, Sarala K.

2017-01-01

Background & objectives: The interactions between HIV and malaria co-infection have been shown to influence each other in their clinical outcomes in Sub-Saharan Africa. This study was carried out in the two States of north east India endemic for both HIV and malaria infections, to study the interactions between the two diseases in the HIV-infected population. Methods: In this prospective study, a total of 333 HIV-infected individuals were followed up for a period of 6-18 months in Mizoram and Manipur during 2010-2011. The study assessed the changes in viral load and also the therapeutic efficacy of artesunate plus sulphadoxine-pyrimethamine (AS+SP) combination therapy in HIV-infected and HIV-uninfected individuals with Plasmodium falciparum malaria. Results: Viral load in HIV-infected malaria patients on day zero (D0) ranged from 1110 to 147,000 copies/ml. The log transformation of the geometric means of HIV viral loads revealed no significant difference on different days of follow up. There was 100 per cent adequate clinical and parasitological response (ACPR) after treating with artemisinin based combination therapy (ACT) both in HIV-infected and HIV-uninfected P. falciparum-positive individuals. Similarly, chloroquine showed 100 per cent ACPR in P. vivax HIV-infected individuals. Interpretation & conclusion: The study showed no significant increase in HIV viral load in malaria cases. All HIV-infected and HIV-uninfected P. falciparum malaria-positive cases responded to the treatment with 100 per cent ACPR. PMID:28749403

Quantitative Genetic Interactions Reveal Layers of Biological Modularity

PubMed Central

Beltrao, Pedro; Cagney, Gerard; Krogan, Nevan J.

2010-01-01

In the past, biomedical research has embraced a reductionist approach, primarily focused on characterizing the individual components that comprise a system of interest. Recent technical developments have significantly increased the size and scope of data describing biological systems. At the same time, advances in the field of systems biology have evoked a broader view of how the underlying components are interconnected. In this essay, we discuss how quantitative genetic interaction mapping has enhanced our view of biological systems, allowing a deeper functional interrogation at different biological scales. PMID:20510918

A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

PubMed

Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

2017-07-11

Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

Interaction rewiring and the rapid turnover of plant-pollinator networks.

PubMed

CaraDonna, Paul J; Petry, William K; Brennan, Ross M; Cunningham, James L; Bronstein, Judith L; Waser, Nickolas M; Sanders, Nathan J

2017-03-01

Whether species interactions are static or change over time has wide-reaching ecological and evolutionary consequences. However, species interaction networks are typically constructed from temporally aggregated interaction data, thereby implicitly assuming that interactions are fixed. This approach has advanced our understanding of communities, but it obscures the timescale at which interactions form (or dissolve) and the drivers and consequences of such dynamics. We address this knowledge gap by quantifying the within-season turnover of plant-pollinator interactions from weekly censuses across 3 years in a subalpine ecosystem. Week-to-week turnover of interactions (1) was high, (2) followed a consistent seasonal progression in all years of study and (3) was dominated by interaction rewiring (the reassembly of interactions among species). Simulation models revealed that species' phenologies and relative abundances constrained both total interaction turnover and rewiring. Our findings reveal the diversity of species interactions that may be missed when the temporal dynamics of networks are ignored. © 2017 John Wiley & Sons Ltd/CNRS.

Fluorescence spectroscopic study on the interaction of resveratrol with lipoxygenase

NASA Astrophysics Data System (ADS)

Pinto, María del Carmen; Duque, Antonio Luis; Macías, Pedro

2010-09-01

The interaction of lipoxygenase with (E)-resveratrol was investigated by fluorescence spectroscopy. The data obtained revealed that the quenching of intrinsic fluorescence of lipoxygenase is produced by the formation of a complex lipoxygenase-(E)-resveratrol. From the value obtained for the binding constant, according to the Stern-Volmer modified equation, was deduced the existence of static quenching mechanism and, as consequence, the existence of a strong interaction between (E)-resveratrol and lipoxygenase. The values obtained for the thermodynamic parameter Δ H (-3.58 kJ mol -1) and Δ S (87.97 J mol -1K -1) suggested the participation of hydrophobic interactions and hydrogen bonds in the stabilization of the complex ligand-protein. From the static quenching we determined that only exist one independent binding site. Based on the Förster energy transfer theory, the distance between the acceptor ((E)-resveratrol) and the donor (Trp residues of lipoxygenase) was calculated to be 3.42 nm. Finally, based on the information obtained from the evaluation of synchronous and three-dimensional fluorescence spectroscopy, we deduced that the interaction of (E)-resveratrol with lipoxygenase produces micro-environmental and conformational alterations of protein in the binding region.

Biophysical studies and NMR structure of YAP2 WW domain - LATS1 PPxY motif complexes reveal the basis of their interaction.

PubMed

Verma, Apoorva; Jing-Song, Fan; Finch-Edmondson, Megan L; Velazquez-Campoy, Adrian; Balasegaran, Shanker; Sudol, Marius; Sivaraman, Jayaraman

2018-01-30

YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1.

Biophysical studies and NMR structure of YAP2 WW domain - LATS1 PPxY motif complexes reveal the basis of their interaction

PubMed Central

Verma, Apoorva; Jing-Song, Fan; Finch-Edmondson, Megan L.; Velazquez-Campoy, Adrian; Balasegaran, Shanker; Sudol, Marius; Sivaraman, Jayaraman

2018-01-01

YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1. PMID:29487715

Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

Molecular Dynamics in Mixed Solvents Reveals Protein-Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions.

PubMed

Arcon, Juan Pablo; Defelipe, Lucas A; Modenutti, Carlos P; López, Elias D; Alvarez-Garcia, Daniel; Barril, Xavier; Turjanski, Adrián G; Martí, Marcelo A

2017-04-24

One of the most important biological processes at the molecular level is the formation of protein-ligand complexes. Therefore, determining their structure and underlying key interactions is of paramount relevance and has direct applications in drug development. Because of its low cost relative to its experimental sibling, molecular dynamics (MD) simulations in the presence of different solvent probes mimicking specific types of interactions have been increasingly used to analyze protein binding sites and reveal protein-ligand interaction hot spots. However, a systematic comparison of different probes and their real predictive power from a quantitative and thermodynamic point of view is still missing. In the present work, we have performed MD simulations of 18 different proteins in pure water as well as water mixtures of ethanol, acetamide, acetonitrile and methylammonium acetate, leading to a total of 5.4 μs simulation time. For each system, we determined the corresponding solvent sites, defined as space regions adjacent to the protein surface where the probability of finding a probe atom is higher than that in the bulk solvent. Finally, we compared the identified solvent sites with 121 different protein-ligand complexes and used them to perform molecular docking and ligand binding free energy estimates. Our results show that combining solely water and ethanol sites allows sampling over 70% of all possible protein-ligand interactions, especially those that coincide with ligand-based pharmacophoric points. Most important, we also show how the solvent sites can be used to significantly improve ligand docking in terms of both accuracy and precision, and that accurate predictions of ligand binding free energies, along with relative ranking of ligand affinity, can be performed.

Environmental confounding in gene-environment interaction studies.

PubMed

Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

2013-07-01

We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

Exploration of molecular interactions in cholesterol superlattices: effect of multibody interactions.

PubMed

Huang, Juyang

2002-08-01

Experimental evidences have indicated that cholesterol may adapt highly regular lateral distributions (i.e., superlattices) in a phospholipid bilayer. We investigated the formations of superlattices at cholesterol mole fraction of 0.154, 0.25, 0.40, and 0.5 using Monte Carlo simulation. We found that in general, conventional pairwise-additive interactions cannot produce superlattices. Instead, a multibody (nonpairwise) interaction is required. Cholesterol superlattice formation reveals that although the overall interaction between cholesterol and phospholipids is favorable, it contains two large opposing components: an interaction favoring cholesterol-phospholipid mixing and an unfavorable acyl chain multibody interaction that increases nonlinearly with the number of cholesterol contacts. The magnitudes of interactions are in the order of kT. The physical origins of these interactions can be explained by our umbrella model. They most likely come from the requirement for polar phospholipid headgroups to cover the nonpolar cholesterol to avoid the exposure of cholesterol to water and from the sharp decreasing of acyl chain conformation entropy due to cholesterol contact. This study together with our previous work demonstrate that the driving force of cholesterol-phospholipid mixing is a hydrophobic interaction, and multibody interactions dominate others over a wide range of cholesterol concentration.

Effect of glycation on human serum albumin-zinc interaction: a biophysical study.

PubMed

Iqbal, Sarah; Qais, Faizan Abul; Alam, Md Maroof; Naseem, Imrana

2018-05-01

Zinc deficiency is common in diabetes. However, the cause of this phenomenon is largely unknown. 80% of the absorbed zinc is transported through the blood in association with human serum albumin (HSA). Under persistent hyperglycemia, HSA frequently undergoes non-enzymatic glycation which can affect its structure and metal-binding function. Hence, in this study, we have examined the interaction of zinc with native and glycated HSA. The protein samples were incubated either in the presence or in the absence of physiologically elevated glucose concentration for 21 days. The samples were then analyzed for structural changes and zinc-binding ability using various spectrometric and calorimetric approaches. The study reveals changes in the three-dimensional structure of the protein upon glycation that cause local unfolding of the molecule. Most such regions are localized in subdomain IIA of HSA which plays a key role in zinc binding. This affects zinc interaction with HSA and could in part explain the perturbed zinc distribution in patients with hyperglycemia. The varying degree of HSA glycation in blood could explain the observed heterogeneity pertaining to zinc deficiency among people suffering from diabetes.

Studies on interaction of insect repellent compounds with odorant binding receptor proteins by in silico molecular docking approach.

PubMed

Gopal, J Vinay; Kannabiran, K

2013-12-01

The aim of the study was to identify the interactions between insect repellent compounds and target olfactory proteins. Four compounds, camphor (C10H16O), carvacrol (C10H14O), oleic acid (C18H34O2) and firmotox (C22H28O5) were chosen as ligands. Seven olfactory proteins of insects with PDB IDs: 3K1E, 1QWV, 1TUJ, 1OOF, 2ERB, 3R1O and OBP1 were chosen for docking analysis. Patch dock was used and pymol for visualizing the structures. The interactions of these ligands with few odorant binding proteins showed binding energies. The ligand camphor had showed a binding energy of -136 kcal/mol with OBP1 protein. The ligand carvacrol interacted with 1QWV and 1TUJ proteins with a least binding energy of -117.45 kcal/mol and -21.78 kcal/mol respectively. The ligand oleic acid interacted with 1OOF, 2ERB, 3R1O and OBP1 with least binding energies. Ligand firmotox interacted with OBP1 and showed least binding energies. Three ligands (camphor, oleic acid and firmotox) had one, two, three interactions with a single protein OBP1 of Nilaparvatha lugens (Rice pest). From this in silico study we identified the interaction patterns for insect repellent compounds with the target insect odarant proteins. The results of our study revealed that the chosen ligands showed hydrogen bond interactions with the target olfactory receptor proteins.

Cation–Anion Interactions within the Nucleic Acid Ion Atmosphere Revealed by Ion Counting

PubMed Central

Gebala, Magdalena; Giambasu, George M.; Lipfert, Jan; Bisaria, Namita; Bonilla, Steve; Li, Guangchao; York, Darrin M.; Herschlag, Daniel

2016-01-01

The ion atmosphere is a critical structural, dynamic, and energetic component of nucleic acids that profoundly affects their interactions with proteins and ligands. Experimental methods that “count” the number of ions thermodynamically associated with the ion atmosphere allow dissection of energetic properties of the ion atmosphere, and thus provide direct comparison to theoretical results. Previous experiments have focused primarily on the cations that are attracted to nucleic acid polyanions, but have also showed that anions are excluded from the ion atmosphere. Herein, we have systematically explored the properties of anion exclusion, testing the zeroth-order model that anions of different identity are equally excluded due to electrostatic repulsion. Using a series of monovalent salts, we find, surprisingly, that the extent of anion exclusion and cation inclusion significantly depends on salt identity. The differences are prominent at higher concentrations and mirror trends in mean activity coefficients of the electrolyte solutions. Salts with lower activity coefficients exhibit greater accumulation of both cations and anions within the ion atmosphere, strongly suggesting that cation–anion correlation effects are present in the ion atmosphere and need to be accounted for to understand electrostatic interactions of nucleic acids. To test whether the effects of cation–anion correlations extend to nucleic acid kinetics and thermodynamics, we followed the folding of P4–P6, a domain of the Tetrahymena group I ribozyme, via single-molecule fluorescence resonance energy transfer in solutions with different salts. Solutions of identical concentration but lower activity gave slower and less favorable folding. Our results reveal hitherto unknown properties of the ion atmosphere and suggest possible roles of oriented ion pairs or anion-bridged cations in the ion atmosphere for electrolyte solutions of salts with reduced activity. Consideration of these new

Extraterrestrial Studies Using Nuclear Interactions

NASA Technical Reports Server (NTRS)

Reedy, Robert C.

2003-01-01

Cosmogenic nuclides were used to study the recent histories of the aubrite Norton County and the pallasite Brenham using calculated production rates. Calculations were done of the rates for making cosmogenic noble-gas isotopes in the Jovian satellite Europa by the interactions of galactic cosmic rays and especially trapped Jovian protons. Cross sections for the production of cosmogenic nuclides were reported and plans made to measure additional cross sections. A new code, MCNPX, was used to numerically simulate the interactions of cosmic rays with matter and the subsequent production of cosmogenic nuclides. A review was written about studies of extraterrestrial matter using cosmogenic radionuclides. Several other projects were done. Results are reviewed here with references to my recent publications for details.

Study of the interaction of lactoferricin B with phospholipid monolayers and bilayers.

PubMed

Arseneault, Marjolaine; Bédard, Sarah; Boulet-Audet, Maxime; Pézolet, Michel

2010-03-02

Bovine lactoferricin (LfcinB) is an antimicrobial peptide obtained from the pepsin cleavage of lactoferrin. The activity of LfcinB has been extensively studied on diverse pathogens, but its mechanism of action still has to be elucidated. Because of its nonspecificity, its mode of action is assumed to be related to interactions with membranes. In this study, the interaction of LfcinB with a negatively charged monolayer of dipalmitoylphosphatidylglycerol has been investigated as a function of the surface pressure of the lipid film using in situ Brewster angle and polarization modulation infrared reflection absorption spectroscopy and on transferred monolayers by atomic force microscopy and polarized attenuated total reflection infrared spectroscopy. The data show clearly that LfcinB forms stable films at the air-water interface. They also reveal that the interaction of LfcinB with the lipid monolayer is modulated by the surface pressure. At low surface pressure, LfcinB inserts within the lipid film with its long molecular axis oriented mainly parallel to the acyl chains, while at high surface pressure, LfcinB is adsorbed under the lipid film, the hairpin being preferentially aligned parallel to the plane of the interface. The threshold for which the behavior changes is 20 mN/m. At this critical surface pressure, LfcinB interacts with the monolayer to form discoidal lipid-peptide assemblies. This structure may actually represent the mechanism of action of this peptide. The results obtained on monolayers are correlated by fluorescent probe release measurements of dye-containing vesicles made of lipids in different phases and support the important role of the lipid fluidity and packing on the activity of LfcinB.

Chromatin interaction networks revealed unique connectivity patterns of broad H3K4me3 domains and super enhancers in 3D chromatin.

PubMed

Thibodeau, Asa; Márquez, Eladio J; Shin, Dong-Guk; Vera-Licona, Paola; Ucar, Duygu

2017-10-31

Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays. In these networks, broad domains and super enhancers interact more frequently with each other compared to their typical counterparts. Network measures and graphlets revealed distinct connectivity patterns associated with these regulatory elements that are robust across cell types and alternative assays. Machine learning models showed that these connectivity patterns could effectively discriminate broad domains from typical promoters and super enhancers from typical enhancers. Finally, targets of broad domains in these networks were enriched in disease-causing SNPs of cognate cell types. Taken together these results suggest a robust and unique organization of the chromatin around broad domains and super enhancers: loci critical for pathologies and cell-specific functions.

Social affiliation in same-class and cross-class interactions.

PubMed

Côté, Stéphane; Kraus, Michael W; Carpenter, Nichelle C; Piff, Paul K; Beermann, Ursula; Keltner, Dacher

2017-02-01

Historically high levels of economic inequality likely have important consequences for relationships between people of the same and different social class backgrounds. Here, we test the prediction that social affiliation among same-class partners is stronger at the extremes of the class spectrum, given that these groups are highly distinctive and most separated from others by institutional and economic forces. An internal meta-analysis of 4 studies (N = 723) provided support for this hypothesis. Participant and partner social class were interactively, rather than additively, associated with social affiliation, indexed by affiliative behaviors and emotions during structured laboratory interactions and in daily life. Further, response surface analyses revealed that paired upper or lower class partners generally affiliated more than average-class pairs. Analyses with separate class indices suggested that these patterns are driven more by parental income and subjective social class than by parental education. The findings illuminate the dynamics of same- and cross-class interactions, revealing that not all same-class interactions feature the same degree of affiliation. They also reveal the importance of studying social class from an intergroup perspective. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Interactions among the early Escherichia coli divisome proteins revealed by bimolecular fluorescence complementation.

PubMed

Pazos, Manuel; Natale, Paolo; Margolin, William; Vicente, Miguel

2013-12-01

We used bimolecular fluorescence complementation (BiFC) assays to detect protein-protein interactions of all possible pairs of the essential Escherichia coli proto-ring components, FtsZ, FtsA and ZipA, as well as the non-essential FtsZ-associated proteins ZapA and ZapB. We found an unexpected interaction between ZipA and ZapB at potential cell division sites, and when co-overproduced, they induced long narrow constrictions at division sites that were dependent on FtsZ. These assays also uncovered an interaction between ZipA and ZapA that was mediated by FtsZ. BiFC with ZapA and ZapB showed that in addition to their expected interaction at midcell, they also interact at the cell poles. BiFC detected interaction between FtsZ and ZapB at midcell and close to the poles. Results from the remaining pairwise combinations confirmed known interactions between FtsZ and ZipA, and ZapB with itself. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.

PubMed

Naqsh e Zahra, Syeda; Khattak, Naureen Aslam; Mir, Asif

2013-01-01

Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL). Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies. YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of -0.132 and -0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1. This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of candidate genes and their important interacting residues likely

Bionano Interaction Study on Antimicrobial Star-Shaped Peptide Polymer Nanoparticles.

PubMed

Lam, Shu J; Wong, Edgar H H; O'Brien-Simpson, Neil M; Pantarat, Namfon; Blencowe, Anton; Reynolds, Eric C; Qiao, Greg G

2016-12-14

'Structurally nanoengineered antimicrobial peptide polymers' (SNAPPs), in the form of star-shaped peptide polymer nanoparticles, have been recently demonstrated as a new class of antimicrobial agents with superior in vitro and in vivo efficacy against Gram-negative pathogens, including multidrug-resistant species. Herein, we present a detailed bionano interaction study on SNAPPs by assessing their antimicrobial activities against several Gram-negative bacteria in complex biological matrices. Simulated body fluid and animal serum were used as test media to reveal factors that influence the antimicrobial efficacy of SNAPPs. With the exception of Acinetobacter baumannii, the presence of divalent cations at physiological concentrations reduced the antimicrobial efficacy of SNAPPs from minimum inhibitory concentrations (MICs) within the nanomolar range (40-300 nM) against Escherichia coli, Pseudomanas aeruginosa, and Klebsiella pneumoniae to 0.6-4.7 μM. By using E. coli as a representative bacterial species, we demonstrated that the reduction in activity was due to a decrease in the ability of SNAPPs to cause outer and inner membrane disruption. This effect could be reversed through coadministration with a chelating agent. Interestingly, the potency of SNAPPs against A. baumannii was retained even under high salt concentrations. The presence of serum proteins was also found to affect the interaction of SNAPPs with bacterial membranes, possibly through intermolecular binding. Collectively, this study highlights the need to consider the possible interactions of (bio)molecules present in vivo with any new antimicrobial agent under development. We also demonstrate that outer membrane disruption/destabilization is an important but hitherto under-recognized target for the antimicrobial action of peptide-based agents, such as antimicrobial peptides (AMPs). Overall, the findings presented herein could aid in the design of more efficient peptide-based antimicrobial agents with

A detailed spectroscopic study on the interaction of Rhodamine 6G with human hemoglobin.

PubMed

Mandal, Paulami; Bardhan, Munmun; Ganguly, Tapan

2010-05-03

UV-vis, time-resolved fluorescence and circular dichroism spectroscopic investigations have been made to reveal the nature of the interactions between xanthene dye Rhodamine 6G and the well known protein hemoglobin. From the analysis of the steady-state and time-resolved fluorescence quenching of Rhodamine 6G in aqueous solutions in presence of hemoglobin, it is revealed that the quenching is static in nature. The primary binding pattern between Rhodamine and hemoglobin has been interpreted as combined effect of hydrophobic association and electrostatic interaction. The binding constants, number of binding sites and thermodynamic parameters at various pH of the environment have been computed. The binding average distance between the energy donor Rhodamine and acceptor hemoglobin has been determined from the Forster's theory. Copyright 2010 Elsevier B.V. All rights reserved.

Study of the magnetic interaction in nanocrystalline Pr-Fe-Co-Nb-B permanent magnets

NASA Astrophysics Data System (ADS)

Dospial, M.; Plusa, D.; Ślusarek, B.

2012-03-01

The magnetic properties of an isotropic, epoxy resin bonded magnets made from Pr-Fe-Co-Nb-B powder were investigated. The magnetization reversal process and magnetic parameters were examined by measurements of the initial magnetization curve, major and minor hysteresis loops and sets of recoil curves. From the initial magnetization curve and the field dependencies of the reversible and irreversible magnetization components derived from the recoil loops it was found that the magnetization reversal process is the combination of the nucleation of reversed domains and pinning of domain walls at the grain boundaries and the reversible rotation of magnetization vector in single domain grains. The interactions between grains were studied by means of δM plots. The nonlinear behavior of δM curve approve that the short range intergrain exchange coupling interactions are dominant in a field up to the sample coercivity. The interaction domains and fine magnetic structure were revealed as the evidence of exchange coupling between soft α-Fe and hard magnetic Nd2Fe14B grains.

Interaction of Chelerythrine with Keyhole Limpet Hemocyanin: a Fluorescence Spectroscopy and Molecular Docking Study

NASA Astrophysics Data System (ADS)

Zhong, M.; Long, R. Q.; Wang, Y. H.; Chen, C. L.

2018-05-01

The quenching mechanism between chelerythrine (CHE) and keyhole limpet hemocyanin (KLH) was investigated using fluorescence spectroscopy and molecular docking. The experiments were conducted at three different temperatures (293, 298, and 303 K). The results revealed that the intrinsic fluorescence of KLH was strongly quenched by CHE through a static quenching mechanism. The thermodynamic parameters (ΔG, ΔH, and ΔS) of the interaction were calculated, indicating that the interaction between CHE and KLH was spontaneous and that van der Waals forces and hydrogen bond formation played major roles in the binding process. The intrinsic fluorescence of the tyrosine and tryptophan residues in KLH was studied by synchronous fluorescence, which suggested that CHE changed the conformation of KLH. Finally, molecular docking was used to obtain detailed information on the binding sites and binding affinities between CHE and KLH.

Spectroscopic studies of the interaction between alprazolam and apo-human serum transferrin as a drug carrier protein.

PubMed

Karimian Amroabadi, Marzieh; Taheri-Kafrani, Asghar; Heidarpoor Saremi, Leily; Rastegari, Ali Asghar

2018-03-01

The interaction between apo-human serum transferrin (Apo-hTf) and alprazolam was investigated using various spectroscopic techniques. The drug quenched the fluorescence intensity of Apo-hTf and the mechanism behind the quenching was static. The thermodynamic parameters (ΔG, ΔH, and ΔS) that obtained from tryptophan fluorescence study revealed that the interactions between alprazolam and Apo-hTf were spontaneous. Collectively, hydrophobic interactions and hydrogen bonding most likely played major roles in Apo-hTf/alprazolam interactions. Also, the absorption spectra of Apo-hTf increased in the presence of increasing concentration of alprazolam, reflecting Apo-hTf structural alteration after drug's binding. The CD results demonstrated that the Apo-hTf/alprazolam interaction does not affect the protein secondary and tertiary structure significantly until the molar ratios (alprazolam/Apo-hTf) of 10, but the conformational changes become visible at higher molar ratios. The DSC results suggested that alprazolam stabilized the Apo-hTf at alprazolam/Apo-hTf molar ratio of 20. Based on the achieved results, this potentially therapeutic agent can significantly bind to Apo-hTf which also further confirmed by molecular docking study. This study on the interaction of the drug with Apo-hTf should be helpful for understanding the transportation and distribution of drugs in vivo, as well as the action mechanism and dynamics of a drug at the molecular level. Copyright © 2017 Elsevier B.V. All rights reserved.

Nano-optical imaging of WS e 2 waveguide modes revealing light-exciton interactions

DOE PAGES

Fei, Z.; Scott, M. E.; Gosztola, D. J.; ...

2016-08-01

We report on a nano-optical imaging study of WSe 2 thin flakes with scanning near-field optical microscopy (NSOM). The NSOM technique allows us to visualize in real space various waveguide photon modes inside WSe 2. By tuning the excitation laser energy, we are able to map the entire dispersion of these waveguide modes both above and below the A exciton energy of WSe 2. We found that all the modes interact strongly with WSe 2 excitons. The outcome of the interaction is that the observed waveguide modes shift to higher momenta right below the A exciton energy. At higher energies,more » on the other hand, these modes are strongly damped due to adjacent B excitons or band-edge absorptions. Lastly, the mode-shifting phenomena are consistent with polariton formation in WSe 2.« less

Studies of Dynamic Protein-Protein Interactions in Bacteria Using Renilla Luciferase Complementation Are Undermined by Nonspecific Enzyme Inhibition

PubMed Central

Hatzios, Stavroula K.; Ringgaard, Simon; Davis, Brigid M.; Waldor, Matthew K.

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology. PMID:22905225

Studies of dynamic protein-protein interactions in bacteria using Renilla luciferase complementation are undermined by nonspecific enzyme inhibition.

PubMed

Hatzios, Stavroula K; Ringgaard, Simon; Davis, Brigid M; Waldor, Matthew K

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology.

Interactions of coal gangue and pine sawdust during combustion of their blends studied using differential thermogravimetric analysis.

PubMed

Zhang, Yuanyuan; Zhang, Zhezi; Zhu, Mingming; Cheng, Fangqin; Zhang, Dongke

2016-08-01

The interactions between coal gangue and pine sawdust during the combustion process were studied using thermogravimetric analysis. The effect of the blending ratio, oxygen concentration and heating rate on the weight loss (TG) and differential thermogravimetric (TGA) profiles was examined. The TG and DTG curves of the blends were not additives of those of the individual materials, suggesting that interactions between coal gangue and pine sawdust had occurred during the combustion, especially in the temperature range of 400-600°C. Kinetic analysis confirmed that the combustion of coal gangue, pine sawdust and their blends was chemical reaction controlled. Further analysis revealed that the interactions between coal gangue and pine sawdust were primarily due to thermal effects rather than structural changes, with the thermal inertia of coal gangue dominating over the behaviour of the blends. The interactions decreased with decreasing the coal gangue ratio in the blend, oxygen concentration and heating rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of thrombin by functionalized C60 nanoparticles revealed via in vitro assays and in silico studies.

PubMed

Liu, Yanyan; Fu, Jianjie; Pan, Wenxiao; Xue, Qiao; Liu, Xian; Zhang, Aiqian

2018-01-01

The studies on the human toxicity of nanoparticles (NPs) are far behind the rapid development of engineered functionalized NPs. Fullerene has been widely used as drug carrier skeleton due to its reported low risk. However, different from other kinds of NPs, fullerene-based NPs (C 60 NPs) have been found to have an anticoagulation effect, although the potential target is still unknown. In the study, both experimental and computational methods were adopted to gain mechanistic insight into the modulation of thrombin activity by nine kinds of C 60 NPs with diverse surface chemistry properties. In vitro enzyme activity assays showed that all tested surface-modified C 60 NPs exhibited thrombin inhibition ability. Kinetic studies coupled with competitive testing using 3 known inhibitors indicated that six of the C 60 NPs, of greater hydrophobicity and hydrogen bond (HB) donor acidity or acceptor basicity, acted as competitive inhibitors of thrombin by directly interacting with the active site of thrombin. A simple quantitative nanostructure-activity relationship model relating the surface substituent properties to the inhibition potential was then established for the six competitive inhibitors. Molecular docking analysis revealed that the intermolecular HB interactions were important for the specific binding of C 60 NPs to the active site canyon, while the additional stability provided by the surface groups through van der Waals interaction also play a key role in the thrombin binding affinity of the NPs. Our results suggest that thrombin is a possible target of the surface-functionalized C 60 NPs relevant to their anticoagulation effect. Copyright © 2017. Published by Elsevier B.V.

A Study of Attitude and Knowledge of the Psychiatry Resident Doctors toward Clinician–Pharmaceutical Industry Interaction

PubMed Central

Balhara, Yatan Pal Singh; Mathur, Shachi; Anand, Nikhilesh

2012-01-01

Background: Pharmaceutical industry and clinicians are the two important stakeholders in the modern-day health care. However, concerns have been expressed about the lack of congruence between the goals of these two. Aims: The current study aimed at exploring the knowledge and attitude of the psychiatry resident doctors toward the clinician–pharmaceutical industry interaction and also at exploring the knowledge of the residents about the new Medical Council of India guidelines on this issue. Materials and Methods: The survey was conducted among psychiatry residents. Descriptive statistics with frequency distribution was carried out by using SPSS version 17.0. Results: It had a good response rate of around 90%. The survey reveals the knowledge and attitude of the psychiatry residents toward the psychiatrist–pharmaceutical industry interaction. Conclusions: The survey provides understanding in knowledge and attitude of the psychiatry residents towards the psychiatrist-pharmaceutical industry interaction. PMID:22661810

Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion.

PubMed

Rosenthal, Sara Brin; Twomey, Colin R; Hartnett, Andrew T; Wu, Hai Shan; Couzin, Iain D

2015-04-14

Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion

PubMed Central

Rosenthal, Sara Brin; Twomey, Colin R.; Hartnett, Andrew T.; Wu, Hai Shan; Couzin, Iain D.

2015-01-01

Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion. PMID:25825752

Molecular interaction studies revealed the bifunctional behavior of triheme cytochrome PpcA from Geobacter sulfurreducens toward the redox active analog of humic substances

DOE PAGES

Dantas, Joana M.; Kokhan, Oleksandr; Pokkuluri, P. Raj; ...

2015-06-09

Humic substances (HS) constitute a significant fraction of natural organic matter in terrestrial and aquatic environments and can act as terminal electron acceptors in anaerobic microbial respiration. Geobacter sulfurreducens has a remarkable respiratory versatility and can utilize the HS analog anthraquinone-2,6-disulfonate (AQDS) as a terminal electron acceptor or its reduced form (AH 2QDS) as an electron donor. Previous studies set the triheme cytochrome PpcA as a key component for HS respiration in G. sulfurreducens, but the process is far from fully understood. In this work, NMR chemical shift perturbation measurements were used to map the interaction region between PpcA andmore » AH 2QDS, and to measure their binding affinity. The results showed that the AH 2QDS binds reversibly to the more solvent exposed edge of PpcA heme IV. The NMR and visible spectroscopies coupled to redox measurements were used to determine the thermodynamic parameters of the PpcA:quinol complex. The higher reduction potential of heme IV (- 127 mV) compared to that of AH 2QDS (- 184 mV) explains why the electron transfer is more favorable in the case of reduction of the cytochrome by the quinol. The clear evidence obtained for the formation of an electron transfer complex between AH 2QDS and PpcA, combined with the fact that the protein also formed a redox complex with AQDS, revealed for the first time the bifunctional behavior of PpcA toward an analog of the HS. In conclusion, such behavior might confer selective advantage to G. sulfurreducens, which can utilize the HS in any redox state available in the environment for its metabolic needs.« less

Ghost-in-the-Machine reveals human social signals for human-robot interaction.

PubMed

Loth, Sebastian; Jettka, Katharina; Giuliani, Manuel; de Ruiter, Jan P

2015-01-01

We used a new method called "Ghost-in-the-Machine" (GiM) to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognize the intentions of customers on the basis of the output of the robotic recognizers. Specifically, we measured which recognizer modalities (e.g., speech, the distance to the bar) were relevant at different stages of the interaction. This provided insights into human social behavior necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognizers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognizers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer's requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human-robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience.

Ghost-in-the-Machine reveals human social signals for human–robot interaction

PubMed Central

Loth, Sebastian; Jettka, Katharina; Giuliani, Manuel; de Ruiter, Jan P.

2015-01-01

We used a new method called “Ghost-in-the-Machine” (GiM) to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognize the intentions of customers on the basis of the output of the robotic recognizers. Specifically, we measured which recognizer modalities (e.g., speech, the distance to the bar) were relevant at different stages of the interaction. This provided insights into human social behavior necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognizers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognizers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer’s requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human–robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience. PMID:26582998

cDNA-AFLP analysis reveals differential gene expression in compatible interaction of wheat challenged with Puccinia striiformis f. sp. tritici

PubMed Central

Wang, Xiaojie; Tang, Chunlei; Zhang, Gang; Li, Yingchun; Wang, Chenfang; Liu, Bo; Qu, Zhipeng; Zhao, Jie; Han, Qingmei; Huang, Lili; Chen, Xianming; Kang, Zhensheng

2009-01-01

Background Puccinia striiformis f. sp. tritici is a fungal pathogen causing stripe rust, one of the most important wheat diseases worldwide. The fungus is strictly biotrophic and thus, completely dependent on living host cells for its reproduction, which makes it difficult to study genes of the pathogen. In spite of its economic importance, little is known about the molecular basis of compatible interaction between the pathogen and wheat host. In this study, we identified wheat and P. striiformis genes associated with the infection process by conducting a large-scale transcriptomic analysis using cDNA-AFLP. Results Of the total 54,912 transcript derived fragments (TDFs) obtained using cDNA-AFLP with 64 primer pairs, 2,306 (4.2%) displayed altered expression patterns after inoculation, of which 966 showed up-regulated and 1,340 down-regulated. 186 TDFs produced reliable sequences after sequencing of 208 TDFs selected, of which 74 (40%) had known functions through BLAST searching the GenBank database. Majority of the latter group had predicted gene products involved in energy (13%), signal transduction (5.4%), disease/defence (5.9%) and metabolism (5% of the sequenced TDFs). BLAST searching of the wheat stem rust fungus genome database identified 18 TDFs possibly from the stripe rust pathogen, of which 9 were validated of the pathogen origin using PCR-based assays followed by sequencing confirmation. Of the 186 reliable TDFs, 29 homologous to genes known to play a role in disease/defense, signal transduction or uncharacterized genes were further selected for validation of cDNA-AFLP expression patterns using qRT-PCR analyses. Results confirmed the altered expression patterns of 28 (96.5%) genes revealed by the cDNA-AFLP technique. Conclusion The results show that cDNA-AFLP is a reliable technique for studying expression patterns of genes involved in the wheat-stripe rust interactions. Genes involved in compatible interactions between wheat and the stripe rust pathogen

Spectroscopic studies on the interaction of cinnamic acid and its hydroxyl derivatives with human serum albumin

NASA Astrophysics Data System (ADS)

Min, Jiang; Meng-Xia, Xie; Dong, Zheng; Yuan, Liu; Xiao-Yu, Li; Xing, Chen

2004-04-01

Cinnamic acid and its derivatives possess various biological effects in remedy of many diseases. Interaction of cinnamic acid and its hydroxyl derivatives, p-coumaric acid and caffeic acid, with human serum albumin (HSA), and concomitant changes in its conformation were studied using fluorescence and Fourier transform infrared spectroscopic methods. Fluorescence data revealed the presence of one binding site on HSA for cinnamic acid and its hydroxyl derivatives, and their binding constants ( KA) are caffeic acid> p-coumaric acid> cinnamic acid when Cdrug/ CHSA ranging from 1 to 10. The changes of the secondary structure of HSA after interacting with the three drugs are estimated, respectively by combining the curve-fitting results of amid I and amid III bands. The α-helix structure has a decrease of ≈9, 5 and 3% after HSA interacted with caffeic acid, p-coumaric acid and cinnamic acid, respectively. It was found that the hydroxyls substituted on aromatic ring of the drugs play an important role in the changes of protein's secondary structure. Combining the result of fluorescence quenching and the changes of secondary structure of HSA after interaction with the three drugs, the drug-HSA interaction mode was discussed.

Molecular modeling and spectroscopic studies on the interaction of the chiral drug venlafaxine hydrochloride with bovine serum albumin

NASA Astrophysics Data System (ADS)

Shahabadi, Nahid; Hadidi, Saba

2014-03-01

This study was designed to examine the interaction of racemic antidepressant drug "S,R-venlafaxine hydrochloride (VEN)" with bovine serum albumin (BSA) under physiological conditions. The mechanism of interaction was studied by spectroscopic techniques combination with molecular modeling. Stern-Volmer analysis of fluorescence quenching data shows the presence of the static quenching mechanism. The thermodynamic parameters indicated that the hydrogen bonding and weak van der Waals interactions are the predominant intermolecular forces stabilizing the complex. The number of binding sites (n) was calculated. Through the site marker competitive experiment, VEN was confirmed to be located in subdomain IIIA of BSA. The binding distance (r = 4.93 nm) between the donor BSA and acceptor VEN was obtained according to Förster's non-radiative energy transfer theory. According to UV-vis spectra and CD data binding of VEN leaded to conformational changes of BSA. Molecular docking simulations of S and R-VEN revealed that both isomers have similar interaction and the same binding sites, from this point of view S and R isomers are equal.

Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions.

PubMed

Turner, Leslie M; Harr, Bettina

2014-12-09

Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.

Ocean dynamics studies. [of current-wave interactions

NASA Technical Reports Server (NTRS)

1974-01-01

Both the theoretical and experimental investigations into current-wave interactions are discussed. The following three problems were studied: (1) the dispersive relation of a random gravity-capillary wave field; (2) the changes of the statistical properties of surface waves under the influence of currents; and (3) the interaction of capillary-gravity with the nonuniform currents. Wave current interaction was measured and the feasibility of using such measurements for remote sensing of surface currents was considered. A laser probe was developed to measure the surface statistics, and the possibility of using current-wave interaction as a means of current measurement was demonstrated.

The genetic regulatory network centered on Pto-Wuschela and its targets involved in wood formation revealed by association studies.

PubMed

Yang, Xiaohui; Wei, Zunzheng; Du, Qingzhang; Chen, Jinhui; Wang, Qingshi; Quan, Mingyang; Song, Yuepeng; Xie, Jianbo; Zhang, Deqiang

2015-11-09

Transcription factors (TFs) regulate gene expression and can strongly affect phenotypes. However, few studies have examined TF variants and TF interactions with their targets in plants. Here, we used genetic association in 435 unrelated individuals of Populus tomentosa to explore the variants in Pto-Wuschela and its targets to decipher the genetic regulatory network of Pto-Wuschela. Our bioinformatics and co-expression analysis identified 53 genes with the motif TCACGTGA as putative targets of Pto-Wuschela. Single-marker association analysis showed that Pto-Wuschela was associated with wood properties, which is in agreement with the observation that it has higher expression in stem vascular tissues in Populus. Also, SNPs in the 53 targets were associated with growth or wood properties under additive or dominance effects, suggesting these genes and Pto-Wuschela may act in the same genetic pathways that affect variation in these quantitative traits. Epistasis analysis indicated that 75.5% of these genes directly or indirectly interacted Pto-Wuschela, revealing the coordinated genetic regulatory network formed by Pto-Wuschela and its targets. Thus, our study provides an alternative method for dissection of the interactions between a TF and its targets, which will strength our understanding of the regulatory roles of TFs in complex traits in plants.

Protein-protein interaction studies reveal the Plasmodium falciparum merozoite surface protein-1 region involved in a complex formation that binds to human erythrocytes.

PubMed

Paul, Gourab; Deshmukh, Arunaditya; Kumar Chourasia, Bishwanath; Kalamuddin, Md; Panda, Ashutosh; Kumar Singh, Susheel; Gupta, Puneet K; Mohmmed, Asif; Chauhan, Virender S; Theisen, Michael; Malhotra, Pawan

2018-03-29

Plasmodium falciparum merozoite surface protein (PfMSP) 1 has been studied extensively as a vaccine candidate antigen. PfMSP-1 undergoes proteolytic processing into four major products, such as p83, p30, p38, and p42, that are associated in the form of non-covalent complex(s) with other MSPs. To delineate MSP1 regions involved in the interaction with other MSPs, here we expressed recombinant proteins (PfMSP-1 65 ) encompassing part of p38 and p42 regions and PfMSP-1 19 PfMSP-1 65 interacted strongly with PfMSP-3, PfMSP-6, PfMSP-7, and PfMSP-9, whereas PfMSP-1 19 did not interact with any of these proteins. Since MSP-1 complex binds human erythrocytes, we examined the ability of these proteins to bind human erythrocyte. Among the proteins of MSP-1 complex, PfMSP-6 and PfMSP-9 bound to human erythrocytes. Serological studies showed that PfMSP-1 65 was frequently recognized by sera from malaria endemic regions, whereas this was not the case for PfMSP-1 19 In contrast, antibodies against PfMSP-1 19 showed much higher inhibition of merozoite invasion compared with antibodies against the larger PfMSP-1 65 fragment. Importantly, anti-PfMSP-1 19 antibodies recognized both recombinant proteins, PfMSP-1 19 and PfMSP-1 65 ; however, anti-PfMSP-1 65 antibody failed to recognize the PfMSP-1 19 protein. Taken together, these results demonstrate that PfMSP-1 sequences upstream of the 19 kDa C-terminal region are involved in molecular interactions with other MSPs, and these sequences may probably serve as a smoke screen to evade antibody response to the membrane-bound C-terminal 19 kDa region. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Crystal structural characterization reveals novel oligomeric interactions of human voltage-dependent anion channel 1.

PubMed

Hosaka, Toshiaki; Okazaki, Masateru; Kimura-Someya, Tomomi; Ishizuka-Katsura, Yoshiko; Ito, Kaori; Yokoyama, Shigeyuki; Dodo, Kosuke; Sodeoka, Mikiko; Shirouzu, Mikako

2017-09-01

Voltage-dependent anion channel 1 (VDAC1), which is located in the outer mitochondrial membrane, plays important roles in various cellular processes. For example, oligomerization of VDAC1 is involved in the release of cytochrome c to the cytoplasm, leading to apoptosis. However, it is unknown how VDAC1 oligomerization occurs in the membrane. In the present study, we determined high-resolution crystal structures of oligomeric human VDAC1 (hVDAC1) prepared by using an Escherichia coli cell-free protein synthesis system, which avoided the need for denaturation and refolding of the protein. Broad-range screening using a bicelle crystallization method produced crystals in space groups C222 and P22 1 2 1 , which diffracted to a resolution of 3.10 and 3.15 Å, respectively. Each crystal contained two hVDAC1 protomers in the asymmetric unit. Dimer within the asymmetrical unit of the crystal in space group C222 were oriented parallel, whereas those of the crystal in space group P22 1 2 1 were oriented anti-parallel. From a model of the crystal in space group C222, which we constructed by using crystal symmetry operators, a heptameric structure with eight patterns of interaction between protomers, including hydrophobic interactions with β-strands, hydrophilic interactions with loop regions, and protein-lipid interactions, was observed. It is possible that by having multiple patterns of interaction, VDAC1 can form homo- or hetero-oligomers not only with other VDAC1 protomers but also with other proteins such as VDAC2, VDAC3 and apoptosis-regulating proteins in the Bcl-2 family. © 2017 The Protein Society.

Topological surface states interacting with bulk excitations in the Kondo insulator SmB6 revealed via planar tunneling spectroscopy.

PubMed

Park, Wan Kyu; Sun, Lunan; Noddings, Alexander; Kim, Dae-Jeong; Fisk, Zachary; Greene, Laura H

2016-06-14

Samarium hexaboride (SmB6), a well-known Kondo insulator in which the insulating bulk arises from strong electron correlations, has recently attracted great attention owing to increasing evidence for its topological nature, thereby harboring protected surface states. However, corroborative spectroscopic evidence is still lacking, unlike in the weakly correlated counterparts, including Bi2Se3 Here, we report results from planar tunneling that unveil the detailed spectroscopic properties of SmB6 The tunneling conductance obtained on the (001) and (011) single crystal surfaces reveals linear density of states as expected for two and one Dirac cone(s), respectively. Quite remarkably, it is found that these topological states are not protected completely within the bulk hybridization gap. A phenomenological model of the tunneling process invoking interaction of the surface states with bulk excitations (spin excitons), as predicted by a recent theory, provides a consistent explanation for all of the observed features. Our spectroscopic study supports and explains the proposed picture of the incompletely protected surface states in this topological Kondo insulator SmB6.

Topological surface states interacting with bulk excitations in the Kondo insulator SmB6 revealed via planar tunneling spectroscopy

PubMed Central

Park, Wan Kyu; Sun, Lunan; Noddings, Alexander; Kim, Dae-Jeong; Fisk, Zachary; Greene, Laura H.

2016-01-01

Samarium hexaboride (SmB6), a well-known Kondo insulator in which the insulating bulk arises from strong electron correlations, has recently attracted great attention owing to increasing evidence for its topological nature, thereby harboring protected surface states. However, corroborative spectroscopic evidence is still lacking, unlike in the weakly correlated counterparts, including Bi2Se3. Here, we report results from planar tunneling that unveil the detailed spectroscopic properties of SmB6. The tunneling conductance obtained on the (001) and (011) single crystal surfaces reveals linear density of states as expected for two and one Dirac cone(s), respectively. Quite remarkably, it is found that these topological states are not protected completely within the bulk hybridization gap. A phenomenological model of the tunneling process invoking interaction of the surface states with bulk excitations (spin excitons), as predicted by a recent theory, provides a consistent explanation for all of the observed features. Our spectroscopic study supports and explains the proposed picture of the incompletely protected surface states in this topological Kondo insulator SmB6. PMID:27233936

Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO2 transport.

PubMed

Hsu, Kate; Lee, Ting-Ying; Periasamy, Ammasi; Kao, Fu-Jen; Li, Li-Tzu; Lin, Chuang-Yu; Lin, Hui-Ju; Lin, Marie

2017-10-01

Human CO 2 respiration requires rapid conversion between CO 2 and HCO 3 - Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchanger 1 (AE1)] provides a passage for HCO 3 - flux across the cell membrane. These 2 proteins are core components of the CO 2 transport metabolon. Intracellular H 2 O is necessary for CO 2 /HCO 3 - conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO 2 transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO 2 /HCO 3 - exchange. By demonstrating AQP1 as a mobile component of the CO 2 transport metabolon, our results uncover a potential role of water channel in blood CO 2 transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO 2 transport. © FASEB.

Molecular modeling reveals binding interface of γ-tubulin with GCP4 and interactions with noscapinoids.

PubMed

Suri, Charu; Joshi, Harish C; Naik, Pradeep Kumar

2015-05-01

The initiation of microtubule assembly within cells is guided by a cone shaped multi-protein complex, γ-tubulin ring complex (γTuRC) containing γ-tubulin and atleast five other γ-tubulin-complex proteins (GCPs), i.e., GCP2, GCP3, GCP4, GCP5, and GCP6. The rim of γTuRC is a ring of γ-tubulin molecules that interacts, via one of its longitudinal interfaces, with GCP2, GCP3, or GCP4 and, via other interface, with α/β-tubulin dimers recruited for the microtubule lattice formation. These interactions however, are not well understood in the absence of crystal structure of functional reconstitution of γTuRC subunits. In this study, we elucidate the atomic interactions between γ-tubulin and GCP4 through computational techniques. We simulated two complexes of γ-tubulin-GCP4 complex (we called dimer1 and dimer2) for 25 ns to obtain a stable complex and calculated the ensemble average of binding free energies of -158.82 and -170.19 kcal/mol for dimer1 and -79.53 and -101.50 kcal/mol for dimer2 using MM-PBSA and MM-GBSA methods, respectively. These highly favourable binding free energy values points to very robust interactions between GCP4 and γ-tubulin. From the results of the free-energy decomposition and the computational alanine scanning calculation, we identified the amino acids crucial for the interaction of γ-tubulin with GCP4, called hotspots. Furthermore, in the endeavour to identify chemical leads that might interact at the interface of γ-tubulin-GCP4 complex; we found a class of compounds based on the plant alkaloid, noscapine that binds with high affinity in a cavity close to γ-tubulin-GCP4 interface compared with previously reported compounds. All noscapinoids displayed stable interaction throughout the simulation, however, most robust interaction was observed for bromo-noscapine followed by noscapine and amino-noscapine. This offers a novel chemical scaffold for γ-tubulin binding drugs near γ-tubulin-GCP4 interface. © 2015 Wiley Periodicals, Inc.

Biosocial Conservation: Integrating Biological and Ethnographic Methods to Study Human-Primate Interactions.

PubMed

Setchell, Joanna M; Fairet, Emilie; Shutt, Kathryn; Waters, Siân; Bell, Sandra

2017-01-01

Biodiversity conservation is one of the grand challenges facing society. Many people interested in biodiversity conservation have a background in wildlife biology. However, the diverse social, cultural, political, and historical factors that influence the lives of people and wildlife can be investigated fully only by incorporating social science methods, ideally within an interdisciplinary framework. Cultural hierarchies of knowledge and the hegemony of the natural sciences create a barrier to interdisciplinary understandings. Here, we review three different projects that confront this difficulty, integrating biological and ethnographic methods to study conservation problems. The first project involved wildlife foraging on crops around a newly established national park in Gabon. Biological methods revealed the extent of crop loss, the species responsible, and an effect of field isolation, while ethnography revealed institutional and social vulnerability to foraging wildlife. The second project concerned great ape tourism in the Central African Republic. Biological methods revealed that gorilla tourism poses risks to gorillas, while ethnography revealed why people seek close proximity to gorillas. The third project focused on humans and other primates living alongside one another in Morocco. Incorporating shepherds in the coproduction of ecological knowledge about primates built trust and altered attitudes to the primates. These three case studies demonstrate how the integration of biological and social methods can help us to understand the sustainability of human-wildlife interactions, and thus promote coexistence. In each case, an integrated biosocial approach incorporating ethnographic data produced results that would not otherwise have come to light. Research that transcends conventional academic boundaries requires the openness and flexibility to move beyond one's comfort zone to understand and acknowledge the legitimacy of "other" kinds of knowledge. It is

The development of interactive online learning tools for the study of anatomy.

PubMed

O'Byrne, Patrick J; Patry, Anne; Carnegie, Jacqueline A

2008-01-01

The study of human anatomy is a core component of health science programs. However large student enrolments and the content-packed curricula associated with these programs have made it difficult for students to have regular access to cadaver laboratories. Adobe Flash MXwas used with cadaver digital photographs and textbook-derived illustrations to develop interactive anatomy images that were made available to undergraduate health science students enrolled in first-year combined anatomy and physiology (ANP) courses at the University of Ottawa. Colour coding was used to direct student attention, facilitate name-structure association, improve visualization of structure contours, assist students in the construction of anatomical pathways, and to reinforce functional or anatomical groupings. The ability of two-dimensional media to support the visualization of three-dimensional structure was extended by developing the fade-through image (students use a sliding bar to move through tissues) as well as the rotating image in which entire organs such as the skull were photographed at eight angles of rotation. Finally, students were provided with interactive exercises that they could repeatedly try to obtain immediate feedback regarding their learning progress. Survey data revealed that the learning and self-testing tools were used widely and that students found them relevant and supportive of their self-learning. Interestingly, student summative examination outcomes did not differ between those students who had access to the online tools and a corresponding student group from the previous academic year who did not. Interactive learning tools can be tailored to meet program-specific learning objectives as a cost-effective means of facilitating the study of human anatomy. Virtual interactive anatomy exercises provide learning opportunities for students outside the lecture room that are of especial value to visual and kinesthetic learners.

Molecular dynamics study of biodegradation of azo dyes via their interactions with AzrC azoreductase.

PubMed

Haghshenas, Hamed; Kay, Maryam; Dehghanian, Fariba; Tavakol, Hossein

2016-01-01

Azo dyes are one of the most important class of dyes, which have been widely used in industries. Because of the environmental pollution of azo dyes, many studies have been performed to study their biodegradation using bacterial systems. In present work, the AzrC of mesophilic gram-positive Bacillus sp. B29 has been considered to study its interaction with five common azo dyes (orange G, acid red 88, Sudan I, orange I, and methyl red). The molecular dynamics simulations have been employed to study the interaction between AzrC and azo dyes. The trajectory was confirmed using root mean square deviation and the root mean square fluctuation analyses. Then, the hydrogen bond and alanine scanning analyses were performed to reveal active site residues. Phe105 (A), Phe125 (B), Phe172 (B), and Pro132 (B) have been found as the most important hydrophobic residues whereas Asn104 (A), Tyr127 (B), and Asn187 (A) have key role in making hydrogen bond. The results of molecular mechanics Poisson-Boltzmann surface area and molecular mechanics generalized Born surface area calculations proved that the hydrophobic azo dyes like Acid red 88 binds more tightly to the AzrC protein. The calculated data suggested MR A 121 (B) I as a potential candidate for improving the AzrC-MR interactions.

Atomistic-level study of the interactions between hIAPP protofibrils and membranes: Influence of pH and lipid composition.

PubMed

Qian, Zhenyu; Zou, Yu; Zhang, Qingwen; Chen, Peijie; Ma, Buyong; Wei, Guanghong; Nussinov, Ruth

2018-02-09

The pathology of type 2 diabetes mellitus is associated with the aggregation of human islet amyloid polypeptide (hIAPP) and aggregation-mediated membrane disruption. The interactions of hIAPP aggregates with lipid membrane, as well as the effects of pH and lipid composition at the atomic level, remain elusive. Herein, using molecular dynamics simulations, we investigate the interactions of hIAPP protofibrillar oligomers with lipids, and the membrane perturbation that they induce, when they are partially inserted in an anionic dipalmitoyl-phosphatidylglycerol (DPPG) membrane or a mixed dipalmitoyl-phosphatidylcholine (DPPC)/DPPG (7:3) lipid bilayer under acidic/neutral pH conditions. We observed that the tilt angles and insertion depths of the hIAPP protofibril are strongly correlated with the pH and lipid composition. At neutral pH, the tilt angle and insertion depth of hIAPP protofibrils at a DPPG bilayer reach ~52° and ~1.62 nm with respect to the membrane surface, while they become ~77° and ~1.75 nm at a mixed DPPC/DPPG membrane. The calculated tilt angle of hIAPP at DPPG membrane is consistent with a recent chiral sum frequency generation spectroscopic study. The acidic pH induces a smaller tilt angle of ~40° and a shallower insertion depth (~1.24 nm) of hIAPP at the DPPG membrane surface, mainly due to protonation of His18 near the turn region. These differences mainly result from a combination of distinct electrostatic, van der Waals, hydrogen bonding and salt-bridge interactions between hIAPP and lipid bilayers. The hIAPP-membrane interaction energy analysis reveals that besides charged residues K1, R11 and H18, aromatic residues Phe15 and Phe23 also exhibit strong interactions with lipid bilayers, revealing the crucial role of aromatic residues in stabilizing the membrane-bound hIAPP protofibrils. hIAPP-membrane interactions disturb the lipid ordering and the local bilayer thickness around the peptides. Our results provide atomic-level information

"Aw, Man Where You Goin'?": Classroom Interaction and the Development of L2 Interactional Competence.

ERIC Educational Resources Information Center

Hall, Joan Kelly

1995-01-01

Examines the discursive structures and linguistic resources of the interactional environments influencing the development of individual communicative competence, with specific reference to providing speaking opportunities to students studying Spanish as a second language. Findings reveal that the ways in which topics are developed differ from how…

CO oxidation reaction on Pt(111) studied by the dynamic Monte Carlo method including lateral interactions of adsorbates.

PubMed

Nagasaka, Masanari; Kondoh, Hiroshi; Nakai, Ikuyo; Ohta, Toshiaki

2007-01-28

The dynamics of adsorbate structures during CO oxidation on Pt(111) surfaces and its effects on the reaction were studied by the dynamic Monte Carlo method including lateral interactions of adsorbates. The lateral interaction energies between adsorbed species were calculated by the density functional theory method. Dynamic Monte Carlo simulations were performed for the oxidation reaction over a mesoscopic scale, where the experimentally determined activation energies of elementary paths were altered by the calculated lateral interaction energies. The simulated results reproduced the characteristics of the microscopic and mesoscopic scale adsorbate structures formed during the reaction, and revealed that the complicated reaction kinetics is comprehensively explained by a single reaction path affected by the surrounding adsorbates. We also propose from the simulations that weakly adsorbed CO molecules at domain boundaries promote the island-periphery specific reaction.

Interaction between dimer interface residues of native and mutated SOD1 protein: a theoretical study.

PubMed

Keerthana, S P; Kolandaivel, P

2015-04-01

Cu-Zn superoxide dismutase 1 (SOD1) is a highly conserved bimetallic protein enzyme, used for the scavenging the superoxide radicals (O2 (-)) produced due to aerobic metabolism in the mitochondrial respiratory chain. Over 100 mutations have been identified and found to be in the homodimeric structure of SOD1. The enzyme has to be maintained in its dimeric state for the structural stability and enzymatic activity. From our investigation, we found that the mutations apart from the dimer interface residues are found to affect the dimer stability of protein and hence enhancing the aggregation and misfolding tendency of mutated protein. The homodimeric state of SOD1 is found to be held together by the non-covalent interactions. The molecular dynamics simulation has been used to study the hydrogen bond interactions between the dimer interface residues of the monomers in native and mutated forms of SOD1 in apo- and holo-states. The results obtained by this analysis reveal the fact that the loss of hydrogen bond interactions between the monomers of the dimer is responsible for the reduced stability of the apo- and holo-mutant forms of SOD1. The conformers with dimer interface residues in native and mutated protein obtained by the molecular dynamics simulation is subjected to quantum mechanical study using M052X/6-31G(d) level of theory. The charge transfer between N-H···O interactions in the dimer interface residues were studied. The weak interaction between the monomers of the dimer accounts for the reduced dimerization and enhanced deformation energy in the mutated SOD1 protein.

Histone modifications influence mediator interactions with chromatin

PubMed Central

Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

2011-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

Meta-analysis reveals complex marine biological responses to the interactive effects of ocean acidification and warming

PubMed Central

Harvey, Ben P; Gwynn-Jones, Dylan; Moore, Pippa J

2013-01-01

Ocean acidification and warming are considered two of the greatest threats to marine biodiversity, yet the combined effect of these stressors on marine organisms remains largely unclear. Using a meta-analytical approach, we assessed the biological responses of marine organisms to the effects of ocean acidification and warming in isolation and combination. As expected biological responses varied across taxonomic groups, life-history stages, and trophic levels, but importantly, combining stressors generally exhibited a stronger biological (either positive or negative) effect. Using a subset of orthogonal studies, we show that four of five of the biological responses measured (calcification, photosynthesis, reproduction, and survival, but not growth) interacted synergistically when warming and acidification were combined. The observed synergisms between interacting stressors suggest that care must be made in making inferences from single-stressor studies. Our findings clearly have implications for the development of adaptive management strategies particularly given that the frequency of stressors interacting in marine systems will be likely to intensify in the future. There is now an urgent need to move toward more robust, holistic, and ecologically realistic climate change experiments that incorporate interactions. Without them accurate predictions about the likely deleterious impacts to marine biodiversity and ecosystem functioning over the next century will not be possible. PMID:23610641

Meta-analysis reveals complex marine biological responses to the interactive effects of ocean acidification and warming.

PubMed

Harvey, Ben P; Gwynn-Jones, Dylan; Moore, Pippa J

2013-04-01

Ocean acidification and warming are considered two of the greatest threats to marine biodiversity, yet the combined effect of these stressors on marine organisms remains largely unclear. Using a meta-analytical approach, we assessed the biological responses of marine organisms to the effects of ocean acidification and warming in isolation and combination. As expected biological responses varied across taxonomic groups, life-history stages, and trophic levels, but importantly, combining stressors generally exhibited a stronger biological (either positive or negative) effect. Using a subset of orthogonal studies, we show that four of five of the biological responses measured (calcification, photosynthesis, reproduction, and survival, but not growth) interacted synergistically when warming and acidification were combined. The observed synergisms between interacting stressors suggest that care must be made in making inferences from single-stressor studies. Our findings clearly have implications for the development of adaptive management strategies particularly given that the frequency of stressors interacting in marine systems will be likely to intensify in the future. There is now an urgent need to move toward more robust, holistic, and ecologically realistic climate change experiments that incorporate interactions. Without them accurate predictions about the likely deleterious impacts to marine biodiversity and ecosystem functioning over the next century will not be possible.

Numerical studies of interacting vortices

NASA Technical Reports Server (NTRS)

Liu, G. C.; Hsu, C. H.

1985-01-01

To get a basic understanding of the physics of flowfields modeled by vortex filaments with finite vortical cores, systematic numerical studies of the interactions of two dimensional vortices and pairs of coaxial axisymmetric circular vortex rings were made. Finite difference solutions of the unsteady incompressible Navier-Stokes equations were carried out using vorticity and stream function as primary variables. Special emphasis was placed on the formulation of appropriate boundary conditions necessary for the calculations in a finite computational domain. Numerical results illustrate the interaction of vortex filaments, demonstrate when and how they merge with each other, and establish the region of validity for an asymptotic analysis.

Computational Study on Full-length Human Ku70 with Double Stranded DNA: Dynamics, Interactions and Functional Implications

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Cucinotta, Francis A.

2009-01-01

The Ku70/80 heterodimer is the first repair protein in the initial binding of double-strand break (DSB) ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. In this study we constructed a full-length human Ku70 structure based on its crystal structure, and performed 20 ns conventional molecular dynamic (CMD) simulations on this protein and several other complexes with short DNA duplexes of different sequences. The trajectories of these simulations indicated that, without the topological support of Ku80, the residues in the bridge and C-terminal arm of Ku70 are more flexible than other experimentally identified domains. We studied the two missing loops in the crystal structure and predicted that they are also very flexible. Simulations revealed that they make an important contribution to the Ku70 interaction with DNA. Dislocation of the previously studied SAP domain was observed in several systems, implying its role in DNA binding. Targeted molecular dynamic (TMD) simulation was also performed for one system with a far-away 14bp DNA duplex. The TMD trajectory and energetic analysis disclosed detailed interactions of the DNA-binding residues during the DNA dislocation, and revealed a possible conformational transition for a DSB end when encountering Ku70 in solution. Compared to experimentally based analysis, this study identified more detailed interactions between DNA and Ku70. Free energy analysis indicated Ku70 alone is able to bind DNA with relatively high affinity, with consistent contributions from various domains of Ku70 in different systems. The functional implications of these domains in the processes of Ku heterodimerization and DNA damage recognition and repair can be characterized in detail based upon this analysis.

NMR Studies of Protein Hydration and Protein-Ligand Interactions

NASA Astrophysics Data System (ADS)

Chong, Yuan

Water on the surface of a protein is called hydration water. Hydration water is known to play a crucial role in a variety of biological processes including protein folding, enzymatic activation, and drug binding. Although the significance of hydration water has been recognized, the underlying mechanism remains far from being understood. This dissertation employs a unique in-situ nuclear magnetic resonance (NMR) technique to study the mechanism of protein hydration and the role of hydration in alcohol-protein interactions. Water isotherms in proteins are measured at different temperatures via the in-situ NMR technique. Water is found to interact differently with hydrophilic and hydrophobic groups on the protein. Water adsorption on hydrophilic groups is hardly affected by the temperature, while water adsorption on hydrophobic groups strongly depends on the temperature around 10 C, below which the adsorption is substantially reduced. This effect is induced by the dramatic decrease in the protein flexibility below 10 C. Furthermore, nanosecond to microsecond protein dynamics and the free energy, enthalpy, and entropy of protein hydration are studied as a function of hydration level and temperature. A crossover at 10 C in protein dynamics and thermodynamics is revealed. The effect of water at hydrophilic groups on protein dynamics and thermodynamics shows little temperature dependence, whereas water at hydrophobic groups has stronger effect above 10 C. In addition, I investigate the role of water in alcohol binding to the protein using the in-situ NMR detection. The isotherms of alcohols are first measured on dry proteins, then on proteins with a series of controlled hydration levels. The free energy, enthalpy, and entropy of alcohol binding are also determined. Two distinct types of alcohol binding are identified. On the one hand, alcohols can directly bind to a few specific sites on the protein. This type of binding is independent of temperature and can be

Investigations on the Interactions of 5-Fluorouracil with Herring Sperm DNA: Steady State/Time Resolved and Molecular Modeling Studies

NASA Astrophysics Data System (ADS)

Chinnathambi, Shanmugavel; Karthikeyan, Subramani; Velmurugan, Devadasan; Hanagata, Nobutaka; Aruna, Prakasarao; Ganesan, Singaravelu

2015-04-01

In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico-biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA-EB systems were examined by fluorescence spectra. The Stern-Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.

Interactions Measurement Payload for Shuttle (IMPS) Definition Phase Study.

DTIC Science & Technology

1984-12-15

7 -AS5 222 INTERACTIONS MEASUREMENT PAYLOAD FOR SHUTTLE (IMPS) 1/3 DEFINITION PHASE STUDY(U) JET PROPULSION LAB PASADENA CA G C HILL 15 DEC 84 JPL-D...OF FUNDING NOS. PROGRAM PROJECT TASK WORK UNIT ELEMENT NO. NO NO. NO. S 11 TITLE fnciude Security Classficalion Interactions Measure 63410F 1822 01...block number, d tor Shuttle The Interactions Measurement Payload for hyttle (IMPS) project will study interactions between large space vehicles, such as

Study on the Mechanism of Interaction between Phthalate Acid Esters and Bovine Hemoglobin.

PubMed

Chi, Zhenxing; Zhao, Jing; You, Hong; Wang, Mingjing

2016-08-03

Phthalate acid esters (PAEs) are widely used in plastic products as a series of chemical softeners. However, PAEs, which now exist in many environmental media such as the atmosphere, water, and soil, have been shown to be environmental endocrine disruptors. Hemoglobin is a functional protein that carries oxygen in the red blood cells of animals. This study aims at revealing the interactions between bovine hemoglobin (BHb) and PAEs using spectroscopic and molecular modeling methods. The results indicate that the selected representative PAEs-dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP)-can interact with BHb to form BHb-PAE complexes with one binding site, mainly relying on hydrophobic forces, with the affinity order DMP > DEP > DBP, opposite to the order of side-chain length. The binding of PAEs can cause conformational and micro-environmental changes in BHb, which may affect the physiological functions of Hb. Furthermore, molecular docking was applied to define the specific binding sites, the results of which show that all the three PAEs can bind into the central cavity of BHb. The study contributes to expound the toxic mechanism of PAEs in vivo from the point of hematological toxicology.

Microscopic study reveals the singular origins of growth

NASA Astrophysics Data System (ADS)

Yaari, G.; Nowak, A.; Rakocy, K.; Solomon, S.

2008-04-01

Anderson [Science 177, 293 (1972)] proposed the concept of complexity in order to describe the emergence and growth of macroscopic collective patterns out of the simple interactions of many microscopic agents. In the physical sciences this paradigm was implemented systematically and confirmed repeatedly by successful confrontation with reality. In the social sciences however, the possibilities to stage experiments to validate it are limited. During the 90's a series of dramatic political and economic events have provided the opportunity to do so. We exploit the resulting empirical evidence to validate a simple agent based alternative to the classical logistic dynamics. The post-liberalization empirical data from Poland confirm the theoretical prediction that the dynamics is dominated by singular rare events which insure the resilience and adaptability of the system. We have shown that growth is led by few singular “growth centers" (Fig. 1), that initially developed at a tremendous rate (Fig. 3), followed by a diffusion process to the rest of the country and leading to a positive growth rate uniform across the counties. In addition to the interdisciplinary unifying potential of our generic formal approach, the present work reveals the strong causal ties between the “softer" social conditions and their “hard" economic consequences.

A Study of Teacher-Learner Interactions: A Continuum Between Monologic and Dialogic Interactions.

PubMed

Kathard, Harsha; Pillay, Daisy; Pillay, Mershen

2015-07-01

Teachers and learners must be able to shift flexibly along the continuum of monologic and dialogic interactional repertoires to advance learning. This article describes how teachers and learners interacted during whole-class instruction along the continuum between monologic and dialogic interaction in primary school classrooms in Western Cape, South Africa. A video-observation method was used to analyze teacher-learner interactions (TLIs) across 15 lessons in intermediate-phase classrooms. TLIs were analyzed in relation to indicators such as authority, questions, feedback, explanation, metalevel connection, and collaboration. The transcriptions of TLIs were described using quantitative and qualitative techniques. The study found that teachers sustained dominant monologic interactions by asserting their authority, asking mainly closed-ended questions, and providing confirming/correcting feedback that constrained the interaction. Learners had limited opportunities for explanations or collaboration. Across most lessons, there were episodic shifts from monologic TLIs to transitional TLIs. These transitions were achieved by using mainly open-ended questions and feedback to expand the interaction. Dialogic TLIs were not evident. Monologic TLIs were dominant, closing down opportunities for communication. Although transitional TLIs were evident, they were episodic and showed the potential for opening interaction opportunities. The absence of dialogic TLIs suggested that collaborative engagement opportunities were unavailable. The opportunity for intervention to increase dialogic TLIs is discussed.

Social interaction in synthetic and natural microbial communities.

PubMed

Xavier, Joao B

2011-04-12

Social interaction among cells is essential for multicellular complexity. But how do molecular networks within individual cells confer the ability to interact? And how do those same networks evolve from the evolutionary conflict between individual- and population-level interests? Recent studies have dissected social interaction at the molecular level by analyzing both synthetic and natural microbial populations. These studies shed new light on the role of population structure for the evolution of cooperative interactions and revealed novel molecular mechanisms that stabilize cooperation among cells. New understanding of populations is changing our view of microbial processes, such as pathogenesis and antibiotic resistance, and suggests new ways to fight infection by exploiting social interaction. The study of social interaction is also challenging established paradigms in cancer evolution and immune system dynamics. Finding similar patterns in such diverse systems suggests that the same 'social interaction motifs' may be general to many cell populations.

Bicuspid aortic valve hemodynamics: a fluid-structure interaction study

NASA Astrophysics Data System (ADS)

Chandra, Santanu; Seaman, Clara; Sucosky, Philippe

2011-11-01

The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV.

How does ytterbium chloride interact with DMPC bilayers? A computational and experimental study.

PubMed

Gonzalez, Miguel A; Barriga, Hanna M G; Richens, Joanna L; Law, Robert V; O'Shea, Paul; Bresme, Fernando

2017-03-29

Lanthanide salts have been studied for many years, primarily in Nuclear Magnetic Resonance (NMR) experiments of mixed lipid-protein systems and more recently to study lipid flip-flop in model membrane systems. It is well recognised that lanthanide salts can influence the behaviour of both lipid and protein systems, however a full molecular level description of lipid-lanthanide interactions is still outstanding. Here we present a study of lanthanide-bilayer interactions, using molecular dynamics computer simulations, fluorescence electrostatic potential experiments and nuclear magnetic resonance. Computer simulations reveal the microscopic structure of DMPC lipid bilayers in the presence of Yb 3+ , and a surprising ability of the membranes to adsorb significant concentrations of Yb 3+ without disrupting the overall membrane structure. At concentrations commonly used in NMR experiments, Yb 3+ ions bind strongly to 5 lipids, inducing a small decrease of the area per lipid and a slight increase of the ordering of the aliphatic chains and the bilayer thickness. The area compressibility modulus increases by a factor of two, with respect to the free-salt case, showing that Yb 3+ ions make the bilayer more rigid. These modifications of the bilayer properties should be taken into account in the interpretation of NMR experiments.

Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations.

PubMed

Bastos, Andre M; Briggs, Farran; Alitto, Henry J; Mangun, George R; Usrey, W Martin

2014-05-28

Oscillatory synchronization of neuronal activity has been proposed as a mechanism to modulate effective connectivity between interacting neuronal populations. In the visual system, oscillations in the gamma-frequency range (30-100 Hz) are thought to subserve corticocortical communication. To test whether a similar mechanism might influence subcortical-cortical communication, we recorded local field potential activity from retinotopically aligned regions in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys viewing stimuli known to produce strong cortical gamma-band oscillations. As predicted, we found robust gamma-band power in V1. In contrast, visual stimulation did not evoke gamma-band activity in the LGN. Interestingly, an analysis of oscillatory phase synchronization of LGN and V1 activity identified synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands. Further analysis of directed connectivity revealed that alpha-band interactions mediated corticogeniculate feedback processing, whereas beta-band interactions mediated geniculocortical feedforward processing. These results demonstrate that although the LGN and V1 display functional interactions in the lower frequency bands, gamma-band activity in the alert monkey is largely an emergent property of cortex. Copyright © 2014 the authors 0270-6474/14/347639-06$15.00/0.

A Experimental Study of Fluctuating Pressure Loads Beneath Swept Shock Wave/boundary Layer Interactions

NASA Astrophysics Data System (ADS)

Garg, Sanjay

An experimental research program providing basic knowledge and establishing a database on the fluctuating pressure loads produced on aerodynamic surfaces beneath three-dimensional shock wave/boundary layer interactions is described. Such loads constitute a fundamental problem of critical concern to future supersonic and hypersonic flight vehicles. A turbulent boundary layer on a flat plate is subjected to interactions with swept planar shock waves generated by sharp fins. Fin angles from 10 ^circ to 20^circ at freestream Mach numbers of 3 and 4 produce a variety of interaction strengths from weak to very strong. Miniature pressure transducers flush-mounted in the flat plate have been used to measure interaction-induced wall pressure fluctuations. The distributions of properties of the pressure fluctuations, such as their rms level, amplitude distribution and power spectra, are also determined. Measurements have been made for the first time in the aft regions of these interactions, revealing fluctuating pressure levels as high as 155 dB, which places them in the category of significant aeroacoustic load generators. The fluctuations near the foot of the fin are dominated by low frequency (0-5 kHz) components, and are caused by a previously unrecognized random motion of the primary attachment line. This phenomenon is probably intimately linked to the unsteadiness of the separation shock at the start of the interaction. The characteristics of the pressure fluctuations are explained in light of the features of the interaction flowfield. In particular, physical mechanisms responsible for the generation of high levels of surface pressure fluctuations are proposed based on the results of the study. The unsteadiness of the flowfield of the surface is also examined via a novel, non-intrusive optical technique. Results show that the entire shock structure generated by the interaction undergoes relatively low-frequency oscillations.

Study of interaction of hypericin and its pharmaceutical preparation by fluorescence techniques.

PubMed

Liu, Jun; Saw, Constance Lay Lay; Olivo, Malini; Sudhaharan, Thankiah; Ahmed, Sohail; Heng, Paul Wan Sia; Wohland, Thorsten

2009-01-01

We report the detection of interactions between a photosensitizer, hypericin (HY), and its solvent system prepared with a formulation additive, polyvinylpyrrolidone (PVP), a commonly used pharmaceutical excipient. Fluorescence correlation spectroscopy (FCS) and fluorescence lifetime imaging microscopy (FLIM) were used to study aggregation and binding of HY in the presence of PVP. Digitized fluorescence endoscopic imaging (DFEI) was used to study the effect of the pharmaceutical formulation in the in vivo tumor implanted chick chorioallantoic membrane (CAM) model. The results presented reveal the coordination of HY-PVP binding, HY disaggregation in the presence of PVP, and strengthened HY tumor uptake selectivity. PVP is thus suggested as a potential adjuvant to previously investigated N-methyl pyrrolidone (NMP) in the HY delivery system as well as a replacement for the conventionally used albumin in the HY bladder instillation fluids preparation for clinical use.

A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human.

PubMed

Vo, Tommy V; Das, Jishnu; Meyer, Michael J; Cordero, Nicolas A; Akturk, Nurten; Wei, Xiaomu; Fair, Benjamin J; Degatano, Andrew G; Fragoza, Robert; Liu, Lisa G; Matsuyama, Akihisa; Trickey, Michelle; Horibata, Sachi; Grimson, Andrew; Yamano, Hiroyuki; Yoshida, Minoru; Roth, Frederick P; Pleiss, Jeffrey A; Xia, Yu; Yu, Haiyuan

2016-01-14

Here, we present FissionNet, a proteome-wide binary protein interactome for S. pombe, comprising 2,278 high-quality interactions, of which ∼ 50% were previously not reported in any species. FissionNet unravels previously unreported interactions implicated in processes such as gene silencing and pre-mRNA splicing. We developed a rigorous network comparison framework that accounts for assay sensitivity and specificity, revealing extensive species-specific network rewiring between fission yeast, budding yeast, and human. Surprisingly, although genes are better conserved between the yeasts, S. pombe interactions are significantly better conserved in human than in S. cerevisiae. Our framework also reveals that different modes of gene duplication influence the extent to which paralogous proteins are functionally repurposed. Finally, cross-species interactome mapping demonstrates that coevolution of interacting proteins is remarkably prevalent, a result with important implications for studying human disease in model organisms. Overall, FissionNet is a valuable resource for understanding protein functions and their evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular mechanics and dynamics studies on the interaction of gallic acid with collagen-like peptides

NASA Astrophysics Data System (ADS)

Madhan, B.; Thanikaivelan, P.; Subramanian, V.; Raghava Rao, J.; Unni Nair, Balachandran; Ramasami, T.

2001-10-01

Molecular modelling approaches have been used to understand the interaction of collagen-like peptides with gallic acid, which mimic vegetable tanning processes involved in protein stabilization. Several interaction sites have been identified and the binding energies of the complexes have been calculated. The calculated binding energies for various geometries are in the range 6-13 kcal/mol. It is found that some complexes exhibit hydrogen bonding, and electrostatic interaction plays a dominant role in the stabilization of the peptide by gallic acid. The π-OH type of interaction is also observed in the peptide stabilization. Molecular dynamics (MD) simulation for 600 ps revealed the possibility of hydrogen bonding between the collagen-like peptide and gallic acid.

Comparative Genomic Analysis Reveals a Diverse Repertoire of Genes Involved in Prokaryote-Eukaryote Interactions within the Pseudovibrio Genus

PubMed Central

Romano, Stefano; Fernàndez-Guerra, Antonio; Reen, F. Jerry; Glöckner, Frank O.; Crowley, Susan P.; O'Sullivan, Orla; Cotter, Paul D.; Adams, Claire; Dobson, Alan D. W.; O'Gara, Fergal

2016-01-01

Strains of the Pseudovibrio genus have been detected worldwide, mainly as part of bacterial communities associated with marine invertebrates, particularly sponges. This recurrent association has been considered as an indication of a symbiotic relationship between these microbes and their host. Until recently, the availability of only two genomes, belonging to closely related strains, has limited the knowledge on the genomic and physiological features of the genus to a single phylogenetic lineage. Here we present 10 newly sequenced genomes of Pseudovibrio strains isolated from marine sponges from the west coast of Ireland, and including the other two publicly available genomes we performed an extensive comparative genomic analysis. Homogeneity was apparent in terms of both the orthologous genes and the metabolic features shared amongst the 12 strains. At the genomic level, a key physiological difference observed amongst the isolates was the presence only in strain P. axinellae AD2 of genes encoding proteins involved in assimilatory nitrate reduction, which was then proved experimentally. We then focused on studying those systems known to be involved in the interactions with eukaryotic and prokaryotic cells. This analysis revealed that the genus harbors a large diversity of toxin-like proteins, secretion systems and their potential effectors. Their distribution in the genus was not always consistent with the phylogenetic relationship of the strains. Finally, our analyses identified new genomic islands encoding potential toxin-immunity systems, previously unknown in the genus. Our analyses shed new light on the Pseudovibrio genus, indicating a large diversity of both metabolic features and systems for interacting with the host. The diversity in both distribution and abundance of these systems amongst the strains underlines how metabolically and phylogenetically similar bacteria may use different strategies to interact with the host and find a niche within its

Characterization of Calmodulin–Fas Death Domain Interaction: An Integrated Experimental and Computational Study

PubMed Central

2015-01-01

The Fas death receptor-activated death-inducing signaling complex (DISC) regulates apoptosis in many normal and cancer cells. Qualitative biochemical experiments demonstrate that calmodulin (CaM) binds to the death domain of Fas. The interaction between CaM and Fas regulates Fas-mediated DISC formation. A quantitative understanding of the interaction between CaM and Fas is important for the optimal design of antagonists for CaM or Fas to regulate the CaM–Fas interaction, thus modulating Fas-mediated DISC formation and apoptosis. The V254N mutation of the Fas death domain (Fas DD) is analogous to an identified mutant allele of Fas in lpr-cg mice that have a deficiency in Fas-mediated apoptosis. In this study, the interactions of CaM with the Fas DD wild type (Fas DD WT) and with the Fas DD V254N mutant were characterized using isothermal titration calorimetry (ITC), circular dichroism spectroscopy (CD), and molecular dynamics (MD) simulations. ITC results reveal an endothermic binding characteristic and an entropy-driven interaction of CaM with Fas DD WT or with Fas DD V254N. The Fas DD V254N mutation decreased the association constant (Ka) for CaM–Fas DD binding from (1.79 ± 0.20) × 106 to (0.88 ± 0.14) × 106 M–1 and slightly increased a standard state Gibbs free energy (ΔG°) for CaM–Fas DD binding from −8.87 ± 0.07 to −8.43 ± 0.10 kcal/mol. CD secondary structure analysis and MD simulation results did not show significant secondary structural changes of the Fas DD caused by the V254N mutation. The conformational and dynamical motion analyses, the analyses of hydrogen bond formation within the CaM binding region, the contact numbers of each residue, and the electrostatic potential for the CaM binding region based on MD simulations demonstrated changes caused by the Fas DD V254N mutation. These changes caused by the Fas DD V254N mutation could affect the van der Waals interactions and electrostatic interactions between CaM and Fas DD, thereby

Protein Interaction Networks Reveal Novel Autism Risk Genes within GWAS Statistical Noise

PubMed Central

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M.

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical “noise” that warrant further analysis for causal variants. PMID:25409314

Protein interaction networks reveal novel autism risk genes within GWAS statistical noise.

PubMed

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical "noise" that warrant further analysis for causal variants.

Ab initio study of the Coulomb interaction in NbxCo clusters: Strong on-site versus weak nonlocal screening

NASA Astrophysics Data System (ADS)

Peters, L.; Şaşıoǧlu, E.; Mertig, I.; Katsnelson, M. I.

2018-01-01

By means of ab initio calculations in conjunction with the random-phase approximation (RPA) within the full-potential linearized augmented plane wave method, we study the screening of the Coulomb interaction in NbxCo (1 ≤x ≤9 ) clusters. In addition, these results are compared with pure bcc Nb bulk. We find that for all clusters the on-site Coulomb interaction in RPA is strongly screened, whereas the intersite nonlocal Coulomb interaction is weakly screened and for some clusters it is unscreened or even antiscreened. This is in strong contrast with pure Nb bulk, where the intersite Coulomb interaction is almost completely screened. Furthermore, constrained RPA calculations reveal that the contribution of the Co 3 d → 3 d channel to the total screening of the Co 3 d electrons is small. Moreover, we find that both the on-site and intersite Coulomb interaction parameters decrease in a reasonable approximation linearly with the cluster size and for clusters having more than 20 Nb atoms a transition from 0D to 3D screening is expected to take place.

Spectroscopy reveals that ethyl esters interact with proteins in wine.

PubMed

Di Gaspero, Mattia; Ruzza, Paolo; Hussain, Rohanah; Vincenzi, Simone; Biondi, Barbara; Gazzola, Diana; Siligardi, Giuliano; Curioni, Andrea

2017-02-15

Impairment of wine aroma after vinification is frequently associated to bentonite treatments and this can be the result of protein removal, as recently demonstrated for ethyl esters. To evaluate the existence of an interaction between wine proteins and ethyl esters, the effects induced by these fermentative aroma compounds on the secondary structure and stability of VVTL1, a Thaumatin-like protein purified from wine, was analyzed by Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The secondary structure of wine VVTL1 was not strongly affected by the presence of selected ethyl esters. In contrast, VVTL1 stability was slightly increased by the addition of ethyl-octanoate, -decanoate and -dodecanoate, but decreased by ethyl-hexanoate. This indicates the existence of an interaction between VVTL1 and at least some aroma compounds produced during fermentation. The data suggest that proteins removal from wine by bentonite can result in indirect removal of at least some aroma compounds associated with them. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary study of the interactions caused by crossing shock waves and a turbulent boundary layer

NASA Technical Reports Server (NTRS)

Ketchum, A. C.; Bogdonoff, S. M.; Fernando, E. M.; Batcho, P. F.

1989-01-01

The subject research, the first phase of an extended study of the interaction of crossing shock waves with a turbulent boundary layer, has revealed the complexity of the resulting flow. Detailed surface visualization and mean wall static pressure distributions show little resemblance to the inviscid flow approximation, and the exploratory high frequency measurements show that the flow downstream of the theoretical inviscid shock crossing position has a significant unsteady characteristic. Further developments of the (unsteady) high frequency measurements are required to fully characterize the unsteadiness and the requirements to include this component in flowfield modeling.

Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

PubMed

Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

2017-06-16

The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

Spectral long-range interaction of temporal incoherent solitons.

PubMed

Xu, Gang; Garnier, Josselin; Picozzi, Antonio

2014-02-01

We study the interaction of temporal incoherent solitons sustained by a highly noninstantaneous (Raman-like) nonlinear response. The incoherent solitons exhibit a nonmutual interaction, which can be either attractive or repulsive depending on their relative initial distance. The analysis reveals that incoherent solitons exhibit a long-range interaction in frequency space, which is in contrast with the expected spectral short-range interaction described by the usual approach based on the Raman-like spectral gain curve. Both phenomena of anomalous interaction and spectral long-range behavior of incoherent solitons are described in detail by a long-range Vlasov equation.

[Early interaction is a prerequisite for favorable psychic development].

PubMed

Pesonen, Anu-Katriina

2010-01-01

Empirical studies on the parent-baby interaction have greatly influenced our insight into the child's psychological development. Initial stages of the research attempted to reveal features in the mother's action that would predict the child's favorable development. Since then, also fathers and the child's development in a more broad sense have been studied. The most prominent progress has taken place in microanalytical methods for these interactions. The research has increased our knowledge of the baby's interactive capabilities and the significance of successful interactive events for the child's development, laying the basis for various interventions related to parenthood.

Revealing the Strong Functional Association of adipor2 and cdh13 with adipoq: A Gene Network Study.

PubMed

Bag, Susmita; Anbarasu, Anand

2015-04-01

In the present study, we have analyzed functional gene interactions of adiponectin gene (adipoq). The key role of adipoq is in regulating energy homeostasis and it functions as a novel signaling molecule for adipose tissue. Modules of highly inter-connected genes in disease-specific adipoq network are derived by integrating gene function and protein interaction data. Among twenty genes in adipoq web, adipoq is effectively conjoined with two genes: Adiponectin receptor 2 (adipor2) and cadherin 13 (cdh13). The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with adipoq are adipor2 and cdh13. Interestingly, the ontological aspect of adipor2 and cdh13 in the adipoq network reveal the fact that adipoq and adipor2 are involved mostly in glucose and lipid metabolic processes. The gene cdh13 indulge in cell adhesion process with adipoq and adipor2. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of adipoq, adipor2, and cdh13 with not only with obesity but also with breast cancer, leukemia, renal cancer, lung cancer, and cervical cancer. The current study provides researchers a comprehensible layout of adipoq network, its functional strategies and candidate disease approach associated with adipoq network.

In Vitro Characterization of Thermostable CAM Rubisco Activase Reveals a Rubisco Interacting Surface Loop1[OPEN

PubMed Central

Shivhare, Devendra

2017-01-01

To maintain metabolic flux through the Calvin-Benson-Bassham cycle in higher plants, dead-end inhibited complexes of Rubisco must constantly be engaged and remodeled by the molecular chaperone Rubisco activase (Rca). In C3 plants, the thermolability of Rca is responsible for the deactivation of Rubisco and reduction of photosynthesis at moderately elevated temperatures. We reasoned that crassulacean acid metabolism (CAM) plants must possess thermostable Rca to support Calvin-Benson-Bassham cycle flux during the day when stomata are closed. A comparative biochemical characterization of rice (Oryza sativa) and Agave tequilana Rca isoforms demonstrated that the CAM Rca isoforms are approximately10°C more thermostable than the C3 isoforms. Agave Rca also possessed a much higher in vitro biochemical activity, even at low assay temperatures. Mixtures of rice and agave Rca form functional hetero-oligomers in vitro, but only the rice isoforms denature at nonpermissive temperatures. The high thermostability and activity of agave Rca mapped to the N-terminal 244 residues. A Glu-217-Gln amino acid substitution was found to confer high Rca activity to rice Rca. Further mutational analysis suggested that Glu-217 restricts the flexibility of the α4-β4 surface loop that interacts with Rubisco via Lys-216. CAM plants thus promise to be a source of highly functional, thermostable Rca candidates for thermal fortification of crop photosynthesis. Careful characterization of their properties will likely reveal further protein-protein interaction motifs to enrich our mechanistic model of Rca function. PMID:28546437

Multifactor-Dimensionality Reduction Reveals High-Order Interactions among Estrogen-Metabolism Genes in Sporadic Breast Cancer

PubMed Central

Ritchie, Marylyn D.; Hahn, Lance W.; Roodi, Nady; Bailey, L. Renee; Dupont, William D.; Parl, Fritz F.; Moore, Jason H.

2001-01-01

One of the greatest challenges facing human geneticists is the identification and characterization of susceptibility genes for common complex multifactorial human diseases. This challenge is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes and with environmental exposures. We introduce multifactor-dimensionality reduction (MDR) as a method for reducing the dimensionality of multilocus information, to improve the identification of polymorphism combinations associated with disease risk. The MDR method is nonparametric (i.e., no hypothesis about the value of a statistical parameter is made), is model-free (i.e., it assumes no particular inheritance model), and is directly applicable to case-control and discordant-sib-pair studies. Using simulated case-control data, we demonstrate that MDR has reasonable power to identify interactions among two or more loci in relatively small samples. When it was applied to a sporadic breast cancer case-control data set, in the absence of any statistically significant independent main effects, MDR identified a statistically significant high-order interaction among four polymorphisms from three different estrogen-metabolism genes. To our knowledge, this is the first report of a four-locus interaction associated with a common complex multifactorial disease. PMID:11404819

Molecular docking and molecular dynamics studies on the interactions of hydroxylated polybrominated diphenyl ethers to estrogen receptor alpha.

PubMed

Lu, Qun; Cai, Zhengqing; Fu, Jie; Luo, Siyi; Liu, Chunsheng; Li, Xiaolin; Zhao, Dongye

2014-03-01

Environmental estrogens have attracted great concerns. Recent studies have indicated that some hydroxylated polybrominated diphenyl ethers (HO-PBDEs) can interact with estrogen receptor (ER), and exhibit estrogenic activity. However, interactions between HO-PBDEs and ER are not well understood. In this work, molecular docking and molecular dynamics (MD) simulations were performed to characterize interactions of two HO-PBDEs (4'-HO-BDE30 and 4'-HO-BDE121) with ERα. Surflex-Dock was employed to reveal the probable binding conformations of the compounds at the active site of ERα; MD simulation was used to determine the detailed binding process. The driving forces of the binding between HO-PBDEs and ERα were van der Waals and electrostatic interactions. The decomposition of the binding free energy indicated that the hydrogen bonds between the residues Glu353, Gly521 and ligands were crucial for anchoring the ligands into the active site of ERα and stabilizing their conformations. The results showed that different interaction modes and different specific interactions with some residues were responsible for the different estrogenic activities of the two HO-PBDEs. Copyright © 2013 Elsevier Inc. All rights reserved.

Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting

PubMed Central

Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev; Weinberg, Aaron; Zimmerman, Peter

2018-01-01

Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance. Using various linear and nonlinear time-to-events survival models in simulation studies, we first show the efficiency of our approach: true pairwise interaction-effects between variables are uncovered, while they may not be accompanied with their corresponding main-effects, and may not be detected by standard semi-parametric regression modeling and test statistics used in survival analysis. Moreover, using a RSF-based cross-validation scheme for generating prediction estimators, we show that informative predictors may be inferred. We applied our approach to an HIV cohort study recording key host gene polymorphisms and their association with HIV change of tropism or AIDS progression. Altogether, this shows how linear or nonlinear pairwise statistical interactions of variables may be efficiently detected with a predictive value in observational studies with time-to-event outcomes. PMID:29453930

Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting.

PubMed

Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev; Weinberg, Aaron; Zimmerman, Peter

2018-02-17

Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance. Using various linear and nonlinear time-to-events survival models in simulation studies, we first show the efficiency of our approach: true pairwise interaction-effects between variables are uncovered, while they may not be accompanied with their corresponding main-effects, and may not be detected by standard semi-parametric regression modeling and test statistics used in survival analysis. Moreover, using a RSF-based cross-validation scheme for generating prediction estimators, we show that informative predictors may be inferred. We applied our approach to an HIV cohort study recording key host gene polymorphisms and their association with HIV change of tropism or AIDS progression. Altogether, this shows how linear or nonlinear pairwise statistical interactions of variables may be efficiently detected with a predictive value in observational studies with time-to-event outcomes.

Dynamic membrane interactions of antibacterial and antifungal biomolecules, and amyloid peptides, revealed by solid-state NMR spectroscopy.

PubMed

Naito, Akira; Matsumori, Nobuaki; Ramamoorthy, Ayyalusamy

2018-02-01

A variety of biomolecules acting on the cell membrane folds into a biologically active structure in the membrane environment. It is, therefore, important to determine the structures and dynamics of such biomolecules in a membrane environment. While several biophysical techniques are used to obtain low-resolution information, solid-state NMR spectroscopy is one of the most powerful means for determining the structure and dynamics of membrane bound biomolecules such as antibacterial biomolecules and amyloidogenic proteins; unlike X-ray crystallography and solution NMR spectroscopy, applications of solid-state NMR spectroscopy are not limited by non-crystalline, non-soluble nature or molecular size of membrane-associated biomolecules. This review article focuses on the applications of solid-state NMR techniques to study a few selected antibacterial and amyloid peptides. Solid-state NMR studies revealing the membrane inserted bent α-helical structure associated with the hemolytic activity of bee venom melittin and the chemical shift oscillation analysis used to determine the transmembrane structure (with α-helix and 3 10 -helix in the N- and C-termini, respectively) of antibiotic peptide alamethicin are discussed in detail. Oligomerization of an amyloidogenic islet amyloid polypeptide (IAPP, or also known as amylin) resulting from its aggregation in a membrane environment, molecular interactions of the antifungal natural product amphotericin B with ergosterol in lipid bilayers, and the mechanism of lipid raft formation by sphingomyelin studied using solid state NMR methods are also discussed in this review article. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

Azadirachtin(A) distinctively modulates subdomain 2 of actin - novel mechanism to induce depolymerization revealed by molecular dynamics study.

PubMed

Pravin Kumar, R; Roopa, L; Sudheer Mohammed, M M; Kulkarni, Naveen

2016-12-01

Azadirachtin(A) (AZA), a potential insecticide from neem, binds to actin and induces depolymerization in Drosophila. AZA binds to the pocket same as that of Latrunculin A (LAT), but LAT inhibits actin polymerization by stiffening the actin structure and affects the ADP-ATP exchange. The mechanism by which AZA induces actin depolymerization is not clearly understood. Therefore, different computational experiments were conducted to delineate the precise mechanism of AZA-induced actin depolymerization. Molecular dynamics studies showed that AZA strongly interacted with subdomain 2 and destabilized the interactions between subdomain 2 of one actin and subdomains 1 and 4 of the adjacent actin, causing the separation of actin subunits. The separation was observed between subdomain 3 of subunit n and subdomain 4 of subunit n + 2. However, the specific triggering point for the separation of the subunits was the destabilization of direct interactions between subdomain 2 of subunit n (Arg39, Val45, Gly46 and Arg62) and subdomain 4 of subunit n + 2 (Asp286, Ile287, Asp288, Ile289, Asp244 and Lys291). These results reveal a unique mechanism of an actin filament modulator that induces depolymerization. This mechanism of AZA can be used to design similar molecules against mammalian actins for cancer therapy.

Observational Study and Parameterization of Aerosol-fog Interactions

NASA Astrophysics Data System (ADS)

Duan, J.; Guo, X.; Liu, Y.; Fang, C.; Su, Z.; Chen, Y.

2014-12-01

Studies have shown that human activities such as increased aerosols affect fog occurrence and properties significantly, and accurate numerical fog forecasting depends on, to a large extent, parameterization of fog microphysics and aerosol-fog interactions. Furthermore, fogs can be considered as clouds near the ground, and enjoy an advantage of permitting comprehensive long-term in-situ measurements that clouds do not. Knowledge learned from studying aerosol-fog interactions will provide useful insights into aerosol-cloud interactions. To serve the twofold objectives of understanding and improving parameterizations of aerosol-fog interactions and aerosol-cloud interactions, this study examines the data collected from fogs, with a focus but not limited to the data collected in Beijing, China. Data examined include aerosol particle size distributions measured by a Passive Cavity Aerosol Spectrometer Probe (PCASP-100X), fog droplet size distributions measured by a Fog Monitor (FM-120), Cloud Condensation Nuclei (CCN), liquid water path measured by radiometers and visibility sensors, along with meteorological variables measured by a Tethered Balloon Sounding System (XLS-Ⅱ) and Automatic Weather Station (AWS). The results will be compared with low-level clouds for similarities and differences between fogs and clouds.

Observed sensitivity during family interactions and cumulative risk: A study of multiple dyads per family.

PubMed

Browne, Dillon T; Leckie, George; Prime, Heather; Perlman, Michal; Jenkins, Jennifer M

2016-07-01

The present study sought to investigate the family, individual, and dyad-specific contributions to observed cognitive sensitivity during family interactions. Moreover, the influence of cumulative risk on sensitivity at the aforementioned levels of the family was examined. Mothers and 2 children per family were observed interacting in a round robin design (i.e., mother-older sibling, mother younger-sibling and sibling-dyad, N = 385 families). Data were dyadic, in that there were 2 directional scores per interaction, and were analyzed using a multilevel formulation of the Social Relations Model. Variance partitioning revealed that cognitive sensitivity is simultaneously a function of families, individuals and dyads, though the importance of these components varies across family roles. Cognitive sensitivity for mothers was primarily attributable to individual differences, whereas cognitive sensitivity for children was predominantly attributable to family and dyadic differences, especially for youngest children. Cumulative risk explained family and individual variance in cognitive sensitivity, particularly when actors were older or in a position of relative competence or authority (i.e., mother to children, older to younger siblings). Overall, this study demonstrates that cognitive sensitivity operates across levels of family organization, and is negatively impacted by psychosocial risk. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Gas-Phase Interaction of Anions with Polyisobutylenes: Collision-Induced Dissociation Study and Quantum Chemical Modeling.

PubMed

Nagy, Lajos; Kuki, Ákos; Deák, György; Purgel, Mihály; Vékony, Ádám; Zsuga, Miklós; Kéki, Sándor

2016-09-01

The gas-phase interaction of anions including fluoride, chloride, bromide, iodide, ethyl sulfate, chlorate, and nitrate with polyisobutylene (PIB) derivatives was studied using collision-induced dissociation (CID). The gas-phase adducts of anions with PIBs ([PIB + anion](-)) were generated from the electrosprayed solution of PIBs in the presence of the corresponding anions. The so-formed adducts subjected to CID showed a loss of anion at different characteristic collision energies, thus allowing the study of the strength of interaction between the anions and nonpolar PIBs having different end-groups. The values of characteristic collision energies (the energy needed to obtain 50% fragmentation) obtained by CID experiments correlated linearly with the binding enthalpies between the anion and PIB, as determined by density functional theory calculations. In the case of halide ions, the critical energies for dissociation, that is, the binding enthalpies for [PIB + anion](-) adducts, increased in the order of I(-) < Br(-) < Cl(-) < F(-). Furthermore, it was found that the binding enthalpies for the adducts formed with halide ions decreased approximately with the square radius of the halide ion, suggesting that the strength of interaction is mainly determined by the "surface" charge density of the halide ion. In addition, the characteristic collision energy versus the number of isobutylene units revealed a linear dependence.

First order reversal curve study of the dipolar interaction in Ni three-dimensional antidot arrays

NASA Astrophysics Data System (ADS)

Li, Bingqing; Chai, Xuzhao; Moeendarbari, Sina; Hao, Yaowu; Gilbert, Dustin A.; Liu, Kai; Zhang, Di; Feng, Gang; Han, Ping; Cheng, X. M.

2014-03-01

Three-dimensional antidot arrays (3DAAs) have attracted considerable attention due to potential applications in sensors, energy storage and transducers. Magnetic 3DAAs also provide an ideal system for studying the effect of dimensionality and morphology on magnetic properties. We report study of dipolar interactions in Ni 3DAAs using the first-order reversal curve (FORC) method. Ordered Ni 3DAAs were fabricated by electrochemical deposition into colloidal crystal templates of self-assembled polystyrene spheres. The samples have the same pore size of about 500 nm but different thicknesses, ranging from 0.3 μm to 1.2 μm, confirmed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). FORCs of the samples with thicknesses of 0.3 μm, 0.8 μm, and 1.2 μm were measured by a vibrating sample magnetometer. The FORC diagram analysis reveals a demagnetizing magnetic dipolar interaction, and a decrease in the interaction strength with the increasing sample thickness, evidenced by a decrease in the spread of the irreversible peak in the bias distribution, as well as a decrease in the tilting of the FORC distribution from the local coercivity axis. Work at BMC and UCD is supported by NSF DMR-1207085 and DMR-1008791, respectively.

Pollen–pistil interactions and self-incompatibility in the Asteraceae: new insights from studies of Senecio squalidus (Oxford ragwort)

PubMed Central

Allen, Alexandra M.; Thorogood, Christopher J.; Hegarty, Matthew J.; Lexer, Christian; Hiscock, Simon J.

2011-01-01

Background Pollen–pistil interactions are an essential prelude to fertilization in angiosperms and determine compatibility/incompatibility. Pollen–pistil interactions have been studied at a molecular and cellular level in relatively few families. Self-incompatibility (SI) is the best understood pollen–pistil interaction at a molecular level where three different molecular mechanisms have been identified in just five families. Here we review studies of pollen–pistil interactions and SI in the Asteraceae, an important family that has been relatively understudied in these areas of reproductive biology. Scope We begin by describing the historical literature which first identified sporophytic SI (SSI) in species of Asteraceae, the SI system later identified and characterized at a molecular level in the Brassicaceae. Early structural and cytological studies in these two families suggested that pollen–pistil interactions and SSI were similar, if not the same. Recent cellular and molecular studies in Senecio squalidus (Oxford ragwort) have challenged this belief by revealing that despite sharing the same genetic system of SSI, the Brassicaceae and Asteraceae molecular mechanisms are different. Key cellular differences have also been highlighted in pollen–stigma interactions, which may arise as a consequence of the Asteraceae possessing a ‘semi-dry’ stigma, rather than the ‘dry’ stigma typical of the Brassicaceae. The review concludes with a summary of recent transcriptomic analyses aimed at identifying proteins regulating pollen–pistil interactions and SI in S. squalidus, and by implication the Asteraceae. The Senecio pistil transcriptome contains many novel pistil-specific genes, but also pistil-specific genes previously shown to play a role in pollen–pistil interactions in other species. Conclusions Studies in S. squalidus have shown that stigma structure and the molecular mechanism of SSI in the Asteraceae and Brassicaceae are different. The

5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells

PubMed Central

Malashchuk, Igor; Lajoie, Brian R.; Mardaryev, Andrei N.; Gdula, Michal R.; Sharov, Andrey A.; Kohwi-Shigematsu, Terumi; Fessing, Michael Y.

2017-01-01

Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and

A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

PubMed Central

Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

2015-01-01

Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

Visualizing Dispersion Interactions

ERIC Educational Resources Information Center

Gottschalk, Elinor; Venkataraman, Bhawani

2014-01-01

An animation and accompanying activity has been developed to help students visualize how dispersion interactions arise. The animation uses the gecko's ability to walk on vertical surfaces to illustrate how dispersion interactions play a role in macroscale outcomes. Assessment of student learning reveals that students were able to develop…

Expression and Protein Interaction Analyses Reveal Combinatorial Interactions of LBD Transcription Factors During Arabidopsis Pollen Development.

PubMed

Kim, Mirim; Kim, Min-Jung; Pandey, Shashank; Kim, Jungmook

2016-11-01

LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor gene family members play key roles in diverse aspects of plant development. LBD10 and LBD27 have been shown to be essential for pollen development in Arabidopsis thaliana. From the previous RNA sequencing (RNA-Seq) data set of Arabidopsis pollen, we identified the mRNAs of LBD22, LBD25 and LBD36 in addition to LBD10 and LBD27 in Arabidopsis pollen. Here we conducted expression and cellular analysis using GFP:GUS (green fluorescent protein:β-glucuronidase) reporter gene and subcellular localization assays using LBD:GFP fusion proteins expressed under the control of their own promoters in Arabidopsis. We found that these LBD proteins display spatially and temporally distinct and overlapping expression patterns during pollen development. Bimolecular fluorescence complementation and GST (glutathione S-transferase) pull-down assays demonstrated that protein-protein interactions occur among the LBDs exhibiting overlapping expression during pollen development. We further showed that LBD10, LBD22, LBD25, LBD27 and LBD36 interact with each other to form heterodimers, which are localized to the nucleus in Arabidopsis protoplasts. Taken together, these results suggest that combinatorial interactions among LBD proteins may be important for their function in pollen development in Arabidopsis. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Structure of the thermophilic l-Arabinose isomerase from Geobacillus kaustophilus reveals metal-mediated intersubunit interactions for activity and thermostability.

PubMed

Choi, Jin Myung; Lee, Yong-Jik; Cao, Thinh-Phat; Shin, Sun-Mi; Park, Min-Kyu; Lee, Han-Seung; di Luccio, Eric; Kim, Seong-Bo; Lee, Sang-Jae; Lee, Sang Jun; Lee, Sung Haeng; Lee, Dong-Woo

2016-04-15

Thermophilic l-arabinose isomerase (AI), which catalyzes the interconversion of l-arabinose and l-ribulose, can be used to produce d-tagatose, a sugar substitute, from d-galactose. Unlike mesophilic AIs, thermophilic AIs are highly dependent on divalent metal ions for their catalytic activity and thermostability at elevated temperatures. However, the molecular basis underlying the substrate preferences and metal requirements of multimeric AIs remains unclear. Here we report the first crystal structure of the apo and holo forms of thermophilic Geobacillus kaustophilus AI (GKAI) in hexamer form. The structures, including those of GKAI in complex with l-arabitol, and biochemical analyses revealed not only how the substrate-binding site of GKAI is formed through displacement of residues at the intersubunit interface when it is bound to Mn(2+), but also revealed the water-mediated H-bonding networks that contribute to the structural integrity of GKAI during catalysis. These observations suggest metal-mediated isomerization reactions brought about by intersubunit interactions at elevated temperatures are responsible for the distinct active site features that promote the substrate specificity and thermostability of thermophilic AIs. Copyright © 2016 Elsevier Inc. All rights reserved.

Monte Carlo studies on neutron interactions in radiobiological experiments

PubMed Central

Shahmohammadi Beni, Mehrdad; Hau, Tak Cheong; Krstic, D.; Nikezic, D.

2017-01-01

Monte Carlo method was used to study the characteristics of neutron interactions with cells underneath a water medium layer with varying thickness. The following results were obtained. (1) The fractions of neutron interaction with 1H, 12C, 14N and 16O nuclei in the cell layer were studied. The fraction with 1H increased with increasing medium thickness, while decreased for 12C, 14N and 16O nuclei. The bulges in the interaction fractions with 12C, 14N and 16O nuclei were explained by the resonance spikes in the interaction cross-section data. The interaction fraction decreased in the order: 1H > 16O > 12C > 14N. (2) In general, as the medium thickness increased, the number of “interacting neutrons” which exited the medium and then further interacted with the cell layer increased. (3) The area under the angular distributions for “interacting neutrons” decreased with increasing incident neutron energy. Such results would be useful for deciphering the reasons behind discrepancies among existing results in the literature. PMID:28704557

Interacting lattice systems with quantum dissipation: A quantum Monte Carlo study

NASA Astrophysics Data System (ADS)

Yan, Zheng; Pollet, Lode; Lou, Jie; Wang, Xiaoqun; Chen, Yan; Cai, Zi

2018-01-01

Quantum dissipation arises when a large system can be split in a quantum system and an environment to which the energy of the former flows. Understanding the effect of dissipation on quantum many-body systems is of particular importance due to its potential relationship with quantum information. We propose a conceptually simple approach to introduce dissipation into interacting quantum systems in a thermodynamical context, in which every site of a one-dimensional (1D) lattice is coupled off-diagonally to its own bath. The interplay between quantum dissipation and interactions gives rise to counterintuitive interpretations such as a compressible zero-temperature state with spontaneous discrete symmetry breaking and a thermal phase transition in a 1D dissipative quantum many-body system as revealed by quantum Monte Carlo path-integral simulations.

Amyloid precursor protein and Presenilin 1 interaction studied by FRET in human H4 cells.

PubMed

Nizzari, Mario; Venezia, Valentina; Bianchini, Paolo; Caorsi, Valentina; Diaspro, Alberto; Repetto, Emanuela; Thellung, Stefano; Corsaro, Alessandro; Carlo, Pia; Schettini, Gennaro; Florio, Tullio; Russo, Claudio

2007-01-01

The mayor pathologic hallmarks of Alzheimer's disease (AD) are senile plaque and neurofibrillary tangles. Senile plaque are primarily made up of deposits of amyloid-beta protein, a proteolytic product derived from the amyloid precursor protein (APP). APP is a transmembrane protein detected into the endoplasmic reticulum, in the Golgi apparatus, at the cell surface, recycled by endocytosis to endosomes, whose physiological function is unclear. Presenilins (PS), are a component of gamma-secretase complex that cleave alpha-CTFs (carboxy-terminal fragment), or beta-CTFs, leaving 40 or 42 amino acids amyloid-beta peptides and 58 or 56 amino acids intracellular domains (AICD). Where the amyloid-beta peptides is generated is not clear. The study of APP-PS interaction in specific cell compartments provides a good opportunity to light upon the molecular mechanisms regulating the activity of the "gamma-secretase complex," and where beta-amyloid is generated. In our study we used a biophysical assay of protein proximity: fluorescence resonance energy transfer (FRET), that can provide information about molecular interactions when two proteins are in the close proximity (<10 nm), to examine the subcellular localization and interaction between APP and PS1 in human neuroglioma cells (H4). Confocal microscopic analysis reveals extensive colocalization in different cells' compartment, and centrosomal or microtubule organizing center (MTOC) localization of APP and PS1, but not necessarily a close molecular interaction. We used FRET to determine if APP and PS1 interact at the cell centrosome. FRET data suggest a close interaction between APP and PS1 in subcellular compartments and at the centrosome of H4 cells. Using this approach we show that APP and PS1 are closely associated in the centrosomes of the H4 cell.

Local Environment and Interactions of Liquid and Solid Interfaces Revealed by Spectral Line Shape of Surface Selective Nonlinear Vibrational Probe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Shun-Li; Fu, Li; Chase, Zizwe A.

Vibrational spectral lineshape contains important detailed information of molecular vibration and reports its specific interactions and couplings to its local environment. In this work, recently developed sub-1 cm-1 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) was used to measure the -C≡N stretch vibration in the 4-n-octyl-4’-cyanobiphenyl (8CB) Langmuir or Langmuir-Blodgett (LB) monolayer as a unique vibrational probe, and the spectral lineshape analysis revealed the local environment and interactions at the air/water, air/glass, air/calcium fluoride and air/-quartz interfaces for the first time. The 8CB Langmuir or LB film is uniform and the vibrational spectral lineshape of its -C≡N group hasmore » been well characterized, making it a good choice as the surface vibrational probe. Lineshape analysis of the 8CB -C≡N stretch SFG vibrational spectra suggests the coherent vibrational dynamics and the structural and dynamic inhomogeneity of the -C≡N group at each interface are uniquely different. In addition, it is also found that there are significantly different roles for water molecules in the LB films on different substrate surfaces. These results demonstrated the novel capabilities of the surface nonlinear spectroscopy in characterization and in understanding the specific structures and chemical interactions at the liquid and solid interfaces in general.« less

Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions

PubMed Central

Turner, Leslie M; Harr, Bettina

2014-01-01

Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone. DOI: http://dx.doi.org/10.7554/eLife.02504.001 PMID:25487987

Comparative 4f-4f absorption spectral study for the interactions of Nd(III) with some amino acids: Preliminary thermodynamics and kinetic studies of interaction of Nd(III):glycine with Ca(II)

NASA Astrophysics Data System (ADS)

Moaienla, T.; Bendangsenla, N.; David Singh, Th.; Sumitra, Ch.; Rajmuhon Singh, N.; Indira Devi, M.

2012-02-01

Spectral analysis of Nd(III) complexes with some amino acids viz.; glycine, L-alanine, L-phenylalanine and L-aspartic acid in the presence and absence of Ca 2+ was carried out in some organic solvents; CH 3OH, CH 3CN, DMF and dioxane using comparative absorption spectra of 4f-4f transitions. The study was carried out by evaluating various energy interaction parameters like Slator-Condon ( Fk), Lande factor ( ξ4f), nephelauxetic ratio ( β), bonding parameter ( b1/2), percent-covalency ( δ) by applying partial and multiple regression analysis. The values of oscillator strength ( Pobs) and Judd-Ofelt electric dipole intensity parameter Tλ ( λ = 2, 4, 6) for different 4f-4f transitions have been calculated. On analysis of the variation of the various energy interaction parameters as well as the changes in the oscillator strength ( Pobs) and Tλ values, reveal the mode of binding with the different ligands. Kinetic studies for the complexation of Nd(III):glycine:Ca(II) have also been discussed at different temperatures in DMF medium and from it the values of activation energy ( Ea) and thermodynamic parameters like Δ H°, Δ S° and Δ G° for the complexation are evaluated.

Levels of Interaction Provided by Online Distance Education Models

ERIC Educational Resources Information Center

Alhih, Mohammed; Ossiannilsson, Ebba; Berigel, Muhammet

2017-01-01

Interaction plays a significant role to foster usability and quality in online education. It is one of the quality standard to reveal the evidence of practice in online distance education models. This research study aims to evaluate levels of interaction in the practices of distance education centres. It is aimed to provide online distance…

A linguistic study of patient-centered interviewing: emergent interactional effects.

PubMed

Hesson, Ashley M; Sarinopoulos, Issidoros; Frankel, Richard M; Smith, Robert C

2012-09-01

To evaluate interactional effects of patient-centered interviewing (PCI) compared to isolated clinician-centered interviewing (CCI). We conducted a pilot study comparing PCI (N=4) to CCI (N=4) for simulated new-patient visits. We rated interviews independently and measured patient satisfaction with the interaction via a validated questionnaire. We conducted interactional sociolinguistic analysis on the interviews and compared across three levels of analysis: turn, topic, and interaction. We found significant differences between PCI and CCI in physician responses to patients' psychosocial cues and concerns. The number and type of physician questions also differed significantly across PCI and CCI sets. Qualitatively, we noted several indicators of physician-patient attunement in the PCI interviews that were not present in the CCI interviews. They spanned diverse aspects of physician and patient speech, suggesting interactional accommodation on the part of both participants. This small pilot study highlights a variety of interactional variables that may underlie the effects associated with patient-centered interviewing (e.g., positive relationships, health outcomes). Question form, phonological accommodation processes, and use of stylistic markers are relatively unexplored in controlled studies of physician-patient interaction. This study characterizes several interactional variables for larger scale studies and contributes to models of patient-centeredness in practice. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Structural study of surfactant-dependent interaction with protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehan, Sumit; Aswal, Vinod K., E-mail: vkaswal@barc.gov.in; Kohlbrecher, Joachim

2015-06-24

Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

Structural study of surfactant-dependent interaction with protein

NASA Astrophysics Data System (ADS)

Mehan, Sumit; Aswal, Vinod K.; Kohlbrecher, Joachim

2015-06-01

Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

APOBEC3G Interacts with ssDNA by Two Modes: AFM Studies

NASA Astrophysics Data System (ADS)

Shlyakhtenko, Luda S.; Dutta, Samrat; Banga, Jaspreet; Li, Ming; Harris, Reuben S.; Lyubchenko, Yuri L.

2015-10-01

APOBEC3G (A3G) protein has antiviral activity against HIV and other pathogenic retroviruses. A3G has two domains: a catalytic C-terminal domain (CTD) that deaminates cytidine, and a N-terminal domain (NTD) that binds to ssDNA. Although abundant information exists about the biological activities of A3G protein, the interplay between sequence specific deaminase activity and A3G binding to ssDNA remains controversial. We used the topographic imaging and force spectroscopy modalities of Atomic Force Spectroscopy (AFM) to characterize the interaction of A3G protein with deaminase specific and nonspecific ssDNA substrates. AFM imaging demonstrated that A3G has elevated affinity for deaminase specific ssDNA than for nonspecific ssDNA. AFM force spectroscopy revealed two distinct binding modes by which A3G interacts with ssDNA. One mode requires sequence specificity, as demonstrated by stronger and more stable complexes with deaminase specific ssDNA than with nonspecific ssDNA. Overall these observations enforce prior studies suggesting that both domains of A3G contribute to the sequence specific binding of ssDNA.

APOBEC3G Interacts with ssDNA by Two Modes: AFM Studies.

PubMed

Shlyakhtenko, Luda S; Dutta, Samrat; Banga, Jaspreet; Li, Ming; Harris, Reuben S; Lyubchenko, Yuri L

2015-10-27

APOBEC3G (A3G) protein has antiviral activity against HIV and other pathogenic retroviruses. A3G has two domains: a catalytic C-terminal domain (CTD) that deaminates cytidine, and a N-terminal domain (NTD) that binds to ssDNA. Although abundant information exists about the biological activities of A3G protein, the interplay between sequence specific deaminase activity and A3G binding to ssDNA remains controversial. We used the topographic imaging and force spectroscopy modalities of Atomic Force Spectroscopy (AFM) to characterize the interaction of A3G protein with deaminase specific and nonspecific ssDNA substrates. AFM imaging demonstrated that A3G has elevated affinity for deaminase specific ssDNA than for nonspecific ssDNA. AFM force spectroscopy revealed two distinct binding modes by which A3G interacts with ssDNA. One mode requires sequence specificity, as demonstrated by stronger and more stable complexes with deaminase specific ssDNA than with nonspecific ssDNA. Overall these observations enforce prior studies suggesting that both domains of A3G contribute to the sequence specific binding of ssDNA.

APOBEC3G Interacts with ssDNA by Two Modes: AFM Studies

PubMed Central

Shlyakhtenko, Luda S.; Dutta, Samrat; Banga, Jaspreet; Li, Ming; Harris, Reuben S.; Lyubchenko, Yuri L.

2015-01-01

APOBEC3G (A3G) protein has antiviral activity against HIV and other pathogenic retroviruses. A3G has two domains: a catalytic C-terminal domain (CTD) that deaminates cytidine, and a N-terminal domain (NTD) that binds to ssDNA. Although abundant information exists about the biological activities of A3G protein, the interplay between sequence specific deaminase activity and A3G binding to ssDNA remains controversial. We used the topographic imaging and force spectroscopy modalities of Atomic Force Spectroscopy (AFM) to characterize the interaction of A3G protein with deaminase specific and nonspecific ssDNA substrates. AFM imaging demonstrated that A3G has elevated affinity for deaminase specific ssDNA than for nonspecific ssDNA. AFM force spectroscopy revealed two distinct binding modes by which A3G interacts with ssDNA. One mode requires sequence specificity, as demonstrated by stronger and more stable complexes with deaminase specific ssDNA than with nonspecific ssDNA. Overall these observations enforce prior studies suggesting that both domains of A3G contribute to the sequence specific binding of ssDNA. PMID:26503602

Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies.

PubMed

Tripathi, Alok Shiomurti; Timiri, Ajay Kumar; Mazumder, Papiya Mitra; Chandewar, Anil

2015-10-01

The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P < 0.001) in rat plasma when co-administered with GLIM on the 70th day of the protocol. Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies.

Interactions of amelogenin with phospholipids

DOE PAGES

Bekshe Lokappa, Sowmya; Chandrababu, Karthik Balakrishna; Dutta, Kaushik; ...

2014-11-22

Amelogenin protein has the potential to interact with other enamel matrix proteins, mineral, and cell surfaces. In this paper, we investigated the interactions of recombinant amelogenin rP172 with small unilamellar vesicles as model membranes, toward the goal of understanding the mechanisms of amelogenin–cell interactions during amelogenesis. Dynamic light scattering (DLS), fluorescence spectroscopy, circular dichroism (CD), and nuclear magnetic resonance (NMR) were used. In the presence of phospholipid vesicles, a blue shift in the Trp fluorescence emission maxima of rP172 was observed (~334 nm) and the Trp residues of rP172 were inaccessible to the aqueous quencher acrylamide. DLS studies indicated complexationmore » of rP172 and phospholipids, although the possibility of fusion of phospholipids following amelogenin addition cannot be ruled out. NMR and CD studies revealed a disorder–order transition of rP172 in a model membrane environment. Strong fluorescence resonance energy transfer from Trp in rP172 to DNS-bound-phospholipid was observed, and fluorescence polarization studies indicated that rP172 interacted with the hydrophobic core region of model membranes. Finally, our data suggest that amelogenin has ability to interact with phospholipids and that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities.« less

Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds

PubMed Central

Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

2014-01-01

In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99–100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. PMID:24444052

[Differential gene expression in incompatible interaction between Lilium regale Wilson and Fusarium oxysporum f. sp. lilii revealed by combined SSH and microarray analysis].

PubMed

Rao, J; Liu, D; Zhang, N; He, H; Ge, F; Chen, C

2014-01-01

Fusarium wilt, caused by a soilborne pathogen Fusarium oxysporum f. sp. lilii, is the major disease of lily (Lilium L.). In order to isolate the genes differentially expressed in a resistant reaction to F. oxysporum in L. regale Wilson, a cDNA library was constructed with L. regale root during F. oxysporum infection using the suppression subtractive hybridization (SSH), and a total of 585 unique expressed sequence tags (ESTs) were obtained. Furthermore, the gene expression profiles in the incompatible interaction between L. regale and F. oxysporum were revealed by oligonucleotide microarray analysis of 585 unique ESTs comparison to the compatible interaction between a susceptible Lilium Oriental Hybrid 'Siberia' and F. oxysporum. The result of expression profile analysis indicated that the genes encoding pathogenesis-related proteins (PRs), antioxidative stress enzymes, secondary metabolism enzymes, transcription factors, signal transduction proteins as well as a large number of unknown genes were involved in early defense response of L. regale to F. oxysporum infection. Moreover, the following quantitative reverse transcription PCR (QRT-PCR) analysis confirmed reliability of the oligonucleotide microarray data. In the present study, isolation of differentially expressed genes in L. regale during response to F. oxysporum helped to uncover the molecular mechanism associated with the resistance of L. regale against F. oxysporum.

Cosmic Interactions

NASA Astrophysics Data System (ADS)

2008-01-01

An image based on data taken with ESO's Very Large Telescope reveals a triplet of galaxies intertwined in a cosmic dance. ESO PR Photo 02/08 ESO PR Photo 02/08 NGC 7173, 7174, and 7176 The three galaxies, catalogued as NGC 7173 (top), 7174 (bottom right) and 7176 (bottom left), are located 106 million light-years away towards the constellation of Piscis Austrinus (the 'Southern Fish'). NGC 7173 and 7176 are elliptical galaxies, while NGC 7174 is a spiral galaxy with quite disturbed dust lanes and a long, twisted tail. This seems to indicate that the two bottom galaxies - whose combined shape bears some resemblance to that of a sleeping baby - are currently interacting, with NGC 7176 providing fresh material to NGC 7174. Matter present in great quantity around the triplet's members also points to the fact that NGC 7176 and NGC 7173 have interacted in the past. Astronomers have suggested that the three galaxies will finally merge into a giant 'island universe', tens to hundreds of times as massive as our own Milky Way. ESO PR Photo 02/08 ESO PR Photo 02b/08 NGC 7173, 7174, and 7176 The triplet is part of a so-called 'Compact Group', as compiled by Canadian astronomer Paul Hickson in the early 1980s. The group, which is the 90th entry in the catalogue and is therefore known as HCG 90, actually contains four major members. One of them - NGC 7192 - lies above the trio, outside of this image, and is another peculiar spiral galaxy. Compact groups are small, relatively isolated, systems of typically four to ten galaxies in close proximity to one another. Another striking example is Robert's Quartet. Compact groups are excellent laboratories for the study of galaxy interactions and their effects, in particular the formation of stars. As the striking image reveals, there are many other galaxies in the field. Some are distant ones, while others seem to be part of the family. Studies made with other telescopes have indeed revealed that the HCG 90 group contains 16 members

Hydrophilic interaction chromatography based solid-phase extraction and MALDI TOF mass spectrometry for revealing the influence of Pseudomonas fluorescens on phospholipids in salmon fillet.

PubMed

Shen, Qing; Yang, Qi; Cheung, Hon-Yeung

2015-02-01

Salmon is a popular food but it is easily susceptible to spoilage by contamination with microorganisms. In this study, a method using hydrophilic interaction chromatography (HILIC)-based solid-phase extraction (SPE) and matrix-assisted laser desorption and ionization time-of-flight/time-of-flight mass spectrometry was developed and applied to reveal the effect of Pseudomonas fluorescens on salmon fillet during the shelf-life period by measuring the changes in the levels of phosphatidylcholine and phosphatidylethanolamine. Fresh samples were inoculated with P. fluorescens (10(6) cfu g(-1)) for 30 s, and lipids were extracted at 0, 24, 48, and 72 h. A homemade SPE cartridge packed with HILIC sorbent (silica derivatized with 1,2-dihydroxypropane) was used for matrix cleanup prior to analysis by mass spectrometry. In total, 30 phospholipids and 16 lysophospholipids were detected and elucidated. The results revealed that the content of phospholipids decreased significantly, whereas that of lysophospholipids increased initially, followed by a gradual reduction as the cold storage time increased. The contamination by P. fluorescens negatively affected the quality of fresh salmon without obvious physical changes, but it posed a potential threat to human health. This study suggests that the well-established method could be used for detecting phospholipids in salmon fillet and perhaps other foods as well.

Valerian: no evidence for clinically relevant interactions.

PubMed

Kelber, Olaf; Nieber, Karen; Kraft, Karin

2014-01-01

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

Valerian: No Evidence for Clinically Relevant Interactions

PubMed Central

Nieber, Karen; Kraft, Karin

2014-01-01

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients. PMID:25093031

Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

PubMed

Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

2014-10-01

It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

Light and noise pollution interact to disrupt interspecific interactions.

PubMed

McMahon, Taegan A; Rohr, Jason R; Bernal, Ximena E

2017-05-01

Studies on the consequences of urbanization often examine the effects of light, noise, and heat pollution independently on isolated species providing a limited understanding of how these combined stressors affect species interactions. Here, we investigate how these factors interact to affect parasitic frog-biting midges (Corethrella spp.) and their túngara frog (Engystomops pustulosus) hosts. A survey of túngara frog calling sites revealed that frog abundance was not significantly correlated with urbanization, light, noise, or temperature. In contrast, frog-biting midges were sensitive to light pollution and noise pollution. Increased light intensity significantly reduced midge abundance at low noise levels. At high noise intensity, there were no midges regardless of light level. Two field experiments controlling light and noise levels to examine attraction of the midges to their host and their feeding behavior confirmed the causality of these field patterns. These findings demonstrate that both light and noise pollution disrupt this host-parasite interaction and highlight the importance of considering interactions among species and types of pollutants to accurately assess the impacts of urbanization on ecological communities. © 2017 by the Ecological Society of America.

Inter-hemispheric interaction facilitates face processing.

PubMed

Compton, Rebecca J

2002-01-01

Many recent studies have revealed that interaction between the left and right cerebral hemispheres can aid in task performance, but these studies have tended to examine perception of simple stimuli such as letters, digits or simple shapes, which may have limited naturalistic validity. The present study extends these prior findings to a more naturalistic face perception task. Matching tasks required subjects to indicate when a target face matched one of two probe faces. Matches could be either across-field, requiring inter-hemispheric interaction, or within-field, not requiring inter-hemispheric interaction. Subjects indicated when faces matched in emotional expression (Experiment 1; n=32) or in character identity (Experiment 2; n=32). In both experiments, across-field performance was significantly better than within-field performance, supporting the primary hypothesis. Further, this advantage was greater for the more difficult character identity task. Results offer qualified support for the hypothesis that inter-hemispheric interaction is especially advantageous as task demands increase.

Nano Cu interaction with single amino acid tyrosine derived self-assemblies; study through XRD, AFM, confocal Raman microscopy, SERS and DFT methods

NASA Astrophysics Data System (ADS)

Govindhan, Raman; Karthikeyan, Balakrishnan

2017-12-01

3,5-Bis(trifluoromethyl)benzylamine derivatives of single amino acid tyrosine produced self-assembled nanotubes (BTTNTs) as simple Phe-Phe. It has been observed that tyrosine derivative gives exclusively micro and nano tubes irrespective of the concentration of the precursor monomer. However, the introduced xenobiotic trifluoromethyl group (TFM) present in key backbone positionsof the self assembly gives the specific therapeutic function has been highlighted. Herein this work study of such self assembled nanotubes were studied through experimental and theoretical methods. The interaction of nanocopper cluster with the nanotubes (Cu@BTTNTs) were extensively studied by various methods like XRD, AFM, confocal Raman microscopy, SERS and theoretical methods like Mulliken's atomic charge analysis. SERS reveals that the interactions of Cu cluster with NH2, OH, NH and phenyl ring π-electrons system of BTTNTs. DFT studies gave the total dipole moment values of Cu@BTTNTs and explained the nature of interaction.

Interaction of Human Hemoglobin with Methotrexate

NASA Astrophysics Data System (ADS)

Zaharia, M.; Gradinaru, R.

2015-05-01

This study focuses on the interaction between methotrexate and human hemoglobin using steady-state ultraviolet-visible and fluorescence quenching methods. Fluorescence quenching was found to be valuable in assessing drug binding to hemoglobin. The quenching of methotrexate is slightly smaller than the quenching observed with related analogs (dihydrofolate and tetrahydrofolate). The quenching studies were performed at four different temperatures and various pH values. The number of binding sites for tryptophan is ~1. Parameter-dependent assays revealed that electrostatic forces play an essential role in the methotrexate-hemoglobin interaction. Furthermore, the complex was easily eluted using gel filtration chromatography.

Who is the competent physics student? A study of students' positions and social interaction in small-group discussions

NASA Astrophysics Data System (ADS)

Due, Karin

2014-06-01

This article describes a study which explored the social interaction and the reproduction and challenge of gendered discourses in small group discussions in physics. Data for the study consisted of video recordings of eight upper secondary school groups solving physics problems and 15 audiotaped individual interviews with participating students. The analysis was based on gender theory viewing gender both as a process and a discourse. Specifically discursive psychology analysis was used to examine how students position themselves and their peers within discourses of physics and gender. The results of the study reveal how images of physics and of "skilled physics student" were constructed in the context of the interviews. These discourses were reconstructed in the students' discussions and their social interactions within groups. Traditional gendered positions were reconstructed, for example with boys positioned as more competent in physics than girls. These positions were however also resisted and challenged.

Water's Interfacial Hydrogen Bonding Structure Reveals the Effective Strength of Surface-Water Interactions.

PubMed

Shin, Sucheol; Willard, Adam P

2018-06-05

We combine all-atom molecular dynamics simulations with a mean field model of interfacial hydrogen bonding to analyze the effect of surface-water interactions on the structural and energetic properties of the liquid water interface. We show that the molecular structure of water at a weakly interacting ( i.e., hydrophobic) surface is resistant to change unless the strength of surface-water interactions are above a certain threshold. We find that below this threshold water's interfacial structure is homogeneous and insensitive to the details of the disordered surface, however, above this threshold water's interfacial structure is heterogeneous. Despite this heterogeneity, we demonstrate that the equilibrium distribution of molecular orientations can be used to quantify the energetic component of the surface-water interactions that contribute specifically to modifying the interfacial hydrogen bonding network. We identify this specific energetic component as a new measure of hydrophilicity, which we refer to as the intrinsic hydropathy.

Abundance and Temperature Dependency of Protein-Protein Interaction Revealed by Interface Structure Analysis and Stability Evolution

NASA Astrophysics Data System (ADS)

He, Yi-Ming; Ma, Bin-Guang

2016-05-01

Protein complexes are major forms of protein-protein interactions and implement essential biological functions. The subunit interface in a protein complex is related to its thermostability. Though the roles of interface properties in thermal adaptation have been investigated for protein complexes, the relationship between the interface size and the expression level of the subunits remains unknown. In the present work, we studied this relationship and found a positive correlation in thermophiles rather than mesophiles. Moreover, we found that the protein interaction strength in complexes is not only temperature-dependent but also abundance-dependent. The underlying mechanism for the observed correlation was explored by simulating the evolution of protein interface stability, which highlights the avoidance of misinteraction. Our findings make more complete the picture of the mechanisms for protein complex thermal adaptation and provide new insights into the principles of protein-protein interactions.

Interactions of carbon dioxide with model organic molecules: A comparative theoretical study

NASA Astrophysics Data System (ADS)

Trung, Nguyen Tien; Nguyen, Minh Tho

2013-08-01

Interaction energies obtained using CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVTZ computations including both ZPE and BSSE corrections range from -2.9 to -14.2 kJ mol-1. While formic acid forms the most stable complex with CO2, formaldehyde yields the least stable complex. Lewis acid-base interaction such as C-N⋯C(CO2), Cdbnd O⋯C(CO2), which overcomes C-H⋯O blue-shifting hydrogen bond, plays a significant role in stabilizing most complexes. However, the strength of (HCOOH, CO2) is mainly determined by O-H⋯O red-shifting hydrogen bond. The C-H⋯O blue-shifting hydrogen bond is revealed upon complexation of CH3OH, HCHO, HCOOH, CH3COCH3 and HCOOCH3 with CO2. Remarkably, existence of weak hydrogen bonded C-H⋯O interaction is not found in the (CH3OCH3, CO2) and (CH3NH2, CO2) pairs.

Predicting Physical Interactions between Protein Complexes*

PubMed Central

Clancy, Trevor; Rødland, Einar Andreas; Nygard, Ståle; Hovig, Eivind

2013-01-01

Protein complexes enact most biochemical functions in the cell. Dynamic interactions between protein complexes are frequent in many cellular processes. As they are often of a transient nature, they may be difficult to detect using current genome-wide screens. Here, we describe a method to computationally predict physical interactions between protein complexes, applied to both humans and yeast. We integrated manually curated protein complexes and physical protein interaction networks, and we designed a statistical method to identify pairs of protein complexes where the number of protein interactions between a complex pair is due to an actual physical interaction between the complexes. An evaluation against manually curated physical complex-complex interactions in yeast revealed that 50% of these interactions could be predicted in this manner. A community network analysis of the highest scoring pairs revealed a biologically sensible organization of physical complex-complex interactions in the cell. Such analyses of proteomes may serve as a guide to the discovery of novel functional cellular relationships. PMID:23438732

Nematode-bacterium symbioses--cooperation and conflict revealed in the "omics" age.

PubMed

Murfin, Kristen E; Dillman, Adler R; Foster, Jeremy M; Bulgheresi, Silvia; Slatko, Barton E; Sternberg, Paul W; Goodrich-Blair, Heidi

2012-08-01

Nematodes are ubiquitous organisms that have a significant global impact on ecosystems, economies, agriculture, and human health. The applied importance of nematodes and the experimental tractability of many species have promoted their use as models in various research areas, including developmental biology, evolutionary biology, ecology, and animal-bacterium interactions. Nematodes are particularly well suited for the investigation of host associations with bacteria because all nematodes have interacted with bacteria during their evolutionary history and engage in a variety of association types. Interactions between nematodes and bacteria can be positive (mutualistic) or negative (pathogenic/parasitic) and may be transient or stably maintained (symbiotic). Furthermore, since many mechanistic aspects of nematode-bacterium interactions are conserved, their study can provide broader insights into other types of associations, including those relevant to human diseases. Recently, genome-scale studies have been applied to diverse nematode-bacterial interactions and have helped reveal mechanisms of communication and exchange between the associated partners. In addition to providing specific information about the system under investigation, these studies also have helped inform our understanding of genome evolution, mutualism, and innate immunity. In this review we discuss the importance and diversity of nematodes, "omics"' studies in nematode-bacterial systems, and the wider implications of the findings.

Nematode-Bacterium Symbioses - Cooperation and Conflict Revealed in the 'Omics' Age

PubMed Central

Murfin, Kristen E.; Dillman, Adler R.; Foster, Jeremy M.; Bulgheresi, Silvia; Slatko, Barton E.; Sternberg, Paul W.; Goodrich-Blair, Heidi

2012-01-01

Nematodes are ubiquitous organisms that have a significant global impact on ecosystems, economies, agriculture, and human health. The applied importance of nematodes and the experimental tractability of many species have promoted their use as models in various research areas, including developmental biology, evolutionary biology, ecology, and animal-bacterium interactions. Nematodes are particularly well suited for investigating host associations with bacteria because all nematodes have interacted with bacteria during their evolutionary history and engage in a diversity of association types. Interactions between nematodes and bacteria can be positive (mutualistic) or negative (pathogenic/parasitic) and may be transient or stably maintained (symbiotic). Furthermore, since many mechanistic aspects of nematode-bacterium interactions are conserved their study can provide broader insights into other types of associations, including those relevant to human diseases. Recently, genome-scale studies have been applied to diverse nematode-bacterial interactions, and have helped reveal mechanisms of communication and exchange between the associated partners. In addition to providing specific information about the system under investigation, these studies also have helped inform our understanding of genome evolution, mutualism, and innate immunity. In this review we will discuss the importance and diversity of nematodes, 'omics' studies in nematode-bacterial systems, and the wider implications of the findings. PMID:22983035

[The interaction between people with Down syndrome and their siblings: an exploratory study].

PubMed

Batista, Bruna Rafaela de; Duarte, Márcia; Cia, Fabiana

2016-10-01

The presence of a disabled person causes transformations in the family that demand a redefinition of the role of each member. Siblings, like all other members, experience frustration, acceptance, guilt and adaptation. In this respect, an attempt was made to; (a) analyze the interaction between a sibling with standard development and a sibling with Down syndrome; (b) identify what information and reaction the siblings with standard development have regarding the diagnosis of Down syndrome; (c) verify whether or not there were changes in the family context and also changes in their own lives after the birth of the sibling with Down syndrome. The survey was conducted through interviews, the participants being seven children with standard development having siblings with Down syndrome. The study showed that the siblings, as well as the other family members, experience processes of acceptance, confusion and other complex emotions related to the disability, albeit they are not as marked as those experienced by their parents. A fact revealed in this study is the importance of support groups for siblings, seeking to handle issues such as prejudice and adverse feelings towards disability. The siblings with standard development must have correct information, as well as support, in order to foster healthy interaction between siblings.

Size-dependent physicochemical and mechanical interactions in battery paste anodes of Si-microwires revealed by Fast-Fourier-Transform Impedance Spectroscopy

NASA Astrophysics Data System (ADS)

Hansen, Sandra; Quiroga-González, Enrique; Carstensen, Jürgen; Adelung, Rainer; Föll, Helmut

2017-05-01

Perfectly aligned silicon microwire arrays show exceptionally high cycling stability with record setting (high) areal capacities of 4.25 mAh cm-2. Those wires have a special, modified length and thickness in order to perform this good. Geometry and sizes are the most important parameters of an anode to obtain batteries with high cycling stability without irreversible losses. The wires are prepared with a unique etching fabrication method, which allows to fabricate wires of very precise sizes. In order to investigate how good randomly oriented silicon wires perform in contrast to the perfect order of the array, the wires are embedded in a paste. This study reveals the fundamental correlation between geometry, mechanics and charge transfer kinetics of silicon electrodes. Using a suitable RC equivalent circuit allows to evaluate data from cyclic voltammetry and simultaneous FFT-Impedance Spectroscopy (FFT-IS), yielding in time-resolved resistances, time constants, and their direct correlation to the phase transformations. The change of the resistances during lithiation and delithiation correlates to kinetics and charge transfer mechanisms. This study demonstrates how the mechanical and physiochemical interactions at the silicon/paste interface inside the paste electrodes lead to void formation around silicon and with it to material loss and capacity fading.

The pragmatics of therapeutic interaction: an empirical study.

PubMed

Lepper, Georgia

2009-10-01

The research reported in this article aims to demonstrate a method for the systematic study of the therapist/patient interaction in psychoanalytic psychotherapy, drawing upon the tradition and methods of 'pragmatics'--the study of language in interaction. A brief introduction to the discipline of pragmatics demonstrates its relevance to the contemporary focus of clinical theory on the here-and-now dynamics of the relationship between analyst and patient. This is followed by a detailed study of five segments from the transcript of a therapeutic dialogue, drawn from a brief psychoanalytic psychotherapy, in which therapist and patient negotiate the meaning of the patient's symptom: Is it psychosomatic? The research seeks to show how the therapeutic process can be observed and studied as an interactional achievement, grounded in general and well-studied procedures through which meaning is intersubjectively developed and shared. Implications of the analysis for clinical theory and practice, and further research, are discussed.

Direct visualization reveals kinetics of meiotic chromosome synapsis

DOE PAGES

Rog, Ofer; Dernburg, Abby  F.

2015-03-17

The synaptonemal complex (SC) is a conserved protein complex that stabilizes interactions along homologous chromosomes (homologs) during meiosis. The SC regulates genetic exchanges between homologs, thereby enabling reductional division and the production of haploid gametes. Here, we directly observe SC assembly (synapsis) by optimizing methods for long-term fluorescence recording in C. elegans. We report that synapsis initiates independently on each chromosome pair at or near pairing centers—specialized regions required for homolog associations. Once initiated, the SC extends rapidly and mostly irreversibly to chromosome ends. Quantitation of SC initiation frequencies and extension rates reveals that initiation is a rate-limiting step inmore » homolog interactions. Eliminating the dynein-driven chromosome movements that accompany synapsis severely retards SC extension, revealing a new role for these conserved motions. This work provides the first opportunity to directly observe and quantify key aspects of meiotic chromosome interactions and will enable future in vivo analysis of germline processes.« less

Flow motifs reveal limitations of the static framework to represent human interactions

NASA Astrophysics Data System (ADS)

Rocha, Luis E. C.; Blondel, Vincent D.

2013-04-01

Networks are commonly used to define underlying interaction structures where infections, information, or other quantities may spread. Although the standard approach has been to aggregate all links into a static structure, some studies have shown that the time order in which the links are established may alter the dynamics of spreading. In this paper, we study the impact of the time ordering in the limits of flow on various empirical temporal networks. By using a random walk dynamics, we estimate the flow on links and convert the original undirected network (temporal and static) into a directed flow network. We then introduce the concept of flow motifs and quantify the divergence in the representativity of motifs when using the temporal and static frameworks. We find that the regularity of contacts and persistence of vertices (common in email communication and face-to-face interactions) result on little differences in the limits of flow for both frameworks. On the other hand, in the case of communication within a dating site and of a sexual network, the flow between vertices changes significantly in the temporal framework such that the static approximation poorly represents the structure of contacts. We have also observed that cliques with 3 and 4 vertices containing only low-flow links are more represented than the same cliques with all high-flow links. The representativity of these low-flow cliques is higher in the temporal framework. Our results suggest that the flow between vertices connected in cliques depend on the topological context in which they are placed and in the time sequence in which the links are established. The structure of the clique alone does not completely characterize the potential of flow between the vertices.

Underlying mechanisms of cyclic peptide inhibitors interrupting the interaction of CK2α/CK2β: comparative molecular dynamics simulation studies.

PubMed

Zhou, Yue; Zhang, Na; Chen, Wenjuan; Zhao, Lijiao; Zhong, Rugang

2016-04-07

Protein-protein interactions (PPIs) are fundamental to all biological processes. Recently, the CK2β-derived cyclic peptide Pc has been demonstrated to efficiently antagonize the CK2α/CK2β interaction and strongly affect the phosphorylation of CK2β-dependent CK2 substrate specificity. The binding affinity of Pc to CK2α is destroyed to different extents by two single-point mutations of Tyr188 to Ala (Y188A) and Phe190 to Ala (F190A), which exert negative effects on the inhibitory activity (IC50) of Pc against the CK2α/CK2β interaction from 3.0 μM to 54.0 μM and ≫100 μM, respectively. However, the structural influences of Y188A and F190A mutations on the CK2α-Pc complex remain unclear. In this study, comparative molecular dynamics (MD) simulations, principal component analysis (PCA), domain cross-correlation map (DCCM) analysis and energy calculations were performed on wild type (WT), Y188A mutant, and F190A mutant systems. The results revealed that ordered communications between hydrophobic and polar interactions were essential for CK2α-Pc binding in the WT system. In addition to the loss of the hydrogen bond between Gln36 of CK2α and Gly189 of Pc in the two mutants, the improper recognition mechanisms occurred through different pathways. These pathways included the weakened hydrophobic interactions in the Y188A mutant as well as decreased polar and hydrophobic interactions in the F190A mutant. The energy analysis results qualitatively elucidated the instability of the two mutants and energetic contributions of the key residues. This study not only revealed the structural mechanisms for the decreased binding affinity of Y188A and F190A mutant CK2α-Pc complexes, but also provided valuable clues for the rational design of CK2α/CK2β subunit interaction inhibitors with high affinity and specificity.

Study on interaction of mangiferin to insulin and glucagon in ternary system

NASA Astrophysics Data System (ADS)

Lin, Hui; Chen, Rui; Liu, Xiaoyan; Sheng, Fenling; Zhang, Haixia

2010-05-01

The binding of mangiferin to insulin and glucagon was investigated in the presence and absence of another Peptide by optical spectroscopy. Fluorescence titration experiments revealed that mangiferin quenched the intrinsic fluorescence of insulin and glucagon by static quenching. The ratios of binding constants of glucagon-mangiferin to insulin-mangiferin at different temperatures were calculated in "pure" and ternary system, respectively. The results indicated that the Peptides were competitive with each other to act on mangiferin. Values of the thermodynamic parameters and the experiments of pH effect proved that the key interacting forces between mangiferin and the Peptides were hydrophobic interaction. In addition, UV-vis absorption, synchronous fluorescence and Fourier transform infrared measurements showed that the conformation of insulin and glucagon were changed after adding mangiferin.

Electrostatic interaction map reveals a new binding position for tropomyosin on F-actin.

PubMed

Rynkiewicz, Michael J; Schott, Veronika; Orzechowski, Marek; Lehman, William; Fischer, Stefan

2015-12-01

Azimuthal movement of tropomyosin around the F-actin thin filament is responsible for muscle activation and relaxation. Recently a model of αα-tropomyosin, derived from molecular-mechanics and electron microscopy of different contractile states, showed that tropomyosin is rather stiff and pre-bent to present one specific face to F-actin during azimuthal transitions. However, a new model based on cryo-EM of troponin- and myosin-free filaments proposes that the interacting-face of tropomyosin can differ significantly from that in the original model. Because resolution was insufficient to assign tropomyosin side-chains, the interacting-face could not be unambiguously determined. Here, we use structural analysis and energy landscapes to further examine the proposed models. The observed bend in seven crystal structures of tropomyosin is much closer in direction and extent to the original model than to the new model. Additionally, we computed the interaction map for repositioning tropomyosin over the F-actin surface, but now extended over a much larger surface than previously (using the original interacting-face). This map shows two energy minima-one corresponding to the "blocked-state" as in the original model, and the other related by a simple 24 Å translation of tropomyosin parallel to the F-actin axis. The tropomyosin-actin complex defined by the second minimum fits perfectly into the recent cryo-EM density, without requiring any change in the interacting-face. Together, these data suggest that movement of tropomyosin between regulatory states does not require interacting-face rotation. Further, they imply that thin filament assembly may involve an interplay between initially seeded tropomyosin molecules growing from distinct binding-site regions on actin.

[Role of food interaction pharmacokinetic studies in drug development. Food interaction studies of theophylline and nifedipine retard and buspirone tablets].

PubMed

Drabant, S; Klebovich, I; Gachályi, B; Renczes, G; Farsang, C

1998-09-01

Due to several mechanism, meals may modify the pharmacokinetics of drug products, thereby eliciting to clinically significant food interaction. Food interactions with the drug substance and with the drug formulation should be distinguished. Food interaction of different drug products containing the same active ingredient can be various depending on the pharmaceutical formulation technology. Particularly, in the case of modified release products, the food/formulation interaction can play an important role in the development of food interaction. Well known example, that bioavailability of theophylline can be influenced in different way (either increased, decreased or unchanged) by concomitant intake of food in the case of different sustained release products. The role and methods of food interaction studies in the different kinds of drug development (new chemical entity, modified release products, generics) are reviewed. Prediction of food effect response on the basis of the physicochemical and pharmacokinetic characteristics of the drug molecule or formulations is discussed. The results of three food interaction studies carried out the products of EGIS Pharmaceuticals Ltd. are also reviewed. The pharmacokinetic parameters of theophyllin 400 mg retard tablet were practically the same in both fasting condition and administration after consumption of a high fat containing standard breakfast. The ingestion of a high fat containing breakfast, increased the AUC of nifedipine from 259.0 +/- 101.2 ng h/ml to 326.7 +/- 122.5 ng h/ml and Cmax from 34.5 +/- 15.9 ng/ml to 74.3 +/- 23.9 ng/ml in case of nifedipine 20 mg retard tablet, in agreement with the data of literature. The statistical evaluation indicated significant differences between the pharmacokinetic parameters in the case of two administrations (before and after meal). The effect of a high fat containing breakfast for a generic version of buspiron 10 mg tablet and the bioequivalence after food consumption were

Electron tomography reveals the fibril structure and lipid interactions in amyloid deposits

PubMed Central

Kollmer, Marius; Meinhardt, Katrin; Haupt, Christian; Liberta, Falk; Wulff, Melanie; Linder, Julia; Handl, Lisa; Heinrich, Liesa; Loos, Cornelia; Schmidt, Matthias; Syrovets, Tatiana; Simmet, Thomas; Westermark, Per; Westermark, Gunilla T.; Horn, Uwe; Schmidt, Volker; Walther, Paul; Fändrich, Marcus

2016-01-01

Electron tomography is an increasingly powerful method to study the detailed architecture of macromolecular complexes or cellular structures. Applied to amyloid deposits formed in a cell culture model of systemic amyloid A amyloidosis, we could determine the structural morphology of the fibrils directly in the deposit. The deposited fibrils are arranged in different networks, and depending on the relative fibril orientation, we can distinguish between fibril meshworks, fibril bundles, and amyloid stars. These networks are frequently infiltrated by vesicular lipid inclusions that may originate from the death of the amyloid-forming cells. Our data support the role of nonfibril components for constructing fibril deposits and provide structural views of different types of lipid–fibril interactions. PMID:27140609

Deciphering microbial interactions and detecting keystone species with co-occurrence networks

PubMed Central

Berry, David; Widder, Stefanie

2014-01-01

Co-occurrence networks produced from microbial survey sequencing data are frequently used to identify interactions between community members. While this approach has potential to reveal ecological processes, it has been insufficiently validated due to the technical limitations inherent in studying complex microbial ecosystems. Here, we simulate multi-species microbial communities with known interaction patterns using generalized Lotka-Volterra dynamics. We then construct co-occurrence networks and evaluate how well networks reveal the underlying interactions and how experimental and ecological parameters can affect network inference and interpretation. We find that co-occurrence networks can recapitulate interaction networks under certain conditions, but that they lose interpretability when the effects of habitat filtering become significant. We demonstrate that networks suffer from local hot spots of spurious correlation in the neighborhood of hub species that engage in many interactions. We also identify topological features associated with keystone species in co-occurrence networks. This study provides a substantiated framework to guide environmental microbiologists in the construction and interpretation of co-occurrence networks from microbial survey datasets. PMID:24904535

Deciphering microbial interactions and detecting keystone species with co-occurrence networks.

PubMed

Berry, David; Widder, Stefanie

2014-01-01

Co-occurrence networks produced from microbial survey sequencing data are frequently used to identify interactions between community members. While this approach has potential to reveal ecological processes, it has been insufficiently validated due to the technical limitations inherent in studying complex microbial ecosystems. Here, we simulate multi-species microbial communities with known interaction patterns using generalized Lotka-Volterra dynamics. We then construct co-occurrence networks and evaluate how well networks reveal the underlying interactions and how experimental and ecological parameters can affect network inference and interpretation. We find that co-occurrence networks can recapitulate interaction networks under certain conditions, but that they lose interpretability when the effects of habitat filtering become significant. We demonstrate that networks suffer from local hot spots of spurious correlation in the neighborhood of hub species that engage in many interactions. We also identify topological features associated with keystone species in co-occurrence networks. This study provides a substantiated framework to guide environmental microbiologists in the construction and interpretation of co-occurrence networks from microbial survey datasets.

Abundance and Temperature Dependency of Protein-Protein Interaction Revealed by Interface Structure Analysis and Stability Evolution

PubMed Central

He, Yi-Ming; Ma, Bin-Guang

2016-01-01

Protein complexes are major forms of protein-protein interactions and implement essential biological functions. The subunit interface in a protein complex is related to its thermostability. Though the roles of interface properties in thermal adaptation have been investigated for protein complexes, the relationship between the interface size and the expression level of the subunits remains unknown. In the present work, we studied this relationship and found a positive correlation in thermophiles rather than mesophiles. Moreover, we found that the protein interaction strength in complexes is not only temperature-dependent but also abundance-dependent. The underlying mechanism for the observed correlation was explored by simulating the evolution of protein interface stability, which highlights the avoidance of misinteraction. Our findings make more complete the picture of the mechanisms for protein complex thermal adaptation and provide new insights into the principles of protein-protein interactions. PMID:27220911

Differential proteomics reveals novel insights into Nosema-honey bee interactions.

PubMed

Kurze, Christoph; Dosselli, Ryan; Grassl, Julia; Le Conte, Yves; Kryger, Per; Baer, Boris; Moritz, Robin F A

2016-12-01

Host manipulation is a common strategy by parasites to reduce host defense responses, enhance development, host exploitation, reproduction and, ultimately, transmission success. As these parasitic modifications can reduce host fitness, increased selection pressure may result in reciprocal adaptations of the host. Whereas the majority of studies on host manipulation have explored resistance against parasites (i.e. ability to prevent or limit an infection), data describing tolerance mechanisms (i.e. ability to limit harm of an infection) are scarce. By comparing differential protein abundance, we provide evidence of host-parasite interactions in the midgut proteomes of N. ceranae-infected and uninfected honey bees from both Nosema-tolerant and Nosema-sensitive lineages. We identified 16 proteins out of 661 protein spots that were differentially abundant between experimental groups. In general, infections of Nosema resulted in an up-regulation of the bee's energy metabolism. Additionally, we identified 8 proteins that were differentially abundant between tolerant and sensitive honey bees regardless of the Nosema infection. Those proteins were linked to metabolism, response to oxidative stress and apoptosis. In addition to bee proteins, we also identified 3 Nosema ceranae proteins. Interestingly, abundance of two of these Nosema proteins were significantly higher in infected Nosema-sensitive honeybees relative to the infected Nosema-tolerant lineage. This may provide a novel candidate for studying the molecular interplay between N. ceranae and its honey bee host in more detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

PubMed Central

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-01-01

Within the framework of ‘Network Physiology’, we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain–heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain–heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems. PMID:27044991

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

NASA Astrophysics Data System (ADS)

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-05-01

Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

Detailed monitoring of a small but recovering population reveals sublethal effects of disease and unexpected interactions with supplemental feeding.

PubMed

Tollington, Simon; Greenwood, Andrew; Jones, Carl G; Hoeck, Paquita; Chowrimootoo, Aurélie; Smith, Donal; Richards, Heather; Tatayah, Vikash; Groombridge, Jim J

2015-07-01

Infectious diseases are widely recognized to have substantial impact on wildlife populations. These impacts are sometimes exacerbated in small endangered populations, and therefore, the success of conservation reintroductions to aid the recovery of such species can be seriously threatened by outbreaks of infectious disease. Intensive management strategies associated with conservation reintroductions can further compound these negative effects in such populations. Exploring the sublethal effects of disease outbreaks among natural populations is challenging and requires longitudinal, individual life-history data on patterns of reproductive success and other indicators of individual fitness. Long-term monitoring data concerning detailed reproductive information of the reintroduced Mauritius parakeet (Psittacula echo) population collected before, during and after a disease outbreak was investigated. Deleterious effects of an outbreak of beak and feather disease virus (BFDV) were revealed on hatch success, but these effects were remarkably short-lived and disproportionately associated with breeding pairs which took supplemental food. Individual BFDV infection status was not predicted by any genetic, environmental or conservation management factors and was not associated with any of our measures of immune function, perhaps suggesting immunological impairment. Experimental immunostimulation using the PHA (phytohaemagglutinin assay) challenge technique did, however, provoke a significant cellular immune response. We illustrate the resilience of this bottlenecked and once critically endangered, island-endemic species to an epidemic outbreak of BFDV and highlight the value of systematic monitoring in revealing inconspicuous but nonetheless substantial ecological interactions. Our study demonstrates that the emergence of such an infectious disease in a population ordinarily associated with increased susceptibility does not necessarily lead to deleterious impacts on population

CO2 and Er:YAG laser interaction with grass tissues

NASA Astrophysics Data System (ADS)

Kim, Jaehun; Ki, Hyungson

2013-01-01

Plant leaves are multi-component optical materials consisting of water, pigments, and dry matter, among which water is the predominant constituent. In this article, we investigate laser interaction with grass using CO2 and Er:YAG lasers theoretically and experimentally, especially targeting water in grass tissues. We have first studied the optical properties of light absorbing constituents of grass theoretically, and then have identified interaction regimes and constructed interaction maps through a systematic experiment. Using the interaction maps, we have studied how interaction regimes change as process parameters are varied. This study reveals some interesting findings concerning carbonization and ablation mechanisms, the effect of laser beam diameter, and the ablation efficiency and quality of CO2 and Er:YAG lasers.

Classroom Talk in Bilingual Class Interaction

ERIC Educational Resources Information Center

Puasa, Kuran; Asrifan, Andi; Chen, Yan

2017-01-01

This study reveals how the classroom talk was in the bilingual classroom interaction. The classroom talk comprises teacher and pupil talk--in which they cover teacher's explanation, teacher's question, teacher's feedback, and modification to teacher's speech; as well as pupil's responses and pupil's questions. The research findings show that the…

Spectroscopic studies on the interaction of cimetidine drug with biologically significant σ- and π-acceptors

NASA Astrophysics Data System (ADS)

Pandeeswaran, M.; Elango, K. P.

2010-05-01

Spectroscopic studies revealed that the interaction of cimetidine drug with electron acceptors iodine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted through the initial formation of ionic intermediate to charge transfer (CT) complex. The CT-complexes of the interactions have been characterized using UV-vis, 1H NMR, FT-IR and GC-MS techniques. The formation of triiodide ion, I 3-, is further confirmed by the observation of the characteristic bands in the far IR spectrum for non-linear I 3- ion with C s symmetry at 156 and 131 cm -1 assigned to νas(I-I) and νs(I-I) of the I-I bond and at 73 cm -1 due to bending δ(I 3-). The rate of formation of the CT-complexes has been measured and discussed as a function of relative permittivity of solvent and temperature. The influence of relative permittivity of the medium on the rate indicated that the intermediate is more polar than the reactants and this observation was further supported by spectral studies. Based on the spectroscopic results plausible mechanisms for the interaction of the drug with the chosen acceptors were proposed and discussed and the point of attachment of the multifunctional cimetidine drug with these acceptors during the formation of CT-complex has been established.

Numerical studies of wall–plasma interactions and ionization phenomena in an ablative pulsed plasma thruster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Lei; School of Astronautics, Beihang University, Beijing 100191; Zeng, Guangshang

2016-07-15

Wall–plasma interactions excited by ablation controlled arcs are very critical physical processes in pulsed plasma thrusters (PPTs). Their effects on the ionization processes of ablated vapor into discharge plasma directly determine PPT performances. To reveal the physics governing the ionization phenomena in PPT discharge, a modified model taking into account the pyrolysis effect of heated polytetrafluoroethylene propellant on the wall–plasma interactions was developed. The feasibility of the modified model was analyzed by creating a one-dimensional simulation of a rectangular ablative PPT. The wall–plasma interaction results based on this modified model were found to be more realistic than for the unmodifiedmore » model; this reflects the dynamic changes of the inflow parameters during discharge in our model. Furthermore, the temporal and spatial variations of the different plasma species in the discharge chamber were numerically studied. The numerical studies showed that polytetrafluoroethylene plasma was mainly composed of monovalent ions; carbon and fluorine ions were concentrated in the upstream and downstream discharge chamber, respectively. The results based on this modified model were in good agreement with the experimental formation times of the various plasma species. A large number of short-lived and highly ionized carbon and fluorine species (divalent and trivalent ions) were created during initial discharge. These highly ionized species reached their peak density earlier than the singly ionized species.« less

Structure of an Arrestin2-clathrin Complex Reveals a Novel Clathrin Binding Domain that Modulates Receptor Trafficking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, D.; Kern, R; Puthenveedu, M

2009-01-01

Non-visual arrestins play a pivotal role as adaptor proteins in regulating the signaling and trafficking of multiple classes of receptors. Although arrestin interaction with clathrin, AP-2, and phosphoinositides contributes to receptor trafficking, little is known about the configuration and dynamics of these interactions. Here, we identify a novel interface between arrestin2 and clathrin through x-ray diffraction analysis. The intrinsically disordered clathrin binding box of arrestin2 interacts with a groove between blades 1 and 2 in the clathrin {beta}-propeller domain, whereas an 8-amino acid splice loop found solely in the long isoform of arrestin2 (arrestin2L) interacts with a binding pocket formedmore » by blades 4 and 5 in clathrin. The apposition of the two binding sites in arrestin2L suggests that they are exclusive and may function in higher order macromolecular structures. Biochemical analysis demonstrates direct binding of clathrin to the splice loop in arrestin2L, whereas functional analysis reveals that both binding domains contribute to the receptor-dependent redistribution of arrestin2L to clathrin-coated pits. Mutagenesis studies reveal that the clathrin binding motif in the splice loop is (L/I){sub 2}GXL. Taken together, these data provide a framework for understanding the dynamic interactions between arrestin2 and clathrin and reveal an essential role for this interaction in arrestin-mediated endocytosis.« less

Interaction of actin filaments with the plasma membrane in Amoeba proteus: studies using a cell model and isolated plasma membrane.

PubMed

Kawakatsu, T; Kikuchi, A; Shimmen, T; Sonobe, S

2000-08-01

We prepared a cell model of Amoeba proteus by mechanical bursting to study the interaction between actin filaments (AFs) and plasma membrane (PM). The cell model prepared in the absence of Ca2+ showed remarkable contraction upon addition of ATP. When the model was prepared in the presence of Ca2+, the cytoplasmic granules formed an aggregate in the central region, having moved away from PM. Although this model showed contraction upon addition of ATP in the presence of Ca2+, less contraction was noted. Staining with rhodamine-phalloidin revealed association of AFs with PM in the former model, and a lesser amount of association in the latter model. The interaction between AFs and PM was also studied using the isolated PM. AFs were associated with PM isolated in the absence of Ca2+, but were not when Ca2+ was present. These results suggest that the interaction between AFs and PM is regulated by Ca2+.

Studying physician effects on patient outcomes: physician interactional style and performance on quality of care indicators.

PubMed

Franks, Peter; Jerant, Anthony F; Fiscella, Kevin; Shields, Cleveland G; Tancredi, Daniel J; Epstein, Ronald M

2006-01-01

Many prior studies which suggest a relationship between physician interactional style and patient outcomes may have been confounded by relying solely on patient reports, examining very few patients per physician, or not demonstrating evidence of a physician effect on the outcomes. We examined whether physician interactional style, measured both by patient report and objective encounter ratings, is related to performance on quality of care indicators. We also tested for the presence of physician effects on the performance indicators. Using data on 100 US primary care physician (PCP) claims data on 1,21,606 of their managed care patients, survey data on 4746 of their visiting patients, and audiotaped encounters of 2 standardized patients with each physician, we examined the relationships between claims-based quality of care indicators and both survey-derived patient perceptions of their physicians and objective ratings of interactional style in the audiotaped standardized patient encounters. Multi-level models examined whether physician effects (variance components) on care indicators were mediated by patient perceptions or objective ratings of interactional style. We found significant physician effects associated with glycohemoglobin and cholesterol testing. There was also a clinically significant association between better patient perceptions of their physicians and more glycohemoglobin testing. Multi-level analyses revealed, however, that the physician effect on glycohemoglobin testing was not mediated by patient perceived physician interaction style. In conclusion, similar to prior studies, we found evidence of an apparent relationship between patient perceptions of their physician and patient outcomes. However, the apparent relationships found in this study between patient perceptions of their physicians and patient care processes do not reflect physician style, but presumably reflect unmeasured patient confounding. Multi-level modeling may contribute to better

Structures and interactions among globular proteins above the isoelectric point in the presence of divalent ions: A small angle neutron scattering and dynamic light scattering study

NASA Astrophysics Data System (ADS)

Kundu, Sarathi; Pandit, Subhankar; Abbas, Sohrab; Aswal, V. K.; Kohlbrecher, J.

2018-02-01

Small angle neutron scattering study reveals that at pD ≈ 7.0, above the isoelectric point of the globular protein Bovine Serum Albumin (BSA), in the presence of different divalent ions (Mg2+, Ca2+, Sr2+ and Ba2+), the short-range attractive interaction remains nearly constant and the intermediate-range repulsive interaction decreases with increasing salt concentration up to a certain concentration value but after that remains unchanged. However, for the monovalent ion (Na+), repulsive interaction decreases gradually up to 1 M salt concentration. Dynamic light scattering study shows that for all ions, diffusion coefficient of BSA decreases with increasing salt concentration and then nearly saturates.

Gene-Based Testing of Interactions in Association Studies of Quantitative Traits

PubMed Central

Ma, Li; Clark, Andrew G.; Keinan, Alon

2013-01-01

Various methods have been developed for identifying gene–gene interactions in genome-wide association studies (GWAS). However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene–gene interaction (GGG) tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein–protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies. PMID:23468652

Structure of the Mtb CarD/RNAP β-lobes complex reveals the molecular basis of interaction and presents a distinct DNA-binding domain for Mtb CarD.

PubMed

Gulten, Gulcin; Sacchettini, James C

2013-10-08

CarD from Mycobacterium tuberculosis (Mtb) is an essential protein shown to be involved in stringent response through downregulation of rRNA and ribosomal protein genes. CarD interacts with the β-subunit of RNAP and this interaction is vital for Mtb's survival during the persistent infection state. We have determined the crystal structure of CarD in complex with the RNAP β-subunit β1 and β2 domains at 2.1 Å resolution. The structure reveals the molecular basis of CarD/RNAP interaction, providing a basis to further our understanding of RNAP regulation by CarD. The structural fold of the CarD N-terminal domain is conserved in RNAP interacting proteins such as TRCF-RID and CdnL, and displays similar interactions to the predicted homology model based on the TRCF/RNAP β1 structure. Interestingly, the structure of the C-terminal domain, which is required for complete CarD function in vivo, represents a distinct DNA-binding fold. Copyright © 2013 Elsevier Ltd. All rights reserved.

The genome of the obligate endobacterium of an AM fungus reveals an interphylum network of nutritional interactions.

PubMed

Ghignone, Stefano; Salvioli, Alessandra; Anca, Iulia; Lumini, Erica; Ortu, Giuseppe; Petiti, Luca; Cruveiller, Stéphane; Bianciotto, Valeria; Piffanelli, Pietro; Lanfranco, Luisa; Bonfante, Paola

2012-01-01

As obligate symbionts of most land plants, arbuscular mycorrhizal fungi (AMF) have a crucial role in ecosystems, but to date, in the absence of genomic data, their adaptive biology remains elusive. In addition, endobacteria are found in their cytoplasm, the role of which is unknown. In order to investigate the function of the Gram-negative Candidatus Glomeribacter gigasporarum, an endobacterium of the AMF Gigaspora margarita, we sequenced its genome, leading to an ∼1.72-Mb assembly. Phylogenetic analyses placed Ca. G. gigasporarum in the Burkholderiaceae whereas metabolic network analyses clustered it with insect endobacteria. This positioning of Ca. G. gigasporarum among different bacterial classes reveals that it has undergone convergent evolution to adapt itself to intracellular lifestyle. The genome annotation of this mycorrhizal-fungal endobacterium has revealed an unexpected genetic mosaic where typical determinants of symbiotic, pathogenic and free-living bacteria are integrated in a reduced genome. Ca. G. gigasporarum is an aerobic microbe that depends on its host for carbon, phosphorus and nitrogen supply; it also expresses type II and type III secretion systems and synthesizes vitamin B12, antibiotics- and toxin-resistance molecules, which may contribute to the fungal host's ecological fitness. Ca. G. gigasporarum has an extreme dependence on its host for nutrients and energy, whereas the fungal host is itself an obligate biotroph that relies on a photosynthetic plant. Our work represents the first step towards unraveling a complex network of interphylum interactions, which is expected to have a previously unrecognized ecological impact.

Electrochemical, spectroscopic, and theoretical studies on the interaction between azathioprine and DNA.

PubMed

Jalali, Fahimeh; Rasaee, Gelareh

2015-11-01

Possible interaction between immunosuppressive drug, azathioprine, and calf thymus DNA was explored by cyclic voltammetry, spectrophotometry, competitive spectrofluorimetry, circular dichroism spectroscopy (CD), and viscosity measurements. Cyclic voltammetry showed negative shift in the reduction peak of azathioprine in the presence of DNA, and large decrease in peak current, referring to the predominance of electrostatic forces. The binding constant was calculated to be 1.22×10(3)M(-1). Absorption hyperchromism without shift in wavelength was observed when DNA was added to azathioprine solution. Competitive fluorescence experiments were conducted by using Hoechst 33258 and methylene blue as probes for minor groove and intercalation binding modes, respectively. The studies showed that azathioprine could release Hoechst 33258, while negligible effect was detected in the case of methylene blue. Stern-Volmer quenching constant (KSV) and complex formation constant (Kf) were obtained from the fluorescence measurements to be 7.6×10(3)M(-1) and 7.76×10(4)M(-1), respectively, at 298K. Enthalpy and entropy changes during the interaction between azathioprine and DNA were calculated from Van't Hoff plot (ΔH=-20.2kJmol(-1); ΔS=26.11Jmol(-1)K(-1) at 298K) which showed an exothermic spontaneous reaction, and involvement of electrostatic forces in the complex formation with DNA. Moreover, circular dichroism studies revealed that azathioprine induced detectable changes in the negative band of DNA spectrum. Viscosity of DNA solution decreased in the presence of azathioprine, showed a non-intercalative mode of interaction. Finally, molecular docking calculations showed that in the lowest energy level of drug-DNA complex, azathioprine approaches the minor grooves of DNA. Copyright © 2015 Elsevier B.V. All rights reserved.

An experimental study of the sources of fluctuating pressure loads beneath swept shock/boundary-layer interactions

NASA Technical Reports Server (NTRS)

Settles, G. S.; Garg, S.

1993-01-01

An experimental research program providing basic knowledge and establishing a database on the fluctuating pressure loads produced on aerodynamic surfaces beneath three dimensional shock wave/boundary layer interactions is described. Such loads constitute a fundamental problem of critical concern to future supersonic and hypersonic flight vehicles. A turbulent boundary layer on a flat plate is subjected to interactions with swept planar shock waves generated by sharp fins at angle of attack. Fin angles from 10 to 20 deg at freestream Mach numbers of 3 and 4 produce a variety of interaction strengths from weak to very strong. Miniature Kulite pressure transducers flush-mounted in the flat plate are used to measure interaction-induced wall pressure fluctuations. The distributions of properties of the pressure fluctuations, such as their ring levels, amplitude distributions, and power spectra, are also determined. Measurements were made for the first time in the aft regions of these interactions, revealing fluctuating pressure levels as high as 160 dB. These fluctuations are dominated by low frequency (0-5 kHz) signals. The maximum ring levels in the interactions show an increasing trend with increasing interaction strength. On the other hand, the maximum ring levels in the forward portion of the interactions decrease linearly with increasing interaction sweep back. These ring pressure distributions and spectra are correlated with the features of the interaction flowfield. The unsteadiness of the off-surface flowfield is studied using a new, non-intrusive technique based on the shadow graph method. The results indicate that the entire lambda-shock structure generated by the interaction undergoes relatively low-frequency oscillations. Some regions where particularly strong fluctuations are generated were identified. Fluctuating pressure measurements are also made along the line of symmetry of an axisymmetric jet impinging upon a flat plate at an angle. This flow was

A Study of Fan Stage/Casing Interaction Models

NASA Technical Reports Server (NTRS)

Lawrence, Charles; Carney, Kelly; Gallardo, Vicente

2003-01-01

The purpose of the present study is to investigate the performance of several existing and new, blade-case interactions modeling capabilities that are compatible with the large system simulations used to capture structural response during blade-out events. Three contact models are examined for simulating the interactions between a rotor bladed disk and a case: a radial and linear gap element and a new element based on a hydrodynamic formulation. The first two models are currently available in commercial finite element codes such as NASTRAN and have been showed to perform adequately for simulating rotor-case interactions. The hydrodynamic model, although not readily available in commercial codes, may prove to be better able to characterize rotor-case interactions.

Positive expectations encourage generalization from a positive intergroup interaction to outgroup attitudes.

PubMed

Deegan, Matthew P; Hehman, Eric; Gaertner, Samuel L; Dovidio, John F

2015-01-01

The current research reveals that while positive expectations about an anticipated intergroup interaction encourage generalization of positive contact to outgroup attitudes, negative expectations restrict the effects of contact on outgroup attitudes. In Study 1, when Blacks and Whites interacted with positive expectations, interaction quality predicted outgroup attitudes to a greater degree than when groups interacted with negative expectations. When expectations (Studies 2 and 3) and the actual interaction quality (Study 4) were manipulated orthogonally, negative expectations about the interaction predicted negative outgroup attitudes, regardless of actual interaction quality. By contrast, participants holding positive expectations who experienced a positive interaction expressed positive outgroup attitudes, whereas when they experienced a negative interaction, they expressed outgroup attitudes as negative as those with negative expectations. Across all four studies, positive expectations encouraged developing outgroup attitudes consistent with interaction quality. © 2014 by the Society for Personality and Social Psychology, Inc.

Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds.

PubMed

Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

2014-04-01

In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99-100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. © 2014 AAFC. New Phytologist © 2014 New Phytologist Trust.

PRMT7 Interacts with ASS1 and Citrullinemia Mutations Disrupt the Interaction.

PubMed

Verma, Mamta; Charles, Ramya Chandar M; Chakrapani, Baskar; Coumar, Mohane Selvaraj; Govindaraju, Gayathri; Rajavelu, Arumugam; Chavali, Sreenivas; Dhayalan, Arunkumar

2017-07-21

Protein arginine methyltransferase 7 (PRMT7) catalyzes the introduction of monomethylation marks at the arginine residues of substrate proteins. PRMT7 plays important roles in the regulation of gene expression, splicing, DNA damage, paternal imprinting, cancer and metastasis. However, little is known about the interaction partners of PRMT7. To address this, we performed yeast two-hybrid screening of PRMT7 and identified argininosuccinate synthetase (ASS1) as a potential interaction partner of PRMT7. We confirmed that PRMT7 directly interacts with ASS1 using pull-down studies. ASS1 catalyzes the rate-limiting step of arginine synthesis in urea cycle and citrulline-nitric oxide cycle. We mapped the interface of PRMT7-ASS1 complex through computational approaches and validated the predicted interface in vivo by site-directed mutagenesis. Evolutionary analysis revealed that the ASS1 residues important for PRMT7-ASS1 interaction have co-evolved with PRMT7. We showed that ASS1 mutations linked to type I citrullinemia disrupt the ASS1-PRMT7 interaction, which might explain the molecular pathogenesis of the disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Initial Development and Pilot Study Design of Interactive Lecture Demonstrations for ASTRO 101

NASA Astrophysics Data System (ADS)

Schwortz, Andria C.; French, D. A; Gutierrez, Joseph V; Sanchez, Richard L; Slater, Timothy F.; Tatge, Coty

2014-06-01

Interactive lecture demonstrations (ILDs) have repeatedly shown to be effective tools for improving student achievement in the context of learning physics. As a first step toward systematic development of interactive lecture demonstrations in ASTRO 101, the introductory astronomy survey course, a systematic review of education research, describing educational computer simulations (ECSs) reveals that initial development requires a targeted study of how ASTRO 101 students respond to ECSs in the non-science majoring undergraduate lecture setting. In this project we have adopted the process by which ILDs were designed, pilot-tested, and successfully implemented in the context of physics teaching (Sokoloff & Thornton, 1997; Sokoloff & Thornton, 2004). We have designed the initial pilot-test set of ASTRO 101 ILD instructional materials relying heavily on ECSs. Both an instructor’s manual and a preliminary classroom-ready student workbook have been developed, and we are implementing a pilot study to explore their effectiveness in communicating scientific content, and the extent to which they might enhance students’ knowledge of and perception about astronomy and science in general. The study design uses a pre-/post-test quasi-experimental study design measuring students’ normalized gain scores, calculated as per Hake (1998) and Prather (2009), using a slightly modified version of S. Slater’s (2011) Test Of Astronomy STandards TOAST combined with other instruments. The results of this initial study will guide the iterative development of ASTRO 101 ILDs that are intended to both be effective at enhancing student achievement and easy for instructors to successfully implement.

Structure of frequency-interacting RNA helicase from Neurospora crassa reveals high flexibility in a domain critical for circadian rhythm and RNA surveillance.

PubMed

Morales, Yalemi; Olsen, Keith J; Bulcher, Jacqueline M; Johnson, Sean J

2018-01-01

The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function.

A Usability Study of Interactive Web-Based Modules

ERIC Educational Resources Information Center

Girard, Tulay; Pinar, Musa

2011-01-01

This research advances the understanding of the usability of marketing case study modules in the area of interactive web-based technologies through the assignment of seven interactive case modules in a Principles of Marketing course. The case modules were provided for marketing students by the publisher, McGraw Hill Irwin, of the…

Supporting High School Student Accomplishment of Biology Content Using Interactive Computer-Based Curricular Case Studies

NASA Astrophysics Data System (ADS)

Oliver, Joseph Steve; Hodges, Georgia W.; Moore, James N.; Cohen, Allan; Jang, Yoonsun; Brown, Scott A.; Kwon, Kyung A.; Jeong, Sophia; Raven, Sara P.; Jurkiewicz, Melissa; Robertson, Tom P.

2017-11-01

Research into the efficacy of modules featuring dynamic visualizations, case studies, and interactive learning environments is reported here. This quasi-experimental 2-year study examined the implementation of three interactive computer-based instructional modules within a curricular unit covering cellular biology concepts in an introductory high school biology course. The modules featured dynamic visualizations and focused on three processes that underlie much of cellular biology: diffusion, osmosis, and filtration. Pre-tests and post-tests were used to assess knowledge growth across the unit. A mixture Rasch model analysis of the post-test data revealed two groups of students. In both years of the study, a large proportion of the students were classified as low-achieving based on their pre-test scores. The use of the modules in the Cell Unit in year 2 was associated with a much larger proportion of the students having transitioned to the high-achieving group than in year 1. In year 2, the same teachers taught the same concepts as year 1 but incorporated the interactive computer-based modules into the cell biology unit of the curriculum. In year 2, 67% of students initially classified as low-achieving were classified as high-achieving at the end of the unit. Examination of responses to assessments embedded within the modules as well as post-test items linked transition to the high-achieving group with correct responses to items that both referenced the visualization and the contextualization of that visualization within the module. This study points to the importance of dynamic visualization within contextualized case studies as a means to support student knowledge acquisition in biology.

Structures and interactions in N-methylacetamide-water mixtures studied by IR spectra and density functional theory

NASA Astrophysics Data System (ADS)

Zhang, Rong; Li, Haoran; Lei, Yi; Han, Shijun

2004-05-01

IR spectra have been performed to study the structures and interactions in N-methylacetamide and water mixtures. Because of the competitions of acceptor and donor of the strong hydrogen bonds, some interesting phenomena of red shifts and blue shifts are observed in νCO and νN-H. It is due to the blue-shifting C-H⋯O hydrogen bond, the νC-H blue shifts more obviously. Then some representative cluster structures are suggested and further investigated by density functional theory method. The changes in bond length and frequency shift of the structures give good reasons for the red shift and blue shift, which represents excellent agreement with the IR experiment. The investigations of IR spectra and DFT calculations reveal that the weak C-H⋯O interactions play different roles compared with the classical strong hydrogen bonds in the NMA-water mixtures.

Genome-wide Hi-C analysis reveals extensive hierarchical chromatin interactions in rice.

PubMed

Dong, Qianli; Li, Ning; Li, Xiaochong; Yuan, Zan; Xie, Dejian; Wang, Xiaofei; Li, Jianing; Yu, Yanan; Wang, Jinbin; Ding, Baoxu; Zhang, Zhibin; Li, Changping; Bian, Yao; Zhang, Ai; Wu, Ying; Liu, Bao; Gong, Lei

2018-06-01

The non-random spatial packing of chromosomes in the nucleus plays a critical role in orchestrating gene expression and genome function. Here, we present a Hi-C analysis of the chromatin interaction patterns in rice (Oryza sativa L.) at hierarchical architectural levels. We confirm that rice chromosomes occupy their own territories with certain preferential inter-chromosomal associations. Moderate compartment delimitation and extensive TADs (Topologically Associated Domains) were determined to be associated with heterogeneous genomic compositions and epigenetic marks in the rice genome. We found subtle features including chromatin loops, gene loops, and off-/near-diagonal intensive interaction regions. Gene chromatin loops associated with H3K27me3 could be positively involved in gene expression. In addition to insulated enhancing effects for neighbor gene expression, the identified rice gene loops could bi-directionally (+/-) affect the expression of looped genes themselves. Finally, web-interleaved off-diagonal IHIs/KEEs (Interactive Heterochromatic Islands or KNOT ENGAGED ELEMENTs) could trap transposable elements (TEs) via the enrichment of silencing epigenetic marks. In parallel, the near-diagonal FIREs (Frequently Interacting Regions) could positively affect the expression of involved genes. Our results suggest that the chromatin packing pattern in rice is generally similar to that in Arabidopsis thaliana but with clear differences at specific structural levels. We conclude that genomic composition, epigenetic modification, and transcriptional activity could act in combination to shape global and local chromatin packing in rice. Our results confirm recent observations in rice and A. thaliana but also provide additional insights into the patterns and features of chromatin organization in higher plants. © 2018 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Mental health and social networks in early adolescence: a dynamic study of objectively-measured social interaction behaviors.

PubMed

Pachucki, Mark C; Ozer, Emily J; Barrat, Alain; Cattuto, Ciro

2015-01-01

How are social interaction dynamics associated with mental health during early stages of adolescence? The goal of this study is to objectively measure social interactions and evaluate the roles that multiple aspects of the social environment--such as physical activity and food choice--may jointly play in shaping the structure of children's relationships and their mental health. The data in this study are drawn from a longitudinal network-behavior study conducted in 2012 at a private K-8 school in an urban setting in California. We recruited a highly complete network sample of sixth-graders (n = 40, 91% of grade, mean age = 12.3), and examined how two measures of distressed mental health (self-esteem and depressive symptoms) are positionally distributed in an early adolescent interaction network. We ascertained how distressed mental health shapes the structure of relationships over a three-month period, adjusting for relevant dimensions of the social environment. Cross-sectional analyses of interaction networks revealed that self-esteem and depressive symptoms are differentially stratified by gender. Specifically, girls with more depressive symptoms have interactions consistent with social inhibition, while boys' interactions suggest robustness to depressive symptoms. Girls higher in self-esteem tended towards greater sociability. Longitudinal network behavior models indicate that gender similarity and perceived popularity are influential in the formation of social ties. Greater school connectedness predicts the development of self-esteem, though social ties contribute to more self-esteem improvement among students who identify as European-American. Cross-sectional evidence shows associations between distressed mental health and students' network peers. However, there is no evidence that connected students' mental health status becomes more similar in their over time because of their network interactions. These findings suggest that mental health during early

Cloning of the unculturable parasite Pasteuria ramosa and its Daphnia host reveals extreme genotype-genotype interactions.

PubMed

Luijckx, Pepijn; Ben-Ami, Frida; Mouton, Laurence; Du Pasquier, Louis; Ebert, Dieter

2011-02-01

The degree of specificity in host-parasite interactions has important implications for ecology and evolution. Unfortunately, specificity can be difficult to determine when parasites cannot be cultured. In such cases, studies often use isolates of unknown genetic composition, which may lead to an underestimation of specificity. We obtained the first clones of the unculturable bacterium Pasteuria ramosa, a parasite of Daphnia magna. Clonal genotypes of the parasite exhibited much more specific interactions with host genotypes than previous studies using isolates. Clones of P. ramosa infected fewer D. magna genotypes than isolates and host clones were either fully susceptible or fully resistant to the parasite. Our finding enhances our understanding of the evolution of virulence and coevolutionary dynamics in this system. We recommend caution when using P. ramosa isolates as the presence of multiple genotypes may influence the outcome and interpretation of some experiments. © 2010 Blackwell Publishing Ltd/CNRS.

On the interaction of deaffrication and consonant harmony*

PubMed Central

Dinnsen, Daniel A.; Gierut, Judith A.; Morrisette, Michele L.; Green, Christopher R.; Farris-Trimble, Ashley W.

2010-01-01

Error patterns in children’s phonological development are often described as simplifying processes that can interact with one another with different consequences. Some interactions limit the applicability of an error pattern, and others extend it to more words. Theories predict that error patterns interact to their full potential. While specific interactions have been documented for certain pairs of processes, no developmental study has shown that the range of typologically predicted interactions occurs for those processes. To determine whether this anomaly is an accidental gap or a systematic peculiarity of particular error patterns, two commonly occurring processes were considered, namely Deaffrication and Consonant Harmony. Results are reported from a cross-sectional and longitudinal study of 12 children (age 3;0 – 5;0) with functional phonological delays. Three interaction types were attested to varying degrees. The longitudinal results further instantiated the typology and revealed a characteristic trajectory of change. Implications of these findings are explored. PMID:20513256

An Exploratory Study of Interactivity in Visualization Tools: "Flow" of Interaction

ERIC Educational Resources Information Center

Liang, Hai-Ning; Parsons, Paul C.; Wu, Hsien-Chi; Sedig, Kamran

2010-01-01

This paper deals with the design of interactivity in visualization tools. There are several factors that can be used to guide the analysis and design of the interactivity of these tools. One such factor is flow, which is concerned with the duration of interaction with visual representations of information--interaction being the actions performed…

Gene–Physical Activity Interactions: Overview of Human Studies

PubMed Central

Rankinen, Tuomo; Bouchard, Claude

2009-01-01

Physical activity level is an important component of the total daily energy expenditure and as such contributes to body weight regulation. A body of data indicates that the level of physical activity plays a role in the risk of excessive weight gain, in weight loss programs, and particularly in the prevention of weight regain. Most studies dealing with potential gene–physical activity interaction effects use an exercise and fitness or performance paradigm as opposed to an obesity-driven model. From these studies, it is clear that there are considerable individual differences in the response to an exercise regimen and that there is a substantial familial aggregation component to the observed heterogeneity. Few studies have focused on the role of specific genes in accounting for the highly prevalent gene–exercise interaction effects. Results for specific genes have been inconsistent with few exceptions. Progress is likely to come when studies will be designed to truly address gene–exercise or physical activity interaction issues and with sample sizes that will provide adequate statistical power. PMID:19037212

Modified interactions among globular proteins below isoelectric point in the presence of mono-, di- and tri-valent ions: A small angle neutron scattering study

NASA Astrophysics Data System (ADS)

Das, Kaushik; Kundu, Sarathi; Mehan, Sumit; Aswal, V. K.

2016-02-01

Both short range attraction and long range electrostatic repulsion exist among globular protein Bovine Serum Albumin in solution below its isoelectric point (pI ≈ 4.8). At pD ≈ 4.0, below pI, protein has a net positive surface charge although local charge inhomogeneity presents. Small angle neutron scattering study reveals that in the presence of both mono-(Na+) and di-(Ni2+) valent ions attractive interaction increases and repulsive interaction decreases with the increase of salt concentration. However, for tri-valent (Fe3+) ions, both attractive and repulsive interaction increases with increasing salt concentration but the relative strength of repulsion is more than the attraction.

Dialogues in the "Global Village:" NNS/NS Collaboration in Classroom Interaction

ERIC Educational Resources Information Center

Hall, Joan Kelly; Hendricks, Sean; Orr, Jeffery Lee

2004-01-01

This study is concerned with interactional involvement and identity construction in a university seminar comprised of native and non-native English speaking students. Findings reveal that in their classroom interactions, these two groups of students take on and perceive others to take on identities that have little to do with their language status…

Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

NASA Astrophysics Data System (ADS)

Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

2015-11-01

Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

Neutron Scattering Studies of Nano-Scale Wood-Water Interactions

NASA Astrophysics Data System (ADS)

Plaza Rodriguez, Nayomi Z.

Understanding and controlling water in wood is critical to both improving forest products moisture durability and developing new sustainable forest products-based technologies. While wood is known to be hygroscopic, there is still a lack of understanding on the nanoscale wood-water interactions necessary for increased moisture-durability and dimensional stability. My PhD thesis focuses on the development and implementation of neutron scattering methods that can provide insight on both the structural and dynamical changes associated with these interactions so that products with improved moisture durability can be developed efficiently. Using small angle neutron scattering (SANS) and a custom-built in situ relative humidity chamber I studied the anisotropic moisture-induced swelling of wood nanostructure. First, I studied the effects of sample preparation by comparing SANS patterns of wiley milled wood and intact latewood cell walls, and found that scattering from intact wood provide more information about the spatial arrangement of the wood nanostructures inside the cell wall. Comparisons between SANS patterns from earlywood and latewood, also showed that the higher cell wall density of latewood cell walls results in patterns with more pronounced anisotropic features. Then, by measuring latewood loblolly pine sections obtained from the same growth ring and prepared in each of the primary wood planes, I tracked the cellulose elementary fibril spacing as a function of humidity in both intact and partially cut cell walls. These studies showed that even though swelling at the elementary fibril spacing is responsible for the majority of the transverse swelling observed at the S2 level, it is not primary plane dependent. Additionally, there were no differences in the elementary fibril spacing between partially-cut and intact cell walls, except at high humidity where the spacing in partially-cut cells was higher. SANS was also used to study the effects of two chemical

Multispacecraft study of shock-flux rope interaction

NASA Astrophysics Data System (ADS)

Blanco-Cano, Xochitl; Burgess, David; Sundberg, Torbjorn; Kajdic, Primoz

2017-04-01

Interplanetary (IP) shocks can be driven in the solar wind by fast coronal mass ejections. These shocks can accelerate particles near the Sun and through the heliosphere, being associated to solar energetic particle (SEP) and energetic storm particle (ESP) events. IP shocks can interact with structures in the solar wind, and with planetary magnetospheres. In this study we show how the properties of an IP shock change when it interacts with a medium scale flux rope (FR) like structure. We use data measurements from CLUSTER, WIND and ACE. These three spacecraft observed the shock-FR interaction at different stages of its evolution. We find that the shock-FR interaction locally changes the shock geometry, affecting ion injection processes, and the upstream and downstream regions. While WIND and ACE observed a quasi-perpendicular shock, CLUSTER crossed a quasi-parallel shock and a foreshock with a variety of ion distributions. The complexity of the ion foreshock can be explained by the dynamics of the shock transitioning from quasi-perpendicular to quasi-parallel, and the geometry of the magnetic field around the flux rope. Interactions such as the one we discuss can occur often along the extended IP shock fronts, and hence their importance towards a better understanding of shock acceleration.

Broadband Microwave Spectroscopy as a Tool to Study Dispersion Interactions in Camphor-Alcohol Systems

NASA Astrophysics Data System (ADS)

Fatima, Mariyam; Perez, Cristobal; Schnell, Melanie

2016-06-01

Many biological processes such as chemical recognition and protein folding are mainly controlled by the interplay between hydrogen bonds and dispersive forces. Broadband rotational spectroscopy studies of weakly bound complexes are able to accurately reveal the structures and internal dynamics of molecular clusters isolated in the gas phase. To investigate the influence of the interplay between different types of weak intermolecular interactions and how it controls the preferred active sites of an amphiphilic molecule, we are using camphor (C10H16O, 1,7,7-trimethylbicyclo[2.2.1]hepta-2-one) with different aliphatic alcohol systems. Camphor is a conformationally rigid bicyclic molecule endowed with considerable steric hindrance and has a single polar group (-C=O). The rotational spectrum of camphor and its structure has been previously reported [1] as well as multiple clusters with water [2]. In order to determine the structure of the camphor-alcohol complexes, we targeted low energy rotational transitions in the 2-8 GHz range under the isolated conditions of a molecular jet in the gas phase. The data obtained suggests that camphor forms one complex with methanol and two with ethanol, with differences in the intermolecular interaction in both complexes. With these results, we aim to study the shift in intermolecular interaction from hydrogen bonding to dispersion with the increase in the size of the aliphatic alcohol. [1] Z. Kisiel, et al., Phys. Chem. Chem. Phys., 5 (2003), 820-826. [2] C. Pérez, et al, J. Phys. Chem. Lett., 7 (2016), 154-160.

Nonlinear optical microscopy reveals invading endothelial cells anisotropically alter three-dimensional collagen matrices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, P.-F.; Yeh, Alvin T.; Bayless, Kayla J.

The interactions between endothelial cells (ECs) and the extracellular matrix (ECM) are fundamental in mediating various steps of angiogenesis, including cell adhesion, migration and sprout formation. Here, we used a noninvasive and non-destructive nonlinear optical microscopy (NLOM) technique to optically image endothelial sprouting morphogenesis in three-dimensional (3D) collagen matrices. We simultaneously captured signals from collagen fibers and endothelial cells using second harmonic generation (SHG) and two-photon excited fluorescence (TPF), respectively. Dynamic 3D imaging revealed EC interactions with collagen fibers along with quantifiable alterations in collagen matrix density elicited by EC movement through and morphogenesis within the matrix. Specifically, we observedmore » increased collagen density in the area between bifurcation points of sprouting structures and anisotropic increases in collagen density around the perimeter of lumenal structures, but not advancing sprout tips. Proteinase inhibition studies revealed membrane-associated matrix metalloproteinase were utilized for sprout advancement and lumen expansion. Rho-associated kinase (p160ROCK) inhibition demonstrated that the generation of cell tension increased collagen matrix alterations. This study followed sprouting ECs within a 3D matrix and revealed that the advancing structures recognize and significantly alter their extracellular environment at the periphery of lumens as they progress.« less

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

PubMed

Astani, Elahe K; Heshmati, Emran; Chen, Chun-Jung; Hadipour, Nasser L

2016-07-01

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

A pollen-specific calmodulin-binding protein, NPG1, interacts with putative pectate lyases.

PubMed

Shin, Sung-Bong; Golovkin, Maxim; Reddy, Anireddy S N

2014-06-12

Previous genetic studies have revealed that a pollen-specific calmodulin-binding protein, No Pollen Germination 1 (NPG1), is required for pollen germination. However, its mode of action is unknown. Here we report direct interaction of NPG1 with pectate lyase-like proteins (PLLs). A truncated form of AtNPG1 lacking the N-terminal tetratricopeptide repeat 1 (TPR1) failed to interact with PLLs, suggesting that it is essential for NPG1 interaction with PLLs. Localization studies with AtNPG1 fused to a fluorescent reporter driven by its native promoter revealed its presence in the cytosol and cell wall of the pollen grain and the growing pollen tube of plasmolyzed pollen. Together, our data suggest that the function of NPG1 in regulating pollen germination is mediated through its interaction with PLLs, which may modify the pollen cell wall and regulate pollen tube emergence and growth.

In vitro drug interaction of levocetirizine and diclofenac: Theoretical and spectroscopic studies.

PubMed

Abo Dena, Ahmed S; Abdel Gaber, Sara A

2017-06-15

Levocetirizine dihydrochloride is known to interact with some anti-inflammatory drugs. We report here a comprehensive integrated theoretical and experimental study for the in vitro drug interaction between levocetirizine dihydrochloride (LEV) and diclofenac sodium (DIC). The interaction of the two drugs was confirmed by the molecular ion peak obtained from the mass spectrum of the product. Moreover, FTIR and 1 HNMR spectra of the individual drugs and their interaction product were inspected to allocate the possible sites of interaction. In addition, quantum mechanical DFT calculations were performed to search for the interaction sites and to verify the types of interactions deduced from the spectroscopic studies such as charge-transfer and non-bonding π-π interactions. It was found that the studied drugs interact with each other in aqueous solution via four types of interactions, namely, ion-pair formation, three weak hydrogen bonds, non-bonding π-π interactions and charge-transfer from DIC to LEV. Copyright © 2017 Elsevier B.V. All rights reserved.

Multispacecraft study of shock-flux rope interaction

NASA Astrophysics Data System (ADS)

Blanco-Cano, X.; Burgess, D.; Sundberg, T.; Kajdic, P.

2016-12-01

Interplanetary (IP) shocks can be driven in the solar wind by fast coronal mass ejections. These shocks play an active role in particle acceleration near the Sun and through the heliosphere, being associated to solar energetic particle (SEP) and energetic storm particle (ESP) events. IP shocks can interact with structures in the solar wind, and with planetary magnetospheres. In this work we study how the properties of an IP shock change when it interacts with a medium scale flux rope (FR). We use measurements from CLUSTER, WIND and ACE. These three spacecraft observed the shock-FR interaction at different stages of its evolution. We find that the shock-FR interaction locally changes the shock geometry, affecting ion injection processes, and the upstream and downstream regions. While WIND and ACE observed a quasi-perpendicular shock, CLUSTER crossed a quasi-parallel shock and a foreshock with a variety of ion distributions. The complexity of the ion foreshock can be explained by the dynamics of the shock transitioning from quasi-perpendicular to quasi-parallel, and the geometry of the magnetic field around the flux rope.

A computational study of anion-modulated cation-π interactions.

PubMed

Carrazana-García, Jorge A; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

2012-05-24

The interaction of anions with cation-π complexes formed by the guanidinium cation and benzene was thoroughly studied by means of computational methods. Potential energy surface scans were performed in order to evaluate the effect of the anion coming closer to the cation-π pair. Several structures of guanidinium-benzene complexes and anion approaching directions were examined. Supermolecule calculations were performed on ternary complexes formed by guanidinium, benzene, and one anion and the interaction energy was decomposed into its different two- and three-body contributions. The interaction energies were further dissected into their electrostatic, exchange, repulsion, polarization and dispersion contributions by means of local molecular orbital energy decomposition analysis. The results confirm that, besides the electrostatic cation-anion attraction, the effect of the anion over the cation-π interaction is mainly due to polarization and can be rationalized following the changes in the anion-π and the nonadditive (three-body) terms of the interaction. When the cation and the anion are on the same side of the π system, the three-body interaction is anticooperative, but when the anion and the cation are on opposite sides of the π system, the three-body interaction is cooperative. As far as we know, this is the first study where this kind of analysis is carried out with a structured cation as guanidinium with a significant biological interest.

A Novel Scoring Approach for Protein Co-Purification Data Reveals High Interaction Specificity

DTIC Science & Technology

2009-09-01

decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E -mail...Methods). ( E ) score distributions, in purification data of Gavin et al. [8], of selected curated interactions in MIPS [18] and SGD-Biogrid (SBMC2...in a network was assessed here by determining interaction frequencies between pairs of degrees, i.e., for two degrees k1 and k2, we counted the total

Exploring the interaction between Salvia miltiorrhiza and human serum albumin: Insights from herb-drug interaction reports, computational analysis and experimental studies

NASA Astrophysics Data System (ADS)

Shao, Xin; Ai, Ni; Xu, Donghang; Fan, Xiaohui

2016-05-01

Human serum albumin (HSA) binding is one of important pharmacokinetic properties of drug, which is closely related to in vivo distribution and may ultimately influence its clinical efficacy. Compared to conventional drug, limited information on this transportation process is available for medicinal herbs, which significantly hampers our understanding on their pharmacological effects, particularly when herbs and drug are co-administrated as polytherapy to the ailment. Several lines of evidence suggest the existence of Salvia miltiorrhiza-Warfarin interaction. Since Warfarin is highly HSA bound in the plasma with selectivity to site I, it is critical to evaluate the possibility of HSA-related herb-drug interaction. Herein an integrated approach was employed to analyze the binding of chemicals identified in S. miltiorrhiza to HSA. Molecular docking simulations revealed filtering criteria for HSA site I compounds that include docking score and key molecular determinants for binding. For eight representative ingredients from the herb, their affinity and specificity to HSA site I was measured and confirmed fluorometrically, which helps to improve the knowledge of interaction mechanisms between this herb and HSA. Our results indicated that several compounds in S. miltiorrhiza were capable of decreasing the binding constant of Warfarin to HSA site I significantly, which may increase free drug concentration in vivo, contributing to the herb-drug interaction observed clinically. Furthermore, the significance of HSA mediated herb-drug interactions was further implied by manual mining on the published literatures on S. miltiorrhiza.

Application of photogrammetry to the study of volcano-glacier interactions on Mount Wrangell, Alaska

NASA Technical Reports Server (NTRS)

Benson, C. S.; Follett, A. B.

1986-01-01

Most Alaskan volcanoes are glacier covered and provide excellent opportunities to study interactions between glaciers and volcanoes. The present paper is concerned with such a study, taking into account the Mt. Wrangell (4317 m) which is the northernmost active volcano (solfatara activity) on the Pacific Rim (62 deg N; 144 deg W). While the first photographs on the summit of Mt. Wrangell were published more than 75 years ago, research there began in 1953 and 1954. Satellite images reveal activity at the summit of Mt. Wrangell. However, the resolution is not sufficient for conducting important measurements regarding ice volume losses. For this reason, vertical aerial photographs of the summit were obtained, and a field trip to the summit was conducted. Aspects of photogrammetry are discussed, taking into account questions of ground control, aerial photography, topographic mapping, digital cross sections, and orthophotos.

Interweaving interactions in virtual worlds: a case study.

PubMed

Cantamesse, Matteo; Galimberti, Carlo; Giacoma, Gianandrea

2011-01-01

The aim of this study was to examine the effect of playing the online game World of Warcraft (WoW), both on adolescent's (effective) social interaction and on the competence they developed on it. Social interactions within the game environment have been investigated by integrating qualitative and quantitative methods: conversation analysis and social network analysis (SNA). From a psychosocial point of view, the in-game interactions, and in particular conversational exchanges, turn out to be a collaborative path of the joint definition of identities and social ties, with reflection on in-game processes and out-game relationship.

NACASETAC BAY: AN INTERACTIVE CASE STUDY

EPA Science Inventory

This interactive case study or "game" was created to provide a "hands on" experience in the application of a weight of evidence approach to sediment assessment. The game proceeds in two phases. In each phase the players work together as a group. A scenario is presented, and the g...

Structure of the Acinetobacter baumannii dithiol oxidase DsbA bound to elongation factor EF-Tu reveals a novel protein interaction site.

PubMed

Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K; King, Gordon J; Halili, Maria A; Heras, Begoña; Martin, Jennifer L

2014-07-18

The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure of the Acinetobacter baumannii Dithiol Oxidase DsbA Bound to Elongation Factor EF-Tu Reveals a Novel Protein Interaction Site

PubMed Central

Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K.; King, Gordon J.; Halili, Maria A.; Heras, Begoña; Martin, Jennifer L.

2014-01-01

The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. PMID:24860094

FTIR studies of the redox partner interaction in cytochrome P450: the Pdx-P450cam couple.

PubMed

Karyakin, Andrey; Motiejunas, Domantas; Wade, Rebecca C; Jung, Christiane

2007-03-01

Recently we have developed a new approach to study protein-protein interactions using Fourier transform infrared spectroscopy in combination with titration experiments and principal component analysis (FTIR-TPCA). In the present paper we review the FTIR-TPCA results obtained for the interaction between cytochrome P450 and the redox partner protein in two P450 systems, the Pseudomonas putida P450cam (CYP101) with putidaredoxin (P450cam-Pdx), and the Bacillus megaterium P450BM-3 (CYP102) heme domain with the FMN domain (P450BMP-FMND). Both P450 systems reveal similarities in the structural changes that occur upon redox partner complex formation. These involve an increase in beta-sheets and alpha-helix content, a decrease in the population of random coil/3(10)-helix structure, a redistribution of turn structures within the interacting proteins and changes in the protonation states or hydrogen-bonding of amino acid carboxylic side chains. We discuss in detail the P450cam-Pdx interaction in comparison with literature data and conclusions drawn from experiments obtained by other spectroscopic techniques. The results are also interpreted in the context of a 3D structural model of the Pdx-P450cam complex.

Broadband Microwave Spectroscopy as a Tool to Study Intermolecular Interactions in the Diphenyl Ether - Water System

NASA Astrophysics Data System (ADS)

Fatima, Mariyam; Perez, Cristobal; Schnell, Melanie

2017-06-01

Many biological processes, such as chemical recognition and protein folding, are mainly controlled by the interplay of hydrogen bonds and dispersive forces. This interplay also occurs between organic molecules and solvent water molecules. Broadband rotational spectroscopy studies of weakly bound complexes are able to accurately reveal the structures and internal dynamics of molecular clusters isolated in the gas phase. Amongst them, water clusters with organic molecules are of particular interest. In this work, we investigate the interplay between different types of weak intermolecular interactions and how it controls the preferred interaction sites of aromatic ethers, where dispersive interactions may play a significant role. We present our results on diphenyl ether (C_{12}H_{10}O, 1,1'-Oxydibenzene) complexed with up to three molecules of water. Diphenyl ether is a flexible molecule, and it offers two competing binding sites for water: the ether oxygen and the aromatic π system. In order to determine the structure of the diphenyl ether-water complexes, we targeted transitions in the 2-8 GHz range using broadband rotational spectroscopy. We identify two isomers with one water, one with two water, and one with three water molecules. Further analysis from isotopic substitution measurements provided accurate structural information. The preferred interactions, as well as the observed structural changes induced upon complexation, will be presented and discussed.

The influence of interactive technology on student performance in an Oklahoma secondary Biology I program

NASA Astrophysics Data System (ADS)

Feltman, Vallery

Over the last decade growth in technologies available to teach students and enhance curriculum has become an important consideration in the educational system. The profile of today's secondary students have also been found to be quite different than those of the past. Their learning styles and preferences are issues that should be addressed by educators. With the growth and availability of new technologies students are increasingly expecting to use these as learning tools in their classrooms. This study investigates how interactive technology may impact student performance. This study specifically focuses on the use of the Apple Ipad in 4 Biology I classrooms. This study used an experimental mixed method design to examine how using Ipads for learning impacted student achievement, motivation to learn, and learning strategies. Qualitatively the study examined observed student behaviors and student perceptions regarding the use of interactive technologies. Data was analyzed using descriptive statistics, t-tests, 2-way ANOVAs, and qualitative analysis. Quantitatively the results revealed no significant difference between students who used the interactive technology to learn and those who did not. Qualitative data revealed behaviors indicative of being highly engaged with the subject matter and the development of critical thinking skills which may improve student performance. Student perceptions also revealed overall positive experiences with using interactive technology in the classroom. It is recommended that further studies be done to look at using interactive technologies for a longer period of time using multiple subjects areas. This would provide a more in-depth exploration of interactive technologies on student achievement.

Mapping temporal dynamics in social interactions with unified structural equation modeling: A description and demonstration revealing time-dependent sex differences in play behavior

PubMed Central

Beltz, Adriene M.; Beekman, Charles; Molenaar, Peter C. M.; Buss, Kristin A.

2013-01-01

Developmental science is rich with observations of social interactions, but few available methodological and statistical approaches take full advantage of the information provided by these data. The authors propose implementation of the unified structural equation model (uSEM), a network analysis technique, for observational data coded repeatedly across time; uSEM captures the temporal dynamics underlying changes in behavior at the individual level by revealing the ways in which a single person influences – concurrently and in the future – other people. To demonstrate the utility of uSEM, the authors applied it to ratings of positive affect and vigor of activity during children’s unstructured laboratory play with unfamiliar, same-sex peers. Results revealed the time-dependent nature of sex differences in play behavior. For girls more than boys, positive affect was dependent upon peers’ prior positive affect. For boys more than girls, vigor of activity was dependent upon peers’ current vigor of activity. PMID:24039386

CD studies on ribonuclease A - oligonucleotides interactions.

PubMed Central

White, M D; Keren-Zur, M; Lapidot, Y

1977-01-01

The interaction of ApU, Aps4U, Aps4Up, ApAps4Up and Gps4U with RNase A was studied by CD difference spectroscopy. The use of 4-thiouridine (s4U) containing oligonucleotides enables to distinguish between the interaction of the different components of the ligand with the enzyme. The mode of binding of the oligonucleotides to the enzyme is described. From this mode of binding it is explained why Aps4U, for example, inhibits RNase A, while s4UpA serves as a substrate. PMID:866194

Virtually Naked: Virtual Environment Reveals Sex-Dependent Nature of Skin Disclosure

PubMed Central

Lomanowska, Anna M.; Guitton, Matthieu J.

2012-01-01

The human tendency to reveal or cover naked skin reflects a competition between the individual propensity for social interactions related to sexual appeal and interpersonal touch versus climatic, environmental, physical, and cultural constraints. However, due to the ubiquitous nature of these constraints, isolating on a large scale the spontaneous human tendency to reveal naked skin has remained impossible. Using the online 3-dimensional virtual world of Second Life, we examined spontaneous human skin-covering behavior unhindered by real-world climatic, environmental, and physical variables. Analysis of hundreds of avatars revealed that virtual females disclose substantially more naked skin than virtual males. This phenomenon was not related to avatar hypersexualization as evaluated by measurement of sexually dimorphic body proportions. Furthermore, analysis of skin-covering behavior of a population of culturally homogeneous avatars indicated that the propensity of female avatars to reveal naked skin persisted despite explicit cultural norms promoting less revealing attire. These findings have implications for further understanding how sex-specific aspects of skin disclosure influence human social interactions in both virtual and real settings. PMID:23300580

Virtually naked: virtual environment reveals sex-dependent nature of skin disclosure.

PubMed

Lomanowska, Anna M; Guitton, Matthieu J

2012-01-01

The human tendency to reveal or cover naked skin reflects a competition between the individual propensity for social interactions related to sexual appeal and interpersonal touch versus climatic, environmental, physical, and cultural constraints. However, due to the ubiquitous nature of these constraints, isolating on a large scale the spontaneous human tendency to reveal naked skin has remained impossible. Using the online 3-dimensional virtual world of Second Life, we examined spontaneous human skin-covering behavior unhindered by real-world climatic, environmental, and physical variables. Analysis of hundreds of avatars revealed that virtual females disclose substantially more naked skin than virtual males. This phenomenon was not related to avatar hypersexualization as evaluated by measurement of sexually dimorphic body proportions. Furthermore, analysis of skin-covering behavior of a population of culturally homogeneous avatars indicated that the propensity of female avatars to reveal naked skin persisted despite explicit cultural norms promoting less revealing attire. These findings have implications for further understanding how sex-specific aspects of skin disclosure influence human social interactions in both virtual and real settings.