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Sample records for induces loop structures

  1. Cisplatin induces loop structures and condensation of single DNA molecules

    PubMed Central

    Hou, Xi-Miao; Zhang, Xing-Hua; Wei, Kong-Ji; Ji, Chao; Dou, Shuo-Xing; Wang, Wei-Chi; Li, Ming; Wang, Peng-Ye

    2009-01-01

    Structural properties of single λ DNA treated with anti-cancer drug cisplatin were studied with magnetic tweezers and AFM. Under the effect of low-concentration cisplatin, the DNA became more flexible, with the persistence length decreased significantly from ∼52 to 15 nm. At a high drug concentration, a DNA condensation phenomenon was observed. Based on experimental results from both single-molecule and AFM studies, we propose a model to explain this kind of DNA condensation by cisplatin: first, di-adducts induce local distortions of DNA. Next, micro-loops of ∼20 nm appear through distant crosslinks. Then, large aggregates are formed through further crosslinks. Finally, DNA is condensed into a compact globule. Experiments with Pt(dach)Cl2 indicate that oxaliplatin may modify the DNA structures in the same way as cisplatin. The observed loop structure formation of DNA may be an important feature of the effect of platinum anti-cancer drugs that are analogous to cisplatin in structure. PMID:19129234

  2. Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.

    PubMed

    Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

    2015-11-01

    Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity. PMID:26239537

  3. The Structure of Coronal Loops

    NASA Technical Reports Server (NTRS)

    Antiochos, Spiro K.

    2009-01-01

    It is widely believed that the simple coronal loops observed by XUV imagers, such as EIT, TRACE, or XRT, actually have a complex internal structure consisting of many (perhaps hundreds) of unresolved, interwoven "strands". According to the nanoflare model, photospheric motions tangle the strands, causing them to reconnect and release the energy required to produce the observed loop plasma. Although the strands, themselves, are unresolved by present-generation imagers, there is compelling evidence for their existence and for the nanoflare model from analysis of loop intensities and temporal evolution. A problem with this scenario is that, although reconnection can eliminate some of the strand tangles, it cannot destroy helicity, which should eventually build up to observable scales. we consider, therefore, the injection and evolution of helicity by the nanoflare process and its implications for the observed structure of loops and the large-scale corona. we argue that helicity does survive and build up to observable levels, but on spatial and temporal scales larger than those of coronal loops. we discuss the implications of these results for coronal loops and the corona, in general .

  4. Structure of stem-loop IV of Tetrahymena telomerase RNA

    PubMed Central

    Chen, Yu; Fender, Jessica; Legassie, Jason D; Jarstfer, Michael B; Bryan, Tracy M; Varani, Gabriele

    2006-01-01

    Conserved domains within the RNA component of telomerase provide the template for reverse transcription, recruit protein components to the holoenzyme and are required for enzymatic activity. Among the functionally essential domains in ciliate telomerase RNA is stem-loop IV, which strongly stimulates telomerase activity and processivity even when provided in trans. The NMR structure of Tetrahymena thermophila stem-loop IV shows a highly structured distal stem-loop linked to a conformationally flexible template-proximal region by a bulge that severely kinks the entire RNA. Through extensive structure–function studies, we identify residues that contribute to both these structural features and to enzymatic activity, with no apparent effect on the binding of TERT protein. We propose that the bending induced by the GA bulge and the flexibility of the template-proximal region allow positioning of the prestructured apical loop during the catalytic cycle. PMID:16778765

  5. Pressure structure of solar coronal loops

    NASA Technical Reports Server (NTRS)

    Krishan, V.

    1987-01-01

    The steady state pressure structure of a coronal loop is discussed in terms of the MHD global invariants of an incompressible plasma. The steady state is represented by the superposition of two Chandrasekhar-Kendall functions corresponding to (n=m=0) and (n=m=1) modes. The relative contribution of the two modes (epsilon) is found to depend on the surface pressure of the coronal loop which is also the pressure of the external medium. The mixed mode state does not exist for high values of the external pressure because epsilon becomes complex.

  6. Fast loop modeling for protein structures

    NASA Astrophysics Data System (ADS)

    Zhang, Jiong; Nguyen, Son; Shang, Yi; Xu, Dong; Kosztin, Ioan

    2015-03-01

    X-ray crystallography is the main method for determining 3D protein structures. In many cases, however, flexible loop regions of proteins cannot be resolved by this approach. This leads to incomplete structures in the protein data bank, preventing further computational study and analysis of these proteins. For instance, all-atom molecular dynamics (MD) simulation studies of structure-function relationship require complete protein structures. To address this shortcoming, we have developed and implemented an efficient computational method for building missing protein loops. The method is database driven and uses deep learning and multi-dimensional scaling algorithms. We have implemented the method as a simple stand-alone program, which can also be used as a plugin in existing molecular modeling software, e.g., VMD. The quality and stability of the generated structures are assessed and tested via energy scoring functions and by equilibrium MD simulations. The proposed method can also be used in template-based protein structure prediction. Work supported by the National Institutes of Health [R01 GM100701]. Computer time was provided by the University of Missouri Bioinformatics Consortium.

  7. Analytic structure of one-loop coefficients

    NASA Astrophysics Data System (ADS)

    Feng, Bo; Wang, Honghui

    2013-05-01

    By the unitarity cut method, analytic expressions of one-loop coefficients have been given in spinor forms. In this paper, we present one-loop coefficients of various bases in Lorentz-invariant contraction forms of external momenta. Using these forms, the analytic structure of these coefficients becomes manifest. Firstly, coefficients of bases contain only second-type singularities while the first-type singularities are included inside scalar bases. Secondly, the highest degree of each singularity is correlated with the degree of the inner momentum in the numerator. Thirdly, the same singularities will appear in different coefficients, thus our explicit results could be used to provide a clear physical picture under various limits (such as soft or collinear limits) when combining contributions from all bases.

  8. The Fundamental Structure of Coronal Loops

    NASA Technical Reports Server (NTRS)

    Winebarger, Amy; Warren, Harry; Cirtain, Jonathan; Kobayashi, Ken; Korreck, Kelly; Golub, Leon; Kuzin, Sergey; Walsh, Robert; DePontieu, Bart; Title, Alan; Weber, Mark

    2012-01-01

    During the past ten years, solar physicists have attempted to infer the coronal heating mechanism by comparing observations of coronal loops with hydrodynamic model predictions. These comparisons often used the addition of sub ]resolution strands to explain the observed loop properties. On July 11, 2012, the High Resolution Coronal Imager (Hi ]C) was launched on a sounding rocket. This instrument obtained images of the solar corona was 0.2 ]0.3'' resolution in a narrowband EUV filter centered around 193 Angstroms. In this talk, we will compare these high resolution images to simultaneous density measurements obtained with the Extreme Ultraviolet Imaging Spectrograph (EIS) on Hinode to determine whether the structures observed with Hi ]C are resolved.

  9. Inhomogeneous Polyakov loop induced by inhomogeneous chiral condensates

    NASA Astrophysics Data System (ADS)

    Hayata, Tomoya; Yamamoto, Arata

    2015-05-01

    We study the spatial inhomogeneity of the Polyakov loop induced by inhomogeneous chiral condensates. We formulate an effective model of gluons on the background fields of chiral condensates, and perform its lattice simulation. On the background of inhomogeneous chiral condensates, the Polyakov loop exhibits an in-phase spatial oscillation with the chiral condensates. We also analyze the heavy quark potential and show that the inhomogeneous Polyakov loop indicates the inhomogeneous confinement of heavy quarks.

  10. Early structure formation from cosmic string loops

    SciTech Connect

    Shlaer, Benjamin; Vilenkin, Alexander; Loeb, Abraham E-mail: vilenkin@cosmos.phy.tufts.edu

    2012-05-01

    We examine the effects of cosmic strings on structure formation and on the ionization history of the universe. While Gaussian perturbations from inflation are known to provide the dominant contribution to the large scale structure of the universe, density perturbations due to strings are highly non-Gaussian and can produce nonlinear structures at very early times. This could lead to early star formation and reionization of the universe. We improve on earlier studies of these effects by accounting for high loop velocities and for the filamentary shape of the resulting halos. We find that for string energy scales Gμ∼>10{sup −7}, the effect of strings on the CMB temperature and polarization power spectra can be significant and is likely to be detectable by the Planck satellite. We mention shortcomings of the standard cosmological model of galaxy formation which may be remedied with the addition of cosmic strings, and comment on other possible observational implications of early structure formation by strings.

  11. Consistency of loop regularization method and divergence structure of QFTs Beyond one-loop order

    NASA Astrophysics Data System (ADS)

    Huang, Da; Li, Ling-Fong; Wu, Yue-Liang

    2013-04-01

    We study the problem how to deal with tensor-type two-loop integrals in the Loop Regularization (LORE) scheme. We use the two-loop photon vacuum polarization in the massless Quantum Electrodynamics (QED) as the example to present the general procedure. In the processes, we find a new divergence structure: the regulated result for each two-loop diagram contains a gauge-violating quadratic harmful divergent term even combined with their corresponding counterterm insertion diagrams. Only when we sum up over all the relevant diagrams do these quadratic harmful divergences cancel, recovering the gauge invariance and locality.

  12. An Antibody Loop Replacement Design Feasibility Study and a Loop-Swapped Dimer Structure

    SciTech Connect

    Clark, L.; Boriack-Sjodin, P; Day, E; Eldredge, J; Fitch, C; Jarpe, M; Miller, S; Li, Y; Simon, K; van Vlijmen, H

    2009-01-01

    A design approach was taken to investigate the feasibility of replacing single complementarity determining region (CDR) antibody loops. This approach may complement simpler mutation-based strategies for rational antibody design by expanding conformation space. Enormous crystal structure diversity is available, making CDR loops logical targets for structure-based design. A detailed analysis for the L1 loop shows that each loop length takes a distinct conformation, thereby allowing control on a length scale beyond that accessible to simple mutations. The L1 loop in the anti-VLA1 antibody was replaced with the L2 loop residues longer in an attempt to add an additional hydrogen bond and fill space on the antibody-antigen interface. The designs expressed well, but failed to improve affinity. In an effort to learn more, one design was crystallized and data were collected at 1.9 {angstrom} resolution. The designed L1 loop takes the qualitatively desired conformation; confirming that loop replacement by design is feasible. The crystal structure also shows that the outermost loop (residues Leu51-Ser68) is domain swapped with another monomer. Tryptophan fluorescence measurements were used to monitor unfolding as a function of temperature and indicate that the loop involved in domain swapping does not unfold below 60C. The domain-swapping is not directly responsible for the affinity loss, but is likely a side-effect of the structural instability which may contribute to affinity loss. A second round of design was successful in eliminating the dimerization through mutation of a residue (Leu51Ser) at the joint of the domain-swapped loop.

  13. Structure Prediction of RNA Loops with a Probabilistic Approach

    PubMed Central

    Li, Jun; Zhang, Jian; Wang, Jun; Li, Wenfei; Wang, Wei

    2016-01-01

    The knowledge of the tertiary structure of RNA loops is important for understanding their functions. In this work we develop an efficient approach named RNApps, specifically designed for predicting the tertiary structure of RNA loops, including hairpin loops, internal loops, and multi-way junction loops. It includes a probabilistic coarse-grained RNA model, an all-atom statistical energy function, a sequential Monte Carlo growth algorithm, and a simulated annealing procedure. The approach is tested with a dataset including nine RNA loops, a 23S ribosomal RNA, and a large dataset containing 876 RNAs. The performance is evaluated and compared with a homology modeling based predictor and an ab initio predictor. It is found that RNApps has comparable performance with the former one and outdoes the latter in terms of structure predictions. The approach holds great promise for accurate and efficient RNA tertiary structure prediction. PMID:27494763

  14. Structure Prediction of RNA Loops with a Probabilistic Approach.

    PubMed

    Li, Jun; Zhang, Jian; Wang, Jun; Li, Wenfei; Wang, Wei

    2016-08-01

    The knowledge of the tertiary structure of RNA loops is important for understanding their functions. In this work we develop an efficient approach named RNApps, specifically designed for predicting the tertiary structure of RNA loops, including hairpin loops, internal loops, and multi-way junction loops. It includes a probabilistic coarse-grained RNA model, an all-atom statistical energy function, a sequential Monte Carlo growth algorithm, and a simulated annealing procedure. The approach is tested with a dataset including nine RNA loops, a 23S ribosomal RNA, and a large dataset containing 876 RNAs. The performance is evaluated and compared with a homology modeling based predictor and an ab initio predictor. It is found that RNApps has comparable performance with the former one and outdoes the latter in terms of structure predictions. The approach holds great promise for accurate and efficient RNA tertiary structure prediction. PMID:27494763

  15. Development of Murray Loop Bridge for High Induced Voltage

    NASA Astrophysics Data System (ADS)

    Isono, Shigeki; Kawasaki, Katsutoshi; Kobayashi, Shin-Ichi; Ishihara, Hayato; Chiyajo, Kiyonobu

    In the case of the cable fault that ground fault resistance is less than 10MΩ, Murray Loop Bridge is excellent as a fault locator in location accuracy and the convenience. But, when the induction of several hundred V is taken from the single core cable which adjoins it, a fault location with the high voltage Murray Loop Bridge becomes difficult. Therefore, we developed Murray Loop Bridge, which could be applied even when the induced voltage of several hundred V occurs in the measurement cable. The evaluation of the fault location accuracy was done with the developed prototype by the actual line and the training equipment.

  16. Dissecting protein-induced DNA looping dynamics in real time

    PubMed Central

    Laurens, Niels; Bellamy, Stuart R. W.; Harms, August F.; Kovacheva, Yana S.; Halford, Stephen E.; Wuite, Gijs J. L.

    2009-01-01

    Many proteins that interact with DNA perform or enhance their specific functions by binding simultaneously to multiple target sites, thereby inducing a loop in the DNA. The dynamics and energies involved in this loop formation influence the reaction mechanism. Tethered particle motion has proven a powerful technique to study in real time protein-induced DNA looping dynamics while minimally perturbing the DNA–protein interactions. In addition, it permits many single-molecule experiments to be performed in parallel. Using as a model system the tetrameric Type II restriction enzyme SfiI, that binds two copies of its recognition site, we show here that we can determine the DNA–protein association and dissociation steps as well as the actual process of protein-induced loop capture and release on a single DNA molecule. The result of these experiments is a quantitative reaction scheme for DNA looping by SfiI that is rigorously compared to detailed biochemical studies of SfiI looping dynamics. We also present novel methods for data analysis and compare and discuss these with existing methods. The general applicability of the introduced techniques will further enhance tethered particle motion as a tool to follow DNA–protein dynamics in real time. PMID:19586932

  17. Automated event generation for loop-induced processes

    DOE PAGESBeta

    Hirschi, Valentin; Mattelaer, Olivier

    2015-10-22

    We present the first fully automated implementation of cross-section computation and event generation for loop-induced processes. This work is integrated in the MadGraph5_aMC@NLO framework. We describe the optimisations implemented at the level of the matrix element evaluation, phase space integration and event generation allowing for the simulation of large multiplicity loop-induced processes. Along with some selected differential observables, we illustrate our results with a table showing inclusive cross-sections for all loop-induced hadronic scattering processes with up to three final states in the SM as well as for some relevant 2 → 4 processes. Furthermore, many of these are computed heremore » for the first time.« less

  18. Automated event generation for loop-induced processes

    SciTech Connect

    Hirschi, Valentin; Mattelaer, Olivier

    2015-10-22

    We present the first fully automated implementation of cross-section computation and event generation for loop-induced processes. This work is integrated in the MadGraph5_aMC@NLO framework. We describe the optimisations implemented at the level of the matrix element evaluation, phase space integration and event generation allowing for the simulation of large multiplicity loop-induced processes. Along with some selected differential observables, we illustrate our results with a table showing inclusive cross-sections for all loop-induced hadronic scattering processes with up to three final states in the SM as well as for some relevant 2 → 4 processes. Furthermore, many of these are computed here for the first time.

  19. Protein short loop prediction in terms of a structural alphabet.

    PubMed

    Tyagi, Manoj; Bornot, Aurélie; Offmann, Bernard; de Brevern, Alexandre G

    2009-08-01

    Loops connect regular secondary structures. In many instances, they are known to play crucial biological roles. To bypass the limitation of secondary structure description, we previously defined a structural alphabet composed of 16 structural prototypes, called Protein Blocks (PBs). It leads to an accurate description of every region of 3D protein backbones and has been used in local structure prediction. In the present study, we used our structural alphabet to predict the loops connecting two repetitive structures. Thus, we showed interest to take into account the flanking regions, leading to prediction rate improvement up to 19.8%, but we also underline the sensitivity of such an approach. This research can be used to propose different structures for the loops and to probe and sample their flexibility. It is a useful tool for ab initio loop prediction and leads to insights into flexible docking approach. PMID:19625218

  20. Observation of Nonlinear Looped Band Structure of Bose-Einstein condensates in an optical lattice

    NASA Astrophysics Data System (ADS)

    Goldschmidt, Elizabeth; Koller, Silvio; Brown, Roger; Wyllie, Robert; Wilson, Ryan; Porto, Trey

    2016-05-01

    We study experimentally the stability of excited, interacting states of bosons in a double-well optical lattice in regimes where the nonlinear interactions are expected to induce ``swallow-tail'' looped band structure. By carefully preparing different initial coherent states and observing their subsequent decay, we observe distinct decay rates, which provide direct evidence for multi-valued band structure. The double well lattice both stabilizes the looped band structure and allows for dynamic preparation of different initial states, including states within the loop structure. We confirm our state preparation procedure with dynamic Gross-Pitaevskii calculations. The excited loop states are found to be more stable than dynamically unstable ground states, but decay faster than expected based on a mean-field stability calculation, indicating the importance of correlations beyond a mean-field description. Now at Georgia Tech Research Institute.

  1. FINE STRUCTURES AND OVERLYING LOOPS OF CONFINED SOLAR FLARES

    SciTech Connect

    Yang, Shuhong; Zhang, Jun; Xiang, Yongyuan

    2014-10-01

    Using the Hα observations from the New Vacuum Solar Telescope at the Fuxian Solar Observatory, we focus on the fine structures of three confined flares and the issue why all the three flares are confined instead of eruptive. All the three confined flares take place successively at the same location and have similar morphologies, so can be termed homologous confined flares. In the simultaneous images obtained by the Solar Dynamics Observatory, many large-scale coronal loops above the confined flares are clearly observed in multi-wavelengths. At the pre-flare stage, two dipoles emerge near the negative sunspot, and the dipolar patches are connected by small loops appearing as arch-shaped Hα fibrils. There exists a reconnection between the small loops, and thus the Hα fibrils change their configuration. The reconnection also occurs between a set of emerging Hα fibrils and a set of pre-existing large loops, which are rooted in the negative sunspot, a nearby positive patch, and some remote positive faculae, forming a typical three-legged structure. During the flare processes, the overlying loops, some of which are tracked by activated dark materials, do not break out. These direct observations may illustrate the physical mechanism of confined flares, i.e., magnetic reconnection between the emerging loops and the pre-existing loops triggers flares and the overlying loops prevent the flares from being eruptive.

  2. Asymmetric structure of five and six membered DNA hairpin loops

    NASA Technical Reports Server (NTRS)

    Baumann, U.; Chang, S.

    1995-01-01

    The tertiary structure of nucleic acid hairpins was elucidated by means of the accessibility of the single-strand-specific nuclease from mung bean. This molecular probe has proven especially useful in determining details of the structural arrangement of the nucleotides within a loop. In this study 3'-labeling is introduced to complement previously used 5'-labeling in order to assess and to exclude possible artifacts of the method. Both labeling procedures result in mutually consistent cleavage patterns. Therefore, methodological artifacts can be excluded and the potential of the nuclease as structural probe is increased. DNA hairpins with five and six membered loops reveal an asymmetric loop structure with a sharp bend of the phosphate-ribose backbone between the second and third nucleotide on the 3'-side of a loop. These hairpin structures differ from smaller loops with 3 or 4 members, which reveal this type of bend between the first and second 3' nucleotide, and resemble with respect to the asymmetry anticodon loops of tRNA.

  3. Structural study of elements of Tetrahymena telomerase RNA stem–loop IV domain important for function

    PubMed Central

    Richards, Rebecca J.; Wu, Haihong; Trantirek, Lukas; O'Connor, Catherine M.; Collins, Kathleen; Feigon, Juli

    2006-01-01

    Tetrahymena telomerase RNA (TER) contains several regions in addition to the template that are important for function. Central among these is the stem–loop IV domain, which is involved in both catalysis and RNP assembly, and includes binding sites for both the holoenzyme assembly protein p65 and telomerase reverse transcriptase (TERT). Stem–loop IV contains two regions with high evolutionary sequence conservation: a central GA bulge between helices, and a terminal loop. We solved the solution structure of loop IV and modeled the structure of the helical region containing the GA bulge, using NMR and residual dipolar couplings. The central GA bulge with flanking C–G base pairs induces a ∼50° semi-rigid bend in the helix. Loop IV is highly structured, and contains a conserved C–U base pair at the top of the helical stem. Analysis of new and previous biochemical data in light of the structure provides a rationale for some of the sequence conservation in this region of TER. The results suggest that during holoenzyme assembly the protein p65 recognizes a bend in stem IV, and this binding to central stem IV helps to position the structured loop IV for interaction with TERT and other region(s) of TER. PMID:16809815

  4. ArchDB 2014: structural classification of loops in proteins

    PubMed Central

    Bonet, Jaume; Planas-Iglesias, Joan; Garcia-Garcia, Javier; Marín-López, Manuel A.; Fernandez-Fuentes, Narcis; Oliva, Baldo

    2014-01-01

    The function of a protein is determined by its three-dimensional structure, which is formed by regular (i.e. β-strands and α-helices) and non-periodic structural units such as loops. Compared to regular structural elements, non-periodic, non-repetitive conformational units enclose a much higher degree of variability—raising difficulties in the identification of regularities, and yet represent an important part of the structure of a protein. Indeed, loops often play a pivotal role in the function of a protein and different aspects of protein folding and dynamics. Therefore, the structural classification of protein loops is an important subject with clear applications in homology modelling, protein structure prediction, protein design (e.g. enzyme design and catalytic loops) and function prediction. ArchDB, the database presented here (freely available at http://sbi.imim.es/archdb), represents such a resource and has been an important asset for the scientific community throughout the years. In this article, we present a completely reworked and updated version of ArchDB. The new version of ArchDB features a novel, fast and user-friendly web-based interface, and a novel graph-based, computationally efficient, clustering algorithm. The current version of ArchDB classifies 149,134 loops in 5739 classes and 9608 subclasses. PMID:24265221

  5. Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability

    PubMed Central

    Sollier, Julie; Stork, Caroline Townsend; García-Rubio, María L.; Paulsen, Renee D.; Aguilera, Andrés; Cimprich, Karlene A.

    2014-01-01

    Summary R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability, however the mechanisms underlying R-loop induced DNA damage remain unknown. Here we demonstrate in human cells that R-loops induced by the absence of diverse RNA processing factors, including the RNA/DNA helicases Aquarius (AQR) and Senataxin (SETX), or by the inhibition of topoisomerase I, are actively processed into DNA double-strand breaks (DSBs) by the nucleotide excision repair endonucleases XPF and XPG. Surprisingly, DSB formation requires the transcription-coupled nucleotide excision repair (TC-NER) factor Cockayne syndrome group B (CSB), but not the global genome repair protein XPC. These findings reveal an unexpected and potentially deleterious role for TC-NER factors in driving R-loop-induced DNA damage and genome instability. PMID:25435140

  6. On the structure of solar and stellar coronae - Loops and loop heat transport

    NASA Technical Reports Server (NTRS)

    Litwin, Christof; Rosner, Robert

    1993-01-01

    We discuss the principal constraints on mechanisms for structuring and heating the outer atmospheres - the coronae - of stars. We argue that the essential cause of highly localized heating in the coronae of stars like the sun is the spatially intermittent nature of stellar surface magnetic fields, and that the spatial scale of the resulting coronal structures is related to the spatial structure of the photospheric fields. We show that significant constraints on coronal heating mechanisms derive from the observed variations in coronal emission, and, in addition, show that the observed structuring perpendicular to coronal magnetic fields imposes severe constraints on mechanisms for heat dispersal in the low-beta atmosphere. In particular, we find that most of commonly considered mechanisms for heat dispersal, such as anomalous diffusion due to plasma turbulence or magnetic field line stochasticity, are much too slow to account for the observed rapid heating of coronal loops. The most plausible mechanism appears to be reconnection at the interface between two adjacent coronal flux bundles. Based on a model invoking hyperresistivity, we show that such a mechanism naturally leads to dominance of isolated single bright coronal loops and to bright coronal plasma structures whose spatial scale transverse to the local magnetic field is comparable to observed dimensions of coronal X-ray loops.

  7. R-loops induce repressive chromatin marks over mammalian gene terminators

    PubMed Central

    Skourti-Stathaki, Konstantina; Kamieniarz-Gdula, Kinga; Proudfoot, Nicholas J.

    2014-01-01

    The formation of R-loops is a natural consequence of the transcription process, caused by invasion of the DNA duplex by nascent transcripts. These structures have been considered rare transcriptional by-products with potential harmful effects on genome integrity, due to the fragility of the displaced DNA coding strand1. However R-loops may also possess beneficial effects as their widespread formation has been detected over CpG island promoters in human genes2,3. Furthermore we have previously shown that R-loops are particularly enriched over G-rich terminator elements. These facilitate RNA polymerase II (Pol II) pausing prior to efficient termination4. Here we reveal an unanticipated link between R-loops and RNA interference (RNAi)-dependent H3K9me2 formation over pause site termination regions of mammalian protein coding genes. We show that R-loops induce antisense transcription over these pause elements which in turn lead to the generation of double-strand RNA (dsRNA) and recruitment of Dicer, Ago1, Ago2, and G9a histone lysine methyltransferase (HKMT). Consequently an H3K9me2 repressive mark is formed and Heterochromatin Protein 1γ (HP1γ) is recruited, that reinforces Pol II pausing prior to efficient transcriptional termination. We predict that R-loops promote a chromatin architecture that defines the termination region for a substantial subset of mammalian genes. PMID:25296254

  8. LINE-OF-SIGHT SHELL STRUCTURE OF THE CYGNUS LOOP

    SciTech Connect

    Uchida, Hiroyuki; Tsunemi, Hiroshi; Katsuda, Satoru; Kimura, Masashi; Kosugi, Hiroko; Takahashi, Hiroaki

    2009-11-10

    We conducted a comprehensive study on the shell structure of the Cygnus Loop using 41 observation data obtained by the Suzaku and the XMM-Newton satellites. To investigate the detailed plasma structure of the Cygnus Loop, we divided our fields of view into 1042 box regions. From the spectral analysis, the spectra obtained from the limb of the Loop are well fitted by the single-component non-equilibrium ionization plasma model. On the other hand, the spectra obtained from the inner regions are well fitted by the two-component model. As a result, we confirmed that the low-temperature and high-temperature components originated from the surrounding interstellar matter (ISM) and the ejecta of the Loop, respectively. From the best-fit results, we showed a flux distribution of the ISM component. The distribution clearly shows the limb-brightening structure, and we found out some low-flux regions. Among them, the south blowout region has the lowest flux. We also found other large low-flux regions at slightly west and northeast from the center. We estimated the former thin shell region to be approx1.{sup 0}3 in diameter and concluded that there exists a blowout along the line of sight in addition to the south blowout. We also calculated the emission measure distribution of the ISM component and showed that the Cygnus Loop is far from the result obtained by a simple Sedov evolution model. From the results, we support that the Cygnus Loop originated from a cavity explosion. The emission measure distribution also suggests that the cavity-wall density is higher in the northeast than that in the southwest. These results suggest that the thickness of the cavity wall surrounding the Cygnus Loop is not uniform.

  9. A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu

    PubMed Central

    Mercier, Evan; Girodat, Dylan; Wieden, Hans-Joachim

    2015-01-01

    The phosphate-binding loop (P-loop) is a conserved sequence motif found in mononucleotide-binding proteins. Little is known about the structural dynamics of this region and its contribution to the observed nucleotide binding properties. Understanding the underlying design principles is of great interest for biomolecular engineering applications. We have used rapid-kinetics measurements in vitro and molecular dynamics (MD) simulations in silico to investigate the relationship between GTP-binding properties and P-loop structural dynamics in the universally conserved Elongation Factor (EF) Tu. Analysis of wild type EF-Tu and variants with substitutions at positions in or adjacent to the P-loop revealed a correlation between P-loop flexibility and the entropy of activation for GTP dissociation. The same variants demonstrate more backbone flexibility in two N-terminal amino acids of the P-loop during force-induced EF-Tu·GTP dissociation in Steered Molecular Dynamics simulations. Amino acids Gly18 and His19 are involved in stabilizing the P-loop backbone via interactions with the adjacent helix C. We propose that these P-loop/helix C interactions function as a conserved P-loop anchoring module and identify the presence of P-loop anchors within several GTPases and ATPases suggesting their evolutionary conservation. PMID:25566871

  10. Structural studies on an internal loop from a hairpin ribozyme

    SciTech Connect

    Cai, Z.; SantaLucia, J. Jr.; Tinoco, I. Jr.

    1994-12-01

    Ribozymes, RNA enzymes, catalyze site-specific RNA cleavage and ligation reactions. We are studying the three-dimensional structure of a hairpin ribozyme derived from the minus strand of tobacco ring spot virus satellite RNA ((-)sTRSV), which has been engineering to specifically cleave the HIV-1 RNA. The minimum structure for the catalytic reaction involves a 50-nucleotide ribozyme and a 14-nucleotide substrate. The proposed secondary structure of the ribozyme-substrate complex consists of four short helices separated by two internal loops. The relatively large size (64-nucleotide) of the ribozyme-substrate complex presents formidable problems in solving the structure using NMR. Therefore we are studying smaller structural subunits of the complex. We are determining the high resolution structure of the symmetric internal loop involving the cleavage site and the flanking helices. One strand of the internal loop was selectively {sup 13}C-labeled at C8 of each purine and C6 of each pyrimidine. By using {sup 13}C-edited two-dimensional NMR, the proton NOESY spectrum was greatly simplified. This allowed unambiguous sequential proton resonance assignments along each strand. Three-dimensional {sup 1}-{sup 13}C HMQC-NOESY was used to further facilitate resonance assignments. We are also enzymatically synthesizing the entire 50-nucleotide ribozyme and will combine it with the {sup 13}C-labeled substrate. Through comparison of the NOE connectivities of the labeled nucleotides from the internal loop alone with those from the entire complex, the differences between the two structures can be elucidated.

  11. Collider study on the loop-induced dark matter mediation

    NASA Astrophysics Data System (ADS)

    Tsai, Yuhsin

    2016-06-01

    Collider experiments are one of the most promising ways to constrain Dark Matter (DM) interactions. For DM couplings involving light mediators, especially for the loop-mediated interactions, a meaningful interpretation of the results requires to go beyond effective field theory. In this note we discuss the study of the magnetic dipole interacting DM, focusing on a model with anarchic dark flavor structure. By including the momentum-dependent form factors that mediate the coupling - given by the Dark Penguin - in collider processes, we study bounds from monophoton, diphoton, and non-pointing photon searches at the LHC. We also compare our results to constraints from the direct detection experiments.

  12. Effect of coronal structure on loop oscillations: exponential profiles

    NASA Astrophysics Data System (ADS)

    Díaz, A. J.; Donnelly, G. R.; Roberts, B.

    2007-12-01

    Aims:The role of longitudinal structuring of the surrounding corona on the modes of oscillation of a coronal magnetic flux tube was studied in Donnelly et al. (2006) for a piecewise uniform profile. Here we investigate whether a more realistic continuous exponential profile changes the conclusions drawn from that paper. Methods: A partial differential equation is derived for the total pressure perturbation of the fast modes, which is then decomposed by separation of variables. The longitudinal part is solved numerically, obtaining a dispersion relation. These results are supported by an analytical investigation in terms of Bessel functions of purely imaginary order. Results: Structure in the interior of the loop shifts the frequencies of the modes (and may trap higher harmonics), an effect which can be understood by taking an averaged profile with a suitable weight. Structure in the environment modifies only slightly the frequencies, but displaces the cutoff frequency. The shift due to the structure in the fundamental period is small, but the ratio between the periods of the fundamental mode and its harmonics can be used to probe the structure. Conclusions: The results support our previous study in a more realistic, continuously varying profile and provide limits to the conclusions drawn in coronal seismology if an unstructured loop is used. Also, the ratio between the period of the fundamental kink (even) mode and its first (odd) harmonic is proven as an extra seismological tool for coronal loops.

  13. The Temperature Structure of Some Typical Flare Loop Systems

    NASA Astrophysics Data System (ADS)

    Gou, T.; Liu, R.; Wang, Y.

    2014-12-01

    Solar flares and coronal mass ejections (CMEs) are the main drivers of disastrous space weather. To understand the physical processes behind solar eruptions is the important base and prerequisite for reliable space weather prediction. Studying thermodynamic properties of flaring structures will help understand the flare energy-release process. Here we show some flares which occur at the solar limb or near the limb and have typical cusp-like flare loops. With high-resolution data provided by six EUV channels of the AIA instrument on board SDO, we utilize the differential emission measure (DEM) method to study the flare loop system, focusing on the temperature of the cusp structure, and the results are compared with previous studies.

  14. Conformational Sampling in Template-Free Protein Loop Structure Modeling: An Overview

    PubMed Central

    Li, Yaohang

    2013-01-01

    Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a “mini protein folding problem” under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized. PMID:24688696

  15. Nucleation of an Allosteric Response via Ligand-induced Loop Folding

    PubMed Central

    Naganathan, Saranga; Beckett, Dorothy

    2009-01-01

    The Escherichia coli biotin repressor, BirA, is an allosteric transcription regulatory protein to which binding of the small ligand corepressor, biotinyl-5’-AMP, promotes homodimerization and subsequent DNA binding. Structural data indicate that the apo- or unliganded repressor is characterized by four partially disordered loops that are ordered in the ligand-bound dimer. While three of these loops participate directly in the dimerization, the fourth, consisting of residues 212-234 is distal to the interface. This loop, which is ordered around the adenine ring of the adenylate in the BirA adenylate structure, is referred to as the adenylate binding loop or ABL. Although residues in the loop do not directly interact with the ligand, a hydrophobic cluster consisting of a tryptophan and two valine side chains assembles over the adenine base. Results of previous measurements suggest that folding of the ABL is integral to the allosteric response. This idea and the role of the hydrophobic cluster in the process were investigated by systematic replacement of each side chain in the cluster with alanine and analysis of the variant proteins for small ligand binding and dimerization. Isothermal titration calorimetry measurements indicate defects in adenylate binding for all ABL variants. Additionally, sedimentation equilibrium measurements reveal that coupling between adenylate binding and dimerization is compromised in each mutant. Partial proteolysis measurements indicate that the mutants are defective in ligand-linked folding of the ABL. These results indicate that the hydrophobic cluster is critical to the ligand-induced disorder-to-order transition in the ABL and that this transition is integral to the allosteric response in the biotin repressor. PMID:17765263

  16. Band-structure loops and multistability in cavity QED

    SciTech Connect

    Prasanna Venkatesh, B.; O'Dell, D. H. J.; Larson, J.

    2011-06-15

    We calculate the band structure of ultracold atoms located inside a laser-driven optical cavity. For parameters where the atom-cavity system exhibits bistability, the atomic band structure develops loop structures akin to the ones predicted for Bose-Einstein condensates in ordinary (noncavity) optical lattices. However, in our case the nonlinearity derives from the cavity back-action rather than from direct interatomic interactions. We find both bi- and tristable regimes associated with the lowest band, and show that the multistability we observe can be analyzed in terms of swallowtail catastrophes. Dynamic and energetic stability of the mean-field solutions is also discussed, and we show that the bistable solutions have, as expected, one unstable and two stable branches. The presence of loops in the atomic band structure has important implications for proposals concerning Bloch oscillations of atoms inside optical cavities [Peden et al., Phys. Rev. A 80, 043803 (2009); Prasanna Venkatesh et al., Phys. Rev. A 80, 063834 (2009)].

  17. Discrete state model and accurate estimation of loop entropy of RNA secondary structures.

    PubMed

    Zhang, Jian; Lin, Ming; Chen, Rong; Wang, Wei; Liang, Jie

    2008-03-28

    Conformational entropy makes important contribution to the stability and folding of RNA molecule, but it is challenging to either measure or compute conformational entropy associated with long loops. We develop optimized discrete k-state models of RNA backbone based on known RNA structures for computing entropy of loops, which are modeled as self-avoiding walks. To estimate entropy of hairpin, bulge, internal loop, and multibranch loop of long length (up to 50), we develop an efficient sampling method based on the sequential Monte Carlo principle. Our method considers excluded volume effect. It is general and can be applied to calculating entropy of loops with longer length and arbitrary complexity. For loops of short length, our results are in good agreement with a recent theoretical model and experimental measurement. For long loops, our estimated entropy of hairpin loops is in excellent agreement with the Jacobson-Stockmayer extrapolation model. However, for bulge loops and more complex secondary structures such as internal and multibranch loops, we find that the Jacobson-Stockmayer extrapolation model has large errors. Based on estimated entropy, we have developed empirical formulae for accurate calculation of entropy of long loops in different secondary structures. Our study on the effect of asymmetric size of loops suggest that loop entropy of internal loops is largely determined by the total loop length, and is only marginally affected by the asymmetric size of the two loops. Our finding suggests that the significant asymmetric effects of loop length in internal loops measured by experiments are likely to be partially enthalpic. Our method can be applied to develop improved energy parameters important for studying RNA stability and folding, and for predicting RNA secondary and tertiary structures. The discrete model and the program used to calculate loop entropy can be downloaded at http://gila.bioengr.uic.edu/resources/RNA.html. PMID:18376982

  18. SELF-ORGANIZED BRAIDING AND THE STRUCTURE OF CORONAL LOOPS

    SciTech Connect

    Berger, Mitchell A.; Asgari-Targhi, Mahboubeh E-mail: m.asgari@ucl.ac.u

    2009-11-01

    The Parker model for heating of the solar corona involves reconnection of braided magnetic flux elements. Much of this braiding is thought to occur at as yet unresolved scales, for example, braiding of threads within an extreme-ultraviolet or X-ray loop. However, some braiding may be still visible at scales accessible to TRACE or Hinode. We suggest that attempts to estimate the amount of braiding at these scales must take into account the degree of coherence of the braid structure. In this paper, we examine the effect of reconnection on the structure of a braided magnetic field. We demonstrate that simple models of braided magnetic fields which balance the input of topological structure with reconnection evolve to a self-organized critical state. An initially random braid can become highly ordered, with coherence lengths obeying power-law distributions. The energy released during reconnection also obeys a power law. Our model gives more frequent (but smaller) energy releases nearer to the ends of a coronal loop.

  19. Structural Basis of Human p70 Ribosomal S6 Kinase-1 Regulation by Activation Loop Phosphorylation

    SciTech Connect

    Sunami, Tomoko; Byrne, Noel; Diehl, Ronald E.; Funabashi, Kaoru; Hall, Dawn L.; Ikuta, Mari; Patel, Sangita B.; Shipman, Jennifer M.; Smith, Robert F.; Takahashi, Ikuko; Zugay-Murphy, Joan; Iwasawa, Yoshikazu; Lumb, Kevin J.; Munshi, Sanjeev K.; Sharma, Sujata

    2010-03-04

    p70 ribosomal S6 kinase (p70S6K) is a downstream effector of the mTOR signaling pathway involved in cell proliferation, cell growth, cell-cycle progression, and glucose homeostasis. Multiple phosphorylation events within the catalytic, autoinhibitory, and hydrophobic motif domains contribute to the regulation of p70S6K. We report the crystal structures of the kinase domain of p70S6K1 bound to staurosporine in both the unphosphorylated state and in the 3{prime}-phosphoinositide-dependent kinase-1-phosphorylated state in which Thr-252 of the activation loop is phosphorylated. Unphosphorylated p70S6K1 exists in two crystal forms, one in which the p70S6K1 kinase domain exists as a monomer and the other as a domain-swapped dimer. The crystal structure of the partially activated kinase domain that is phosphorylated within the activation loop reveals conformational ordering of the activation loop that is consistent with a role in activation. The structures offer insights into the structural basis of the 3{prime}-phosphoinositide-dependent kinase-1-induced activation of p70S6K and provide a platform for the rational structure-guided design of specific p70S6K inhibitors.

  20. Porous Foam Based Wick Structures for Loop Heat Pipes

    NASA Technical Reports Server (NTRS)

    Silk, Eric A.

    2012-01-01

    As part of an effort to identify cost efficient fabrication techniques for Loop Heat Pipe (LHP) construction, NASA Goddard Space Flight Center's Cryogenics and Fluids Branch collaborated with the U.S. Naval Academy s Aerospace Engineering Department in Spring 2012 to investigate the viability of carbon foam as a wick material within LHPs. The carbon foam was manufactured by ERG Aerospace and machined to geometric specifications at the U.S. Naval Academy s Materials, Mechanics and Structures Machine Shop. NASA GSFC s Fractal Loop Heat Pipe (developed under SBIR contract #NAS5-02112) was used as the validation LHP platform. In a horizontal orientation, the FLHP system demonstrated a heat flux of 75 Watts per square centimeter with deionized water as the working fluid. Also, no failed start-ups occurred during the 6 week performance testing period. The success of this study validated that foam can be used as a wick structure. Furthermore, given the COTS status of foam materials this study is one more step towards development of a low cost LHP.

  1. Effect of loop structure of bovine lactoferricin on apoptosis in Jurkat cells.

    PubMed

    Zhang, Tie-nan; Yang, Wei; Liu, Ning

    2010-06-01

    Bovine lactoferricin (LfcinB) is a cationic peptide that selectively induces apoptosis in Jurkat cells. However less is known about the influence of this kind of apoptosis on the intra-cellular ceramide metabolism and the structure-function relationship between the loop structure of LfcinB and its action of inducing apoptosis in Jurkat cells. In the present study, the artificially synthesized LfcinB and LfcinB-derived peptide (Cys 19 residue in LfcinB was replaced by Ala) was added in Jurkat cells, the nucleolus shape was observed by fluorescent microscopy, the ceramide concentration in Jurkat cells was determined by reversed phase high performance liquid chromatography (RP-HPLC). The results of MTT assay showed that LfcinB inhibited proliferation of Jurkat cells, and the inhibition rate was approximately 18.90%. Moreover, the inhibition rate of LfcinB together with MAPP was upto approximately 59.89%. The RP-HPLC result showed that LfcinB improved the ceramide level in Jurkat cells. By using the DNA fragmentation assay and observing the nucleolus shape, the result displayed deficiency of the loop structure could cause LfcinB losing the biological activity of inducing apoptosis in Jurkat cells. PMID:20237822

  2. Plasmon induced transparency in loop-stub resonator-coupled waveguide systems

    NASA Astrophysics Data System (ADS)

    Ye, Jiulin; Wang, Faqiang; Liang, Ruisheng; Wei, Zhongchao; Meng, Hongyun; Zhong, Jiewen; Jiang, Lihua

    2016-07-01

    We firstly investigate plasmon induced transparency (PIT) effect in a metal-dielectric-metal (MDM) waveguide coupled to a single loop stub resonator by finite difference time domain method (FDTD). Compared with previous PIT sup based on MDM waveguide, PIT phenomena can be realized in a single plasmonic composite nanocavity without employment of additional optical elements. Plasmon induced transparency windows can be controlled by adjusting the geometrical parameters of the vertical branches or the horizontal branch in the plasmonic structure. The red-shift of PIT peak is almost linearly proportional to the refractive index of the horizontal branch. This plasmonic system takes the advantages of easy fabrication and compactness. The results may pave a way for the dynamic control of light in highly integrated optical circuits, which can realize ultrafast switching, light storage and nanosensor devices.

  3. Structure and dynamics of DNA loops on nucleosomes studied with atomistic, microsecond-scale molecular dynamics

    PubMed Central

    Pasi, Marco; Lavery, Richard

    2016-01-01

    DNA loop formation on nucleosomes is strongly implicated in chromatin remodeling and occurs spontaneously in nucleosomes subjected to superhelical stress. The nature of such loops depends crucially on the balance between DNA deformation and DNA interaction with the nucleosome core. Currently, no high-resolution structural data on these loops exist. Although uniform rod models have been used to study loop size and shape, these models make assumptions concerning DNA mechanics and DNA–core binding. We present here atomic-scale molecular dynamics simulations for two different loop sizes. The results point to the key role of localized DNA kinking within the loops. Kinks enable the relaxation of DNA bending strain to be coupled with improved DNA–core interactions. Kinks lead to small, irregularly shaped loops that are asymmetrically positioned with respect to the nucleosome core. We also find that loop position can influence the dynamics of the DNA segments at the extremities of the nucleosome. PMID:27098037

  4. Structure and dynamics of DNA loops on nucleosomes studied with atomistic, microsecond-scale molecular dynamics.

    PubMed

    Pasi, Marco; Lavery, Richard

    2016-06-20

    DNA loop formation on nucleosomes is strongly implicated in chromatin remodeling and occurs spontaneously in nucleosomes subjected to superhelical stress. The nature of such loops depends crucially on the balance between DNA deformation and DNA interaction with the nucleosome core. Currently, no high-resolution structural data on these loops exist. Although uniform rod models have been used to study loop size and shape, these models make assumptions concerning DNA mechanics and DNA-core binding. We present here atomic-scale molecular dynamics simulations for two different loop sizes. The results point to the key role of localized DNA kinking within the loops. Kinks enable the relaxation of DNA bending strain to be coupled with improved DNA-core interactions. Kinks lead to small, irregularly shaped loops that are asymmetrically positioned with respect to the nucleosome core. We also find that loop position can influence the dynamics of the DNA segments at the extremities of the nucleosome. PMID:27098037

  5. Short loop length and high thermal stability determine genomic instability induced by G-quadruplex-forming minisatellites

    PubMed Central

    Piazza, Aurèle; Adrian, Michael; Samazan, Frédéric; Heddi, Brahim; Hamon, Florian; Serero, Alexandre; Lopes, Judith; Teulade-Fichou, Marie-Paule; Phan, Anh Tuân; Nicolas, Alain

    2015-01-01

    G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids, with various biological roles. However, structural features dictating their formation and/or functionin vivo are unknown. InS. cerevisiae, the pathological persistency of G4 within the CEB1 minisatellite induces its rearrangement during leading-strand replication. We now show that several other G4-forming sequences remain stable. Extensive mutagenesis of the CEB25 minisatellite motif reveals that only variants with very short (≤ 4 nt) G4 loops preferentially containing pyrimidine bases trigger genomic instability. Parallel biophysical analyses demonstrate that shortening loop length does not change the monomorphic G4 structure of CEB25 variants but drastically increases its thermal stability, in correlation with thein vivo instability. Finally, bioinformatics analyses reveal that the threat for genomic stability posed by G4 bearing short pyrimidine loops is conserved inC. elegans and humans. This work provides a framework explanation for the heterogeneous instability behavior of G4-forming sequencesin vivo, highlights the importance of structure thermal stability, and questions the prevailing assumption that G4 structures with short or longer loops are as likely to formin vivo. PMID:25956747

  6. Nucleotide Excision Repair, Mismatch Repair, and R-Loops Modulate Convergent Transcription-Induced Cell Death and Repeat Instability

    PubMed Central

    Lin, Yunfu; Wilson, John H.

    2012-01-01

    Expansion of CAG•CTG tracts located in specific genes is responsible for 13 human neurodegenerative disorders, the pathogenic mechanisms of which are not yet well defined. These disease genes are ubiquitously expressed in human tissues, and transcription has been identified as one of the major pathways destabilizing the repeats. Transcription-induced repeat instability depends on transcription-coupled nucleotide excision repair (TC-NER), the mismatch repair (MMR) recognition component MSH2/MSH3, and RNA/DNA hybrids (R-loops). Recently, we reported that simultaneous sense and antisense transcription–convergent transcription–through a CAG repeat not only promotes repeat instability, but also induces a cell stress response, which arrests the cell cycle and eventually leads to massive cell death via apoptosis. Here, we use siRNA knockdowns to investigate whether NER, MMR, and R-loops also modulate convergent-transcription-induced cell death and repeat instability. We find that siRNA-mediated depletion of TC-NER components increases convergent transcription-induced cell death, as does the simultaneous depletion of RNase H1 and RNase H2A. In contrast, depletion of MSH2 decreases cell death. These results identify TC-NER, MMR recognition, and R-loops as modulators of convergent transcription-induced cell death and shed light on the molecular mechanism involved. We also find that the TC-NER pathway, MSH2, and R-loops modulate convergent transcription-induced repeat instability. These observations link the mechanisms of convergent transcription-induced repeat instability and convergent transcription-induced cell death, suggesting that a common structure may trigger both outcomes. PMID:23056461

  7. Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 × 1 Nucleotide UU Internal Loop Conformations

    SciTech Connect

    Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D.

    2012-03-27

    RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[{und UU}GGGC(C{und U}G){sub 3}GUCC]{sub 2}, refined to 2.20 and 1.52 {angstrom} resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 x 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 {angstrom} structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 x 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 x 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 {angstrom} structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 x 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 x 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.

  8. Myotonic dystrophy type 1 RNA crystal structures reveal heterogeneous 1 × 1 nucleotide UU internal loop conformations.

    PubMed

    Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W; Disney, Matthew D

    2011-11-15

    RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[UUGGGC(CUG)(3)GUCC](2), refined to 2.20 and 1.52 Å resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 × 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 Å structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 × 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 × 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 Å structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 × 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 × 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands. PMID:21988728

  9. Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1×1 Nucleotide UU Internal Loop Conformations⊥

    PubMed Central

    Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D.

    2011-01-01

    RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5′CUG/3′GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures are disclosed of a model DM1 triplet repeating construct, 5′r(UUGGGC(CUG)3GUCC)2, refined to 2.20 Å and 1.52 Å resolution. Here, differences in orientation of the 5′ dangling UU end between the two structures induce changes in the backbone groove width, which reveals that non-canonical 1×1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 Å structure, CUGa, the 5′UU forms one hydrogen-bonded pairs with a 5′UU of a neighboring helix in the unit cell to form a pseudo-infinite helix. The central 1×1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1×1 nucleotide UU internal loops each form a one hydrogen-bonded pair. In the 1.52 Å structure, CUGb, the 5′ UU dangling end is tucked into the major groove of the duplex. While the canonical paired bases show no change in base pairing, in CUGb the terminal 1×1 nucleotide UU internal loops form now two hydrogen-bonded pairs. Thus, the shift in major groove induced by the 5′UU dangling end alters non-canonical base patterns. Collectively, these structures indicate that 1×1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands. PMID:21988728

  10. Three-dimensional MHD modeling of flare-induced waves in coronal loops: thermal effects

    NASA Astrophysics Data System (ADS)

    Provornikova, Elena; Ofman, Leon; Wang, Tongjiang

    EUV imaging and spectroscopic observations from several space missions (SOHO, TRACE, Hinode/EIS, SDO/AIA) have revealed the presence of MHD waves in solar coronal loops. Past analysis of SOHO/SUMER data suggested that slow magnetosonic waves in hot coronal loops are excited by flares at the loop`s footpoint. Recent Hinode/EIS observed propagating disturbances in active region loops were interpreted as flows as well as waves most likely generated by plasma outflows or jets. In order to understand dynamics of plasma in coronal loops due to flares or jets at the lower corona boundary, we perform full 3D MHD modeling of an active region and consider different mechanisms of wave excitation. We assume an initial equilibrium of the model active region with dipole magnetic field structure, gravitationally stratified density and temperature obtained from polytropic equation of state of the background coronal plasma. We extend previous isothermal studies by including full energy equation with empirical heating and radiative losses terms in the model. We study waves in both, short and long loops, and consider two excitation mechanisms in the model: impulsive plasma injection into the steady plasma upflow along the magnetic field lines, and impulsive heating at the footpoint of the loop. We show initiation and evolution of flows, excitation and damping of waves and flow-wave interaction in the loops. We compare our new results with previous models and observations.

  11. Dimerization of HIV-1 genomic RNA of subtypes A and B: RNA loop structure and magnesium binding.

    PubMed Central

    Jossinet, F; Paillart, J C; Westhof, E; Hermann, T; Skripkin, E; Lodmell, J S; Ehresmann, C; Ehresmann, B; Marquet, R

    1999-01-01

    Retroviruses encapsidate their genome as a dimer of homologous RNA molecules noncovalently linked close to their 5' ends. The dimerization initiation site (DIS) of human immunodeficiency virus type 1 (HIV-1) RNA is a hairpin structure that contains in the loop a 6-nt self-complementary sequence flanked by two 5' and one 3' purines. The self-complementary sequence, as well as the flanking purines, are crucial for dimerization of HIV-1 RNA, which is mediated by formation of a "kissing-loop" complex between the DIS of each monomer. Here, we used chemical modification interference, lead-induced cleavage, and three-dimensional modeling to compare dimerization of subtype A and B HIV-1 RNAs. The DIS loop sequences of these RNAs are AGGUGCACA and AAGCGCGCA, respectively. In both RNAs, ethylation of most but not all phosphate groups in the loop and methylation of the N7 position of the G residues in the self-complementary sequence inhibited dimerization. These results demonstrate that small perturbations of the loop structure are detrimental to dimerization. Conversely, methylation of the N1 position of the first and last As in the loop were neutral or enhanced dimerization, a result consistent with these residues forming a noncanonical sheared base pair. Phosphorothioate interference, lead-induced cleavage, and Brownian-dynamics simulation revealed an unexpected difference in the dimerization mechanism of these RNAs. Unlike subtype B, subtype A requires binding of a divalent cation in the loop to promote RNA dimerization. This difference should be taken into consideration in the design of antidimerization molecules aimed at inhibiting HIV-1 replication. PMID:10496223

  12. The structure, stability and flaring of solar coronal loops

    NASA Technical Reports Server (NTRS)

    Van Hoven, G.

    1982-01-01

    A review is given of recent progress in the theory of the magnetohydrodynamic behavior of coronal loops, beginning with a brief characterization of thy observations. The equilibrium magnetic field is described, along with the consequences of the empirical requirement for short-term, or infinite-conductivity, stability which is shown to be dominated by the end-effect influence of thy quasi-rigid photosphere. A new loop-flare model is then developed, which takes account of the finite loop length. The primary resistive-sausage-mode instability exhibits the necessary threshold behavior, and produces a number of spatially and energetically distinct flare-release manifestations.

  13. Iterative structure within the five-particle two-loop amplitude

    SciTech Connect

    Cachazo, Freddy; Spradlin, Marcus; Volovich, Anastasia

    2006-08-15

    We find an unexpected iterative structure within the two-loop five-gluon amplitude in N=4 supersymmetric Yang-Mills theory. Specifically, we show that a subset of diagrams contributing to the full amplitude, including a two-loop pentagon-box integral with nontrivial dependence on five kinematical variables, satisfies an iterative relation in terms of one-loop scalar box diagrams. The implications of this result for the possible iterative structure of the full two-loop amplitude are discussed.

  14. Oriented matroids—combinatorial structures underlying loop quantum gravity

    NASA Astrophysics Data System (ADS)

    Brunnemann, Johannes; Rideout, David

    2010-10-01

    We analyze combinatorial structures which play a central role in determining spectral properties of the volume operator (Ashtekar A and Lewandowski J 1998 Adv. Theor. Math. Phys. 1 388) in loop quantum gravity (LQG). These structures encode geometrical information of the embedding of arbitrary valence vertices of a graph in three-dimensional Riemannian space and can be represented by sign strings containing relative orientations of embedded edges. We demonstrate that these signature factors are a special representation of the general mathematical concept of an oriented matroid (Ziegler G M 1998 Electron. J. Comb.; Björner A et al 1999 Oriented Matroids (Cambridge: Cambridge University Press)). Moreover, we show that oriented matroids can also be used to describe the topology (connectedness) of directed graphs. Hence, the mathematical methods developed for oriented matroids can be applied to the difficult combinatorics of embedded graphs underlying the construction of LQG. As a first application we revisit the analysis of Brunnemann and Rideout (2008 Class. Quantum Grav. 25 065001 and 065002), and find that enumeration of all possible sign configurations used there is equivalent to enumerating all realizable oriented matroids of rank 3 (Ziegler G M 1998 Electron. J. Comb.; Björner A et al 1999 Oriented Matroids (Cambridge: Cambridge University Press)), and thus can be greatly simplified. We find that for 7-valent vertices having no coplanar triples of edge tangents, the smallest non-zero eigenvalue of the volume spectrum does not grow as one increases the maximum spin jmax at the vertex, for any orientation of the edge tangents. This indicates that, in contrast to the area operator, considering large jmax does not necessarily imply large volume eigenvalues. In addition we give an outlook to possible starting points for rewriting the combinatorics of LQG in terms of oriented matroids.

  15. Structural and sequence patterns in the loops of beta alpha beta units.

    PubMed

    Edwards, M S; Sternberg, J E; Thornton, J M

    1987-06-01

    The conformation and sequences of the 129 loops of 70 beta alpha beta units from 17 alpha/beta proteins were analysed for patterns. Many different conformations of the loop regions were observed, but 18 of the loops could be classified into one of four loop families with distinctive conformation and sequence patterns. (i) Adjacent alpha beta loops with one residue between the alpha-helix and beta-strand. The residue is a glycine with conformationally restricted phi/psi angles; (ii) adjacent alpha beta loops of three residues with a conformationally restricted glycine as the first of the loop followed by an analine or histidine residue and a third residue with helical phi/psi angles; (iii) adjacent beta alpha loops of 3/4 residues previously reported to bind nucleotides and which have three glycine residues in the loop region; (iv) non-adjacent beta alpha loops of 0 residues with a serine or threonine as the last residue of the beta-strand. The analysis provides information for the model building of loops and prediction of secondary structure from amino acid sequences. PMID:3507703

  16. Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures.

    PubMed

    Aviñó, Anna; Portella, Guillem; Ferreira, Ruben; Gargallo, Raimundo; Mazzini, Stefania; Gabelica, Valérie; Orozco, Modesto; Eritja, Ramon

    2014-02-01

    Guanine-rich sequences show large structural variability, with folds ranging from duplex to triplex and quadruplex helices. Quadruplexes are polymorphic, and can show multiple stoichiometries, parallel and antiparallel strand alignments, and different topological arrangements. We analyze here the equilibrium between intramolecular antiparallel and intermolecular parallel G-quadruplexes in the thrombin-binding aptamer (TBA) sequence. Our theoretical and experimental studies demonstrate that an apparently simple modification at the loops of TBA induces a large change in the monomeric antiparallel structure of TBA to yield a parallel G-quadruplex showing a novel T-tetrad. The present results illustrate the extreme polymorphism of G-quadruplexes and the ease with which their conformation in solution can be manipulated by nucleotide modification. PMID:24304855

  17. MicroRNAs Constitute a Negative Feedback Loop in Streptococcus pneumoniae-Induced Macrophage Activation.

    PubMed

    Griss, Kathrin; Bertrams, Wilhelm; Sittka-Stark, Alexandra; Seidel, Kerstin; Stielow, Christina; Hippenstiel, Stefan; Suttorp, Norbert; Eberhardt, Martin; Wilhelm, Jochen; Vera, Julio; Schmeck, Bernd

    2016-07-15

    Streptococcus pneumoniae causes high mortality as a major pneumonia-inducing pathogen. In pneumonia, control of innate immunity is necessary to prevent organ damage. We assessed the role of microRNAs (miRNAs) as regulators in pneumococcal infection of human macrophages. Exposure of primary blood-derived human macrophages with pneumococci resulted in transcriptional changes in several gene clusters and a significant deregulation of 10 microRNAs. Computational network analysis retrieved miRNA-146a as one putatively important regulator of pneumococci-induced host cell activation. Its induction depended on bacterial structural integrity and was completely inhibited by blocking Toll-like receptor 2 (TLR-2) or depleting its mediator MyD88. Furthermore, induction of miRNA-146a release did not require the autocrine feedback of interleukin 1β and tumor necrosis factor α released from infected macrophages, and it repressed the TLR-2 downstream mediators IRAK-1 and TRAF-6, as well as the inflammatory factors cyclooxygenase 2 and interleukin 1β. In summary, pneumococci recognition induces a negative feedback loop, preventing excessive inflammation via miR-146a and potentially other miRNAs. PMID:26984146

  18. Heavy ion irradiation induced dislocation loops in AREVA's M5® alloy

    NASA Astrophysics Data System (ADS)

    Hengstler-Eger, R. M.; Baldo, P.; Beck, L.; Dorner, J.; Ertl, K.; Hoffmann, P. B.; Hugenschmidt, C.; Kirk, M. A.; Petry, W.; Pikart, P.; Rempel, A.

    2012-04-01

    Pressurized water reactor (PWR) Zr-based alloy structural materials show creep and growth under neutron irradiation as a consequence of the irradiation induced microstructural changes in the alloy. A better scientific understanding of these microstructural processes can improve simulation programs for structural component deformation and simplify the development of advanced deformation resistant alloys. As in-pile irradiation leads to high material activation and requires long irradiation times, the objective of this work was to study whether ion irradiation is an applicable method to simulate typical PWR neutron damage in Zr-based alloys, with AREVA's M5® alloy as reference material. The irradiated specimens were studied by electron backscatter diffraction (EBSD), positron Doppler broadening spectroscopy (DBS) and in situ transmission electron microscopy (TEM) at different dose levels and temperatures. The irradiation induced microstructure consisted of - and -type dislocation loops with their characteristics corresponding to typical neutron damage in Zr-based alloys; it can thus be concluded that heavy ion irradiation under the chosen conditions is an excellent method to simulate PWR neutron damage.

  19. Structure of the β2-α2 loop and interspecies prion transmission

    PubMed Central

    Bett, Cyrus; Fernández-Borges, Natalia; Kurt, Timothy D.; Lucero, Melanie; Nilsson, K. Peter R.; Castilla, Joaquín; Sigurdson, Christina J.

    2012-01-01

    Prions are misfolded, aggregated conformers of the prion protein that can be transmitted between species. The precise determinants of interspecies transmission remain unclear, although structural similarity between the infectious prion and host prion protein is required for efficient conversion to the misfolded conformer. The β2-α2 loop region of endogenous prion protein, PrPC, has been implicated in barriers to prion transmission. We recently discovered that conversion was efficient when incoming and host prion proteins had similar β2-α2 loop structures; however, the roles of primary vs. secondary structural homology could not be distinguished. Here we uncouple the effect of primary and secondary structural homology of the β2-α2 loop on prion conversion. We inoculated prions from animals having a disordered or an ordered β2-α2 loop into mice having a disordered loop or an ordered loop due to a single residue substitution (D167S). We found that prion conversion was driven by a homologous primary structure and occurred independently of a homologous secondary structure. Similarly, cell-free conversion using PrPC from mice with disordered or ordered loops and prions from 5 species correlated with primary but not secondary structural homology of the loop. Thus, our findings support a model in which efficient interspecies prion conversion is determined by small stretches of the primary sequence rather than the secondary structure of PrP.—Bett, C., Fernández-Borges, N., Kurt, T. D., Lucero, M., Nilsson, K. P. R., Castilla, J., Sigurdson, C. J. Structure of the β2-α2 loop and interspecies prion transmission. PMID:22490928

  20. Fields induced by three-dimensional dislocation loops in anisotropic magneto-electro-elastic bimaterials

    NASA Astrophysics Data System (ADS)

    Han, Xueli; Pan, Ernie; Sangghaleh, Ali

    2013-08-01

    The coupled elastic, electric and magnetic fields produced by an arbitrarily shaped three-dimensional dislocation loop in general anisotropic magneto-electro-elastic (MEE) bimaterials are derived. First, we develop line-integral expressions for the fields induced by a general dislocation loop. Then, we obtain analytical solutions for the fields, including the extended Peach-Koehler force, due to some useful dislocation segments such as straight line and elliptic arc. The present solutions contain the piezoelectric, piezomagnetic and purely elastic solutions as special cases. As numerical examples, the fields induced by a square and an elliptic dislocation loop in MEE bimaterials are studied. Our numerical results show the coupling effects among different fields, along with various interesting features associated with the dislocation and interface.

  1. Looping around Reprogramming: The Topological Memory of Induced Pluripotency.

    PubMed

    Gonzales, Kevin Andrew Uy; Ng, Huck-Hui

    2016-05-01

    Genome architecture is associated with cellular identity, but how this organization changes during reprogramming is not well understood. Now in Cell Stem Cell, Krijger et al. (2016) and Beagan et al. (2016) report 3D chromatin interaction maps before and after reprogramming, providing evidence for topological memory in induced pluripotent stem cells. PMID:27152435

  2. Structure of Staphylococcal Enterotoxin E in Complex with TCR Defines the Role of TCR Loop Positioning in Superantigen Recognition.

    PubMed

    Rödström, Karin E J; Regenthal, Paulina; Lindkvist-Petersson, Karin

    2015-01-01

    T cells are crucial players in cell-mediated immunity. The specificity of their receptor, the T cell receptor (TCR), is central for the immune system to distinguish foreign from host antigens. Superantigens are bacterial toxins capable of inducing a toxic immune response by cross-linking the TCR and the major histocompatibility complex (MHC) class II and circumventing the antigen specificity. Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure. There are clear structural changes in the TCR loops upon superantigen binding. In particular, the HV4 loop moves to circumvent steric clashes upon complex formation. In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR α-chain and the MHC, suggesting that the TCR α-chain is of importance for complex formation. PMID:26147596

  3. Introducing a Rigid Loop Structure from Deer into Mouse Prion Protein Increases Its Propensity for Misfolding In Vitro

    PubMed Central

    Kyle, Leah M.; John, Theodore R.; Schätzl, Hermann M.; Lewis, Randolph V.

    2013-01-01

    Prion diseases are fatal neurodegenerative disorders characterized by misfolding of the cellular prion protein (PrPc) into the disease-associated isoform (PrPSc) that has increased β-sheet content and partial resistance to proteolytic digestion. Prion diseases from different mammalian species have varying propensities for transmission upon exposure of an uninfected host to the infectious agent. Chronic Wasting Disease (CWD) is a highly transmissible prion disease that affects free ranging and farmed populations of cervids including deer, elk and moose, as well as other mammals in experimental settings. The molecular mechanisms allowing CWD to maintain comparatively high transmission rates have not been determined. Previous work has identified a unique structural feature in cervid PrP, a rigid loop between β-sheet 2 and α-helix 2 on the surface of the protein. This study was designed to test the hypothesis that the rigid loop has a direct influence on the misfolding process. The rigid loop was introduced into murine PrP as the result of two amino acid substitutions: S170N and N174T. Wild-type and rigid loop murine PrP were expressed in E. coli and purified. Misfolding propensity was compared for the two proteins using biochemical techniques and cell free misfolding and conversion systems. Murine PrP with a rigid loop misfolded in cell free systems with greater propensity than wild type murine PrP. In a lipid-based conversion assay, rigid loop PrP converted to a PK resistant, aggregated isoform at lower concentrations than wild-type PrP. Using both proteins as substrates in real time quaking-induced conversion, rigid loop PrP adopted a misfolded isoform more readily than wild type PrP. Taken together, these findings may help explain the high transmission rates observed for CWD within cervids. PMID:23825561

  4. The conserved active-site loop residues of ferrochelatase induce porphyrin conformational changes necessary for catalysis.

    SciTech Connect

    Haddad, Raid Edward; Shelnutt, John Allen; Shi, Zhen; Ferreira, Gloria C.; Franco, Ricardo T.

    2005-05-01

    Binding of porphyrin to murine ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, is investigated by employing a set of variants harboring mutations in a putative porphyrin-binding loop. Using resonance Raman (RR) spectroscopy, the structural properties of the ferrochelatase-bound porphyrins are examined, especially with respect to the porphyrin deformation occurring in the environment of the active site. This deformation is thought to be a key step in the enzymatic insertion of ferrous iron into the porphyrin ring to make heme. Our previous RR spectroscopic studies of binding of porphyrin to murine ferrochelatase led us to propose that the wild-type enzyme induces porphyrin distortion even in the absence of the metal ion substrate. Here, we broaden this view by presenting evidence that the degree of a specific nonplanar porphyrin deformation contributes to the catalytic efficiency of ferrochelatase and its variants. The results also suggest that the conserved Trp256 (murine ferrochelatase numbering) is partially responsible for the observed porphyrin deformation. Binding of porphyrin to the ferrochelatase variants causes a decrease in the intensity of RR out-of-plane vibrational mode {gamma}{sub 15}, a saddling-like mode that is strong in the wild-type enzyme. In particular, the variant with a catalytic efficiency 1 order of magnitude lower than that of the wild-type enzyme is estimated to produce less than 30% of the wild-type saddling deformation. These results suggest that specific conserved loop residues (especially Trp256) are directly involved in the saddling of the porphyrin substrate.

  5. Simulation of polarization and butterfly hysteresis loops in bismuth layer-structured ferroelectric thin films

    NASA Astrophysics Data System (ADS)

    Ye, Z.; Tang, M. H.; Cheng, C. P.; Zhou, Y. C.; Zheng, X. J.; Hu, Z. S.

    2006-11-01

    Modeling of the hysteresis loop of ferroelectric thin films has been thought very difficult owing to its nonlinear and history-dependent electric field effects. Here we extend the Preisach model [Z. Phys. 94, 277 (1935)] by using the distribution function integral and superposition method. The model shows improved hysteresis loop that agrees reasonably well with the experimental data measured from the bismuth layer-structured ferroelectric thin films. Compared with the previous model, the current model provides polarization-field (P-E) loop with full and symmetric shape, suitable coercive field (Ec), and few undesirable parameters. The butterfly loop of perovskite-type ferroelectric thin films is also simulated. Additionally, the approach is able to describe the unsaturated loops obtained under various ac electric fields, which is very useful in circuit simulation of ferroelectric field effect transistor or ferroelectric capacitor.

  6. Solution-state structure of an intramolecular G-quadruplex with propeller, diagonal and edgewise loops

    PubMed Central

    Marušič, Maja; Šket, Primož; Bauer, Lubos; Viglasky, Viktor; Plavec, Janez

    2012-01-01

    We herein report on the formation and high-resolution NMR solution-state structure determination of a G-quadruplex adopted by d[G3ATG3ACACAG4ACG3] comprised of four G-tracts with the third one consisting of four guanines that are intervened with non-G streches of different lengths. A single intramolecular antiparallel (3+1) G-quadruplex exhibits three stacked G-quartets connected with propeller, diagonal and edgewise loops of different lengths. The propeller and edgewise loops are well structured, whereas the longer diagonal loop is more flexible. To the best of our knowledge, this is the first high-resolution G-quadruplex structure where all of the three main loop types are present. PMID:22532609

  7. Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals.

    PubMed

    Sanz, Lionel A; Hartono, Stella R; Lim, Yoong Wearn; Steyaert, Sandra; Rajpurkar, Aparna; Ginno, Paul A; Xu, Xiaoqin; Chédin, Frédéric

    2016-07-01

    R-loops are three-stranded nucleic acid structures formed upon annealing of an RNA strand to one strand of duplex DNA. We profiled R-loops using a high-resolution, strand-specific methodology in human and mouse cell types. R-loops are prevalent, collectively occupying up to 5% of mammalian genomes. R-loop formation occurs over conserved genic hotspots such as promoter and terminator regions of poly(A)-dependent genes. In most cases, R-loops occur co-transcriptionally and undergo dynamic turnover. Detailed epigenomic profiling revealed that R-loops associate with specific chromatin signatures. At promoters, R-loops associate with a hyper-accessible state characteristic of unmethylated CpG island promoters. By contrast, terminal R-loops associate with an enhancer- and insulator-like state and define a broad class of transcription terminators. Together, this suggests that the retention of nascent RNA transcripts at their site of expression represents an abundant, dynamic, and programmed component of the mammalian chromatin that affects chromatin patterning and the control of gene expression. PMID:27373332

  8. A light-induced shortcut in the planktonic microbial loop.

    PubMed

    Ptacnik, Robert; Gomes, Ana; Royer, Sarah-Jeanne; Berger, Stella A; Calbet, Albert; Nejstgaard, Jens C; Gasol, Josep M; Isari, Stamatina; Moorthi, Stefanie D; Ptacnikova, Radka; Striebel, Maren; Sazhin, Andrey F; Tsagaraki, Tatiana M; Zervoudaki, Soultana; Altoja, Kristi; Dimitriou, Panagiotis D; Laas, Peeter; Gazihan, Ayse; Martínez, Rodrigo A; Schabhüttl, Stefanie; Santi, Ioulia; Sousoni, Despoina; Pitta, Paraskevi

    2016-01-01

    Mixotrophs combine photosynthesis with phagotrophy to cover their demands in energy and essential nutrients. This gives them a competitive advantage under oligotropihc conditions, where nutrients and bacteria concentrations are low. As the advantage for the mixotroph depends on light, the competition between mixo- and heterotrophic bacterivores should be regulated by light. To test this hypothesis, we incubated natural plankton from the ultra-oligotrophic Eastern Mediterranean in a set of mesocosms maintained at 4 light levels spanning a 10-fold light gradient. Picoplankton (heterotrophic bacteria (HB), pico-sized cyanobacteria, and small-sized flagellates) showed the fastest and most marked response to light, with pronounced predator-prey cycles, in the high-light treatments. Albeit cell specific activity of heterotrophic bacteria was constant across the light gradient, bacterial abundances exhibited an inverse relationship with light. This pattern was explained by light-induced top-down control of HB by bacterivorous phototrophic eukaryotes (PE), which was evidenced by a significant inverse relationship between HB net growth rate and PE abundances. Our results show that light mediates the impact of mixotrophic bacterivores. As mixo- and heterotrophs differ in the way they remineralize nutrients, these results have far-reaching implications for how nutrient cycling is affected by light. PMID:27404551

  9. A light-induced shortcut in the planktonic microbial loop

    PubMed Central

    Ptacnik, Robert; Gomes, Ana; Royer, Sarah-Jeanne; Berger, Stella A.; Calbet, Albert; Nejstgaard, Jens C.; Gasol, Josep M.; Isari, Stamatina; Moorthi, Stefanie D.; Ptacnikova, Radka; Striebel, Maren; Sazhin, Andrey F.; Tsagaraki, Tatiana M.; Zervoudaki, Soultana; Altoja, Kristi; Dimitriou, Panagiotis D.; Laas, Peeter; Gazihan, Ayse; Martínez, Rodrigo A.; Schabhüttl, Stefanie; Santi, Ioulia; Sousoni, Despoina; Pitta, Paraskevi

    2016-01-01

    Mixotrophs combine photosynthesis with phagotrophy to cover their demands in energy and essential nutrients. This gives them a competitive advantage under oligotropihc conditions, where nutrients and bacteria concentrations are low. As the advantage for the mixotroph depends on light, the competition between mixo- and heterotrophic bacterivores should be regulated by light. To test this hypothesis, we incubated natural plankton from the ultra-oligotrophic Eastern Mediterranean in a set of mesocosms maintained at 4 light levels spanning a 10-fold light gradient. Picoplankton (heterotrophic bacteria (HB), pico-sized cyanobacteria, and small-sized flagellates) showed the fastest and most marked response to light, with pronounced predator-prey cycles, in the high-light treatments. Albeit cell specific activity of heterotrophic bacteria was constant across the light gradient, bacterial abundances exhibited an inverse relationship with light. This pattern was explained by light-induced top-down control of HB by bacterivorous phototrophic eukaryotes (PE), which was evidenced by a significant inverse relationship between HB net growth rate and PE abundances. Our results show that light mediates the impact of mixotrophic bacterivores. As mixo- and heterotrophs differ in the way they remineralize nutrients, these results have far-reaching implications for how nutrient cycling is affected by light. PMID:27404551

  10. The Effect of Loops on the Structural Organization of α-Helical Membrane Proteins

    PubMed Central

    Tastan, Oznur; Klein-Seetharaman, Judith; Meirovitch, Hagai

    2009-01-01

    Loops connecting the transmembrane (TM) α-helices in membrane proteins are expected to affect the structural organization of the thereby connected helices and the helical bundles as a whole. This effect, which has been largely ignored previously, is studied here by analyzing the x-ray structures of 41 α-helical membrane proteins. First we define the loop flexibility ratio, R, and find that 53% of the loops are stretched, where a stretched loop constrains the distance between the two connected helices. The significance of this constraining effect is supported by experiments carried out with bacteriorhodopsin and rhodopsin, in which cutting or eliminating their (predominately stretched) loops has led to a decrease in protein stability, and for rhodopsin, in most cases, also to the destruction of the structure. We show that for nonstretched loops in the extramembranous regions, the fraction of hydrophobic residues is comparable to that for soluble proteins; furthermore (as is also the case for soluble proteins), the hydrophobic residues in these regions are preferentially buried. This is expected to lead to the compact structural organization of the loops, which is transferred to the TM helices, causing them to assemble. We argue that a soluble protein complexed with a membrane protein similarly promotes compactness; other properties of such complexes are also studied. We calculate complementary attractive interactions between helices, including hydrogen bonds and van der Waals interactions of sequential motifs, such as GXXXG. The relative and combined effects of all these factors on the association of the TM helices are discussed and protein structures with only a few of these factors are analyzed. Our study emphasizes the need for classifying membrane proteins into groups according to structural organization. This classification should be considered when procedures for structural analysis or prediction are developed and applied. Detailed analysis of each structure

  11. Dislocation dynamics simulations of interactions between gliding dislocations and radiation induced prismatic loops in zirconium

    NASA Astrophysics Data System (ADS)

    Drouet, Julie; Dupuy, Laurent; Onimus, Fabien; Mompiou, Frédéric; Perusin, Simon; Ambard, Antoine

    2014-06-01

    The mechanical behavior of Pressurized Water Reactor fuel cladding tubes made of zirconium alloys is strongly affected by neutron irradiation due to the high density of radiation induced dislocation loops. In order to investigate the interaction mechanisms between gliding dislocations and loops in zirconium, a new nodal dislocation dynamics code, adapted to Hexagonal Close Packed metals, has been used. Various configurations have been systematically computed considering different glide planes, basal or prismatic, and different characters, edge or screw, for gliding dislocations with -type Burgers vectors. Simulations show various interaction mechanisms such as (i) absorption of a loop on an edge dislocation leading to the formation of a double super-jog, (ii) creation of a helical turn, on a screw dislocation, that acts as a strong pinning point or (iii) sweeping of a loop by a gliding dislocation. It is shown that the clearing of loops is more favorable when the dislocation glides in the basal plane than in the prismatic plane explaining the easy dislocation channeling in the basal plane observed after neutron irradiation by transmission electron microscopy.

  12. Empirical Measurements of Loop Structures in the Sun's Transition Region Compared with Energy Balance Models

    NASA Astrophysics Data System (ADS)

    Chesny, David; Oluseyi, H. M.; Orange, N. B.; DeBoth, D.; Preuss, L.; Neira, C.; Ebert, M.; Cohen, L.

    2011-01-01

    We have measured the properties of solar upper transition region loop structures barely resolvable in 1-arcsecond resolution data from the Transition Region and Coronal Explorer (TRACE) satellite and from the Solar Ultraviolet Measurements of Emitted Radiation (SUMER) instrument aboard the SOHO satellite for the purpose of investigating the mechanisms that generate and energize these structures. The images were wavelet transformed to elucidate and isolate fine-scale loops, whose lengths, widths, emergent flux, flows, and underlying magnetic field were measured. It was found that the loops' magnetic geometries were well-fit by potential field models. However, hydrostatic models were unable to self-consistently reproduce the loop's observed properties for a wide range of parameter space.

  13. Unresolved fine-scale structure in solar coronal loop-tops

    SciTech Connect

    Scullion, E.; Van der Voort, L. Rouppe; Wedemeyer, S.; Antolin, P.

    2014-12-10

    New and advanced space-based observing facilities continue to lower the resolution limit and detect solar coronal loops in greater detail. We continue to discover even finer substructures within coronal loop cross-sections, in order to understand the nature of the solar corona. Here, we push this lower limit further to search for the finest coronal loop substructures, through taking advantage of the resolving power of the Swedish 1 m Solar Telescope/CRisp Imaging Spectro-Polarimeter (CRISP), together with co-observations from the Solar Dynamics Observatory/Atmospheric Image Assembly (AIA). High-resolution imaging of the chromospheric Hα 656.28 nm spectral line core and wings can, under certain circumstances, allow one to deduce the topology of the local magnetic environment of the solar atmosphere where its observed. Here, we study post-flare coronal loops, which become filled with evaporated chromosphere that rapidly condenses into chromospheric clumps of plasma (detectable in Hα) known as a coronal rain, to investigate their fine-scale structure. We identify, through analysis of three data sets, large-scale catastrophic cooling in coronal loop-tops and the existence of multi-thermal, multi-stranded substructures. Many cool strands even extend fully intact from loop-top to footpoint. We discover that coronal loop fine-scale strands can appear bunched with as many as eight parallel strands within an AIA coronal loop cross-section. The strand number density versus cross-sectional width distribution, as detected by CRISP within AIA-defined coronal loops, most likely peaks at well below 100 km, and currently, 69% of the substructure strands are statistically unresolved in AIA coronal loops.

  14. Unresolved Fine-scale Structure in Solar Coronal Loop-tops

    NASA Astrophysics Data System (ADS)

    Scullion, E.; Rouppe van der Voort, L.; Wedemeyer, S.; Antolin, P.

    2014-12-01

    New and advanced space-based observing facilities continue to lower the resolution limit and detect solar coronal loops in greater detail. We continue to discover even finer substructures within coronal loop cross-sections, in order to understand the nature of the solar corona. Here, we push this lower limit further to search for the finest coronal loop substructures, through taking advantage of the resolving power of the Swedish 1 m Solar Telescope/CRisp Imaging Spectro-Polarimeter (CRISP), together with co-observations from the Solar Dynamics Observatory/Atmospheric Image Assembly (AIA). High-resolution imaging of the chromospheric Hα 656.28 nm spectral line core and wings can, under certain circumstances, allow one to deduce the topology of the local magnetic environment of the solar atmosphere where its observed. Here, we study post-flare coronal loops, which become filled with evaporated chromosphere that rapidly condenses into chromospheric clumps of plasma (detectable in Hα) known as a coronal rain, to investigate their fine-scale structure. We identify, through analysis of three data sets, large-scale catastrophic cooling in coronal loop-tops and the existence of multi-thermal, multi-stranded substructures. Many cool strands even extend fully intact from loop-top to footpoint. We discover that coronal loop fine-scale strands can appear bunched with as many as eight parallel strands within an AIA coronal loop cross-section. The strand number density versus cross-sectional width distribution, as detected by CRISP within AIA-defined coronal loops, most likely peaks at well below 100 km, and currently, 69% of the substructure strands are statistically unresolved in AIA coronal loops.

  15. Strain-induced electrostatic enhancements of BiFeO3 nanowire loops.

    PubMed

    Liu, Jun; Prashanthi, Kovur; Li, Zhi; McGee, Ryan T; Ahadi, Kaveh; Thundat, Thomas

    2016-08-17

    Semiconductor nanowires (NWs), due to their intriguing structural and physical properties, offer tremendous potential for future technological applications. The existence of strain in NWs can greatly affect, for instance, their mechanical, electrical and optical properties. Here, we report an extraordinary electrostatic response of semiconductor BiFeO3 NW loops, based on Kelvin probe force microscopy (KPFM) and electrostatic force microscopy (EFM). A substantial ∼300 mV surface potential difference, accompanied by an ∼29% higher surface charge density, was found on the NW loop. We also found that the electrostatic enhancement is strongly related to the strain present at the curvature of the NW loops. We propose that the electric polarization coupled with mechanical strain (piezoelectric effect) or strain gradient (flexoelectricity) as possible reasons to account for our observation. These findings provide new insights into multiferroic based semiconductor NWs under external stimuli as well as significant inspiration towards strain sensors and electromechanical devices with multifunctional sensing abilities. PMID:27477993

  16. A modular perspective of protein structures; application to fragment based loop modeling

    PubMed Central

    Fernandez-Fuentes, Narcis; Fiser, Andras

    2013-01-01

    Summary Proteins can be decomposed into supersecondary structure modules. We used a generic definition of supersecondary structure elements, so-called Smotifs, which are composed of two flanking regular secondary structures connected by a loop, to explore the evolution and current variety of structure building blocks. Here, we discuss recent observations about the saturation of Smotif geometries in protein structures and how it opens new avenues in protein structure modeling and design. As a first application of these observations we describe our loop conformation modeling algorithm, ArchPred that takes advantage of Smotifs classification. In this application, instead of focusing on specific loop properties the method narrows down possible template conformations in other, often not homologous structures, by identifying the most likely supersecondary structure environment that cradles the loop. Beyond identifying the correct starting supersecondary structure geometry, it takes into account information of fit of anchor residues, sterical clashes, match of predicted and observed dihedral angle preferences, and local sequence signal. PMID:22987351

  17. Structure of a cardiotoxic phospholipase A(2) from Ophiophagus hannah with the "pancreatic loop".

    PubMed

    Zhang, Hai-Long; Xu, Su-Juan; Wang, Qiu-Yan; Song, Shi-Ying; Shu, Yu-Yan; Lin, Zheng-Jiong

    2002-06-01

    The crystal structure of an acidic phospholipase A(2) from Ophiophagus hannah (king cobra) has been determined by molecular replacement at 2.6-A resolution to a crystallographic R factor of 20.5% (R(free)=23.3%) with reasonable stereochemistry. The venom enzyme contains an unusual "pancreatic loop." The conformation of the loop is well defined and different from those in pancreas PLA(2), showing its structural variability. This analysis provides the first structure of a PLA(2)-type cardiotoxin. The sites related to the cardiotoxic and myotoxic activities are explored and the oligomer observed in the crystalline state is described. PMID:12217659

  18. Protein loop modeling using a new hybrid energy function and its application to modeling in inaccurate structural environments.

    PubMed

    Park, Hahnbeom; Lee, Gyu Rie; Heo, Lim; Seok, Chaok

    2014-01-01

    Protein loop modeling is a tool for predicting protein local structures of particular interest, providing opportunities for applications involving protein structure prediction and de novo protein design. Until recently, the majority of loop modeling methods have been developed and tested by reconstructing loops in frameworks of experimentally resolved structures. In many practical applications, however, the protein loops to be modeled are located in inaccurate structural environments. These include loops in model structures, low-resolution experimental structures, or experimental structures of different functional forms. Accordingly, discrepancies in the accuracy of the structural environment assumed in development of the method and that in practical applications present additional challenges to modern loop modeling methods. This study demonstrates a new strategy for employing a hybrid energy function combining physics-based and knowledge-based components to help tackle this challenge. The hybrid energy function is designed to combine the strengths of each energy component, simultaneously maintaining accurate loop structure prediction in a high-resolution framework structure and tolerating minor environmental errors in low-resolution structures. A loop modeling method based on global optimization of this new energy function is tested on loop targets situated in different levels of environmental errors, ranging from experimental structures to structures perturbed in backbone as well as side chains and template-based model structures. The new method performs comparably to force field-based approaches in loop reconstruction in crystal structures and better in loop prediction in inaccurate framework structures. This result suggests that higher-accuracy predictions would be possible for a broader range of applications. The web server for this method is available at http://galaxy.seoklab.org/loop with the PS2 option for the scoring function. PMID:25419655

  19. Structural characterization of the second intra-discal loop of the photoreceptor tetraspanin RDS.

    PubMed

    Chakraborty, Dibyendu; Rodgers, Karla K; Conley, Shannon M; Naash, Muna I

    2013-01-01

    Vertebrate photoreceptors contain a unique tetraspanin protein known as 'retinal degeneration slow' (RDS). Mutations in the RDS gene have been identified in a variety of human retinal degenerative diseases, and more than 70% of these mutations are located in the second intra-discal (D2) loop, highlighting the importance of this region. Here we examined the conformational and thermal stability properties of the D2 loop of RDS, as well as interactions with ROM-1, a non-glycosylated homolog of RDS. The RDS D2 loop was expressed in Escherichia coli as a fusion protein with maltose binding protein (MBP). The fusion protein, referred to as MBP-D2, was purified to homogeneity. Circular dichroism spectroscopy showed that the wild-type (WT) D2 loop consists of approximately 21% α-helix, approximately 20% β-sheet and approximately 59% random coil. D2 loop fusion proteins carrying disease-causing mutations in RDS (e.g. R172W, C214S, N244H/K) were also examined, and conformational changes were observed (compared to wild-type D2). In particular, the C150S, C214S and N244H proteins showed significant reductions in α-helicity. However, the thermal stability of the mutants was unchanged compared to wild-type, and all the mutants were capable of interacting with ROM-1, indicating that this functional aspect of the isolated D2 loop remained intact in the mutants despite the observed conformational changes. An I-TASSER model of the RDS D2 loop predicted a structure consistent with the circular dichroism experiments and the structure of the conserved region of the D2 loop of other tetraspanin family members. These results provide significant insight into the mechanism of RDS complex formation and the disease process underlying RDS-associated retinal degeneration. PMID:23121719

  20. Aggregation and secondary loop structure of oligonucleotides do not determine their ability to inhibit TLR9.

    PubMed

    Ashman, Robert F; Goeken, J Adam; Lenert, Petar S

    2011-08-01

    Toll-like receptor 9 (TLR9) is an endosomal DNA sensor that warns us of the presence of infectious danger and triggers a rapid pro-inflammatory response in dendritic cells, macrophages, and B cells. The consequences of uncontrolled TLR9 activation can be detrimental for the host, contributing to the pathogenesis of bacterial septic shock or autoimmune diseases, such as systemic lupus erythematosus. Therefore, we need to develop TLR9 antagonists. We and others have created inhibitory oligonucleotides (INH-ODN) that are capable of sequence-dependent inhibition of TLR9-induced activation in both human and mouse cells. However, it is not clear whether marked differences in INH-ODN activity related to base sequence derived from polymerization of INH-ODNs or their ability to complex with stimulatory CpG-oligonucleotides (ST-ODN). Furthermore, the 5' end of INH-ODNs may assume a particular loop configuration that may be needed for binding to a critical site on TLR9. Here, we show that 1) G-tetrads required for ODN stacking were compatible with INH-ODN activity but were not necessary; 2) there was no relationship between activity and self-association at endosomal pH; 3) there was no evidence for direct binding between ST-ODNs and INH-ODNs; 4) when a 3G sequence was disrupted, despite a preserved stem-loop formation, INH-ODN activity was abolished. These results support the conclusion that certain features of the primary linear sequence are critical for TLR9 inhibition, but changes in secondary structure or in ODN aggregation are irrelevant. PMID:21376154

  1. Crystal Structures and Molecular Dynamics Simulations of Thermophilic Malate Dehydrogenase Reveal Critical Loop Motion for Co-Substrate Binding

    PubMed Central

    Luo, Huei-Ru; Wu, Szu-Pei; Hsu, Chun-Hua

    2013-01-01

    Malate dehydrogenase (MDH) catalyzes the conversion of oxaloacetate and malate by using the NAD/NADH coenzyme system. The system is used as a conjugate for enzyme immunoassays of a wide variety of compounds, such as illegal drugs, drugs used in therapeutic applications and hormones. We elucidated the biochemical and structural features of MDH from Thermus thermophilus (TtMDH) for use in various biotechnological applications. The biochemical characterization of recombinant TtMDH revealed greatly increased activity above 60°C and specific activity of about 2,600 U/mg with optimal temperature of 90°C. Analysis of crystal structures of apo and NAD-bound forms of TtMDH revealed a slight movement of the binding loop and few structural elements around the co-substrate binding packet in the presence of NAD. The overall structures did not change much and retained all related positions, which agrees with the CD analyses. Further molecular dynamics (MD) simulation at higher temperatures were used to reconstruct structures from the crystal structure of TtMDH. Interestingly, at the simulated structure of 353 K, a large change occurred around the active site such that with increasing temperature, a mobile loop was closed to co-substrate binding region. From biochemical characterization, structural comparison and MD simulations, the thermal-induced conformational change of the co-substrate binding loop of TtMDH may contribute to the essential movement of the enzyme for admitting NAD and may benefit the enzyme's activity. PMID:24386145

  2. Dangling bond deflection model: Growth of gel network with loop structure

    NASA Astrophysics Data System (ADS)

    Ma, Hang-Shing; Jullien, Rémi; Scherer, George W.

    2002-04-01

    It has been shown that the closed-loop structure in the model gel networks is responsible for their stiffness. However, the creation of loops has been underestimated in most of the existing kinetic aggregation models [e.g., DLCA (diffusion-limited cluster-cluster aggregation) and derivatives]. A dangling bond deflection (DEF) mechanism is proposed to model the fluctuation of dangling branches or dead ends under thermal excitation. The random deflections of the dangling branches can create loops in the network by forming intracluster bonds, and proceed during both the gelling and aging processes. The resulting DLCADEF networks have extensive loop structure with a negligible number of dangling branches. Its growth kinetics and fractal behavior resemble those of real gels, including volume-invariant gel time and fractal dimension of about 2. The DLCADEF model is the first attempt to model the gel growth with loop formation by the physically realistic fluctuation mechanism. The mechanical properties of the resulting networks will be studied and verified by comparison with real gels.

  3. A genetic algorithm based molecular modeling technique for RNA stem-loop structures.

    PubMed Central

    Ogata, H; Akiyama, Y; Kanehisa, M

    1995-01-01

    A new modeling technique for arriving at the three dimensional (3-D) structure of an RNA stem-loop has been developed based on a conformational search by a genetic algorithm and the following refinement by energy minimization. The genetic algorithm simultaneously optimizes a population of conformations in the predefined conformational space and generates 3-D models of RNA. The fitness function to be optimized by the algorithm has been defined to reflect the satisfaction of known conformational constraints. In addition to a term for distance constraints, the fitness function contains a term to constrain each local conformation near to a prepared template conformation. The technique has been applied to the two loops of tRNA, the anticodon loop and the T-loop, and has found good models with small root mean square deviations from the crystal structure. Slightly different models have also been found for the anticodon loop. The analysis of a collection of alternative models obtained has revealed statistical features of local variations at each base position. Images PMID:7533901

  4. Fast Protein Loop Sampling and Structure Prediction Using Distance-Guided Sequential Chain-Growth Monte Carlo Method

    PubMed Central

    Tang, Ke; Zhang, Jinfeng; Liang, Jie

    2014-01-01

    Loops in proteins are flexible regions connecting regular secondary structures. They are often involved in protein functions through interacting with other molecules. The irregularity and flexibility of loops make their structures difficult to determine experimentally and challenging to model computationally. Conformation sampling and energy evaluation are the two key components in loop modeling. We have developed a new method for loop conformation sampling and prediction based on a chain growth sequential Monte Carlo sampling strategy, called Distance-guided Sequential chain-Growth Monte Carlo (DiSGro). With an energy function designed specifically for loops, our method can efficiently generate high quality loop conformations with low energy that are enriched with near-native loop structures. The average minimum global backbone RMSD for 1,000 conformations of 12-residue loops is Å, with a lowest energy RMSD of Å, and an average ensemble RMSD of Å. A novel geometric criterion is applied to speed up calculations. The computational cost of generating 1,000 conformations for each of the x loops in a benchmark dataset is only about cpu minutes for 12-residue loops, compared to ca cpu minutes using the FALCm method. Test results on benchmark datasets show that DiSGro performs comparably or better than previous successful methods, while requiring far less computing time. DiSGro is especially effective in modeling longer loops (– residues). PMID:24763317

  5. Closed-loop structural stability for linear-quadratic optimal systems

    NASA Technical Reports Server (NTRS)

    Wong, P. K.; Athans, M.

    1975-01-01

    This paper contains an explicit parameterization of a subclass of linear constant gain feedback maps that never destabilize an originally open-loop stable system. These results can then be used to obtain several new structural stability results for multi-input linear-quadratic feedback optimal designs.

  6. Towards the use of Structural Loop Analysis to Study System Behaviour of Socio-Ecological Systems.

    NASA Astrophysics Data System (ADS)

    Abram, Joseph; Dyke, James

    2016-04-01

    Maintaining socio-ecological systems in desirable states is key to developing a growing economy, alleviating poverty and achieving a sustainable future. While the driving forces of an environmental system are often well known, the dynamics impacting these drivers can be hidden within a tangled structure of causal chains and feedback loops. A lack of understanding of a system's dynamic structure and its influence on a system's behaviour can cause unforeseen side-effects during model scenario testing and policy implementation. Structural Loop analysis of socio-ecological system models identifies dominant feedback structures during times of behavioural shift, allowing the user to monitor key influential drivers during model simulation. This work carries out Loop Eigenvalue Elasticity Analysis (LEEA) on three system dynamic models, exploring tipping points in lake systems undergoing eutrophication. The purpose is to explore the potential benefits and limitations of the technique in the field of socio-ecology. The LEEA technique shows promise for socio-ecological systems which undergo regime shifts or express oscillatory trends, but shows limited usefulness with large models. The results of this work highlight changes in feedback loop dominance, years prior to eutrophic tipping events in lake systems. LEEA could be used as an early warning signal to impending system changes, complementary to other known early warning signals. This approach could improve our understanding during critical times of a system's behaviour, changing how we approach model analysis and the way scenario testing and policy implementation are addressed in socio-ecological system models.

  7. Microwave photonic notch filter based on a dual-Sagnac-loop structure.

    PubMed

    Wang, Xudong; Chan, Erwin H W; Minasian, Robert A

    2010-11-20

    A new single-wavelength, coherence-free microwave photonic notch filter is presented. The concept is based on a dual-Sagnac-loop structure that functions with a new principle in which the two loops operate with different free spectral ranges, and which generate noncommensurate taps. It has the ability to generate a narrow notch response and can operate to high frequencies. Experimental results demonstrate a notch filter with a narrow notch width, a flat passband, and high stop-band attenuation of over 40dB. PMID:21102681

  8. Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis.

    PubMed

    Wang, Dong; Bushnell, David A; Westover, Kenneth D; Kaplan, Craig D; Kornberg, Roger D

    2006-12-01

    New structures of RNA polymerase II (pol II) transcribing complexes reveal a likely key to transcription. The trigger loop swings beneath a correct nucleoside triphosphate (NTP) in the nucleotide addition site, closing off the active center and forming an extensive network of interactions with the NTP base, sugar, phosphates, and additional pol II residues. A histidine side chain in the trigger loop, precisely positioned by these interactions, may literally "trigger" phosphodiester bond formation. Recognition and catalysis are thus coupled, ensuring the fidelity of transcription. PMID:17129781

  9. Structure of D-alanine-D-alanine ligase from Yersinia pestis: nucleotide phosphate recognition by the serine loop.

    PubMed

    Tran, Huyen Thi; Hong, Myoung Ki; Ngo, Ho Phuong Thuy; Huynh, Kim Hung; Ahn, Yeh Jin; Wang, Zhong; Kang, Lin Woo

    2016-01-01

    D-Alanyl-D-alanine is an essential precursor of bacterial peptidoglycan and is synthesized by D-alanine-D-alanine ligase (DDL) with hydrolysis of ATP; this reaction makes DDL an important drug target for the development of antibacterial agents. Five crystal structures of DDL from Yersinia pestis (YpDDL) were determined at 1.7-2.5 Å resolution: apo, AMP-bound, ADP-bound, adenosine 5'-(β,γ-imido)triphosphate-bound, and D-alanyl-D-alanine- and ADP-bound structures. YpDDL consists of three domains, in which four loops, loop 1, loop 2 (the serine loop), loop 3 (the ω-loop) and loop 4, constitute the binding sites for two D-alanine molecules and one ATP molecule. Some of them, especially the serine loop and the ω-loop, show flexible conformations, and the serine loop is mainly responsible for the conformational change in substrate nucleotide phosphates. Enzyme-kinetics assays were carried out for both the D-alanine and ATP substrates and a substrate-binding mechanism was proposed for YpDDL involving conformational changes of the loops. PMID:26894530

  10. Tertiary structure-dependence of misfolding substitutions in loops of the maltose-binding protein.

    PubMed

    Raffy, S; Sassoon, N; Hofnung, M; Betton, J M

    1998-10-01

    We previously identified and characterized amino acid substitutions in a loop connecting helix I to strand B, the alphaI/betaB loop, of the N-domain that are critical for in vivo folding of the maltose-binding protein (MalE31). The tertiary context-dependence of this mutation in MalE folding was assessed by probing the tolerance of an equivalent alphabeta loop of the C-domain to the same amino acid substitutions (MalE219). Moving the loop mutation from the N- to the C-domain eliminated the in vivo misfolding step that led to the formation of inclusion bodies. In vitro, both loop variants exhibited an important decrease of stability, but their intrinsic tendency to aggregate was well correlated with their periplasmic fates in Escherichia coli. Furthermore, the noncoincidence of the unfolding and refolding transition curves and increase of light scattering during the refolding of MalE31 indicate that a competing off-pathway reaction could occurs on the folding pathway of this variant. These results strongly support the notion that the formation of super-secondary structures of the N-domain is a rate-limiting step in the folding pathway of MalE. PMID:9792100

  11. Alteration of Sugar-Induced Conformational Changes of the Melibiose Permease by Mutating Arg141 in Loop 4-5

    PubMed Central

    León, Xavier; Leblanc, Gérard; Padrós, Esteve

    2009-01-01

    Abstract The melibiose permease (MelB) from Escherichia coli couples the uptake of melibiose to that of Na+, Li+, or H+. In this work, we applied attenuated total reflection Fourier transform infrared (ATR-FTIR) difference spectroscopy to obtain information about the structural changes involved in substrate interaction with the R141C mutant and with the wild-type MelB reacted with N-ethylmaleimide (NEM). These modified permeases have the ability to bind the substrates but fail to transport them. It is shown that the sugar-induced ATR-FTIR difference spectra of the R141C mutant are different from those corresponding to the Cys-less permease from which it is derived. There are alterations of peaks assigned to turns and β-structures located most likely in loop 4-5. In addition, and quite notably, a peak at 1659 cm−1, assigned to changes at the level of one α-helix subpopulation, disappears in the melibiose-induced difference spectrum in the presence of Na+, suggesting a reduction of the conformational change capacity of the mutated MelB. These helices may involve structural components that couple the cation- and sugar-binding sites. On the other hand, MelB-NEM difference spectra are proportionally less disrupted than the R141C ones. Hence, the transport cycle of these two permeases, modified at two different loops, is most likely impaired at a different stage. It is proposed that the R141C mutant leads to the generation of a partially defective ternary complex that is unable to catalyze the subsequent conformational change necessary for substrate translocation. PMID:19527646

  12. Behaviour of oscillations in loop structures above active regions

    NASA Astrophysics Data System (ADS)

    Kolobov, D. Y.; Kobanov, N. I.; Chelpanov, A. A.; Kochanov, A. A.; Anfinogentov, S. A.; Chupin, S. A.; Myshyakov, I. I.; Tomin, V. E.

    2015-12-01

    In this study we combine the multiwavelength ultraviolet-optical (Solar Dynamics Observatory, SDO) and radio (Nobeyama Radioheliograph, NoRH) observations to get further insight into space-frequency distribution of oscillations at different atmospheric levels of the Sun. We processed the observational data on NOAA 11711 active region and found oscillations propagating from the photospheric level through the transition region upward into the corona. The power maps of low-frequency (1-2 mHz) oscillations reproduce well the fan-like coronal structures visible in the Fe IX 171 Å line. High frequency oscillations (5-7 mHz) propagate along the vertical magnetic field lines and concentrate inside small-scale elements in the umbra and at the umbra-penumbra boundary. We investigated the dependence of the dominant oscillation frequency upon the distance from the sunspot barycentre to estimate inclination of magnetic tubes in higher levels of sunspots where it cannot be measured directly, and found that this angle is close to 40° above the umbra boundaries in the transition region.

  13. Post-flare loops embedded in a hot coronal fan-like structure

    NASA Technical Reports Server (NTRS)

    Svestka, Z.; Farnik, F.; Hudson, H. S.; Hick, P.

    1997-01-01

    Limb events were demonstrated on the sun in which rising post-flare loops were embedded in hot structures looking in soft X-rays like fans of rays, formed during the flare and extending high into the corona. One of these structures is analyzed and it is suggested that these fans of rays represent temporary ministreamers, along which mass flows into interplanetary space. This suggestion is supported by maps of solar wind density constructed from scintillation measurements.

  14. NMR structure of the A730 loop of the Neurospora VS ribozyme: insights into the formation of the active site

    PubMed Central

    Bonneau, Eric; Girard, Nicolas; Boisbouvier, Jérôme; Legault, Pascale

    2011-01-01

    The Neurospora VS ribozyme is a small nucleolytic ribozyme with unique primary, secondary and global tertiary structures, which displays mechanistic similarities to the hairpin ribozyme. Here, we determined the high-resolution NMR structure of a stem–loop VI fragment containing the A730 internal loop, which forms part of the active site. In the presence of magnesium ions, the A730 loop adopts a structure that is consistent with existing biochemical data and most likely reflects its conformation in the VS ribozyme prior to docking with the cleavage site internal loop. Interestingly, the A730 loop adopts an S-turn motif that is also present in loop B within the hairpin ribozyme active site. The S-turn appears necessary to expose the Watson–Crick edge of a catalytically important residue (A756) so that it can fulfill its role in catalysis. The A730 loop and the cleavage site loop of the VS ribozyme display structural similarities to internal loops found in the active site of the hairpin ribozyme. These similarities provided a rationale to build a model of the VS ribozyme active site based on the crystal structure of the hairpin ribozyme. PMID:21266483

  15. Structural Variation and Uniformity among Tetraloop-Receptor Interactions and Other Loop-Helix Interactions in RNA Crystal Structures

    PubMed Central

    Wu, Li; Chai, Dinggeng; Fraser, Marie E.; Zimmerly, Steven

    2012-01-01

    Tetraloop-receptor interactions are prevalent structural units in RNAs, and include the GAAA/11-nt and GNRA-minor groove interactions. In this study, we have compiled a set of 78 nonredundant loop-helix interactions from X-ray crystal structures, and examined them for the extent of their sequence and structural variation. Of the 78 interactions in the set, only four were classical GAAA/11-nt motifs, while over half (48) were GNRA-minor groove interactions. The GNRA-minor groove interactions were not a homogeneous set, but were divided into five subclasses. The most predominant subclass is characterized by two triple base pair interactions in the minor groove, flanked by two ribose zipper contacts. This geometry may be considered the “standard” GNRA-minor groove interaction, while the other four subclasses are alternative ways to form interfaces between a minor groove and tetraloop. The remaining 26 structures in the set of 78 have loops interacting with mostly idiosyncratic receptors. Among the entire set, a number of sequence-structure correlations can be identified, which may be used as initial hypotheses in predicting three-dimensional structures from primary sequences. Conversely, other sequence patterns are not predictive; for example, GAAA loop sequences and GG/CC receptors bind to each other with three distinct geometries. Finally, we observe an example of structural evolution in group II introns, in which loop-receptor motifs are substituted for each other while maintaining the larger three-dimensional geometry. Overall, the study gives a more complete view of RNA loop-helix interactions that exist in nature. PMID:23152878

  16. The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts.

    PubMed

    Chikada, Hiromi; Ito, Keiichi; Yanagida, Ayaka; Nakauchi, Hiromitsu; Kamiya, Akihide

    2015-01-01

    Hepatic stem/progenitor cells, hepatoblasts, have a high proliferative ability and can differentiate into mature hepatocytes and cholangiocytes. Therefore, these cells are considered to be useful for regenerative medicine and drug screening for liver diseases. However, it is problem that in vitro maturation of hepatoblasts is insufficient in the present culture system. In this study, a novel regulator to induce hepatic differentiation was identified and the molecular function of this factor was examined in embryonic day 13 hepatoblast culture with maturation factor, oncostatin M and extracellular matrices. Overexpression of the basic helix-loop-helix type transcription factor, Mist1, induced expression of mature hepatocytic markers such as carbamoyl-phosphate synthetase1 and several cytochrome P450 (CYP) genes in this culture system. In contrast, Mist1 suppressed expression of cholangiocytic markers such as Sox9, Sox17, Ck19, and Grhl2. CYP3A metabolic activity was significantly induced by Mist1 in this hepatoblast culture. In addition, Mist1 induced liver-enriched transcription factors, CCAAT/enhancer-binding protein α and Hepatocyte nuclear factor 1α, which are known to be involved in liver functions. These results suggest that Mist1 partially induces mature hepatocytic expression and function accompanied by the down-regulation of cholangiocytic markers. PMID:26456005

  17. The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts

    PubMed Central

    Chikada, Hiromi; Ito, Keiichi; Yanagida, Ayaka; Nakauchi, Hiromitsu; Kamiya, Akihide

    2015-01-01

    Hepatic stem/progenitor cells, hepatoblasts, have a high proliferative ability and can differentiate into mature hepatocytes and cholangiocytes. Therefore, these cells are considered to be useful for regenerative medicine and drug screening for liver diseases. However, it is problem that in vitro maturation of hepatoblasts is insufficient in the present culture system. In this study, a novel regulator to induce hepatic differentiation was identified and the molecular function of this factor was examined in embryonic day 13 hepatoblast culture with maturation factor, oncostatin M and extracellular matrices. Overexpression of the basic helix-loop-helix type transcription factor, Mist1, induced expression of mature hepatocytic markers such as carbamoyl-phosphate synthetase1 and several cytochrome P450 (CYP) genes in this culture system. In contrast, Mist1 suppressed expression of cholangiocytic markers such as Sox9, Sox17, Ck19, and Grhl2. CYP3A metabolic activity was significantly induced by Mist1 in this hepatoblast culture. In addition, Mist1 induced liver-enriched transcription factors, CCAAT/enhancer-binding protein α and Hepatocyte nuclear factor 1α, which are known to be involved in liver functions. These results suggest that Mist1 partially induces mature hepatocytic expression and function accompanied by the down-regulation of cholangiocytic markers. PMID:26456005

  18. A CC′ Loop Decoy Peptide Blocks the Interaction Between Act1 and IL-17RA to Attenuate IL-17- and IL-25-Induced Inflammation

    PubMed Central

    Liu, Caini; Swaidani, Shadi; Qian, Wen; Kang, Zizhen; Sun, Paige; Han, Yue; Wang, Chenhui; Gulen, Muhammet Fatih; Yin, Weiguo; Zhang, Chunjiang; Fox, Paul L; Aronica, Mark; Hamilton, Thomas A; Misra, Saurav; Deng, Junpeng; Li, Xiaoxia

    2012-01-01

    Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes that encode inflammatory factors and they are implicated in the pathology of various inflammatory diseases. Nuclear factor κB (NF-κB) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for IL-17 and IL-25 signaling, and it is recruited to their receptors through heterotypic interactions between their SEFIR [SEF (similar expression to fibroblast growth factor genes)/IL-17R] domains. Modeling of SEFIR domains has shown their structural similarity with the Toll-IL-1 receptor (TIR) domains of Toll-like receptors (TLRs) and the IL-1R. Whereas the BB′ loop of TIR is required for TIR-TIR interactions, we found that deletion of the BB′ loop from Act1 or IL-17RA (a common subunit of IL-17R and IL-25R) did not affect Act1–IL-17RA interactions. Instead, deletion of the CC′ loop from Act1 or IL-17RA abolished the interaction between Act1 and IL-17RA, suggesting that SEFIR and TIR domains interact in different manners. Surface plasmon resonance measurements showed that a peptide corresponding to the CC′ loop bound directly to IL-17RA. A cell-permeable decoy peptide based on the CC′ loop sequence inhibited IL-17- and IL-25-mediated signaling, and it inhibited IL-17- and IL-25-induced responses in vitro and pulmonary inflammation in vivo. Together, these findings provide the molecular basis for the specificity of SEFIR versus TIR domain interactions and consequent signaling. Moreover, we suggest that the CC′ loop motif of SEFIR domains is a promising target for therapeutic strategies against IL-17- and IL-25-asssociated inflammatory diseases. PMID:22045852

  19. A CC' loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation.

    PubMed

    Liu, Caini; Swaidani, Shadi; Qian, Wen; Kang, Zizhen; Sun, Paige; Han, Yue; Wang, Chenhui; Gulen, Muhammet Fatih; Yin, Weiguo; Zhang, Chunjiang; Fox, Paul L; Aronica, Mark; Hamilton, Thomas A; Misra, Saurav; Deng, Junpeng; Li, Xiaoxia

    2011-01-01

    Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes encoding inflammatory factors and are implicated in the pathology of various inflammatory diseases. Nuclear factor κB (NF-κB) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for signaling by either IL-17 or IL-25, and it is recruited to their receptors (IL-17R and IL-25R) through heterotypic interactions between the SEFIR [SEF (similar expression to fibroblast growth factor genes) and IL-17R] domain of Act1 and that of the receptor. SEFIR domains have structural similarity with the Toll-IL-1 receptor (TIR) domains of Toll-like receptors and IL-1R. Whereas the BB' loop of TIR is required for TIR-TIR interactions, we found that deletion of the BB' loop from Act1 or IL-17RA (a common subunit of both IL-17R and IL-25R) did not affect Act1-IL-17RA interactions; rather, deletion of the CC' loop from Act1 or IL-17RA abolished the interaction between both proteins. Surface plasmon resonance measurements showed that a peptide corresponding to the CC' loop of Act1 bound directly to IL-17RA. A cell-permeable decoy peptide based on the CC' loop sequence inhibited IL-17- or IL-25-mediated signaling in vitro, as well as IL-17- and IL-25-induced pulmonary inflammation in mice. Together, these findings provide the molecular basis for the specificity of SEFIR-SEFIR versus TIR-TIR domain interactions and consequent signaling. Moreover, we suggest that the CC' loop motif of SEFIR domains is a promising target for therapeutic strategies against inflammatory diseases associated with IL-17 or IL-25 signaling. PMID:22045852

  20. Determining the 3D Structure of the Corona Using Vertical Height Constraints on Observed Active Region Loops

    NASA Astrophysics Data System (ADS)

    Gary, G. Allen; Hu, Qiang; Lee, Jong Kwan; Aschwanden, Markus J.

    2014-10-01

    The corona associated with an active region is structured by high-temperature, magnetically dominated closed and open loops. The projected 2D geometry of these loops is captured in EUV filtergrams. In this study using SDO/AIA 171 Å filtergrams, we expand our previous method to derive the 3D structure of these loops, independent of heliostereoscopy. We employ an automated loop recognition scheme (Occult-2) and fit the extracted loops with 2D cubic Bézier splines. Utilizing SDO/HMI magnetograms, we extrapolate the magnetic field to obtain simple field models within a rectangular cuboid. Using these models, we minimize the misalignment angle with respect to Bézier control points to extend the splines to 3D (Gary, Hu, and Lee 2014). The derived Bézier control points give the 3D structure of the fitted loops. We demonstrate the process by deriving the position of 3D coronal loops in three active regions (AR 11117, AR 11158, and AR 11283). The numerical minimization process converges and produces 3D curves which are consistent with the height of the loop structures when the active region is seen on the limb. From this we conclude that the method can be important in both determining estimates of the 3D magnetic field structure and determining the best magnetic model among competing advanced magnetohydrodynamics or force-free magnetic-field computer simulations.

  1. The 5S rRNA loop E: chemical probing and phylogenetic data versus crystal structure.

    PubMed Central

    Leontis, N B; Westhof, E

    1998-01-01

    A significant fraction of the bases in a folded, structured RNA molecule participate in noncanonical base pairing interactions, often in the context of internal loops or multi-helix junction loops. The appearance of each new high-resolution RNA structure provides welcome data to guide efforts to understand and predict RNA 3D structure, especially when the RNA in question is a functionally conserved molecule. The recent publication of the crystal structure of the "Loop E" region of bacterial 5S ribosomal RNA is such an event [Correll CC, Freeborn B, Moore PB, Steitz TA, 1997, Cell 91:705-712]. In addition to providing more examples of already established noncanonical base pairs, such as purine-purine sheared pairings, trans-Hoogsteen UA, and GU wobble pairs, the structure provides the first high-resolution views of two new purine-purine pairings and a new GU pairing. The goal of the present analysis is to expand the capabilities of both chemical probing and phylogenetic analysis to predict with greater accuracy the structures of RNA molecules. First, in light of existing chemical probing data, we investigate what lessons could be learned regarding the interpretation of this widely used method of RNA structure probing. Then we analyze the 3D structure with reference to molecular phylogeny data (assuming conservation of function) to discover what alternative base pairings are geometrically compatible with the structure. The comparisons between previous modeling efforts and crystal structures show that the intricate involvements of ions and water molecules in the maintenance of non-Watson-Crick pairs render the process of correctly identifying the interacting sites in such pairs treacherous, except in cases of trans-Hoogsteen A/U or sheared A/G pairs for the adenine N1 site. The phylogenetic analysis identifies A/A, A/C, A/U and C/A, C/C, and C/U pairings isosteric with sheared A/G, as well as A/A and A/C pairings isosteric with both G/U and G/G bifurcated pairings

  2. Modulated drug release from the stem-and-loop structured oligodeoxynucleotide upon UV-A irradiation in the presence of target DNA.

    PubMed

    Tanabe, Kazuhito; Nakata, Hiroyuki; Mukai, Shin; Nishimoto, Sei-ichi

    2005-11-01

    o-Nitrobenzyl photochemistry as induced by UV-A irradiation was applied to a photoactivated drug releasing system based on a molecular beacon strategy. A stem-and-loop structured oligodeoxynucleotide (ODN) possessing a photoreactive o-nitrobenzyl chromophore at the 3'-end and 1-aminonaphthalene quencher at the 5'-end underwent conformational change into a conventional double strand structure by hybridization with a specified target DNA. The intrinsic stem-and-loop structure suppressed photoactivated release of benzoic acid as a phantom drug from the o-nitrobenzyl chromophore because of intramolecular quenching by the 1-aminonaphthalene unit in close proximity to the chromophore. Formation of the double strand structure in the presence of perfectly matched target DNA minimized occurrence of intramolecular quenching and thereby enhanced the photoactivated drug release. PMID:16240005

  3. Radiation-induced strengthening and absorption of dislocation loops in ferritic Fe-Cr alloys: the role of Cr segregation.

    PubMed

    Terentyev, D; Bakaev, A

    2013-07-01

    The understanding of radiation-induced strengthening in ferritic FeCr-based steels remains an essential issue in the assessment of materials for fusion and fission reactors. Both early and recent experimental works on Fe-Cr alloys reveal Cr segregation on radiation-induced nanostructural features (mainly dislocation loops), whose impact on the modification of the mechanical response of the material might be key for explaining quantitatively the radiation-induced strengthening in these alloys. In this work, we use molecular dynamics to study systematically the interaction of dislocations with 1/2<111> and <100> loops in all possible orientations, both enriched by Cr atoms and undecorated, for different temperatures, loop sizes and dislocation velocities. The configurations of the enriched loops have been obtained using a non-rigid lattice Monte Carlo method. The study reveals that Cr segregation influences the interaction mechanisms with both 1/2<111> and <100> loops. The overall effect of Cr enrichment is to penalize the mobility of intrinsically glissile 1/2<111> loops, modifying the reaction mechanisms as a result. The following three most important effects associated with Cr enrichment have been revealed: (i) absence of dynamic drag; (ii) suppression of complete absorption; (iii) enhanced strength of small dislocation loops (2 nm and smaller). Overall the effect of the Cr enrichment is therefore to increase the unpinning stress, so experimentally 'invisible' nanostructural features may also contribute to radiation-induced strengthening. The reasons for the modification of the mechanisms are explained and the impact of the loading conditions is discussed. PMID:23756468

  4. The Effective Field Theory of Large Scale Structures at two loops

    SciTech Connect

    Carrasco, John Joseph M.; Foreman, Simon; Green, Daniel; Senatore, Leonardo E-mail: sfore@stanford.edu E-mail: senatore@stanford.edu

    2014-07-01

    Large scale structure surveys promise to be the next leading probe of cosmological information. It is therefore crucial to reliably predict their observables. The Effective Field Theory of Large Scale Structures (EFTofLSS) provides a manifestly convergent perturbation theory for the weakly non-linear regime of dark matter, where correlation functions are computed in an expansion of the wavenumber k of a mode over the wavenumber associated with the non-linear scale k{sub NL}. Since most of the information is contained at high wavenumbers, it is necessary to compute higher order corrections to correlation functions. After the one-loop correction to the matter power spectrum, we estimate that the next leading one is the two-loop contribution, which we compute here. At this order in k/k{sub NL}, there is only one counterterm in the EFTofLSS that must be included, though this term contributes both at tree-level and in several one-loop diagrams. We also discuss correlation functions involving the velocity and momentum fields. We find that the EFTofLSS prediction at two loops matches to percent accuracy the non-linear matter power spectrum at redshift zero up to k∼ 0.6 h Mpc{sup −1}, requiring just one unknown coefficient that needs to be fit to observations. Given that Standard Perturbation Theory stops converging at redshift zero at k∼ 0.1 h Mpc{sup −1}, our results demonstrate the possibility of accessing a factor of order 200 more dark matter quasi-linear modes than naively expected. If the remaining observational challenges to accessing these modes can be addressed with similar success, our results show that there is tremendous potential for large scale structure surveys to explore the primordial universe.

  5. An Induced Global Magnetic Field Looping Around the Magnetotail of Venus

    NASA Astrophysics Data System (ADS)

    Chai, Lihui; Wei, Yong; Wan, Weixing; Zhang, Tielong; Fraenz, Markus; Dubinin, Eduard; Zhang, Hui; Rong, Zhaojin; Barabash, Stas

    2016-04-01

    Venus serves as the prototype of solar wind interaction with unmagnetized planetary bodies with atmospheres. It has no intrinsic dipole or crustal magnetic field, the only magnetic field is believed to be formed by the draped interplanetary magnetic field (IMF). However, the large-scale magnetic field observed over the north polar region of Venus has a bias in the dawnward direction and seemingly unresponsive to the IMF's direction. Here we show that besides the draped field, there is a second type of induced global magnetic field at Venus, and the dawnward field is only a part of it. This global field has a distribution in a cylindrical shell around the magnetotail and a counterclockwise direction looking from the planetary tail toward the Sun, which demonstrates that there are two currents flowing out and in of the planet along the inner and outer boundaries of the looping field, respectively. [Chai et al., 2016, JGR, doi:10.1002/2015JA021904

  6. Structure Prediction of the Second Extracellular Loop in G-Protein-Coupled Receptors

    PubMed Central

    Kmiecik, Sebastian; Jamroz, Michal; Kolinski, Michal

    2014-01-01

    G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs. PMID:24896119

  7. Reinforced concrete structural corrosion monitoring using Hi-Bi photonic crystal fibres in a fiber loop structure

    NASA Astrophysics Data System (ADS)

    Bravo, M.; McCague, C.; Fabian, M.; Jaroszewicz, L.; Mergo, P.; Lopez-Amo, M.; Grattan, K. T. V.; Sun, T.

    2014-05-01

    A novel sensing approach has been developed for in-situ corrosion monitoring of steel in reinforced concrete structures, using a fibre loop interferometer sensor system based on a Hi-Bi photonic crystal fibre (PCF). To do so an accurate fibre alignment procedure has been implemented in order to improve the performance of the sensor system embedded into the concrete structure when it is subjected to an accelerated corrosion test. The positive results obtained have confirmed the effectiveness of such a sensor system for applications in structural health monitoring.

  8. Heat Removal from Bipolar Transistor by Loop Heat Pipe with Nickel and Copper Porous Structures

    PubMed Central

    Smitka, Martin; Malcho, Milan

    2014-01-01

    Loop heat pipes (LHPs) are used in many branches of industry, mainly for cooling of electrical elements and systems. The loop heat pipe is a vapour-liquid phase-change device that transfers heat from evaporator to condenser. One of the most important parts of the LHP is the porous wick structure. The wick structure provides capillary force to circulate the working fluid. To achieve good thermal performance of LHP, capillary wicks with high permeability and porosity and fine pore radius are expected. The aim of this work was to develop porous structures from copper and nickel powder with different grain sizes. For experiment copper powder with grain size of 50 and 100 μm and nickel powder with grain size of 10 and 25 μm were used. Analysis of these porous structures and LHP design are described in the paper. And the measurements' influences of porous structures in LHP on heat removal from the insulated gate bipolar transistor (IGBT) have been made. PMID:24959622

  9. Heat removal from bipolar transistor by loop heat pipe with nickel and copper porous structures.

    PubMed

    Nemec, Patrik; Smitka, Martin; Malcho, Milan

    2014-01-01

    Loop heat pipes (LHPs) are used in many branches of industry, mainly for cooling of electrical elements and systems. The loop heat pipe is a vapour-liquid phase-change device that transfers heat from evaporator to condenser. One of the most important parts of the LHP is the porous wick structure. The wick structure provides capillary force to circulate the working fluid. To achieve good thermal performance of LHP, capillary wicks with high permeability and porosity and fine pore radius are expected. The aim of this work was to develop porous structures from copper and nickel powder with different grain sizes. For experiment copper powder with grain size of 50 and 100 μm and nickel powder with grain size of 10 and 25 μm were used. Analysis of these porous structures and LHP design are described in the paper. And the measurements' influences of porous structures in LHP on heat removal from the insulated gate bipolar transistor (IGBT) have been made. PMID:24959622

  10. Radiation Enhanced Absorption of Frank Loops by Nanovoids in Cu

    NASA Astrophysics Data System (ADS)

    Chen, Y.; Zhang, X.; Wang, J.

    2016-01-01

    Neutron and heavy ion irradiations generally induce voids in metallic materials, and continuous radiations typically result in void swelling and mechanical failure of the irradiated materials. Recent experiments showed that nanovoids in nanotwinned copper could act as sinks for radiation-induced Frank loops, significantly mitigating radiation damage. In this paper, we report on structural evolution of Frank loops under cascades and address the role of nanovoids in absorbing Frank loops in detail by using molecular dynamics simulations. Results show that a stand-alone Frank loop is stable under cascades. When Frank loops are adjacent to nanovoids, the diffusion of a group of atoms from the loop into nanovoids is accomplished via the formation and propagation of dislocation loops. The loop-nanovoid interactions result in the shrinkage of the nanovoids and the Frank loops.

  11. Antagonist-Induced Conformational Changes in Dopamine Transporter Extracellular Loop Two Involve Residues in a Potential Salt Bridge

    PubMed Central

    Gaffaney, Jon D.; Shetty, Madhur; Felts, Bruce; Pramod, Akula-Bala; Foster, James D.; Henry, L. Keith; Vaughan, Roxanne A.

    2014-01-01

    Ligand-induced changes in the conformation of extracellular loop (EL) 2 in the rat (r) dopamine transporter (DAT) were examined using limited proteolysis with endoproteinase Asp-N and detection of cleavage products by epitope-specific immunoblotting. The principle N-terminal fragment produced by Asp-N was a 19 kDa peptide likely derived by proteolysis of EL2 residue D174, which is present just past the extracellular end of TM3. Production of this fragment was significantly decreased by binding of cocaine and other uptake blockers, but was not affected by substrates or Zn2+, indicating the presence of a conformational change at D174 that may be related to the mechanism of transport inhibition. DA transport activity and cocaine analog binding were decreased by Asp-N treatment, suggesting a requirement for EL2 integrity in these DAT functions. In a previous study we demonstrated that ligand-induced protease resistance also occurred at R218 on the C-terminal side of rDAT EL2. Here using substituted cysteine accessibility analysis of human (h) DAT we confirm cocaine-induced alterations in reactivity of the homologous R219 and identify conformational sensitivity of V221. Focused molecular modeling of D174 and R218 based on currently available Aquifex aeolicus leucine transporter crystal structures places these residues within 2.9 Å of one another, suggesting their proximity as a structural basis for their similar conformational sensitivities and indicating their potential to form a salt bridge. These findings extend our understanding of DAT EL2 and its role in transport and binding functions. PMID:24269640

  12. Antagonist-induced conformational changes in dopamine transporter extracellular loop two involve residues in a potential salt bridge.

    PubMed

    Gaffaney, Jon D; Shetty, Madhur; Felts, Bruce; Pramod, Akula-Bala; Foster, James D; Henry, L Keith; Vaughan, Roxanne A

    2014-07-01

    Ligand-induced changes in the conformation of extracellular loop (EL) 2 in the rat (r) dopamine transporter (DAT) were examined using limited proteolysis with endoproteinase Asp-N and detection of cleavage products by epitope-specific immunoblotting. The principle N-terminal fragment produced by Asp-N was a 19kDa peptide likely derived by proteolysis of EL2 residue D174, which is present just past the extracellular end of TM3. Production of this fragment was significantly decreased by binding of cocaine and other uptake blockers, but was not affected by substrates or Zn(2+), indicating the presence of a conformational change at D174 that may be related to the mechanism of transport inhibition. DA transport activity and cocaine analog binding were decreased by Asp-N treatment, suggesting a requirement for EL2 integrity in these DAT functions. In a previous study we demonstrated that ligand-induced protease resistance also occurred at R218 on the C-terminal side of rDAT EL2. Here using substituted cysteine accessibility analysis of human (h) DAT we confirm cocaine-induced alterations in reactivity of the homologous R219 and identify conformational sensitivity of V221. Focused molecular modeling of D174 and R218 based on currently available Aquifex aeolicus leucine transporter crystal structures places these residues within 2.9Å of one another, suggesting their proximity as a structural basis for their similar conformational sensitivities and indicating their potential to form a salt bridge. These findings extend our understanding of DAT EL2 and its role in transport and binding functions. PMID:24269640

  13. Non-perturbative corrections to the one-loop free energy induced by a massive scalar field on a stationary slowly varying in space gravitational background

    NASA Astrophysics Data System (ADS)

    Kalinichenko, Igor; Kazinski, Peter

    2014-08-01

    The explicit expressions for the one-loop non-perturbative corrections to the gravitational effective action induced by a scalar field on a stationary gravitational background are obtained both at zero and finite temperatures. The perturbative and non-perturbative contributions to the one-loop effective action are explicitly separated. It is proved that, after a suitable renormalization, the perturbative part of the effective action at zero temperature can be expressed in a covariant form solely in terms of the metric and its derivatives. This part coincides with the known large mass expansion of the one-loop effective action. The non-perturbative part of the renormalized one-loop effective action at zero temperature is proved to depend explicitly on the Killing vector defining the vacuum state of quantum fields. This part cannot be expressed in a covariant way through the metric and its derivatives alone. The implications of this result for the structure and symmetries of the effective action for gravity are discussed.

  14. Structural Study of a Flexible Active Site Loop in Human Indoleamine 2,3-Dioxygenase and Its Functional Implications.

    PubMed

    Álvarez, Lucía; Lewis-Ballester, Ariel; Roitberg, Adrián; Estrin, Darío A; Yeh, Syun-Ru; Marti, Marcelo A; Capece, Luciana

    2016-05-17

    Human indoleamine 2,3-dioxygenase catalyzes the oxidative cleavage of tryptophan to N-formyl kynurenine, the initial and rate-limiting step in the kynurenine pathway. Additionally, this enzyme has been identified as a possible target for cancer therapy. A 20-amino acid protein segment (the JK loop), which connects the J and K helices, was not resolved in the reported hIDO crystal structure. Previous studies have shown that this loop undergoes structural rearrangement upon substrate binding. In this work, we apply a combination of replica exchange molecular dynamics simulations and site-directed mutagenesis experiments to characterize the structure and dynamics of this protein region. Our simulations show that the JK loop can be divided into two regions: the first region (JK loop(C)) displays specific and well-defined conformations and is within hydrogen bonding distance of the substrate, while the second region (JK loop(N)) is highly disordered and exposed to the solvent. The peculiar flexible nature of JK loop(N) suggests that it may function as a target for post-translational modifications and/or a mediator for protein-protein interactions. In contrast, hydrogen bonding interactions are observed between the substrate and Thr379 in the highly conserved "GTGG" motif of JK loop(C), thereby anchoring JK loop(C) in a closed conformation, which secures the appropriate substrate binding mode for catalysis. Site-directed mutagenesis experiments confirm the key role of this residue, highlighting the importance of the JK loop(C) conformation in regulating the enzymatic activity. Furthermore, the existence of the partially and totally open conformations in the substrate-free form suggests a role of JK loop(C) in controlling substrate and product dynamics. PMID:27112409

  15. Defining the loop structures in proteins based on composite β-turn mimics.

    PubMed

    Dhar, Jesmita; Chakrabarti, Pinak

    2015-06-01

    Asx- and ω-turns are β-turn mimics, which replace the conventional main-chain hydrogen bonds seen in the latter by those involving the side chains, and both involve three residues. In this paper we analyzed the cases where these turns occur together--side by side, with or without any gap, overlapping and in any order. These composite turns (of length 3-15 residues), occurring at ∼1 per 100 residues, may constitute the full length of many loops, and when the residues in the two component turns overlap or are adjacent to each other, the composite may take well-defined shape. It is thus possible for non-regular regions in protein structure to form local structural motifs, akin to the regular geometrical features exhibited by secondary structures. Composites having the order ω-turns followed by Asx-turns can constitute N-terminal helix capping motif. Ternary composite turns (made up of ω-, Asx- and ST-turns), some with characteristic shape, have also been identified. Delineation of composite turns would help in characterizing loops in protein structures, which often have functional roles. Some sequence patterns seen in composites can be used for their incorporation in protein design. PMID:25870305

  16. The integration of water loop heat pump and building structural thermal storage systems

    SciTech Connect

    Marseille, T.J.; Schliesing, J.S.

    1990-09-01

    Commercial buildings often have extensive periods where one space needs cooling and another heating. Even more common is the need for heating during one part of the day and cooling during another in the same spaces. If a building's heating and cooling system could be integrated with the building's structural mass such that the mass can be used to collect, store, and deliver energy, significant energy might be saved. Computer models were developed to simulate this interaction for an existing office building in Seattle, Washington that has a decentralized water-source heat pump system. Metered data available for the building was used to calibrate a base'' building model (i.e., nonintegrated) prior to simulation of the integrated system. In the simulated integration strategy a secondary water loop was manifolded to the main HVAC hydronic loop. tubing in this loop was embedded in the building's concrete floor slabs. Water was routed to this loop by a controller to charge or discharge thermal energy to and from the slabs. The slabs were also in thermal communication with the conditioned spaces. Parametric studies of the building model, using weather data for five other cities in addition to Seattle, predicted that energy can be saved on cooling dominated days. On hot, dry days and during the night the cooling tower can beneficially be used as a free cooling'' source for thermally charging'' the floor slabs using cooled water. Through the development of an adaptive/predictive control strategy, annual HVAC energy savings as large as 30% appear to be possible in certain climates. 8 refs., 13 figs.

  17. Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate

    PubMed Central

    Ababou, Abdessamad; Koronakis, Vassilis

    2016-01-01

    Gram-negative bacteria such as E. coli use tripartite efflux pumps such as AcrAB-TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding. PMID:27403665

  18. Crystal Structures of Trypanosoma cruzi UDP-Galactopyranose Mutase Implicate Flexibility of the Histidine Loop in Enzyme Activation

    SciTech Connect

    Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle; Sobrado, Pablo; Tanner, John J.

    2012-11-01

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3 {angstrom} movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10-50, primarily by decreasing k{sub cat}. Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens.

  19. Improving the accuracy of the structure prediction of the third hypervariable loop of the heavy chains of antibodies

    PubMed Central

    Messih, Mario Abdel; Lepore, Rosalba; Marcatili, Paolo; Tramontano, Anna

    2014-01-01

    Motivation: Antibodies are able to recognize a wide range of antigens through their complementary determining regions formed by six hypervariable loops. Predicting the 3D structure of these loops is essential for the analysis and reengineering of novel antibodies with enhanced affinity and specificity. The canonical structure model allows high accuracy prediction for five of the loops. The third loop of the heavy chain, H3, is the hardest to predict because of its diversity in structure, length and sequence composition. Results: We describe a method, based on the Random Forest automatic learning technique, to select structural templates for H3 loops among a dataset of candidates. These can be used to predict the structure of the loop with a higher accuracy than that achieved by any of the presently available methods. The method also has the advantage of being extremely fast and returning a reliable estimate of the model quality. Availability and implementation: The source code is freely available at http://www.biocomputing.it/H3Loopred/ Contact: anna.tramontano@uniroma1.it Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:24930144

  20. Structural delineation of stem-loop RNA binding by human TAF15 protein.

    PubMed

    Kashyap, Maruthi; Ganguly, Akshay Kumar; Bhavesh, Neel Sarovar

    2015-01-01

    Human TATA binding protein associated factor 2 N (TAF15) and Fused in sarcoma (FUS) are nucleic acid binding proteins belonging to the conserved FET family of proteins. They are involved in diverse processes such as pre-mRNA splicing, mRNA transport, and DNA binding. The absence of information regarding the structural mechanism employed by the FET family in recognizing and discriminating their cognate and non-cognate RNA targets has hampered the attainment of consensus on modes of protein-RNA binding for this family. Our study provides a molecular basis of this RNA recognition using a combination of solution-state NMR spectroscopy, calorimetry, docking and molecular dynamics simulation. Analysis of TAF15-RRM solution structure and its binding with stem-loop RNA has yielded conclusive evidence of a non-canonical mode of RNA recognition. Rather than classical stacking interactions that occur across nitrogen bases and aromatic amino acids on ribonucleoprotein sites, moderate-affinity hydrogen bonding network between the nitrogen bases in the stem-loop RNA and a concave face on the RRM surface primarily mediate TAF15-RRM RNA interaction. We have compared the binding affinities across a set of single-stranded RNA oligonucleotides to conclusively establish that RNA binding is dependent upon structural elements in the RNA rather than sequence. PMID:26612539

  1. Structural delineation of stem-loop RNA binding by human TAF15 protein

    PubMed Central

    Kashyap, Maruthi; Ganguly, Akshay Kumar; Bhavesh, Neel Sarovar

    2015-01-01

    Human TATA binding protein associated factor 2 N (TAF15) and Fused in sarcoma (FUS) are nucleic acid binding proteins belonging to the conserved FET family of proteins. They are involved in diverse processes such as pre-mRNA splicing, mRNA transport, and DNA binding. The absence of information regarding the structural mechanism employed by the FET family in recognizing and discriminating their cognate and non-cognate RNA targets has hampered the attainment of consensus on modes of protein-RNA binding for this family. Our study provides a molecular basis of this RNA recognition using a combination of solution-state NMR spectroscopy, calorimetry, docking and molecular dynamics simulation. Analysis of TAF15-RRM solution structure and its binding with stem-loop RNA has yielded conclusive evidence of a non-canonical mode of RNA recognition. Rather than classical stacking interactions that occur across nitrogen bases and aromatic amino acids on ribonucleoprotein sites, moderate-affinity hydrogen bonding network between the nitrogen bases in the stem-loop RNA and a concave face on the RRM surface primarily mediate TAF15-RRM RNA interaction. We have compared the binding affinities across a set of single-stranded RNA oligonucleotides to conclusively establish that RNA binding is dependent upon structural elements in the RNA rather than sequence. PMID:26612539

  2. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase.

    PubMed

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J; Davies, Gareth; Holdgate, Geoffrey A; Phillips, Chris; Tucker, Julie A; Norman, Richard A; Scott, Andrew D; Higazi, Daniel R; Lowe, David; Thompson, Gary S; Breeze, Alexander L

    2015-01-01

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp-Phe-Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called 'DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a 'DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and 'molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1. PMID:26203596

  3. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase

    NASA Astrophysics Data System (ADS)

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J.; Davies, Gareth; Holdgate, Geoffrey A.; Phillips, Chris; Tucker, Julie A.; Norman, Richard A.; Scott, Andrew D.; Higazi, Daniel R.; Lowe, David; Thompson, Gary S.; Breeze, Alexander L.

    2015-07-01

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp-Phe-Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called `DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a `DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and `molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1.

  4. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase

    PubMed Central

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J.; Davies, Gareth; Holdgate, Geoffrey A.; Phillips, Chris; Tucker, Julie A.; Norman, Richard A.; Scott, Andrew D.; Higazi, Daniel R.; Lowe, David; Thompson, Gary S.; Breeze, Alexander L.

    2015-01-01

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp–Phe–Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called ‘DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a ‘DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and ‘molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1. PMID:26203596

  5. The one-loop matter bispectrum in the Effective Field Theory of Large Scale Structures

    DOE PAGESBeta

    Angulo, Raul E.; Foreman, Simon; Schmittfull, Marcel; Senatore, Leonardo

    2015-10-14

    With this study, given the importance of future large scale structure surveys for delivering new cosmological information, it is crucial to reliably predict their observables. The Effective Field Theory of Large Scale Structures (EFTofLSS) provides a manifestly convergent perturbative scheme to compute the clustering of dark matter in the weakly nonlinear regime in an expansion in k/kNL, where k is the wavenumber of interest and kNL is the wavenumber associated to the nonlinear scale. It has been recently shown that the EFTofLSS matches to 1% level the dark matter power spectrum at redshift zero up to k ≃ 0.3 hmore » Mpc–1 and k ≃ 0.6 h Mpc–1 at one and two loops respectively, using only one counterterm that is fit to data. Similar results have been obtained for the momentum power spectrum at one loop. This is a remarkable improvement with respect to former analytical techniques. Here we study the prediction for the equal-time dark matter bispectrum at one loop. We find that at this order it is sufficient to consider the same counterterm that was measured in the power spectrum. Without any remaining free parameter, and in a cosmology for which kNL is smaller than in the previously considered cases (σ8=0.9), we find that the prediction from the EFTofLSS agrees very well with N-body simulations up to k ≃ 0.25 h Mpc–1, given the accuracy of the measurements, which is of order a few percent at the highest k's of interest. While the fit is very good on average up to k ≃ 0.25 h Mpc–1, the fit performs slightly worse on equilateral configurations, in agreement with expectations that for a given maximum k, equilateral triangles are the most nonlinear.« less

  6. Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

    PubMed Central

    Wongsurawat, Thidathip; Jenjaroenpun, Piroon; Kwoh, Chee Keong; Kuznetsov, Vladimir

    2012-01-01

    R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes. We found that ∼59% of these transcribed sequences contain at least one RLFS. We created R-loopDB (http://rloop.bii.a-star.edu.sg/), the database that collects all RLFS identified within over half of the human genes and links to the UCSC Genome Browser for information integration and visualisation across a variety of bioinformatics sources. We found that many oncogenes and tumour suppressors (e.g. Tp53, BRCA1, BRCA2, Kras and Ptprd) and neurodegenerative diseases related genes (e.g. ATM, Park2, Ptprd and GLDC) could be prone to significant R-loop formation. Our findings suggest that R-loops provide a novel level of RNA–DNA interactome complexity, playing key roles in gene expression controls, mutagenesis, recombination process, chromosomal rearrangement, alternative splicing, DNA-editing and epigenetic modifications. RLFSs could be used as a novel source of prospective therapeutic targets. PMID:22121227

  7. Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers.

    PubMed

    Breda, Laura; Motta, Irene; Lourenco, Silvia; Gemmo, Chiara; Deng, Wulan; Rupon, Jeremy W; Abdulmalik, Osheiza Y; Manwani, Deepa; Blobel, Gerd A; Rivella, Stefano

    2016-08-25

    Overcoming the silencing of the fetal γ-globin gene has been a long-standing goal in the treatment of sickle cell disease (SCD). The major transcriptional enhancer of the β-globin locus, called the locus control region (LCR), dynamically interacts with the developmental stage-appropriate β-type globin genes via chromatin looping, a process requiring the protein Ldb1. In adult erythroid cells, the LCR can be redirected from the adult β- to the fetal γ-globin promoter by tethering Ldb1 to the human γ-globin promoter with custom-designed zinc finger (ZF) proteins (ZF-Ldb1), leading to reactivation of γ-globin gene expression. To compare this approach to pharmacologic reactivation of fetal hemoglobin (HbF), hematopoietic cells from patients with SCD were treated with a lentivirus expressing the ZF-Ldb1 or with chemical HbF inducers. The HbF increase in cells treated with ZF-Ldb1 was more than double that observed with decitabine and pomalidomide; butyrate had an intermediate effect whereas tranylcypromine and hydroxyurea showed relatively low HbF reactivation. ZF-Ldb1 showed comparatively little toxicity, and reduced sickle hemoglobin (HbS) synthesis as well as sickling of SCD erythroid cells under hypoxic conditions. The efficacy and low cytotoxicity of lentiviral-mediated ZF-Ldb1 gene transfer compared with the drug regimens support its therapeutic potential for the treatment of SCD. PMID:27405777

  8. Loop Heat Pipe Temperature Oscillation Induced by Gravity Assist and Reservoir Heating

    NASA Technical Reports Server (NTRS)

    Ku, Jentung; Garrison, Matthew; Patel, Deepak; Robinson, Franklin; Ottenstein, Laura

    2015-01-01

    The Laser Thermal Control System (LCTS) for the Advanced Topographic Laser Altimeter System (ATLAS) to be installed on NASA's Ice, Cloud, and Land Elevation Satellite (ICESat-2) consists of a constant conductance heat pipe and a loop heat pipe (LHP) with an associated radiator. During the recent thermal vacuum testing of the LTCS where the LHP condenser/radiator was placed in a vertical position above the evaporator and reservoir, it was found that the LHP reservoir control heater power requirement was much higher than the analytical model had predicted. Even with the control heater turned on continuously at its full power, the reservoir could not be maintained at its desired set point temperature. An investigation of the LHP behaviors found that the root cause of the problem was fluid flow and reservoir temperature oscillations, which led to persistent alternate forward and reversed flow along the liquid line and an imbalance between the vapor mass flow rate in the vapor line and liquid mass flow rate in the liquid line. The flow and temperature oscillations were caused by an interaction between gravity and reservoir heating, and were exacerbated by the large thermal mass of the instrument simulator which modulated the net heat load to the evaporator, and the vertical radiator/condenser which induced a variable gravitational pressure head. Furthermore, causes and effects of the contributing factors to flow and temperature oscillations intermingled.

  9. The structure of the isolated, central hairpin of the HDV antigenomic ribozyme: novel structural features and similarity of the loop in the ribozyme and free in solution.

    PubMed Central

    Kolk, M H; Heus, H A; Hilbers, C W

    1997-01-01

    The structure of an RNA hairpin containing a seven-nucleotide loop that is present in the self-cleaving sequence of hepatitis delta virus antigenomic RNA was determined by high resolution NMR spectroscopy. The loop, which is composed of only one purine and six pyrimidines, has a suprisingly stable structure, mainly supported by sugar hydroxyl hydrogen bonds and base-base and base-phosphate stacking interactions. Compared with the structurally well-determined, seven-membered anticodon loop in tRNA, the sharp turn which affects the required 180 degrees change in direction of the sugar-phosphate backbone in the loop is shifted one nucleotide in the 3' direction. This change in direction can be characterized as a reversed U-turn. It is expected that the reversed U-turn may be found frequently in other molecules as well. There is evidence for a new non-Watson-Crick UC base pair formed between the first and the last residue in the loop, while most of the other bases in the loop are pointing outwards making them accessible to solvent. From chemical modification, mutational and photocrosslinking studies, a similar picture develops for the structure of the hairpin in the active ribozyme indicating that the loop structure in the isolated hairpin and in the ribozyme is very similar. PMID:9218809

  10. Low-order design and high-order simulation of active closed-loop control for aerospace structures under construction

    NASA Technical Reports Server (NTRS)

    Balas, Mark J.

    1989-01-01

    Partially constructed/assembled structures in space are complicated enough but their dynamics will also be operating in closed-loop with feedback controllers. The dynamics of such structures are modeled by large-scale finite element models. The model dimension L is extremely large (approximately 10,000) while the numbers of actuators (M) and sensors (P) are small. The model parameters M(sub m) mass matrix, D(sub o) damping matrix, and K(sub o) stiffness matrix, are all symmetric and sparse (banded). Thus simulation of open-loop structure models of very large dimension can be accomplished by special integration techniques for sparse matrices. The problem of simulation of closed-loop control of such structures is complicated by the addition of controllers. Simulation of closed-loop controlled structures is an essential part of the controller design and evaluation process. Current research in the following areas is presented: high-order simulation of actively controlled aerospace structures; low-order controller design and SCI compensation for unmodeled dynamics; prediction of closed-loop stability using asymptotic eigenvalue series; and flexible robot manipulator control experiment.

  11. Formation of large-scale structure from cosmic-string loops and cold dark matter

    NASA Technical Reports Server (NTRS)

    Melott, Adrian L.; Scherrer, Robert J.

    1987-01-01

    Some results from a numerical simulation of the formation of large-scale structure from cosmic-string loops are presented. It is found that even though G x mu is required to be lower than 2 x 10 to the -6th (where mu is the mass per unit length of the string) to give a low enough autocorrelation amplitude, there is excessive power on smaller scales, so that galaxies would be more dense than observed. The large-scale structure does not include a filamentary or connected appearance and shares with more conventional models based on Gaussian perturbations the lack of cluster-cluster correlation at the mean cluster separation scale as well as excessively small bulk velocities at these scales.

  12. The temperature structure and pressure balance of magnetic loops in active regions. [in solar atmosphere

    NASA Technical Reports Server (NTRS)

    Foukal, P.

    1975-01-01

    EUV observations show many active region loops in lines formed at temperatures between 10,000 and 2,000,000 K. The brightest loops are associated with flux tubes leading to the umbrae of sunspots. It is shown that the high visibility of certain loops in transition region lines is due principally to a sharp radial decrease of temperature to chromospheric values toward the loop axis. The plasma density of these cool loops is not significantly greater than in the hot gas immediately surrounding it. Consequently, the internal gas pressure of the cool material is clearly lower. The hot material immediately surrounding the cool loops is generally denser than the external corona by a factor 3-4. When the active region is examined in coronal lines, this hot high pressure plasma shows up as loops that are generally parallel to the cool loops but significantly displaced laterally.

  13. The thermal structure of solar coronal loops and implications for physical models of coronae

    NASA Technical Reports Server (NTRS)

    Raymond, J. C.; Foukal, P.

    1982-01-01

    EUV spectra of three active region loops observed above the solar limb with the SO55 spectrometer on Skylab are analyzed. It is noted that the lengths, peak temperatures, and pressures of the loops are typical of the X-ray coronal loops to which static models have been applied. It is found that the physical parameters of the coronal loop plasma derived from EUV spectra and raster pictures are not well represented by the static models. Although the loops also contain a significant quantity of cool plasma, no physical reason is found to differentiate them from other active region loops of similar length, pressure, and temperature. Several line ratios in the loop spectrum suggest departures from ionization equilibrium caused by rapid cooling. The source of this cooling material is discussed with reference to several models of loop dynamics.

  14. A linear control design structure to maintain loop properties during limit operation in a multi-nozzle turbofan engine

    NASA Technical Reports Server (NTRS)

    Mattern, Duane; Ouzts, Peter

    1991-01-01

    The implementation of multi-variable control systems on turbofan engines requires the use of limit protection to maintain safe engine operation. Since a turbofan engine typically encounters limits during transient operation, the use of a limit protection scheme that modifies the feedback loop may void the desired 'guarantees' associated with linear multi-variable control design methods, necessitating considerable simulation to validate the control with limited protection. An alternative control design structure is proposed that maintains the desired linear feedback properties when certain safety limits are encountered by moving the limit protection scheme outside the feedback loop. This proposed structure is compared to a structure with a limit protection scheme that modifies the feedback loop properties. The two design structures are compared using both linear and nonlinear simulations. The evaluation emphasizes responses where the fan surge margin limit is encountered.

  15. A linear control design structure to maintain loop properties during limit operation in a multi-nozzle turbofan engine

    NASA Technical Reports Server (NTRS)

    Mattern, Duane; Ouzts, Peter

    1991-01-01

    The implementation of multi-variable control systems on turbofan engines requires the use of limit protection to maintain safe engine operation. Since a turbofan engine typically encounters limits during transient operation, the use of a limit protection scheme that modifies the feedback loop may void the desired 'guarantees' associated with linear multi-variable control design methods, necessitating considerable simulation to validate the control with limit protection. An alternative control design structure is proposed that maintains the desired linear feedback properties when certain safety limits are encountered by moving the limit protection scheme outside of the feedback loop. This proposed structure is compared to a structure with a limit protection scheme that modifies the feedback loop properties. The two design structures are compared using both linear and nonlinear simulations. The evaluation emphasizes responses where the fan surge margin limit is encountered.

  16. The MEMS Loop Heat Pipe Based on Coherent Porous Silicon - The Modified System Test Structure

    NASA Astrophysics Data System (ADS)

    Cytrynowicz, Debra; Medis, Praveen; Parimi, Srinivas; Shuja, Ahmed; Thurman Henderson, H.; Gerner, Frank M.

    2004-02-01

    The previous papers presented at STAIF 2002 and STAIF 2003 discussed the design, fabrication and characterization of the evaporator section and the initial test cell of a planar MEMS loop heat pipe based upon coherent porous silicon or ``CPS'' technology. The potentially revolutionary advantage of CPS technology is that it is planar and allows for pores or capillaries of absolutely uniform diameter. Coherent porous silicon can be mass-produced by various MEMS fabrication techniques. The preliminary experiments made with the original test structure exhibited the desired temperature and pressure differences, but these differences were extremely small and oscillatory. This paper describes modifications made to the initial test cell design, which were intended to improve its evacuated, closed loop performance. Included among these changes were the redesign of the compensation chamber and condenser, an increase in the porosity of the coherent porous silicon wick, the fabrication of silicon top ``hot'' plates with an increased depth of the vapor reservoir and the integration of metal resistive heater elements onto the backside of the top plates to simulate the input heat. Some changes were made in the test sequence to produce more discernable differences in temperatures and pressures. The most recent results of the tests made with the modified system will be presented.

  17. The integration of water loop heat pump and building structural thermal storage systems

    SciTech Connect

    Marseille, T.J.; Schliesing, J.S.

    1991-10-01

    Many commercial buildings need heat in one part and, at the same time, cooling in another part. Even more common is the need for heating during one part of the day and cooling during another in the same spaces. If that energy could be shifted or stored for later use, significant energy might be saved. If a building's heating and cooling subsystems could be integrated with the building's structural mass and used to collect, store, and deliver energy, the energy might be save cost-effectively. To explore this opportunity, researchers at the Pacific Northwest Laboratory (PNL) examined the thermal interactions between the heating, ventilating, and air-conditioning (HVAC) system and the structure of a commercial building. Computer models were developed to simulate the interactions in an existing building located in Seattle, Washington, to determine how these building subsystems could be integrated to improve energy efficiency. The HVAC subsystems in the existing building were modeled. These subsystems consist of decentralized water-source heat pumps (WSHP) in a closed water loop, connected to cooling towers for heat rejection during cooling mode and boilers to augment heating. An initial base case'' computer model of the Seattle building, as-built, was developed. Metered data available for the building were used to calibrate this model to ensure that the analysis would provide information that closely reflected the operation of a real building. The HVAC system and building structure were integrated in the model using the concrete floor slabs as thermal storage media. The slabs may be actively charged during off-peak periods with the chilled water in the loop and then either actively or passively discharged into the conditioned space during peak periods. 21 refs., 37 figs., 17 tabs.

  18. Mutation of the 5'-untranslated region stem-loop structure inhibits α1(I) collagen expression in vivo.

    PubMed

    Parsons, Christopher J; Stefanovic, Branko; Seki, Ekihiro; Aoyama, Tomonori; Latour, Anne M; Marzluff, William F; Rippe, Richard A; Brenner, David A

    2011-03-11

    Type I collagen is a heterotrimeric extracellular matrix protein consisting of two α1(I) chains and one α2(I) chain. During liver fibrosis, activated hepatic stellate cells (HSCs) are the major source of the type I collagen that accumulates in the damaged tissue. Expression of α1(I) and α2(I) collagen mRNA is increased 60-fold compared with quiescent stellate cells and is due predominantly to post-transcriptional message regulation. Specifically, a stem-loop structure in the 5'-untranslated region of α1(I) collagen mRNA may regulate mRNA expression in activated HSCs through its interaction with stem-loop binding proteins. The stem-loop may also be necessary for efficient production and folding of the type I collagen heterotrimer. To assess the role of the stem-loop in type I collagen expression in vivo, we generated a knock-in mouse harboring a mutation that abolished the stem-loop structure. Heterozygous and homozygous knock-in mice exhibited a normal phenotype. However, steady-state levels of α1(I) collagen mRNA decreased significantly in homozygous mutant MEFs as well as HSCs; intracellular and secreted type I collagen protein levels also decreased. Homozygous mutant mice developed less liver fibrosis. These results confirm an important role of the 5' stem-loop in regulating type I collagen mRNA and protein expression and provide a mouse model for further study of collagen-associated diseases. PMID:21193410

  19. Two aspects of one loop structure: Unitarity delay in the Standard Model and modular invariance in string theory

    SciTech Connect

    Ahn, C.

    1989-08-01

    We study two aspects of one loop structures in quantum field theories which describe two different areas of particle physics: the one loop unitarity behavior of the Standard Model of electroweak interactions and modular invariance of string model theory. Loop expansion has its importance in that it contains quantum fluctuations due to all physical states in the theory. Therefore, by studying the various models to one loop, we can understand how the contents of the theory can contribute to physically measurable quantities and how the consistency at quantum level restricts the physical states of the theory, as well. In the first half of the thesis, we study one loop corrections to the process {ital e}{sup +}{ital e}{sup {minus}} {yields} {ital W}{sup +}{ital W}{sup {minus}}. In this process, there is a delicate unitarity-saving cancellation between s-channel and t-channel tree level Feynman diagrams. If the one loop contribution due to heavy particles corrects the channels asymmetrically, the cancellation, hence unitarity, will be delayed up to the mass scale of these heavy particles. We refer to this phenomena as the unitarity delay effect. Due to this effect, cross section below these mass scales can have significant radiative corrections which may provide an appropriate window through which we can see the high energy structure of the Standard Model from relatively low energy experiments. In the second half, we will show how quantum consistency can restrict the physical states in string theory. 53 refs., 13 figs.

  20. Properties and Modeling of Unresolved Fine Structure Loops Observed in the Solar Transition Region by IRIS

    NASA Astrophysics Data System (ADS)

    Brooks, David H.; Reep, Jeffrey W.; Warren, Harry P.

    2016-08-01

    Recent observations from the Interface Region Imaging Spectrograph (IRIS) have discovered a new class of numerous low-lying dynamic loop structures, and it has been argued that they are the long-postulated unresolved fine structures (UFSs) that dominate the emission of the solar transition region. In this letter, we combine IRIS measurements of the properties of a sample of 108 UFSs (intensities, lengths, widths, lifetimes) with one-dimensional non-equilibrium ionization simulations, using the HYDRAD hydrodynamic model to examine whether the UFSs are now truly spatially resolved in the sense of being individual structures rather than being composed of multiple magnetic threads. We find that a simulation of an impulsively heated single strand can reproduce most of the observed properties, suggesting that the UFSs may be resolved, and the distribution of UFS widths implies that they are structured on a spatial scale of 133 km on average. Spatial scales of a few hundred kilometers appear to be typical for a range of chromospheric and coronal structures, and we conjecture that this could be an important clue for understanding the coronal heating process.

  1. BHK cell proteins that bind to the 3' stem-loop structure of the West Nile virus genome RNA.

    PubMed Central

    Blackwell, J L; Brinton, M A

    1995-01-01

    The first 83 3' nucleotides of the genome RNA of the flavivirus West Nile encephalitis virus (WNV) form a stable stem-loop (SL) structure which is followed in the genome by a smaller SL. These 3' structures are highly conserved among divergent flaviviruses, suggesting that they may function as cis-acting signals for RNA replication and as such might specifically bind to cellular or viral proteins. Cellular proteins from uninfected and WNV-infected BHK-21 S100 cytoplasmic extracts formed three distinct complexes with the WNV plus-strand 3' SL [(+)3'SL] RNA in a gel mobility shift assay. Subsequent competitor gel shift analyses showed that two of these RNA-protein complexes, complexes 1 and 2, contained cell proteins that specifically bound to the WNV (+)3'SL RNA. UV-induced cross-linking and Northwestern blotting analyses detected WNV (+)3'SL RNA-binding proteins of 56, 84, and 105 kDa. When the S100 cytoplasmic extracts were partially purified by ion-exchange chromatography, a complex that comigrated with complex 1 was detected in fraction 19, while a complex that comigrated with complex 2 was detected in fraction 17. UV-induced cross-linking experiments indicated that an 84-kDa cell protein in fraction 17 and a 105-kDa protein in fraction 19 bound specifically to the WNV (+)3'SL RNA. In addition to binding to the (+)3'SL RNA, the 105-kDa protein bound to the SL structure located at the 3' end of the WNV minus-strand RNA. Initial mapping studies indicated that the 84- and 105-kDa proteins bind to different regions of the (+)3'SL RNA. The 3'-terminal SL RNA of another flavivirus, dengue virus type 3, specifically competed with the WNV (+)3'SL RNA in gel shift assays, suggesting that the host proteins identified in this study are flavivirus specific. PMID:7637011

  2. Concerted loop motion triggers induced fit of FepA to ferric enterobactin

    PubMed Central

    Smallwood, Chuck R.; Jordan, Lorne; Trinh, Vy; Schuerch, Daniel W.; Gala, Amparo; Hanson, Mathew; Shipelskiy, Yan; Majumdar, Aritri; Newton, Salete M.C.

    2014-01-01

    Spectroscopic analyses of fluorophore-labeled Escherichia coli FepA described dynamic actions of its surface loops during binding and transport of ferric enterobactin (FeEnt). When FeEnt bound to fluoresceinated FepA, in living cells or outer membrane fragments, quenching of fluorophore emissions reflected conformational motion of the external vestibular loops. We reacted Cys sulfhydryls in seven surface loops (L2, L3, L4, L5, L7 L8, and L11) with fluorophore maleimides. The target residues had different accessibilities, and the labeled loops themselves showed variable extents of quenching and rates of motion during ligand binding. The vestibular loops closed around FeEnt in about a second, in the order L3 > L11 > L7 > L2 > L5 > L8 > L4. This sequence suggested that the loops bind the metal complex like the fingers of two hands closing on an object, by individually adsorbing to the iron chelate. Fluorescence from L3 followed a biphasic exponential decay as FeEnt bound, but fluorescence from all the other loops followed single exponential decay processes. After binding, the restoration of fluorescence intensity (from any of the labeled loops) mirrored cellular uptake that depleted FeEnt from solution. Fluorescence microscopic images also showed FeEnt transport, and demonstrated that ferric siderophore uptake uniformly occurs throughout outer membrane, including at the poles of the cells, despite the fact that TonB, its inner membrane transport partner, was not detectable at the poles. PMID:24981231

  3. The one-loop matter bispectrum in the Effective Field Theory of Large Scale Structures

    SciTech Connect

    Angulo, Raul E.; Foreman, Simon; Schmittfull, Marcel; Senatore, Leonardo

    2015-10-14

    With this study, given the importance of future large scale structure surveys for delivering new cosmological information, it is crucial to reliably predict their observables. The Effective Field Theory of Large Scale Structures (EFTofLSS) provides a manifestly convergent perturbative scheme to compute the clustering of dark matter in the weakly nonlinear regime in an expansion in k/kNL, where k is the wavenumber of interest and kNL is the wavenumber associated to the nonlinear scale. It has been recently shown that the EFTofLSS matches to 1% level the dark matter power spectrum at redshift zero up to k ≃ 0.3 h Mpc–1 and k ≃ 0.6 h Mpc–1 at one and two loops respectively, using only one counterterm that is fit to data. Similar results have been obtained for the momentum power spectrum at one loop. This is a remarkable improvement with respect to former analytical techniques. Here we study the prediction for the equal-time dark matter bispectrum at one loop. We find that at this order it is sufficient to consider the same counterterm that was measured in the power spectrum. Without any remaining free parameter, and in a cosmology for which kNL is smaller than in the previously considered cases (σ8=0.9), we find that the prediction from the EFTofLSS agrees very well with N-body simulations up to k ≃ 0.25 h Mpc–1, given the accuracy of the measurements, which is of order a few percent at the highest k's of interest. While the fit is very good on average up to k ≃ 0.25 h Mpc–1, the fit performs slightly worse on equilateral configurations, in agreement with expectations that for a given maximum k, equilateral triangles are the most nonlinear.

  4. Real-time Closed-loop Control in a Rodent Model of Medically-induced Coma Using Burst Suppression

    PubMed Central

    Ching, ShiNung; Liberman, Max Y.; Chemali, Jessica J.; Westover, M. Brandon; Kenny, Jonathan; Solt, Ken; Purdon, Patrick L.; Brown, Emery N.

    2013-01-01

    Background A medically-induced coma is an anesthetic state of profound brain inactivation created to treat status epilepticus and to provide cerebral protection following traumatic brain injuries. We hypothesized that a closed-loop anesthetic delivery system could automatically and precisely control the electroencephalogram state of burst suppression and efficiently maintain a medically-induced coma. Methods In six rats, we implemented a closed-loop anesthetic delivery system for propofol consisting of: a computer-controlled pump infusion, a two-compartment pharmacokinetics model defining propofol’s electroencephalogram effects, the burst suppression probability algorithm to compute in real time from the electroencephalogram the brain’s burst suppression state, an on-line parameter estimation procedure and a proportional-integral controller. In the control experiment each rat was randomly assigned to one of the six burst suppression probability target trajectories constructed by permuting the burst suppression probability levels of 0.4, 0.65 and 0.9 with linear transitions between levels. Results In each animal the controller maintained approximately 60 min of tight, real-time control of burst suppression by tracking each burst suppression probability target level for 15 min and two between-level transitions for 5 to 10 min. The posterior probability that the closed-loop anesthetic delivery system was reliable across all levels was 0.94 [95% confidence interval; (0.77 to 1.00) n = 18] and that the system was accurate was 1.00 [95% confidence interval; (0.84 to 1.00) n = 18]. Conclusion Our findings establish the feasibility of using a closed-loop anesthetic delivery systems to achieve in real-time reliable and accurate control of burst suppression in rodents and suggest a paradigm to precisely control medically-induced coma in patients. PMID:23770601

  5. Structures of apo IRF-3 and IRF-7 DNA binding domains: effect of loop L1 on DNA binding

    SciTech Connect

    De Ioannes, Pablo; Escalante, Carlos R.; Aggarwal, Aneel K.

    2013-11-20

    Interferon regulatory factors IRF-3 and IRF-7 are transcription factors essential in the activation of interferon-{beta} (IFN-{beta}) gene in response to viral infections. Although, both proteins recognize the same consensus IRF binding site AANNGAAA, they have distinct DNA binding preferences for sites in vivo. The X-ray structures of IRF-3 and IRF-7 DNA binding domains (DBDs) bound to IFN-{beta} promoter elements revealed flexibility in the loops (L1-L3) and the residues that make contacts with the target sequence. To characterize the conformational changes that occur on DNA binding and how they differ between IRF family members, we have solved the X-ray structures of IRF-3 and IRF-7 DBDs in the absence of DNA. We found that loop L1, carrying the conserved histidine that interacts with the DNA minor groove, is disordered in apo IRF-3 but is ordered in apo IRF-7. This is reflected in differences in DNA binding affinities when the conserved histidine in loop L1 is mutated to alanine in the two proteins. The stability of loop L1 in IRF-7 derives from a unique combination of hydrophobic residues that pack against the protein core. Together, our data show that differences in flexibility of loop L1 are an important determinant of differential IRF-DNA binding.

  6. Modulation of exercise-induced spinal loop properties in response to oxygen availability.

    PubMed

    Rupp, Thomas; Racinais, Sébastien; Bringard, Aurélien; Lapole, Thomas; Perrey, Stéphane

    2015-03-01

    This study investigated the effects of acute hypoxia on spinal reflexes and soleus muscle function after a sustained contraction of the plantar flexors at 40% of maximal voluntary isometric contraction (MVC). Fifteen males (age 25.3 ± 0.9 year) performed the fatigue task at two different inspired O₂ fractions (FiO₂ = 0.21/0.11) in a randomized and single-blind fashion. Before, at task failure and after 6, 12 and 18 min of passive recovery, the Hoffman-reflex (H max) and M-wave (M max) were recorded at rest and voluntary activation (VA), surface electromyogram (RMSmax), M-wave (M sup) and V-wave (V sup) were recorded during MVC. Normalized H-reflex (H max/M max) was significantly depressed pre-exercise in hypoxia compared with normoxia (0.31 ± 0.08 and 0.36 ± 0.08, respectively, P < 0.05). Hypoxia did not affect time to task failure (mean time of 453.9 ± 32.0 s) and MVC decrease at task failure (-18% in normoxia vs. -16% in hypoxia). At task failure, VA (-8%), RMSmax/M sup (-11%), H max/M max (-27%) and V sup/M sup (-37%) decreased (P < 0.05), but with no FiO2 effect. H max/M max restored significantly throughout recovery in hypoxia but not in normoxia, while V sup/M sup restored significantly during recovery in normoxia but not in hypoxia (P < 0.05). Collectively, these findings indicate that central adaptations resulting from sustained submaximal fatiguing contraction were not different in hypoxia and normoxia at task failure. However, the FiO₂-induced differences in spinal loop properties pre-exercise and throughout recovery suggest possible specific mediation by the hypoxic-sensitive group III and IV muscle afferents, supraspinal regulation mechanisms being mainly involved in hypoxia while spinal ones may be predominant in normoxia. PMID:25361617

  7. Solution structure of the lymphocyte receptor Nkrp1a reveals a distinct conformation of the long loop region as compared to in the crystal structure.

    PubMed

    Rozbeský, Daniel; Adámek, David; Pospíšilová, Eliška; Novák, Petr; Chmelík, Josef

    2016-09-01

    Mouse Nkrp1a receptor is a C-type lectin-like receptor expressed on the surface of natural killer cells that play an important role against virally infected and tumor cells. The recently solved crystal structure of Nkrp1a raises questions about a long loop region which was uniquely extended from the central region in the crystal. To understand the functional significance of the loop, the solution structure of Nkrp1a using nuclear magnetic resonance (NMR) spectroscopy was determined. A notable difference between the crystal and NMR structure of Nkrp1a appears in the conformation of the long loop region. While the extended loop points away from the central core and mediates formation of a domain swapped dimer in the crystal, the solution structure is monomeric with the loop tightly anchored to the central region. The findings described the first solution structure in the Nkrp1 family and revealed intriguing similarities and differences to the crystal structure. Proteins 2016; 84:1304-1311. © 2016 Wiley Periodicals, Inc. PMID:27238500

  8. Mutation-induced loop opening and energetics for binding of tamiflu to influenza N8 neuraminidase.

    PubMed

    Kar, Parimal; Knecht, Volker

    2012-05-31

    Tamiflu, also known as oseltamivir (OTV), binds to influenza A neuraminidase (H5N1) with very high affinity (0.32 nM). However, this inhibitor binds to other neuraminidases as well. In the present work, a systematic computational study is performed to investigate the mechanism underlying the binding of oseltamivir to N8 neuraminidase (NA) in "open" and "closed" conformations of the 150-loop through molecular dynamics simulations and the popular and well established molecular mechanics Poisson-Boltzmann (MM-PBSA) free energy calculation method. Whereas the closed conformation is stable for wild type N8, it transforms into the open conformation for the mutants Y252H, H274Y, and R292K, indicating that bound to oseltamivir these mutants are preferentially in the open conformation. Our calculations show that the binding of wild type oseltamivir to the closed conformation of N8 neuraminidase is energetically favored compared to the binding to the open conformation. We observe water mediated binding of oseltamivir to the N8 neuraminidase in both conformations which is not seen in the case of binding of the same drug to the H5N1 neuraminidase. The decomposition of the binding free energy reveals the mechanisms underlying the binding and changes in affinity due to mutations. Considering the mutant N8 variants in the open conformation adopted during the simulations, we observe a significant loss in the size of the total binding free energy for the N8(Y252H)-OTV, N8(H274Y)-OTV, and N8(R292K)-OTV complexes compared to N8(WT)-OTV, mainly due to the decrease in the size of the intermolecular electrostatic energy. For R292K, an unfavorable shift in the van der Waals interactions also contributes to the drug resistance. The mutations cause a significant expansion in the active site cavity, increasing its solvent accessible surface compared to the crystal structures of both the open and closed conformations. Our study underscores the need to consider dynamics in rationalizing the

  9. Mutually tangled colloidal knots and induced defect loops in nematic fields

    NASA Astrophysics Data System (ADS)

    Martinez, Angel; Ravnik, Miha; Lucero, Brice; Visvanathan, Rayshan; Žumer, Slobodan; Smalyukh, Ivan I.

    2014-03-01

    Colloidal dispersions in liquid crystals can serve as asoft-matter toolkit for the self-assembly of composite materials with pre-engineered properties and structures that are highly dependent on particle-induced topological defects. Here, we demonstrate that bulk and surface defects in nematic fluids can be patterned by tuning the topology of colloidal particles dispersed in them. In particular, by taking advantage of two-photon photopolymerization techniques to make knot-shaped microparticles, we show that the interplay of the topologies of the knotted particles, the nematic field and the induced defects leads to knotted, linked and other topologically non-trivial field configurations. These structures match theoretical predictions made on the basis of the minimization of the elastic free energy and satisfy topological constraints. Our approach may find uses in self-assembled topological superstructures of knotted particles linked by nematic fields, in topological scaffolds supporting the decoration of defect networks with nanoparticles, and in modelling other physical systems exhibiting topologically analogous phenomena.

  10. Structural Insights Into Substrate Recognition by the Neurospora Varkud Satellite Ribozyme: Importance of U-Turns at the Kissing-Loop Junction

    PubMed Central

    2013-01-01

    Substrate recognition by the Neurospora Varkud satellite ribozyme depends on the formation of a magnesium-dependent kissing-loop interaction between the stem-loop I (SLI) substrate and stem-loop V (SLV) of the catalytic domain. From mutagenesis studies, it has been established that this I/V kissing-loop interaction involves three Watson–Crick base pairs and is associated with a structural rearrangement of the SLI substrate that facilitates catalysis. Here, we report the NMR structural characterization of this I/V kissing-loop using isolated stem-loops. NMR studies were performed on different SLI/SLV complexes containing a common SLV and shiftable, preshifted, or double-stranded SLI variants. These studies confirm the presence of three Watson–Crick base pairs at the kissing-loop junction and provide evidence for the structural rearrangement of shiftable SLI variants upon SLV binding. NMR structure determination of an SLI/SLV complex demonstrates that both the SLI and SLV loops adopt U-turn structures, which facilitates intermolecular Watson–Crick base pairing. Several other interactions at the I/V interface, including base triples and base stacking, help create a continuously stacked structure. These NMR studies provide a structural basis to understand the stability of the I/V kissing-loop interaction and lead us to propose a kinetic model for substrate activation in the VS ribozyme. PMID:24325625

  11. Recognition and binding of a helix-loop-helix peptide to carbonic anhydrase occurs via partly folded intermediate structures.

    PubMed

    Lignell, Martin; Becker, Hans-Christian

    2010-02-01

    We have studied the association of a helix-loop-helix peptide scaffold carrying a benzenesulfonamide ligand to carbonic anhydrase using steady-state and time-resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for biosensing applications, is labeled with the fluorescent probe dansyl, which serves as a polarity-sensitive reporter of the binding event. Using maximum entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry reveals three characteristic fluorescence lifetime groups, interpreted as differently interacting peptide/protein structures. We characterize these peptide/protein complexes as mostly bound but unfolded, bound and partly folded, and strongly bound and folded. Furthermore, analysis of the fluorescence anisotropy decay resulted in three different dansyl rotational correlation times, namely 0.18, 1.2, and 23 ns. Using the amplitudes of these times, we can correlate the lifetime groups with the corresponding fluorescence anisotropy component. The 23-ns rotational correlation time, which appears with the same amplitude as a 17-ns fluorescence lifetime, shows that the dansyl fluorophore follows the rotational diffusion of carbonic anhydrase when it is a part of the folded peptide/protein complex. A partly folded and partly hydrated interfacial structure is manifested in an 8-ns dansyl fluorescence lifetime and a 1.2-ns rotational correlation time. This structure, we believe, is similar to a molten-globule-like interfacial structure, which allows segmental movement and has a higher degree of solvent exposure of dansyl. Indirect excitation of dansyl on the helix-loop-helix peptide through Förster energy transfer from one or several tryptophans in the carbonic anhydrase shows that the helix-loop-helix scaffold binds to a tryptophan-rich domain of the carbonic anhydrase. We conclude that binding of the peptide to carbonic anhydrase involves a transition from a disordered to an ordered structure of the helix-loop

  12. Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study

    PubMed Central

    Lim, Kah Wai; Jenjaroenpun, Piroon; Low, Zhen Jie; Khong, Zi Jian; Ng, Yi Siang; Kuznetsov, Vladimir Andreevich; Phan, Anh Tuân

    2015-01-01

    Duplex stem-loops and four-stranded G-quadruplexes have been implicated in (patho)biological processes. Overlap of stem-loop- and quadruplex-forming sequences could give rise to quadruplex–duplex hybrids (QDH), which combine features of both structural forms and could exhibit unique properties. Here, we present a combined genomic and structural study of stem-loop-containing quadruplex sequences (SLQS) in the human genome. Based on a maximum loop length of 20 nt, our survey identified 80 307 SLQS, embedded within 60 172 unique clusters. Our analysis suggested that these should cover close to half of total SLQS in the entire genome. Among these, 48 508 SLQS were strand-specifically located in genic/promoter regions, with the majority of genes displaying a low number of SLQS. Notably, genes containing abundant SLQS clusters were strongly associated with brain tissues. Enrichment analysis of SLQS-positive genes and mapping of SLQS onto transcriptional/mutagenesis hotspots and cancer-associated genes, provided a statistical framework supporting the biological involvements of SLQS. In vitro formation of diverse QDH by selective SLQS hits were successfully verified by nuclear magnetic resonance spectroscopy. Folding topologies of two SLQS were elucidated in detail. We also demonstrated that sequence changes at mutation/single-nucleotide polymorphism loci could affect the structural conformations adopted by SLQS. Thus, our predicted SLQS offer novel insights into the potential involvement of QDH in diverse (patho)biological processes and could represent novel regulatory signals. PMID:25958397

  13. Possible use of spin-vortex-induced loop currents as qubits: A numerical simulation for two-qubit system

    NASA Astrophysics Data System (ADS)

    Wakaura, Hikaru; Koizumi, Hiroyasu

    2016-02-01

    We propose new qubits; they are nano-sized persistent loop currents called, the spin-vortex-induced loop currents (SVILCs), predicted to exist in hole doped cuprate superconductors in one of the proposed mechanisms of the cuprate superconductivity. In the SVILC theory for the cuprate superconductivity, the superconducting state arises when the network of SVILCs generates a macroscopic current as a collection of the loop currents. The predicted SVILC has a number of properties that are suitable for qubits: each SVILC is characterized by topological winding number, thus, expected to be robust against environmental perturbations; because of the smallness of their size, they can be assembled into a large qubit-number system in a small space. Energy levels of different current patterns of the SVILC system are split by an external inhomogeneous magnetic field, and they are used as qubit states. The quantum gate control is achieved by the Rabi oscillation using electric dipole transitions. We have calculated the transition dipole moments between different SVILC qubit states. Some of the calculated values are relatively large, around 10-30 C m. We have also performed a numerical simulation for the Glover's search algorithm using the two-qubit SVILC system. The search completes in a nanosecond order using the electromagnetic field with electric field amplitude 105 V/m. The present results indicate the quantum gate control capability of the SVILC qubits, and suggest the potentiality to satisfy DiVincenzo's criteria for quantum computers.

  14. A Portable Hot Spot Recognition Loop Transfers Sequence Preferences from APOBEC Family Members to Activation-induced Cytidine Deaminase*

    PubMed Central

    Kohli, Rahul M.; Abrams, Shaun R.; Gajula, Kiran S.; Maul, Robert W.; Gearhart, Patricia J.; Stivers, James T.

    2009-01-01

    Enzymes of the AID/APOBEC family, characterized by the targeted deamination of cytosine to generate uracil within DNA, mediate numerous critical immune responses. One family member, activation-induced cytidine deaminase (AID), selectively introduces uracil into antibody variable and switch regions, promoting antibody diversity through somatic hypermutation or class switching. Other family members, including APOBEC3F and APOBEC3G, play an important role in retroviral defense by acting on viral reverse transcripts. These enzymes are distinguished from one another by targeting cytosine within different DNA sequence contexts; however, the reason for these differences is not known. Here, we report the identification of a recognition loop of 9–11 amino acids that contributes significantly to the distinct sequence motifs of individual family members. When this recognition loop is grafted from the donor APOBEC3F or 3G proteins into the acceptor scaffold of AID, the mutational signature of AID changes toward that of the donor proteins. These loop-graft mutants of AID provide useful tools for dissecting the biological impact of DNA sequence preferences upon generation of antibody diversity, and the results have implications for the evolution and specialization of the AID/APOBEC family. PMID:19561087

  15. Repetitive formation and decay of current sheets in magnetic loops: An origin of diverse magnetic structures

    SciTech Connect

    Kumar, Dinesh; Bhattacharyya, R.; Smolarkiewicz, P. K.

    2015-01-15

    In this work, evolution of an incompressible, thermally homogeneous, infinitely conducting, viscous magnetofluid is numerically explored as the fluid undergoes repeated events of magnetic reconnection. The initial magnetic field is constructed by a superposition of two linear force-free fields and has similar morphology as the magnetic loops observed in the solar corona. The results are presented for computations with three distinct sets of footpoint geometries. To onset reconnection, we rely on numerical model magnetic diffusivity, in the spirit of implicit large eddy simulation. It is generally expected that in a high Lundquist number fluid, repeated magnetic reconnections are ubiquitous and hence can lead to a host of magnetic structures with considerable observational importance. In particular, the simulations presented here illustrate formations of magnetic islands, rotating magnetic helices and rising flux ropes—depending on the initial footpoint geometry but through the common process of repeated magnetic reconnections. Further, we observe the development of extended current sheets in two case studies, where the footpoint reconnections generate favorable dynamics.

  16. Structure of force networks in tapped particulate systems of disks and pentagons. I. Clusters and loops.

    PubMed

    Pugnaloni, Luis A; Carlevaro, C Manuel; Kramár, M; Mischaikow, K; Kondic, L

    2016-06-01

    The force network of a granular assembly, defined by the contact network and the corresponding contact forces, carries valuable information about the state of the packing. Simple analysis of these networks based on the distribution of force strengths is rather insensitive to the changes in preparation protocols or to the types of particles. In this and the companion paper [Kondic et al., Phys. Rev. E 93, 062903 (2016)10.1103/PhysRevE.93.062903], we consider two-dimensional simulations of tapped systems built from frictional disks and pentagons, and study the structure of the force networks of granular packings by considering network's topology as force thresholds are varied. We show that the number of clusters and loops observed in the force networks as a function of the force threshold are markedly different for disks and pentagons if the tangential contact forces are considered, whereas they are surprisingly similar for the network defined by the normal forces. In particular, the results indicate that, overall, the force network is more heterogeneous for disks than for pentagons. Such differences in network properties are expected to lead to different macroscale response of the considered systems, despite the fact that averaged measures (such as force probability density function) do not show any obvious differences. Additionally, we show that the states obtained by tapping with different intensities that display similar packing fraction are difficult to distinguish based on simple topological invariants. PMID:27415342

  17. Structure of force networks in tapped particulate systems of disks and pentagons. I. Clusters and loops

    NASA Astrophysics Data System (ADS)

    Pugnaloni, Luis A.; Carlevaro, C. Manuel; Kramár, M.; Mischaikow, K.; Kondic, L.

    2016-06-01

    The force network of a granular assembly, defined by the contact network and the corresponding contact forces, carries valuable information about the state of the packing. Simple analysis of these networks based on the distribution of force strengths is rather insensitive to the changes in preparation protocols or to the types of particles. In this and the companion paper [Kondic et al., Phys. Rev. E 93, 062903 (2016), 10.1103/PhysRevE.93.062903], we consider two-dimensional simulations of tapped systems built from frictional disks and pentagons, and study the structure of the force networks of granular packings by considering network's topology as force thresholds are varied. We show that the number of clusters and loops observed in the force networks as a function of the force threshold are markedly different for disks and pentagons if the tangential contact forces are considered, whereas they are surprisingly similar for the network defined by the normal forces. In particular, the results indicate that, overall, the force network is more heterogeneous for disks than for pentagons. Such differences in network properties are expected to lead to different macroscale response of the considered systems, despite the fact that averaged measures (such as force probability density function) do not show any obvious differences. Additionally, we show that the states obtained by tapping with different intensities that display similar packing fraction are difficult to distinguish based on simple topological invariants.

  18. High temperature stress-induced ``double loop-like'' phase transitions in Bi-based perovskites

    NASA Astrophysics Data System (ADS)

    Webber, K. G.; Zhang, Y.; Jo, Wook; Daniels, J. E.; Rödel, J.

    2010-07-01

    Polycrystalline 0.94(Bi1/2Na1/2)TiO3-0.06BaTiO3 samples were tested under uniaxial mechanical compression at various temperatures in the vicinity of the polar tetragonal to nonpolar tetragonal phase boundary. They are shown to display double loop-like stress-strain behavior, marked by a closed ferroelastic hysteresis loop. Thus, it forms a mechanical analog to the polarization-electric field hysteresis behavior of barium titanate above the Curie temperature. As temperature is increased there is an apparent loss of macroscopically observable ferroelasticity, despite the persistence of tetragonality. Macroscopic experimental results are discussed in conjunction with temperature-dependent and stress-dependent high-energy x-ray diffraction data. This reveals a phase transition below the Curie temperature, marked by a discontinuous change in lattice parameters and octahedral tilting during compressive mechanical loading.

  19. Regulative Loops, Step Loops and Task Loops

    ERIC Educational Resources Information Center

    VanLehn, Kurt

    2016-01-01

    This commentary suggests a generalization of the conception of the behavior of tutoring systems, which the target article characterized as having an outer loop that was executed once per task and an inner loop that was executed once per step of the task. A more general conception sees these two loops as instances of regulative loops, which…

  20. Structure-function relationships of curaremimetic neurotoxin loop 2 and of a structurally similar segment of rabies virus glycoprotein in their interaction with the nicotinic acetylcholine receptor

    SciTech Connect

    Lentz, T.L. )

    1991-11-12

    Peptides corresponding to portions of curaremimetic neurotoxin loop 2 and to a structurally similar segment of rabies virus glycoprotein were synthetically modified in order to gain information on structure-function relationships of neurotoxin loop 2 interactions with the acetylcholine receptor. Binding of synthetic peptides to the acetylcholine receptor of Torpedo electric organ membranes was assessed by measuring their ability to inhibit the binding of {sup 125}I-{alpha}-bungarotoxin to the receptor. The peptides showing the highest affinity for the receptor were a peptide corresponding to the sequence of loop 2 (residues 25-44) of Ophiophagus hannah (king cobra) toxin b and the structurally similar segment of CVS rabies virus glycoprotein. These affinities were comparable to those of d-tubocurarine and suberyldicholine. These results demonstrate the importance of loop 2 in the neurotoxin interaction with the receptor. N- and C-terminal deletions of the loop 2 peptides and substitution of residues invariant or highly conserved among neurotoxins were performed in order to determine the role of individual residues in binding. Residues 25-40 are the most crucial in the interaction with the acetylcholine receptor. Since this region of the glycoprotein contains residues corresponding to all of the functionally invariant neurotoxin residues, it may interact with the acetylcholine receptor through a mechanism similar to that of the neurotoxins.

  1. Stable loop in the crystal structure of the intercalated four-stranded cytosine-rich metazoan telomere

    NASA Technical Reports Server (NTRS)

    Kang, C.; Berger, I.; Lockshin, C.; Ratliff, R.; Moyzis, R.; Rich, A.

    1995-01-01

    In most metazoans, the telomeric cytosine-rich strand repeating sequence is d(TAACCC). The crystal structure of this sequence was solved to 1.9-A resolution. Four strands associate via the cytosine-containing parts to form a four-stranded intercalated structure held together by C.C+ hydrogen bonds. The base-paired strands are parallel to each other, and the two duplexes are intercalated into each other in opposite orientations. One TAA end forms a highly stabilized loop with the 5' thymine Hoogsteen-base-paired to the third adenine. The 5' end of this loop is in close proximity to the 3' end of one of the other intercalated cytosine strands. Instead of being entirely in a DNA duplex, this structure suggests the possibility of an alternative conformation for the cytosine-rich telomere strands.

  2. Using the Theory of Elasticity to Model the Structure of DNA Loops

    NASA Astrophysics Data System (ADS)

    Balaeff, Alexander; Mahadevan, L.; Schulten, Klaus

    2000-03-01

    A fast computational method to study the conformation and energetics of short DNA loops is presented. The DNA is modeled as an electrically charged elastic rod. The ensemble of equilibrium conformations of the DNA loop, attainable for given boundary conditions, is generated as a set of numerical solutions to the equations of the Kirchhoff-Love theory of elasticity. The equations are augmented by electrostatic and van der Waals force terms. These modifications allow one to account for the DNA self-repulsion and to model the DNA loop interactions with other macromolecules, involved in a biomolecular system. We demonstrate the application of the method to the test system: the looped lac operon promoter of E. coli clamped by the repressor protein and stabilized by the catabolite gene activator protein. The developed coarse-grained modeling method provides the basis for multi-resolution modeling of protein-DNA complexes, e.g., in combination with all-atom molecular dynamics simulations.

  3. Structural basis of conformational transitions in the active site and 80′s loop in the FK506-binding protein FKBP12

    PubMed Central

    Mustafi, Sourajit M.; Brecher, Matthew; Zhang, Jing; Li, Hongmin; Lemaster, David M.; Hernández, Griselda

    2014-01-01

    The extensive set of NMR doublings exhibited by the immunophilin FKBP12 (FK506-binding protein 12) arose from a slow transition to the cis-peptide configuration at Gly89 near the tip of the 80′s loop, the site for numerous protein-recognition interactions for both FKBP12 and other FKBP domain proteins. The 80′s loop also exhibited linebroadening, indicative of microsecond to millisecond conformational dynamics, but only in the trans-peptide state. The G89A variant shifted the trans–cis peptide equilibrium from 88:12 to 33:67, whereas a proline residue substitution induced fully the cis-peptide configuration. The 80′s loop conformation in the G89P crystal structure at 1.50 Å resolution differed from wild-type FKBP12 primarily at residues 88, 89 and 90, and it closely resembled that reported for FKBP52. Structure-based chemical-shift predictions indicated that the microsecond to millisecond dynamics in the 80′s loop probably arose from a concerted main chain (ψ88 and ϕ89) torsion angle transition. The indole side chain of Trp59 at the base of the active-site cleft was reoriented ~90o and the adjacent backbone was shifted in the G89P crystal structure. NOE analysis of wild-type FKBP12 demonstrated that this indole populates the perpendicular orientation at 20%. The 15N relaxation analysis was consistent with the indole reorientation occurring in the nanosecond timeframe. Recollection of the G89P crystal data at 1.20 Å resolution revealed a weaker wild-type-like orientation for the indole ring. Differences in the residues that underlie the Trp59 indole ring and altered interactions linking the 50′s loop to the active site suggested that reorientation of this ring may be disfavoured in the other six members of the FKBP domain family that bear this active-site tryptophan residue. PMID:24405377

  4. Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease

    PubMed Central

    Zühlsdorf, Martin; Werten, Sebastiaan; Klupp, Barbara G.; Palm, Gottfried J.; Mettenleiter, Thomas C.; Hinrichs, Winfried

    2015-01-01

    Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 Å, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino-acid residues encompassing two consecutive arginine residues (Arg136 and Arg137); both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 Å, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration-dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration-dependent equilibrium of monomeric and dimeric protease in solution. PMID:26161660

  5. Conserved structural motifs located in distal loops of aphthovirus internal ribosome entry site domain 3 are required for internal initiation of translation.

    PubMed Central

    López de Quinto, S; Martínez-Salas, E

    1997-01-01

    A comparison of picornavirus internal ribosome entry site (IRES) secondary structures revealed the existence of conserved motifs located on loops. We have carried out a mutational analysis to test their requirement for IRES-driven translation. The GUAA sequence, located in the aphthovirus 3A loop, did not tolerate substitutions that disrupt the GNRA motif. Interestingly, this motif was found at similar positions in all picornavirus IRESs, suggesting that it may form part of a tertiary-structure element. The RAAA tetranucleotide located in the 3B loop was conserved only in cardiovirus and aphthovirus. A mutational analysis of the RAAA motif revealed that activities of 3B loop mutants correlated with both the presence of a sequence close to CAAA at the new 3B loop and the absence of reorganization of the 3B and 3C stem-loops. In support of this conclusion, insertion of a large number of nucleotides close to the 3B loop, which was predicted to reorganize the 3B-3C stem-loop structure, led to defective IRES elements. We conclude that the aphthovirus IRES loops located at the most distal part of domain 3, which carries GNRA and RAAA motifs, are essential for IRES function. PMID:9094703

  6. Polarimetric fiber vibration sensor based on polarization-diversity loop structure

    NASA Astrophysics Data System (ADS)

    Park, Kyoungsoo; Kim, Young Suk; Jo, Songhyun; Lee, Yong Wook

    2015-07-01

    Here, we demonstrated a polarimetric fiber vibration sensor based on a polarization-diversity loop structure (PDLS) by using polarization-maintaining photonic crystal fiber (PM-PCF). The PDLS is composed of a polarization beam splitter, PM-PCF, and polarization controllers, forming a Sagnac birefringence interferometer (SBI) that has periodic interference spectra. When static strain is applied to PM-PCF used as a sensor head, spectral shift is observed in the output interference spectrum of the SBI of the sensor. If a monochromatic light source such as a laser diode is introduced into the SBI, the output optical power of the SBI is determined by its wavelength-dependent transmittance. If the wavelength of the light source is properly located at a spectral region where the transmittance of the SBI linearly varies, therefore, the magnitude of strain applied to PM-PCF can be found by observing the output voltage variation of a photodetector connected to the output port of the SBI. To investigate the vibration response of the proposed sensor with respect to various types of vibration, vibration diverse in the amplitude and frequency was applied to 8-cm-long PM-PCF by using a cylindrical piezoelectric transducer or a metal cantilever. First, vibration characteristics were examined for single frequency vibration in a range of 1-3000 Hz. Then, the sensor response to naturally damped vibration was explored. It was experimentally observed that the cut-off frequency was ~1900 Hz in the frequency response, and the peak value of the sensor output signal increased with the amount of impulse for naturally damped vibration.

  7. Effective field theory of large scale structure at two loops: The apparent scale dependence of the speed of sound

    NASA Astrophysics Data System (ADS)

    Baldauf, Tobias; Mercolli, Lorenzo; Zaldarriaga, Matias

    2015-12-01

    We study the effective field theory (EFT) of large-scale structure for cosmic density and momentum fields. We show that the finite part of the two-loop calculation and its counterterms introduces an apparent scale dependence for the leading-order parameter cs2 of the EFT starting at k =0.1 h Mpc-1 . These terms limit the range over which one can trust the one-loop EFT calculation at the 1% level to k <0.1 h Mpc-1 at redshift z =0 . We construct a well-motivated one-parameter ansatz to fix the relative size of the one- and two-loop counterterms using their high-k sensitivity. Although this one-parameter model is a very restrictive choice for the counterterms, it explains the apparent scale dependence of cs2 seen in simulations. It is also able to capture the scale dependence of the density power spectrum up to k ≈0.3 h Mpc-1 at the 1% level at redshift z =0 . Considering a simple scheme for the resummation of large-scale motions, we find that the two-loop calculation reduces the need for this IR resummation at k <0.2 h Mpc-1 . Finally, we extend our calculation to momentum statistics and show that the same one-parameter model can also describe density-momentum and momentum-momentum statistics.

  8. One and two loop anomalous dimensions for the chiral-odd structure function h{sub 1}

    SciTech Connect

    Kumano, S. |; Miyama, M.

    1997-09-01

    Because the chiral-odd structure function h{sub 1} will be measured in the polarized Drell-Yan process, it is important to predict the behavior of h{sub 1} before the measurement. In order to study the Q{sup 2} evolution of h{sub 1}, the authors discuss one and two loop anomalous dimensions which are calculated in the Feynman gauge and minimal subtraction scheme.

  9. A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators

    PubMed Central

    Palasingam, Paaventhan; Kolatkar, Prasanna R.

    2012-01-01

    Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative group of helix-loop-helix (HLH) transcription regulators, are well-characterized key players in cellular fate determination during development in mammals as well as Drosophila. Although not oncogenes themselves, their upregulation by various oncogenic proteins (such as Ras, Myc) and their inhibitory effects on cell cycle proteins (such as pRb) hint at their possible roles in tumorigenesis. Furthermore, their potency as inhibitors of cellular differentiation, through their heterodimerization with subsequent inactivation of the ubiquitous E proteins, suggest possible novel roles in engineering induced pluripotent stem cells (iPSCs). We present the high-resolution 2.1Å crystal structure of ID2 (HLH domain), coupled with novel biochemical insights in the presence of a divalent ion, possibly calcium (Ca2+), in the loop of ID proteins, which appear to be crucial for the structure and activity of ID proteins. These new insights will pave the way for new rational drug designs, in addition to current synthetic peptide options, against this potent player in tumorigenesis as well as more efficient ways for stem cells reprogramming. PMID:23119064

  10. Phase speed and frequency-dependent damping of longitudinal intensity oscillations in coronal loop structures observed with AIA/SDO

    NASA Astrophysics Data System (ADS)

    Abedini, A.

    2016-04-01

    Longitudinal intensity oscillations along coronal loops that are interpreted as signatures of magneto-acoustic waves are observed frequently in different coronal structures. The aim of this paper is to estimate the physical parameters of the slow waves and the quantitative dependence of these parameters on their frequencies in the solar corona loops that are situated above active regions with the Atmospheric Imaging Assembly (AIA) onboard Solar Dynamic Observatory (SDO). The observed data on 2012-Feb-12, consisting of 300 images with an interval of 24 seconds in the 171 Å and 193 Å passbands is analyzed for evidence of propagating features as slow waves along the loop structures. Signatures of longitudinal intensity oscillations that are damped rapidly as they travel along the loop structures were found, with periods in the range of a few minutes to few tens of minutes. Also, the projected (apparent) phase speeds, projected damping lengths, damping times and damping qualities of filtered intensities centred on the dominant frequencies are measured in the range of Cs ≃38-79 km s^{-1}, Ld≃ 23-68 Mm, τd≃7-21 min and τ_{d/P}≃0.34-0.77, respectively. The theoretical and observational results of this study indicate that the damping times and damping lengths increase with increasing the oscillation periods, and are highly sensitive function of oscillation period, but the projected speeds and the damping qualities are not very sensitive to the oscillation periods. Furthermore, the magnitude values of physical parameters are in good agreement with the prediction of the theoretical dispersion relations of high-frequency MHD waves (>1.1 mHz) in a coronal plasma with electron number density in the range of ne≃107-10^{12} cm^{-3}.

  11. An explanation of one-loop induced h → μτ decay

    NASA Astrophysics Data System (ADS)

    Baek, Seungwon; Nomura, Takaaki; Okada, Hiroshi

    2016-08-01

    We discuss a possibility to explain the excess of h → μτ at one-loop level. We introduce three generations of vector-like lepton doublet L‧ and two singlet scalars S1,2 which are odd under Z2, while all the standard model fields are even under this discrete symmetry. We show that S1 can be a good dark matter candidate. We show that we can explain the dark matter relic abundance, large part of the discrepancy of muon g - 2 between experiments and the standard model predictions, as well as the h → μτ excess of ∼ 1%, while evading constraints from experiments of dark matter direct detection and charged lepton flavor violating processes. We also consider prospects of production of S2 at LHC with energy √{ s} = 14 TeV.

  12. Collision-Induced Dissociation Fragmentation Inside Disulfide C-Terminal Loops of Natural Non-Tryptic Peptides

    NASA Astrophysics Data System (ADS)

    Samgina, Tatiana Y.; Vorontsov, Egor A.; Gorshkov, Vladimir A.; Artemenko, Konstantin A.; Zubarev, Roman A.; Ytterberg, Jimmy A.; Lebedev, Albert T.

    2013-07-01

    Collision-induced dissociation (CID) spectra of long non-tryptic peptides are usually quite complicated and rather difficult to interpret. Disulfide bond formed by two cysteine residues at C-terminus of frog skin peptides precludes one to determine sequence inside the forming loop. Thereby, chemical modification of S-S bonds is often used in "bottom up" sequencing approach. However, low-energy CID spectra of natural non-tryptic peptides with C-terminal disulfide cycle demonstrate an unusual fragmentation route, which may be used to elucidate the "hidden" C-terminal sequence. Low charge state protonated molecules experience peptide bond cleavage at the N-terminus of C-terminal cysteine. The forming isomeric acyclic ions serve as precursors for a series of b-type ions revealing sequence inside former disulfide cycle. The reaction is preferable for peptides with basic lysine residues inside the cycle. It may also be activated by acidic protons of Asp and Glu residues neighboring the loop. The observed cleavages may be quite competitive, revealing the sequence inside disulfide cycle, although S-S bond rupture does not occur in this case.

  13. Closed-loop control of flow-induced sound in a flow duct with downstream resonant cavities.

    PubMed

    Lu, Z B; Halim, D; Cheng, L

    2013-03-01

    A closed-loop-controlled surface perturbation technique was developed for controlling the flow-induced sound in a flow duct and acoustic resonance inside downstream cavities. The surface perturbation was created by piezo-ceramic THUNDER (THin layer composite UNimorph Driver and sEnsoR) actuators embedded underneath the surface of a test model with a semi-circular leading edge. A modified closed-loop control scheme based on the down-sampling theory was proposed and implemented due to the practical vibration characteristic limitation of THUNDER actuators. The optimally tuned control achieved a sound pressure reduction of 17.5 dB in the duct and 22.6 dB inside the cavity at the vortex shedding frequency, respectively. Changes brought up by the control in both flow and acoustic fields were analyzed in terms of the spectrum phase shift of the flow field over the upper surface of the test model, and a shift in the vortex shedding frequency. The physical mechanism behind the control was investigated in the view of developing an optimal control strategy. PMID:23464018

  14. The Kinetics of Dislocation Loop Formation in Ferritic Alloys Through the Aggregation of Irradiation Induced Defects

    NASA Astrophysics Data System (ADS)

    Kohnert, Aaron Anthony

    The mechanical properties of materials are often degraded over time by exposure to irradiation environments, a phenomenon that has hindered the development of multiple nuclear reactor design concepts. Such property changes are the result of microstructural changes induced by the collision of high energy particles with the atoms in a material. The lattice defects generated in these recoil events migrate and interact to form extended damage structures. This study has used theoretical models based on the mean field chemical reaction rate theory to analyze the aggregation of isolated lattice defects into larger microstructural features that are responsible for long term property changes, focusing on the development of black dot damage in ferritic iron based alloys. The purpose of such endeavors is two-fold. Primarily, such models explain and quantify the processes through which these microstructures form. Additionally, models provide insight into the behavior and properties of the point defects and defect clusters which drive general microstructural evolution processes. The modeling effort presented in this work has focused on physical fidelity, drawing from a variety of sources of information to characterize the unobservable defect generation and agglomeration processes that give rise to the observable features reported in experimental data. As such, the models are based not solely on isolated point defect creation, as is the case with many older rate theory approaches, but instead on realistic estimates of the defect cluster population produced in high energy cascade damage events. Experimental assessments of the microstructural changes evident in transmission electron microscopy studies provide a means to measure the efficacy of the kinetic models. Using common assumptions of the mobility of defect clusters generated in cascade damage conditions, an unphysically high density of damage features develops at the temperatures of interest with a temperature dependence

  15. Novel C Induced Structures on Si(111)

    NASA Astrophysics Data System (ADS)

    Flores, M.; Häberle, P.

    2003-12-01

    We report thermally induced roughness at the nanometer scale, formed in the process of obtaining the (7×7) reconstruction on Si(111). C contamination seems to be the precursor in the formation of the different structures associated to this roughness. The large scale rearrangements, observed after the SiO2 high temperature induced desorption, show various shapes, namely: pyramids, raspberry shapes and tori.

  16. The crystal structure of HIV reverse-transcription primer tRNA(Lys,3) shows a canonical anticodon loop.

    PubMed Central

    Bénas, P; Bec, G; Keith, G; Marquet, R; Ehresmann, C; Ehresmann, B; Dumas, P

    2000-01-01

    We have solved to 3.3 A resolution the crystal structure of the HIV reverse-transcription primer tRNA(Lys,3). The overall structure is exactly comparable to the well-known L-shape structure first revealed by yeast tRNA(Phe). In particular, it unambiguously shows a canonical anticodon loop. This contradicts previous results in short RNA fragment studies and leads us to conclude that neither frameshifting specificities of tRNA(Lys) nor tRNA(Lys,3) primer selection by HIV are due to a specific three-dimensional anticodon structure. Comparison of our structure with the results of an NMR study on a hairpin representing a nonmodified anticodon stem-loop makes plausible the conclusion that chemical modifications of the wobble base U34 to 5-methoxycarbonyl-methyl-2-thiouridine and of A37 to 2-methylthio-N-6-threonylcarbamoyl-adenosine would be responsible for a canonical 7-nt anticodon-loop structure, whereas the unmodified form would result in a noncanonical UUU short triloop. The hexagonal crystal packing is remarkable and shows tight dimers of tRNAs forming a right-handed double superhelix. Within the dimers, the tRNAs are associated head-to-tail such that the CCA end of one tRNA interacts with the anticodon of the symmetry-related tRNA. This provides us with a partial view of a codon-anticodon interaction and gives insights into the positioning of residue 37, and of its posttranscriptional modifications, relative to the first base of the codon. PMID:11073212

  17. Structure of the Neisserial outer membrane protein Opa₆₀: loop flexibility essential to receptor recognition and bacterial engulfment.

    PubMed

    Fox, Daniel A; Larsson, Per; Lo, Ryan H; Kroncke, Brett M; Kasson, Peter M; Columbus, Linda

    2014-07-16

    The structure and dynamics of Opa proteins, which we report herein, are responsible for the receptor-mediated engulfment of Neisseria gonorrheae or Neisseria meningitidis by human cells and can offer deep understanding into the molecular recognition of pathogen-host receptor interactions. Such interactions are vital to understanding bacterial pathogenesis as well as the mechanism of foreign body entry to a human cell, which may provide insights for the development of targeted pharmaceutical delivery systems. The size and dynamics of the extracellular loops of Opa60 required a hybrid refinement approach wherein membrane and distance restraints were used to generate an initial NMR structural ensemble, which was then further refined using molecular dynamics in a DMPC bilayer. The resulting ensemble revealed that the extracellular loops, which bind host receptors, occupy compact conformations, interact with each other weakly, and are dynamic on the nanosecond time scale. We predict that this conformational sampling is critical for enabling diverse Opa loop sequences to engage a common set of receptors. PMID:24813921

  18. Structure of the Neisserial Outer Membrane Protein Opa60: Loop Flexibility Essential to Receptor Recognition and Bacterial Engulfment

    PubMed Central

    2015-01-01

    The structure and dynamics of Opa proteins, which we report herein, are responsible for the receptor-mediated engulfment of Neisseria gonorrheae or Neisseria meningitidis by human cells and can offer deep understanding into the molecular recognition of pathogen–host receptor interactions. Such interactions are vital to understanding bacterial pathogenesis as well as the mechanism of foreign body entry to a human cell, which may provide insights for the development of targeted pharmaceutical delivery systems. The size and dynamics of the extracellular loops of Opa60 required a hybrid refinement approach wherein membrane and distance restraints were used to generate an initial NMR structural ensemble, which was then further refined using molecular dynamics in a DMPC bilayer. The resulting ensemble revealed that the extracellular loops, which bind host receptors, occupy compact conformations, interact with each other weakly, and are dynamic on the nanosecond time scale. We predict that this conformational sampling is critical for enabling diverse Opa loop sequences to engage a common set of receptors. PMID:24813921

  19. Dark-matter production through loop-induced processes at the LHC: the s-channel mediator case

    NASA Astrophysics Data System (ADS)

    Mattelaer, Olivier; Vryonidou, Eleni

    2015-09-01

    We show how studies relevant for mono-X searches at the LHC in simplified models featuring a dark-matter candidate and an s-channel mediator can be performed within the MadGraph5_aMC@NLO framework. We focus on gluon-initiated loop-induced processes, mostly relevant to the case where the mediator couples preferentially to third generation quarks and in particular to the top quark. Our implementation allows us to study signatures at hadron colliders involving missing transverse energy plus jets or plus neutral bosons (γ ,Z,H), possibly including the effects of extra radiation by multi-parton merging and matching to the parton shower.

  20. Aircraft propeller induced structure-borne noise

    NASA Technical Reports Server (NTRS)

    Unruh, James F.

    1989-01-01

    A laboratory-based test apparatus employing components typical of aircraft construction was developed that would allow the study of structure-borne noise transmission due to propeller induced wake/vortex excitation of in-wake structural appendages. The test apparatus was employed to evaluate several aircraft installation effects (power plant placement, engine/nacelle mass loading, and wing/fuselage attachment methods) and several structural response modifications for structure-borne noise control (the use of wing blocking mass/fuel, wing damping treaments, and tuned mechanical dampers). Most important was the development of in-flight structure-borne noise transmission detection techniques using a combination of ground-based frequency response function testing and in-flight structural response measurement. Propeller wake/vortex excitation simulation techniques for improved ground-based testing were also developed to support the in-flight structure-borne noise transmission detection development.

  1. A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

    PubMed Central

    Rössger, Katrin; Charpin-El-Hamri, Ghislaine; Fussenegger, Martin

    2013-01-01

    Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders. PMID:24281397

  2. Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632.

    PubMed

    Yamaguchi, Hiroto; Miwa, Yukiko; Kasa, Miyuki; Kitano, Ken; Amano, Mutsuki; Kaibuchi, Kozo; Hakoshima, Toshio

    2006-09-01

    Rho-kinase is a main player in the regulation of cytoskeletal events and a promising drug target in the treatment of both vascular and neurological disorders. Here we report the crystal structure of the Rho-kinase catalytic domain in complex with the specific inhibitor Y-27632. Comparison with the structure of PKA bound to this inhibitor revealed a potential induced-fit binding mode that can be accommodated by the phosphate binding loop. This binding mode resembles to that observed in the Rho-kinase-fasudil complex. A structural database search indicated that a pocket underneath the phosphate-binding loop is present that favors binding to a small aromatic ring. Introduction of such a ring group might spawn a new modification scheme of pre-existing protein kinase inhibitors for improved binding capability. PMID:16891330

  3. Optimization of the GB/SA Solvation Model for Predicting the Structure of Surface Loops in Proteins

    PubMed Central

    Szarecka, Agnieszka; Meirovitch, Hagai

    2006-01-01

    Implicit solvation models are commonly optimized with respect to experimental data or Poisson Boltzmann (PB) results obtained for small molecules, where the force field sometimes is not considered. In previous studies we have developed an optimization procedure for cyclic peptides and surface loops in proteins based on the entire system studied and the specific force field used. Thus, the loop has been modeled by the simplified solvation function Etot = EFF(ɛ=2r) + ∑i σiAi, where EFF(ɛ=nr) is the AMBER force field energy with a distance dependent dielectric function, ɛ=nr, Ai is the solvent accessible surface area of atom i, and σi is its atomic solvation parameter. During the optimization process the loop is free to move while the protein template is held fixed in its X-ray structure. To improve on the results of this model, in the present work we apply our optimization procedure to the physically more rigorous solvation model, the generalized Born with surface area (GB/SA) (together with the all-atom AMBER force field) as suggested by Still and coworkers (J. Phys. Chem.A 1997, 101, 3005). The six parameters of the GB/SA model namely, P1-P5 and the surface area parameter, σ (programmed in the program TINKER) are re-optimized for a “training” group of nine loops, and from the individual sets of optimized parameters a best-fit set is defined. The best-fit set and Still’s original set of parameters (where Lys, Arg, His, Glu, and Asp are charged or neutralized) were applied to the training group as well as to a “test” group of seven loops and the energy gaps and the corresponding RMSD values were calculated. These GB/SA results based on the three sets of parameters have been found to be comparable; surprisingly, however, they are somewhat inferior (e.g.., of larger energy gaps) to those obtained previously from the simplified model described above. We discuss recent results for loops obtained by other solvation models and potential directions for

  4. Dynameomics: Data-driven methods and models for utilizing large-scale protein structure repositories for improving fragment-based loop prediction

    PubMed Central

    Rysavy, Steven J; Beck, David AC; Daggett, Valerie

    2014-01-01

    Protein function is intimately linked to protein structure and dynamics yet experimentally determined structures frequently omit regions within a protein due to indeterminate data, which is often due protein dynamics. We propose that atomistic molecular dynamics simulations provide a diverse sampling of biologically relevant structures for these missing segments (and beyond) to improve structural modeling and structure prediction. Here we make use of the Dynameomics data warehouse, which contains simulations of representatives of essentially all known protein folds. We developed novel computational methods to efficiently identify, rank and retrieve small peptide structures, or fragments, from this database. We also created a novel data model to analyze and compare large repositories of structural data, such as contained within the Protein Data Bank and the Dynameomics data warehouse. Our evaluation compares these structural repositories for improving loop predictions and analyzes the utility of our methods and models. Using a standard set of loop structures, containing 510 loops, 30 for each loop length from 4 to 20 residues, we find that the inclusion of Dynameomics structures in fragment-based methods improves the quality of the loop predictions without being dependent on sequence homology. Depending on loop length, ∼25–75% of the best predictions came from the Dynameomics set, resulting in lower main chain root-mean-square deviations for all fragment lengths using the combined fragment library. We also provide specific cases where Dynameomics fragments provide better predictions for NMR loop structures than fragments from crystal structures. Online access to these fragment libraries is available at http://www.dynameomics.org/fragments. PMID:25142412

  5. The structure of fast sausage waves in current-carrying coronal loops

    NASA Astrophysics Data System (ADS)

    Bembitov, D. B.; Mikhalyaev, B. B.; Ruderman, M. S.

    2014-09-01

    We study fast sausage waves in a model coronal loop that consists of a cylindrical core with axial magnetic field and coaxial annulus with purely azimuthal magnetic field. The magnetic field is discontinuous at the tube and core boundaries, and there are surface currents with the opposite directions on these boundaries. The principal mode of fast sausage waves in which the magnetic pressure perturbation has no nodes in the radial direction can exist for arbitrary wavelength. The results for the fundamental radial mode of sausage waves are applied to the interpretation of observed periodic pulsations of microwave emission in flaring loops with periods of a few tens of seconds. Radial plasma motion has opposite directions at the tube and core boundaries. This leads to the periodic contraction and expansion of the annulus. We assume that the principal mode of fast sausage waves in the current-carrying coronal loops is able to produce a current sheet. However, the nonlinear analysis is needed to confirm this conjecture.

  6. An investigation of coronal active region loop structures using AS&E rocket X-ray images

    NASA Technical Reports Server (NTRS)

    Webb, D. F.

    1983-01-01

    Simultaneous high spatial resolution observations at 6 cm in soft X-rays, in photospheric magnetograms, and in optical filtergrams were used to compare the most intense sources of centimetric emission in two active regions to coronal loops, sunspots, chromospheric structures, and photospheric magnetic fields. Results show that the majority of the bright microwave components are not associated with sunspots or X-ray emission. A nonthermal mechanism appears necessary to explain the brightest microwave components, discrete regions of continuous particle acceleration may be common in active regions. Studies of the plasma parameters of selected loops imply that the radio emission is consistent with gyro-resonance absorption at the third and fourth harmonic, at least from part of each loop. Results are presented for: (1) X-ray and microwave observations of active regions; (2) comparison of coronal holes observed in soft X-rays and Hel 10830 A spectrosheliograms; and (3) the reappearance of polar coronal holes and the evolution of the solar magnetic field.

  7. Thumb-loops up for catalysis: a structure/function investigation of a functional loop movement in a GH11 xylanase

    PubMed Central

    Paës, Gabriel; Cortés, Juan; Siméon, Thierry; O'Donohue, Michael J.; Tran, Vinh

    2012-01-01

    Dynamics is a key feature of enzyme catalysis. Unfortunately, current experimental and computational techniques do not yet provide a comprehensive understanding and description of functional macromolecular motions. In this work, we have extended a novel computational technique, which combines molecular modeling methods and robotics algorithms, to investigate functional motions of protein loops. This new approach has been applied to study the functional importance of the so-called thumb-loop in the glycoside hydrolase family 11 xylanase from Thermobacillus xylanilyticus (Tx-xyl). The results obtained provide new insight into the role of the loop in the glycosylation/deglycosylation catalytic cycle, and underline the key importance of the nature of the residue located at the tip of the thumb-loop. The effect of mutations predicted in silico has been validated by in vitro site-directed mutagenesis experiments. Overall, we propose a comprehensive model of Tx-xyl catalysis in terms of substrate and product dynamics by identifying the action of the thumb-loop motion during catalysis. PMID:24688637

  8. Lipopolysaccharide induces the expression of an autocrine prolactin loop enhancing inflammatory response in monocytes

    PubMed Central

    2013-01-01

    Background Prolactin from pituitary gland helps maintain homeostasis but it is also released in immune cells where its function is not completely understood. Pleiotropic functions of prolactin (PRL) might be mediated by different isoforms of its receptor (PRLr). Methods The aim of this study was to investigate the relationship between the eventual synthesis of PRL and PRLr isoforms with the inflammatory response in monocytes. We used THP-1 and monocytes isolated from healthy subjects stimulated with lipopolysaccharide (LPS). Western blot, real time PCR and immunocytochemistry were performed to identify both molecules. The bioactivity of the PRL was assessed using a bioassay and ELISA to detect pro inflammatory cytokines. Results PRLr mRNA and PRL mRNA were synthesized in THP-1 monocytes activated with LPS with peaks of 300-fold and 130-fold, respectively. The long (100 kDa) and the intermediate (50 kDa) isoforms of PRLr and big PRL (60 kDa) were time-dependent upregulated for monocytes stimulated with LPS. This expression was confirmed in monocytes from healthy subjects. The PRLr intermediate isoform and the big PRL were found soluble in the culture media and later in the nucleus in THP-1 monocytes stimulated with LPS. Big PRL released by monocytes showed bioactivity in Nb2 Cells, and both PRL and PRLr, synthesized by monocytes were related with levels of nitrites and proinflammatory citokines. Conclusions Our results suggest the expression of a full-autocrine loop of PRL enhances the inflammatory response in activated monocytes. This response mediated by big PRL may contribute to the eradication of potential pathogens during innate immune response in monocytes but may also contribute to inflammatory disorders. PMID:23731754

  9. Experimental observations of the coupling between induced currents and mechanical motion in torsionally supported square loops and plates. Part 2. Data inventory

    SciTech Connect

    Weissenburger, D.W.; Bialek, J.M.; Cargulia, G.J.; Ulrickson, M.; Knott, M.J.; Turner, L.R.; Wehrle, R.B.

    1984-12-01

    A series of experiments was successfully conducted to investigate the coupling between induced currents and rigid body rotation in square loops and plates. The experiments were performed with the Fusion Electromagnetic Induction Experiment (FELIX) facility at the Argonne National Laboratory. The observed data exhibited the magnetic damping and magnetic stiffness effects ehich arise in coupled systems and agreed very well with previous analytic calculations.

  10. Paracrine CCL20 loop induces epithelial-mesenchymal transition in breast epithelial cells.

    PubMed

    Marsigliante, S; Vetrugno, C; Muscella, A

    2016-07-01

    We previously found that CCL20 induced primarily cultured healthy breast cell proliferation and migration. The objective of this study was to investigate the hypothesis that CCL20 modulated the epithelial-mesenchymal transition (EMT) of primarily cultured healthy breast epithelial cells and the angiogenesis in areas adjacent to the tumor. Key results showed that CCL20 (a) down-regulated E-cadherin and ZO-1; (b) up-regulated N-cadherin, vimentin, and Snail expressions; (c) increased mRNA and secretion of VEGF and (d) increased angiogenic micro vessel sprouting. Thus, the signal transduction pathways evoked by CCL20 were investigated. We showed that NF-kB p65 down-regulation (by small interfering RNA, siRNA) reversed CCL20-induced Snail and blocked the up-regulation of vimentin and N-cadherin mRNAs. Furthermore, PI3K/AKT inhibition (by LY294002) completely blocked CCL20-induced Snail and NF-kB activation. Inhibition of JNK1/2 (by SP60125) or PKC-α (by siRNA) or src (by PP1) blocked NF-kB activation and Snail expression suggesting that these kinases are all upstream of NF-kB/Snail. Inhibition of mTOR (by rapamycin) abolished the effects of CCL20 on N-cadherin and vimentin protein synthesis. Furthermore, siRNA of PKC-δ inhibited the phosphorylation of CCL20-induced mTOR and S6, increased vimentin and N-cadherin expressions and, finally, blocked the CCL20 induced-EMT. CCL20 increased mRNA and secretion of VEGF by healthy breast cells by using PKC-α, src, Akt, NF-kB, and Snail signalling. In summary, tumor cells signal to the surrounding healthy cells through CCL20 inducing the modulation of the expression of molecules involved in EMT and promoting angiogenesis directly and indirectly through the secretion of VEGF, a major contributor to angiogenesis. © 2015 Wiley Periodicals, Inc. PMID:26154142

  11. Thermally induced all-optical inverter and dynamic hysteresis loops in graphene oxide dispersions.

    PubMed

    Melle, Sonia; Calderón, Oscar G; Egatz-Gómez, Ana; Cabrera-Granado, E; Carreño, F; Antón, M A

    2015-11-01

    We experimentally study the temporal dynamics of amplitude-modulated laser beams propagating through a water dispersion of graphene oxide sheets in a fiber-to-fiber U-bench. Nonlinear refraction induced in the sample by thermal effects leads to both phase reversing of the transmitted signals and dynamic hysteresis in the input-output power curves. A theoretical model including beam propagation and thermal lensing dynamics reproduces the experimental findings. PMID:26560566

  12. Autoantibodies against the Second Extracellular Loop of M3R Do neither Induce nor Indicate Primary Sjögren’s Syndrome

    PubMed Central

    Chen, Yan; Zheng, Junfeng; Huang, Qiaoniang; Deng, Fengyuan; Huang, Renliang; Zhao, Wenjie; Yin, Junping; Song, Lina; Chen, Juan; Gao, Xing; Liu, Zuguo; Petersen, Frank; Yu, Xinhua

    2016-01-01

    Objectives Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren’s syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. Methods BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. Results Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. Conclusions Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis. PMID:26901532

  13. Quantum Structure of Field Theory and Standard Model Based on Infinity-Free Loop Regularization/renormalization

    NASA Astrophysics Data System (ADS)

    Wu, Yue-Liang

    2014-04-01

    To understand better the quantum structure of field theory and standard model in particle physics, it is necessary to investigate carefully the divergence structure in quantum field theories (QFTs) and work out a consistent framework to avoid infinities. The divergence has got us into trouble since developing quantum electrodynamics in 1930s. Its treatment via the renormalization scheme is satisfied not by all physicists, like Dirac and Feynman who have made serious criticisms. The renormalization group analysis reveals that QFTs can in general be defined fundamentally with the meaningful energy scale that has some physical significance, which motivates us to develop a new symmetry-preserving and infinity-free regularization scheme called loop regularization (LORE). A simple regularization prescription in LORE is realized based on a manifest postulation that a loop divergence with a power counting dimension larger than or equal to the space-time dimension must vanish. The LORE method is achieved without modifying original theory and leads the divergent Feynman loop integrals well-defined to maintain the divergence structure and meanwhile preserve basic symmetries of original theory. The crucial point in LORE is the presence of two intrinsic energy scales which play the roles of ultraviolet cutoff Mc and infrared cutoff μs to avoid infinities. As Mc can be made finite when taking appropriately both the primary regulator mass and number to be infinity to recover the original integrals, the two energy scales Mc and μs in LORE become physically meaningful as the characteristic energy scale and sliding energy scale, respectively. The key concept in LORE is the introduction of irreducible loop integrals (ILIs) on which the regularization prescription acts, which leads to a set of gauge invariance consistency conditions between the regularized tensor-type and scalar-type ILIs. An interesting observation in LORE is that the evaluation of ILIs with ultraviolet

  14. Quantum Structure of Field Theory and Standard Model Based on Infinity-Free Loop Regularization/renormalization

    NASA Astrophysics Data System (ADS)

    Wu, Yue-Liang

    2014-02-01

    To understand better the quantum structure of field theory and standard model in particle physics, it is necessary to investigate carefully the divergence structure in quantum field theories (QFTs) and work out a consistent framework to avoid infinities. The divergence has got us into trouble since developing quantum electrodynamics in 1930s. Its treatment via the renormalization scheme is satisfied not by all physicists, like Dirac and Feynman who have made serious criticisms. The renormalization group analysis reveals that QFTs can in general be defined fundamentally with the meaningful energy scale that has some physical significance, which motivates us to develop a new symmetry-preserving and infinity-free regularization scheme called loop regularization (LORE). A simple regularization prescription in LORE is realized based on a manifest postulation that a loop divergence with a power counting dimension larger than or equal to the space-time dimension must vanish. The LORE method is achieved without modifying original theory and leads the divergent Feynman loop integrals well-defined to maintain the divergence structure and meanwhile preserve basic symmetries of original theory. The crucial point in LORE is the presence of two intrinsic energy scales which play the roles of ultraviolet cutoff Mc and infrared cutoff μs to avoid infinities. As Mc can be made finite when taking appropriately both the primary regulator mass and number to be infinity to recover the original integrals, the two energy scales Mc and μs in LORE become physically meaningful as the characteristic energy scale and sliding energy scale, respectively. The key concept in LORE is the introduction of irreducible loop integrals (ILIs) on which the regularization prescription acts, which leads to a set of gauge invariance consistency conditions between the regularized tensor-type and scalar-type ILIs. An interesting observation in LORE is that the evaluation of ILIs with ultraviolet

  15. Structure and dynamics of parallel beta-sheets, hydrophobic core, and loops in Alzheimer's A beta fibrils.

    PubMed

    Buchete, Nicolae-Viorel; Hummer, Gerhard

    2007-05-01

    We explore the relative contributions of different structural elements to the stability of Abeta fibrils by molecular-dynamics simulations performed over a broad range of temperatures (298 K to 398 K). Our fibril structures are based on solid-state nuclear magnetic resonance experiments of Abeta(1-40) peptides, with sheets of parallel beta-strands connected by loops and stabilized by interior salt bridges. We consider models with different interpeptide interfaces, and different staggering of the N- and C-terminal beta-strands along the fibril axis. Multiple 10-20 ns molecular-dynamics simulations show that fibril segments with 12 peptides are stable at ambient temperature. The different models converge toward an interdigitated side-chain packing, and present water channels solvating the interior D23/K28 salt bridges. At elevated temperatures, we observe the early phases of fibril dissociation as a loss of order in the hydrophilic loops connecting the two beta-strands, and in the solvent-exposed N-terminal beta-sheets. As the most dramatic structural change, we observe collective sliding of the N- and C-terminal beta-sheets on top of each other. The interior C-terminal beta-sheets in the hydrophobic core remain largely intact, indicating that their formation and stability is crucial to the dissociation/elongation and stability of Abeta fibrils. PMID:17293399

  16. Viral Nucleases Induce an mRNA Degradation-Transcription Feedback Loop in Mammalian Cells.

    PubMed

    Abernathy, Emma; Gilbertson, Sarah; Alla, Ravi; Glaunsinger, Britt

    2015-08-12

    Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the cellular 5'-3' mRNA exonuclease Xrn1, thereby suppressing cellular gene expression and facilitating viral evasion of host defenses. We reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA Polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial viral endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription and that gamma-herpesviruses use this feedback mechanism to facilitate viral gene expression. PMID:26211836

  17. Laminated BEAM loops

    NASA Astrophysics Data System (ADS)

    Danisch, Lee A.

    1996-10-01

    BEAM sensors include treated loops of optical fiber that modulate optical throughput with great sensitivity and linearity, in response to curvature of the loop out of its plane. This paper describes BEAM sensors that have two loops treated in opposed fashion, hermetically sealed in flexible laminations. The sensors include an integrated optoelectronics package that extracts curvature information from the treated portion of the loops while rejecting common mode errors. The laminated structure is used to sense various parameters including displacement, force, pressure, flow, and acceleration.

  18. Robust Feedback Control of Flow Induced Structural Radiation of Sound

    NASA Technical Reports Server (NTRS)

    Heatwole, Craig M.; Bernhard, Robert J.; Franchek, Matthew A.

    1997-01-01

    A significant component of the interior noise of aircraft and automobiles is a result of turbulent boundary layer excitation of the vehicular structure. In this work, active robust feedback control of the noise due to this non-predictable excitation is investigated. Both an analytical model and experimental investigations are used to determine the characteristics of the flow induced structural sound radiation problem. The problem is shown to be broadband in nature with large system uncertainties associated with the various operating conditions. Furthermore the delay associated with sound propagation is shown to restrict the use of microphone feedback. The state of the art control methodologies, IL synthesis and adaptive feedback control, are evaluated and shown to have limited success for solving this problem. A robust frequency domain controller design methodology is developed for the problem of sound radiated from turbulent flow driven plates. The control design methodology uses frequency domain sequential loop shaping techniques. System uncertainty, sound pressure level reduction performance, and actuator constraints are included in the design process. Using this design method, phase lag was added using non-minimum phase zeros such that the beneficial plant dynamics could be used. This general control approach has application to lightly damped vibration and sound radiation problems where there are high bandwidth control objectives requiring a low controller DC gain and controller order.

  19. Usefulness of implantable loop recorders in office-based practice for evaluation of syncope in patients with and without structural heart disease.

    PubMed

    Mason, Pamela K; Wood, Mark A; Reese, Daniel B; Lobban, John H; Mitchell, Mark A; DiMarco, John P

    2003-11-01

    Early use of an implantable loop recorder for evaluating unexplained syncope in an office-based electrophysiology practice is an effective approach in patients with and without structural heart disease. Documentation of rhythm with an implantable loop recorder at the time of symptoms is possible in approximately 50% and 80% of patients in both groups after 1 and 2 years of follow-up, respectively. PMID:14583373

  20. THE SPECIFIC ACCELERATION RATE IN LOOP-STRUCTURED SOLAR FLARES-IMPLICATIONS FOR ELECTRON ACCELERATION MODELS

    SciTech Connect

    Guo, Jingnan; Emslie, A. Gordon; Piana, Michele E-mail: piana@dima.unige.it

    2013-03-20

    We analyze electron flux maps based on RHESSI hard X-ray imaging spectroscopy data for a number of extended coronal-loop flare events. For each event, we determine the variation of the characteristic loop length L with electron energy E, and we fit this observed behavior with models that incorporate an extended acceleration region and an exterior 'propagation' region, and which may include collisional modification of the accelerated electron spectrum inside the acceleration region. The models are characterized by two parameters: the plasma density n in, and the longitudinal extent L{sub 0} of, the acceleration region. Determination of the best-fit values of these parameters permits inference of the volume that encompasses the acceleration region and of the total number of particles within it. It is then straightforward to compute values for the emission filling factor and for the specific acceleration rate (electrons s{sup -1} per ambient electron above a chosen reference energy). For the 24 events studied, the range of inferred filling factors is consistent with a value of unity. The inferred mean value of the specific acceleration rate above E{sub 0} = 20 keV is {approx}10{sup -2} s{sup -1}, with a 1{sigma} spread of about a half-order-of-magnitude above and below this value. We compare these values with the predictions of several models, including acceleration by large-scale, weak (sub-Dreicer) fields, by strong (super-Dreicer) electric fields in a reconnecting current sheet, and by stochastic acceleration processes.

  1. Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop.

    PubMed

    Martella, Andrea; Silvestri, Cristoforo; Maradonna, Francesca; Gioacchini, Giorgia; Allarà, Marco; Radaelli, Giuseppe; Overby, Darryl R; Di Marzo, Vincenzo; Carnevali, Oliana

    2016-05-01

    The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor, affecting different organs; however, little is known about its mechanism of action in the liver, in which it triggers triglyceride accumulation. Adult zebrafish (Danio rerio) exposed to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-arachidonoylglycerol and anandamide and a concomitant decrease in palmitoylethanolamide. These changes were associated with variations in the expression of key endocannabinoid catabolic and metabolic enzymes and an increase in the expression of the endocannabinoid receptor cnr1. Acute and chronic in vitro treatments with nano- and micromolar BPA doses showed increased anandamide levels in line with decreased activity of fatty acid amide hydrolase, the main anandamide hydrolytic enzyme, and induced triglyceride accumulation in HHL-5 cells in a CB1-dependent manner. We conclude that BPA is able to produce hepatosteatosis in zebrafish and human hepatocytes by up-regulating the endocannabinoid system. PMID:27014939

  2. Reduction of enterotoxin induced fluid accumulation in ileal loops of neonatal calves with anti-F5 fimbriae recombinant antibody.

    PubMed

    Sahagun-Ruiz, Alfredo; Velazquez, Leticia V; Bhaskaran, Shoba; Jay, Chris M; Morales-Salinas, E; Rathore, Keerti; Wagner, Gale G; Waghela, Suryakant D

    2015-12-01

    Neonatal calf colibacillosis caused by enterotoxigenic Escherichia coli (ETEC) is an economically significant problem in most parts of the world. The most common ETEC found in calves express the F5 (K99) fimbriae, which are necessary for the attachment of the bacteria to the ganglioside receptors on enterocytes. It is known that prevention of ETEC F5(+) adhesion to its ganglioside receptors with specific antibodies protects calves from colibacillosis. Previously we have described the development and characterization of a mouse recombinant antibody fragment (moRAb) that prevents F5 fimbrial protein induced agglutination of horse red blood cells (HRBC), which exhibit the same gangloside receptor for F5 fimbriae. Here we demonstrate that this recombinant antibody fragment inhibits in vitro the attachment of ETEC F5(+) bacteria to HRBC as well as isolated calf enterocytes, and in vivo it decreases fluid accumulation in intestinal loops of calves. Thus, correct oral administration of this anti-F5 moRAb may serve as an immunoprophylactic for cost effective control of colibacillosis in calves. PMID:26521056

  3. A Rapid, Manual Method to Map Coronal-Loop Structures of an Active Region Using Cubic Bézier Curves and Its Applications to Misalignment Angle Analysis

    NASA Astrophysics Data System (ADS)

    Gary, G. Allen; Hu, Qiang; Lee, Jong Kwan

    2014-03-01

    A rapid and flexible manual method is described that maps individual coronal loops of a 2D EUV image as Bézier curves using only four points per loop. Using the coronal loops as surrogates of magnetic-field lines, the mapping results restrict the magnetic-field models derived from extrapolations of magnetograms to those admissible and inadmissible via a fitness parameter. We outline explicitly how the coronal loops can be employed in constraining competing magnetic-field models by transforming 2D coronal-loop images into 3D field lines. The magnetic-field extrapolations must satisfy not only the lower boundary conditions of the vector field (the vector magnetogram) but also must have a set of field lines that satisfies the mapped coronal loops in the volume, analogous to an upper boundary condition. This method uses the minimization of the misalignment angles between the magnetic-field model and the best set of 3D field lines that match a set of closed coronal loops. The presented method is an important tool in determining the fitness of magnetic-field models for the solar atmosphere. The magnetic-field structure is crucial in determining the overall dynamics of the solar atmosphere.

  4. Vortex induced motion in compliant structures

    NASA Astrophysics Data System (ADS)

    Song, Arnold; Tuttman, Max; Breuer, Kenneth

    2008-11-01

    The coupling of the unsteady shedding of vortices from the leading and trailing edges of a flat plate can lead to large scale oscillations of a structure. Examples of these large motions abound in engineered structures (Traffic signs vibrating in the wind, wing flutter, chattering venetian blinds, etc.) and in nature (the rustling of leaves on a tree in the wind). In all of these examples, the efficiency of energy extraction from the flow to the structure increases dramatically as the vortex shedding and structural vibrations near resonance. As the motion becomes more exaggerated, the fluid-structure interaction becomes increasingly nonlinear as the motion of the plate becomes increasingly important to the vortex shedding dynamics. We present experimental results from two related systems tested in a low speed wind tunnel (using high-speed videography, PIV and hotwire anemometry) (i) a rectangular cantilevered flat plate free to bend and twist, and (ii) a flexible ribbon pinned at its two ends and exposed to the flow. In both systems, a rich phase map of vortex-induced vibrations is described in which both mechanisms for vortex shedding and structural vibration can be tuned independently using geometry, material properties and flow conditions.

  5. Telomere targeting with a novel G-quadruplex-interactive ligand BRACO-19 induces T-loop disassembly and telomerase displacement in human glioblastoma cells.

    PubMed

    Zhou, Guangtong; Liu, Xinrui; Li, Yunqian; Xu, Songbai; Ma, Chengyuan; Wu, Xinmin; Cheng, Ye; Yu, Zhiyun; Zhao, Gang; Chen, Yong

    2016-03-22

    Interference with telomerase and telomere maintenance is emerging as an attractive target for anticancer therapies. Ligand-induced stabilization of G-quadruplex formation by the telomeric DNA 3'-overhang inhibits telomerase from catalyzing telomeric DNA synthesis and from capping telomeric ends, making these ligands good candidates for chemotherapeutic purposes. BRACO-19 is one of the most effective and specific ligand for telomeric G4. It is shown here that BRACO-19 suppresses proliferation and reduces telomerase activity in human glioblastoma cells, paralleled by the displacement of telomerase from nuclear to cytoplasm. Meanwhile, BRACO-19 triggers extensive DNA damage response at telomere, which may result from uncapping and disassembly of telomeric T-loop structure, characterized by the formation of anaphase bridge and telomere fusion, as well as the release of telomere-binding protein from telomere. The resulting dysfunctional telomere ultimately provokes p53 and p21-mediated cell cycle arrest, apoptosis and senescence. Notably, normal primary astrocytes do not respond to the treatment of BRACO-19, suggesting the agent's good selectivity for cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs for various tumors including malignant gliomas. PMID:26908447

  6. Probability of pipe failure in the reactor coolant loops of Combustion Engineering PWR Plants. Volume 3. Double-ended guillotine break indirectly induced by earthquakes

    SciTech Connect

    Ravindra, M.K.; Campbell, R.D.; Kennedy, R.P.; Banon, H.

    1985-01-01

    The requirements to design nuclear power plants for the effects of an instantaneous double-ended guillotine break (DEGB) of reactor coolant loop (RCL) piping have led to excessive design costs, interference of normal plant operation and maintenance, and unnecessary radiation exposure of plant maintenance personnel. This report describes an aspect of the NRC/Lawrence Livermore National Laboratory sponsored research program aimed at investigating whether the probability of DEGB in RCL Piping of nuclear power plants is acceptably small and the requirements to design for the DEGB effects (e.g., provision of pipe whip restraints) may be removed. This study estimated the probability of indirect DEGB in RCL piping as a consequence of seismic-induced structural failures within the containment of Combustion Engineering supplied pressurized water reactor nuclear power plants in the United States. The median probability of indirect DEGB was estimated to be in the range of 10/sup -6/ per year for older plants, and less than 10/sup -8/ per year for modern plants; using very conservative assumptions, the 90% subjective probability value (confidence) of P/sub DEGB/ was found to be less than 5 x 10/sup -5/ per year for older plants and less than 3 x 10/sup -7/ per year for modern plants.

  7. Probability of pipe failure in the reactor coolant loops of Babcock and Wilcox PWR plants. Volume 2. Guillotine break indirectly induced by earthquakes

    SciTech Connect

    Ravindra, M.K.; Campbell, R.D.; Kipp, T.R.; Sues, R.H.

    1985-07-01

    The requirements to design nuclear power plants for the effects of an instantaneous double-ended guillotine break (DEGB) of the reactor coolant loop (RCL) piping have led to excessive design costs, interference with normal plant operation and maintenance, and unnecessary radiation exposure of plant maintenance personnel. This report describes an aspect of the NRC/Lawrence Livermore National Laboratory sponsored research program aimed at exploring whether the probability of DEGB in RCL Piping of nuclear power plants is acceptably small and the requirements to design for the DEGB effects (e.g., provision of pipe whip restraints) may be removed. This study estimates the probability of indirect DEGB in RCL piping as a consequence of seismic-induced structural failures within the containment of Babcock and Wilcox supplied pressurized water reactor nuclear power plants in the United States. The median probability of indirect DEGB was estimated to range between 6 x 10/sup -11/ and 1 x 10/sup -7/ per year. Using very conservative assumptions, the 90% subjective probability value (confidence) of P/sub DEGB/ was found to be less than 1 x 10/sup -5/ per year. 19 refs., 19 figs., 11 tabs.

  8. Probability of pipe failure in the reactor coolant loop of Westinghouse PWR plants. Volume 3. Guillotine break indirectly induced by earthquakes

    SciTech Connect

    Ravindra, M.K.; Campbell, R.D.; Kennedy, R.P.; Banon, H.

    1985-02-01

    The requirements to design nuclear power plants for the effects of an instantaneous double-ended guillotine break (DEGB) of reactor coolant loop (RCL) piping have led to excessive design costs, interference of normal plant operation and maintenance, and unnecessary radiation exposure of plant maintenance personnel. This report describes an aspect of the NRC/Lawrence Livermore National Laboratory sponsored research program aimed at investigating whether the probability of DEGB in RCL piping of nuclear power plants is acceptably small and the requirements to design for the DEGB effects (e.g., provision of pipe whip restraints) may be removed. This study estimated the probability of indirect DEGB in RCL piping as a consequence of seismic-induced structural failures within the containment of Westinghouse supplied pressurized water reactor nuclear power plants in the United States. The median probability of indirect DEGB was estimated to be about 3x10/sup -6/ per year with a 10% to 90% subjective probability range approximately from 1x10/sup -7/ per year to 5x10/sup -5/ per year.

  9. Telomere targeting with a novel G-quadruplex-interactive ligand BRACO-19 induces T-loop disassembly and telomerase displacement in human glioblastoma cells

    PubMed Central

    Zhou, Guangtong; Liu, Xinrui; Li, Yunqian; Xu, Songbai; Ma, Chengyuan; Wu, Xinmin; Cheng, Ye; Yu, Zhiyun; Zhao, Gang; Chen, Yong

    2016-01-01

    Interference with telomerase and telomere maintenance is emerging as an attractive target for anticancer therapies. Ligand-induced stabilization of G-quadruplex formation by the telomeric DNA 3′-overhang inhibits telomerase from catalyzing telomeric DNA synthesis and from capping telomeric ends, making these ligands good candidates for chemotherapeutic purposes. BRACO-19 is one of the most effective and specific ligand for telomeric G4. It is shown here that BRACO-19 suppresses proliferation and reduces telomerase activity in human glioblastoma cells, paralleled by the displacement of telomerase from nuclear to cytoplasm. Meanwhile, BRACO-19 triggers extensive DNA damage response at telomere, which may result from uncapping and disassembly of telomeric T-loop structure, characterized by the formation of anaphase bridge and telomere fusion, as well as the release of telomere-binding protein from telomere. The resulting dysfunctional telomere ultimately provokes p53 and p21-mediated cell cycle arrest, apoptosis and senescence. Notably, normal primary astrocytes do not respond to the treatment of BRACO-19, suggesting the agent's good selectivity for cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs for various tumors including malignant gliomas. PMID:26908447

  10. PAK1IP1, a ribosomal stress-induced nucleolar protein, regulates cell proliferation via the p53–MDM2 loop

    PubMed Central

    Yu, Weishi; Qiu, Zhongwei; Gao, Na; Wang, Liren; Cui, Hengxiang; Qian, Yu; Jiang, Li; Luo, Jian; Yi, Zhengfang; Lu, Hua; Li, Dali; Liu, Mingyao

    2011-01-01

    Cell growth and proliferation are tightly controlled via the regulation of the p53–MDM2 feedback loop in response to various cellular stresses. In this study, we identified a nucleolar protein called PAK1IP1 as another regulator of this loop. PAK1IP1 was induced when cells were treated with chemicals that disturb ribosome biogenesis. Overexpression of PAK1IP1 inhibited cell proliferation by inducing p53-dependent G1 cell-cycle arrest. PAK1IP1 bound to MDM2 and inhibited its ability to ubiquitinate and to degrade p53, consequently leading to the accumulation of p53 levels. Interestingly, knockdown of PAK1IP1 in cells also inhibited cell proliferation and induced p53-dependent G1 arrest. Deficiency of PAK1IP1 increased free ribosomal protein L5 and L11 which were required for PAK1IP1 depletion-induced p53 activation. Taken together, our results reveal that PAK1IP1 is a new nucleolar protein that is crucial for rRNA processing and plays a regulatory role in cell proliferation via the p53–MDM2 loop. PMID:21097889

  11. Bimodal loop-gap resonator

    NASA Astrophysics Data System (ADS)

    Piasecki, W.; Froncisz, W.; Hyde, James S.

    1996-05-01

    A bimodal loop-gap resonator for use in electron paramagnetic resonance (EPR) spectroscopy at S band is described. It consists of two identical one-loop-one-gap resonators in coaxial juxtaposition. In one mode, the currents in the two loops are parallel and in the other antiparallel. By introducing additional capacitors between the loops, the frequencies of the two modes can be made to coincide. Details are given concerning variable coupling to each mode, tuning of the resonant frequency of one mode to that of the other, and adjustment of the isolation between modes. An equivalent circuit is given and network analysis carried out both experimentally and theoretically. EPR applications are described including (a) probing of the field distributions with DPPH, (b) continuous wave (cw) EPR with a spin-label line sample, (c) cw electron-electron double resonance (ELDOR), (d) modulation of saturation, and (e) saturation-recovery (SR) EPR. Bloch induction experiments can be performed when the sample extends half way through the structure, but microwave signals induced by Mx and My components of magnetization cancel when it extends completely through. This latter situation is particularly favorable for SR, modulation of saturation, and ELDOR experiments, which depend on observing Mz indirectly using a second weak observing microwave source.

  12. Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1.

    PubMed

    van den Boom, Johannes; Trusch, Franziska; Hoppstock, Lukas; Beuck, Christine; Bayer, Peter

    2016-01-01

    Type 2 asparaginases, a subfamily of N-terminal nucleophile (Ntn) hydrolases, are activated by limited proteolysis. This activation yields a heterodimer and a loop region at the C-terminus of the α-subunit is released. Since this region is unresolved in all type 2 asparaginase crystal structures but is close to the active site residues, we explored this loop region in six members of the type 2 asparaginase family using homology modeling. As the loop model for the childhood cancer-relevant protease Taspase1 differed from the other members, Taspase1 activation as well as the conformation and dynamics of the 56 amino acids loop were investigated by CD and NMR spectroscopy. We propose a helix-turn-helix motif, which can be exploited as novel anticancer target to inhibit Taspase1 proteolytic activity. PMID:26974973

  13. Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1

    PubMed Central

    van den Boom, Johannes; Trusch, Franziska; Hoppstock, Lukas; Beuck, Christine; Bayer, Peter

    2016-01-01

    Type 2 asparaginases, a subfamily of N-terminal nucleophile (Ntn) hydrolases, are activated by limited proteolysis. This activation yields a heterodimer and a loop region at the C-terminus of the α-subunit is released. Since this region is unresolved in all type 2 asparaginase crystal structures but is close to the active site residues, we explored this loop region in six members of the type 2 asparaginase family using homology modeling. As the loop model for the childhood cancer-relevant protease Taspase1 differed from the other members, Taspase1 activation as well as the conformation and dynamics of the 56 amino acids loop were investigated by CD and NMR spectroscopy. We propose a helix-turn-helix motif, which can be exploited as novel anticancer target to inhibit Taspase1 proteolytic activity. PMID:26974973

  14. Phase transition and hysteresis loop in structured games with global updating

    NASA Astrophysics Data System (ADS)

    Wang, Wen-Xu; Lü, Jinhu; Chen, Guanrong; Hui, P. M.

    2008-04-01

    We present a global payoff-based strategy updating model for studying cooperative behavior of a networked population. We adopt the Prisoner’s Dilemma game and the snowdrift game as paradigms for characterizing the interactions among individuals. We investigate the model on regular, small-world, and scale-free networks, and find multistable cooperation states depending on the initial cooperator density. In particular for the snowdrift game on small-world and scale-free networks, there exist a discontinuous phase transition and hysteresis loops of cooperator density. We explain the observed properties by theoretical predictions and simulation results of the average number of neighbors of cooperators and defectors, respectively. Our work indicates that individuals with more neighbors have a trend to preserve their initial strategies, which has strong impacts on the strategy updating of individuals with fewer neighbors; while the fact that individuals with few neighbors have to become cooperators to avoid gaining the lowest payoff plays significant roles in maintaining and spreading of cooperation strategy.

  15. The loop 5 element structurally and kinetically coordinates dimers of the human kinesin-5, Eg5.

    PubMed

    Waitzman, Joshua S; Larson, Adam G; Cochran, Jared C; Naber, Nariman; Cooke, Roger; Jon Kull, F; Pate, Edward; Rice, Sarah E

    2011-12-01

    Eg5 is a homotetrameric kinesin-5 motor protein that generates outward force on the overlapping, antiparallel microtubules (MTs) of the mitotic spindle. Upon binding an MT, an Eg5 dimer releases one ADP molecule, undergoes a slow (∼0.5 s(-1)) isomerization, and finally releases a second ADP, adopting a tightly MT-bound, nucleotide-free (APO) conformation. This conformation precedes ATP binding and stepping. Here, we use mutagenesis, steady-state and pre-steady-state kinetics, motility assays, and electron paramagnetic resonance spectroscopy to examine Eg5 monomers and dimers as they bind MTs and initiate stepping. We demonstrate that a critical element of Eg5, loop 5 (L5), accelerates ADP release during the initial MT-binding event. Furthermore, our electron paramagnetic resonance data show that L5 mediates the slow isomerization by preventing Eg5 dimer heads from binding the MT until they release ADP. Finally, we find that Eg5 having a seven-residue deletion within L5 can still hydrolyze ATP and move along MTs, suggesting that L5 is not required to accelerate subsequent steps of the motor along the MT. Taken together, these properties of L5 explain the kinetic effects of L5-directed inhibition on Eg5 activity and may direct further interventions targeting Eg5 activity. PMID:22261065

  16. The Loop 5 Element Structurally and Kinetically Coordinates Dimers of the Human Kinesin-5, Eg5

    PubMed Central

    Waitzman, Joshua S.; Larson, Adam G.; Cochran, Jared C.; Naber, Nariman; Cooke, Roger; Kull, F. Jon; Pate, Edward; Rice, Sarah E.

    2011-01-01

    Eg5 is a homotetrameric kinesin-5 motor protein that generates outward force on the overlapping, antiparallel microtubules (MTs) of the mitotic spindle. Upon binding an MT, an Eg5 dimer releases one ADP molecule, undergoes a slow (∼0.5 s−1) isomerization, and finally releases a second ADP, adopting a tightly MT-bound, nucleotide-free (APO) conformation. This conformation precedes ATP binding and stepping. Here, we use mutagenesis, steady-state and pre-steady-state kinetics, motility assays, and electron paramagnetic resonance spectroscopy to examine Eg5 monomers and dimers as they bind MTs and initiate stepping. We demonstrate that a critical element of Eg5, loop 5 (L5), accelerates ADP release during the initial MT-binding event. Furthermore, our electron paramagnetic resonance data show that L5 mediates the slow isomerization by preventing Eg5 dimer heads from binding the MT until they release ADP. Finally, we find that Eg5 having a seven-residue deletion within L5 can still hydrolyze ATP and move along MTs, suggesting that L5 is not required to accelerate subsequent steps of the motor along the MT. Taken together, these properties of L5 explain the kinetic effects of L5-directed inhibition on Eg5 activity and may direct further interventions targeting Eg5 activity. PMID:22261065

  17. Solution structure of the K-turn and Specifier Loop domains from the Bacillus subtilis tyrS T box leader RNA†

    PubMed Central

    Wang, Jiachen; Nikonowicz, Edward P.

    2011-01-01

    In Gram-positive bacteria, the RNA transcripts of many amino acid biosynthetic and aminoacyltRNA synthetase genes contain 5' untranslated regions, or leader RNAs, that function as riboswitches. These T bxo riboswitches bind cognate tRNA molecules and regulate gene expression by a transcription attenuation mechanism. The Specifier Loop domain of the leader RNA contains nucleotides that pair with nucleotides in the tRNA anticodon loop and is flanked on one side by a kink-turn, or GA, sequence motif. We have determined the solution NMR structure of the kink-turn (K-turn) sequence element within the context of the Specifier Loop domain. The K-turn sequence motif has several non-canonical base pairs typical of K-turn structures but adopts an extended conformation. The Specifier Loop domain contains a loop E structural motif and the single strand Specifier nucleotides stack with their Watson-Crick edges displaced toward the minor groove. Mg2+ leads to significant bending of the helix axis at the base of the Specifier Loop domain, but does not alter the K-turn. ITC indicates that the K-turn sequence causes a small enhancement of the interaction between tRNA anticodon arm with the Specifier Loop domain. One possibility is that the K-turn structure is formed and stabilized when tRNA binds the T box riboswitch and interacts with Stem I and the antiterminator helix. This motif in turn anchors the orientation of Stem I relative to the 3' half of the leader RNA, further stabilizing the tRNA-T box complex. PMID:21333656

  18. The K-loop, a general feature of the Pyrococcus C/D guide RNAs, is an RNA structural motif related to the K-turn

    PubMed Central

    Nolivos, Sophie; Carpousis, Agamemnon J.; Clouet-d'Orval, Béatrice

    2005-01-01

    The C/D guide RNAs predicted from the genomic sequences of three species of Pyrococcus delineate a family of small non-coding archaeal RNAs involved in the methylation of rRNA and tRNA. The C/D guides assemble into ribonucleoprotein (RNP) that contains the methyltransferase. The protein L7Ae, a key structural component of the RNP, binds to a Kink-turn (K-turn) formed by the C/D motif. The K-turn is a structure that consists of two RNA stems separated by a short asymmetric loop with a characteristic sharp bend (kink) between the two stems. The majority of the pyrococcal C/D guides contain a short 3 nt-spacer between the C′/D′ motifs. We show here that conserved terminal stem–loops formed by the C′/D′ motif of the Pyrococcus C/D RNAs are also L7Ae-binding sites. These stem–loops are related to the K-turn by sequence and structure, but they consist of a single stem closed by a terminal loop. We have named this structure the K-loop. We show that conserved non-canonical base pairs in the stem of the K-loop are necessary for L7Ae binding. For the C/D guides with a 3 nt-spacer we show that the sequence and length is also important. The K-loop could improve the stability of the C/D guide RNAs in Pyrococcal species, which are extreme hyperthermophiles. PMID:16293637

  19. Reovirus FAST Proteins Drive Pore Formation and Syncytiogenesis Using a Novel Helix-Loop-Helix Fusion-Inducing Lipid Packing Sensor

    PubMed Central

    Sarker, Muzaddid; de Antueno, Roberto; Langelaan, David N.; Parmar, Hiren B.; Shin, Kyungsoo; Rainey, Jan K.; Duncan, Roy

    2015-01-01

    Pore formation is the most energy-demanding step during virus-induced membrane fusion, where high curvature of the fusion pore rim increases the spacing between lipid headgroups, exposing the hydrophobic interior of the membrane to water. How protein fusogens breach this thermodynamic barrier to pore formation is unclear. We identified a novel fusion-inducing lipid packing sensor (FLiPS) in the cytosolic endodomain of the baboon reovirus p15 fusion-associated small transmembrane (FAST) protein that is essential for pore formation during cell-cell fusion and syncytiogenesis. NMR spectroscopy and mutational studies indicate the dependence of this FLiPS on a hydrophobic helix-loop-helix structure. Biochemical and biophysical assays reveal the p15 FLiPS preferentially partitions into membranes with high positive curvature, and this partitioning is impeded by bis-ANS, a small molecule that inserts into hydrophobic defects in membranes. Most notably, the p15 FLiPS can be functionally replaced by heterologous amphipathic lipid packing sensors (ALPS) but not by other membrane-interactive amphipathic helices. Furthermore, a previously unrecognized amphipathic helix in the cytosolic domain of the reptilian reovirus p14 FAST protein can functionally replace the p15 FLiPS, and is itself replaceable by a heterologous ALPS motif. Anchored near the cytoplasmic leaflet by the FAST protein transmembrane domain, the FLiPS is perfectly positioned to insert into hydrophobic defects that begin to appear in the highly curved rim of nascent fusion pores, thereby lowering the energy barrier to stable pore formation. PMID:26061049

  20. Crystal Structure of the Lactose Operon Repressor and Its Complexes with DNA and Inducer

    NASA Astrophysics Data System (ADS)

    Lewis, Mitchell; Chang, Geoffrey; Horton, Nancy C.; Kercher, Michele A.; Pace, Helen C.; Schumacher, Maria A.; Brennan, Richard G.; Lu, Ponzy

    1996-03-01

    The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isopropyl-β-D-1-thiogalactoside (IPTG) and the lac repressor complexed with a 21-base pair symmetric operator DNA have been determined. These three structures show the conformation of the molecule in both the induced and repressed states and provide a framework for understanding a wealth of biochemical and genetic information. The DNA sequence of the lac operon has three lac repressor recognition sites in a stretch of 500 base pairs. The crystallographic structure of the complex with DNA suggests that the tetrameric repressor functions synergistically with catabolite gene activator protein (CAP) and participates in the quaternary formation of repression loops in which one tetrameric repressor interacts simultaneously with two sites on the genomic DNA.

  1. Structure-guided Design and Immunological Characterization of Immunogens Presenting the HIV-1 gp120 V3 Loop on a CTB Scaffold

    SciTech Connect

    M Totrov; X Jiang; X Kong; S Cohen; C Krachmarov; A Salomon; C Williams; M Seaman; R Abagyan; et al.

    2011-12-31

    V3 loop is a major neutralizing determinant of the HIV-1 gp120. Using 3D structures of cholera toxin B subunit (CTB), complete V3 in the gp120 context, and V3 bound to a monoclonal antibody (mAb), we designed two V3-scaffold immunogen constructs (V3-CTB). The full-length V3-CTB presenting the complete V3 in a structural context mimicking gp120 was recognized by the large majority of our panel of 24 mAbs. The short V3-CTB presenting a V3 fragment in the conformation observed in the complex with the 447-52D Fab, exhibited high-affinity binding to this mAb. The immunogens were evaluated in rabbits using DNA-prime/protein-boost protocol. Boosting with the full-length V3-CTB induced high anti-V3 titers in sera that potently neutralize multiple HIV virus strains. The short V3-CTB was ineffective. The results suggest that very narrow antigenic profile of an immunogen is associated with poor Ab response. An immunogen with broader antigenic activity elicits robust Ab response.

  2. Structural differences within the loop E motif imply alternative mechanisms of viroid processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viroids replicate via a rolling circle mechanism, and cleavage/ligation requires extensive rearrangement of the highly base-paired native structure. For Potato spindle tuber viroid (PSTVd), the switch from cleavage to ligation is driven by the change from a multi-branched tetraloop structure to a l...

  3. Investigation of Deterioration Behavior of Hysteretic Loops in Nonlinear Static Procedure Analysis of Concrete Structures with Shear Walls

    NASA Astrophysics Data System (ADS)

    Ghodrati Amiri, G.; Amidi, S.; Khorasani, M.

    2008-07-01

    In the recent years, scientists developed the seismic rehabilitation of structures and their view points were changed from sufficient strength to the performance of structures (Performance Base Design) to prepare a safe design. Nonlinear Static Procedure analysis (NSP) or pushover analysis is a new method that is chosen for its speed and simplicity in calculations. "Seismic Rehabilitation Code for Existing Buildings" and FEMA 356 considered this method. Result of this analysis is a target displacement that is the base of the performance and rehabilitation procedure of the structures. Exact recognition of that displacement could develop the workability of pushover analysis. In these days, Nonlinear Dynamic Analysis (NDP) is only method can exactly apply the seismic ground motions. In this case because it consumes time, costs very high and is more difficult than other methods, is not applicable as much as NSP. A coefficient used in NSP for determining the target displacement is C2 (Stiffness and Strength Degradations Coefficient) and is applicable for correcting the errors due to eliminating the stiffness and strength degradations in hysteretic loops. In this study it has been tried to analysis three concrete frames with shear walls by several accelerations that scaled according to FEMA 273 and FEMA 356. These structures were designed with Iranian 2800 standard (vers.3). Finally after the analyzing by pushover method and comparison results with dynamic analysis, calculated C2 was comprised with values in rehabilitation codes.

  4. Investigation of Deterioration Behavior of Hysteretic Loops in Nonlinear Static Procedure Analysis of Concrete Structures with Shear Walls

    SciTech Connect

    Ghodrati Amiri, G.; Amidi, S.; Khorasani, M.

    2008-07-08

    In the recent years, scientists developed the seismic rehabilitation of structures and their view points were changed from sufficient strength to the performance of structures (Performance Base Design) to prepare a safe design. Nonlinear Static Procedure analysis (NSP) or pushover analysis is a new method that is chosen for its speed and simplicity in calculations. 'Seismic Rehabilitation Code for Existing Buildings' and FEMA 356 considered this method. Result of this analysis is a target displacement that is the base of the performance and rehabilitation procedure of the structures. Exact recognition of that displacement could develop the workability of pushover analysis. In these days, Nonlinear Dynamic Analysis (NDP) is only method can exactly apply the seismic ground motions. In this case because it consumes time, costs very high and is more difficult than other methods, is not applicable as much as NSP. A coefficient used in NSP for determining the target displacement is C2 (Stiffness and Strength Degradations Coefficient) and is applicable for correcting the errors due to eliminating the stiffness and strength degradations in hysteretic loops. In this study it has been tried to analysis three concrete frames with shear walls by several accelerations that scaled according to FEMA 273 and FEMA 356. These structures were designed with Iranian 2800 standard (vers.3). Finally after the analyzing by pushover method and comparison results with dynamic analysis, calculated C2 was comprised with values in rehabilitation codes.

  5. Structures of paraoxon-inhibited human acetylcholinesterase reveal perturbations of the acyl loop and the dimer interface.

    PubMed

    Franklin, Matthew C; Rudolph, Michael J; Ginter, Christopher; Cassidy, Michael S; Cheung, Jonah

    2016-09-01

    Irreversible inhibition of the essential nervous system enzyme acetylcholinesterase by organophosphate nerve agents and pesticides may quickly lead to death. Oxime reactivators currently used as antidotes are generally less effective against pesticide exposure than nerve agent exposure, and pesticide exposure constitutes the majority of cases of organophosphate poisoning in the world. The current lack of published structural data specific to human acetylcholinesterase organophosphate-inhibited and oxime-bound states hinders development of effective medical treatments. We have solved structures of human acetylcholinesterase in different states in complex with the organophosphate insecticide, paraoxon, and oximes. Reaction with paraoxon results in a highly perturbed acyl loop that causes a narrowing of the gorge in the peripheral site that may impede entry of reactivators. This appears characteristic of acetylcholinesterase inhibition by organophosphate insecticides but not nerve agents. Additional changes seen at the dimer interface are novel and provide further examples of the disruptive effect of paraoxon. Ternary structures of paraoxon-inhibited human acetylcholinesterase in complex with the oximes HI6 and 2-PAM reveals relatively poor positioning for reactivation. This study provides a structural foundation for improved reactivator design for the treatment of organophosphate intoxication. Proteins 2016; 84:1246-1256. © 2016 Wiley Periodicals, Inc. PMID:27191504

  6. The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120

    PubMed Central

    Billings, Erik; Rao, Mangala; Williams, Constance; Zolla-Pazner, Susan; Bailer, Robert T.; Koup, Richard A.; Madnote, Sirinan; Arworn, Duangnapa; Shen, Xiaoying; Tomaras, Georgia D.; Currier, Jeffrey R.; Jiang, Mike; Magaret, Craig; Andrews, Charla; Gottardo, Raphael; Gilbert, Peter; Cardozo, Timothy J.; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Paris, Robert; Greene, Kelli; Gao, Hongmei; Gurunathan, Sanjay; Tartaglia, Jim; Sinangil, Faruk; Korber, Bette T.; Montefiori, David C.; Mascola, John R.; Robb, Merlin L.; Haynes, Barton F.; Ngauy, Viseth; Michael, Nelson L.; Kim, Jerome H.; de Souza, Mark S.

    2012-01-01

    Abstract The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200–3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100–200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169–184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100–800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100–3200) and 3570 (range: 200–12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition. PMID:23035746

  7. Defect Induced Electronic Structure of Uranofullerene

    PubMed Central

    Dai, Xing; Cheng, Cheng; Zhang, Wei; Xin, Minsi; Huai, Ping; Zhang, Ruiqin; Wang, Zhigang

    2013-01-01

    The interaction between the inner atoms/cluster and the outer fullerene cage is the source of various novel properties of endohedral metallofullerenes. Herein, we introduce an adatom-type spin polarization defect on the surface of a typical endohedral stable U2@C60 to predict the associated structure and electronic properties of U2@C61 based on the density functional theory method. We found that defect induces obvious changes in the electronic structure of this metallofullerene. More interestingly, the ground state of U2@C61 is nonet spin in contrast to the septet of U2@C60. Electronic structure analysis shows that the inner U atoms and the C ad-atom on the surface of the cage contribute together to this spin state, which is brought about by a ferromagnetic coupling between the spin of the unpaired electrons of the U atoms and the C ad-atom. This discovery may provide a possible approach to adapt the electronic structure properties of endohedral metallofullerenes. PMID:23439318

  8. A new crystal form of human tear lipocalin reveals high flexibility in the loop region and induced fit in the ligand cavity

    SciTech Connect

    Breustedt, Daniel A.; Chatwell, Lorenz; Skerra, Arne

    2009-10-01

    The crystal structure of tear lipocalin determined in space group P2{sub 1} revealed large structural deviations from the previously solved X-ray structure in space group C2, especially in the loop region and adjoining parts of the β-barrel which give rise to the ligand-binding site. These findings illustrate a novel mechanism for promiscuity in ligand recognition by the lipocalin protein family. Tear lipocalin (TLC) with the bound artificial ligand 1,4-butanediol has been crystallized in space group P2{sub 1} with four protein molecules in the asymmetric unit and its X-ray structure has been solved at 2.6 Å resolution. TLC is a member of the lipocalin family that binds ligands with diverse chemical structures, such as fatty acids, phospholipids and cholesterol as well as microbial siderophores and the antibiotic rifampin. Previous X-ray structural analysis of apo TLC crystallized in space group C2 revealed a rather large bifurcated ligand pocket and a partially disordered loop region at the entrace to the cavity. Analysis of the P2{sub 1} crystal form uncovered major conformational changes (i) in β-strands B, C and D, (ii) in loops 1, 2 and 4 at the open end of the β-barrel and (iii) in the extended C-terminal segment, which is attached to the β-barrel via a disulfide bridge. The structural comparison indicates high conformational plasticity of the loop region as well as of deeper parts of the ligand pocket, thus allowing adaptation to ligands that differ vastly in size and shape. This illustrates a mechanism for promiscuity in ligand recognition which may also be relevant for some other physiologically important members of the lipocalin protein family.

  9. NMR structure and dynamics of the RNA-binding site for the histone mRNA stem-loop binding protein.

    PubMed Central

    DeJong, Eric S; Marzluff, William F; Nikonowicz, Edward P

    2002-01-01

    The 3' end of replication-dependent histone mRNAs terminate in a conserved sequence containing a stem-loop. This 26-nt sequence is the binding site for a protein, stem-loop binding protein (SLBP), that is involved in multiple aspects of histone mRNA metabolism and regulation. We have determined the structure of the 26-nt sequence by multidimensional NMR spectroscopy. There is a 16-nt stem-loop motif, with a conserved 6-bp stem and a 4-nt loop. The loop is closed by a conserved U.A base pair that terminates the canonical A-form stem. The pyrimidine-rich 4-nt loop, UUUC, is well organized with the three uridines stacking on the helix, and the fourth base extending across the major groove into the solvent. The flanking nucleotides at the base of the hairpin stem do not assume a unique conformation, despite the fact that the 5' flanking nucleotides are a critical component of the SLBP binding site. PMID:11871662

  10. Structures induced by companions in galactic discs

    NASA Astrophysics Data System (ADS)

    Kyziropoulos, P. E.; Efthymiopoulos, C.; Gravvanis, G. A.; Patsis, P. A.

    2016-09-01

    Using N-body simulations we study the structures induced on a galactic disc by repeated flybys of a companion in decaying eccentric orbit around the disc. Our system is composed by a stellar disc, bulge and live dark matter halo, and we study the system's dynamical response to a sequence of a companion's flybys, when we vary i) the disc's temperature (parameterized by Toomre's Q-parameter) and ii) the companion's mass and initial orbit. We use a new 3D Cartesian grid code: MAIN (Mesh-adaptive Approximate Inverse N-body solver). The main features of MAIN are reviewed, with emphasis on the use of a new Symmetric Factored Approximate Sparse Inverse (SFASI) matrix in conjunction with the multigrid method that allows the efficient solution of Poisson's equation in three space variables. We find that: i) companions need to be assigned initial masses in a rather narrow window of values in order to produce significant and more long-standing non-axisymmetric structures (bars and spirals) in the main galaxy's disc by the repeated flyby mechanism. ii) a crucial phenomenon is the antagonism between companion-excited and self-excited modes on the disc. Values of Q > 1.5 are needed in order to allow for the growth of the companion-excited modes to prevail over the the growth of the disc's self-excited modes. iii) We give evidence that the companion-induced spiral structure is best represented by a density wave with pattern speed nearly constant in a region extending from the ILR to a radius close to, but inside, corotation.

  11. Coronal Density Structure and its Role in Wave Damping in Loops

    NASA Astrophysics Data System (ADS)

    Cargill, P. J.; De Moortel, I.; Kiddie, G.

    2016-05-01

    It has long been established that gradients in the Alfvén speed, and in particular the plasma density, are an essential part of the damping of waves in the magnetically closed solar corona by mechanisms such as resonant absorption and phase mixing. While models of wave damping often assume a fixed density gradient, in this paper the self-consistency of such calculations is assessed by examining the temporal evolution of the coronal density. It is shown conceptually that for some coronal structures, density gradients can evolve in a way that the wave-damping processes are inhibited. For the case of phase mixing we argue that (a) wave heating cannot sustain the assumed density structure and (b) inclusion of feedback of the heating on the density gradient can lead to a highly structured density, although on long timescales. In addition, transport coefficients well in excess of classical are required to maintain the observed coronal density. Hence, the heating of closed coronal structures by global oscillations may face problems arising from the assumption of a fixed density gradient, and the rapid damping of oscillations may have to be accompanied by a separate (non-wave-based) heating mechanism to sustain the required density structuring.

  12. Utilising a loop structure to allow a microfiber coupler with larger taper diameters to be used for sensing

    NASA Astrophysics Data System (ADS)

    Wei, Fangfang; Farrell, Gerald; Wu, Qiang; Semenova, Yuliya

    2016-05-01

    This paper examines a technique that utilizes a Sagnac loop with a microfiber coupler (MFC) as a coupler which allows the MFC to operate effectively as a sensor but with larger than normal tapered fiber diameters. The proposed structure is found to be suitable for temperature and refractive index (RI) sensing. It is shown that a variation in the surrounding of the MFC RI results in a shift of the output spectrum, while a temperature variation leads to changes in the intensity of the interference dips. A decrease in the waist diameter of the MFC results in an increase in the sensitivity to temperature. For MFC structures based on a 5.6 μm and a 3 μm fiber waist diameter, the minimum transmission power level of a selected spectral dip decreases by 1.7 dB and 5.03 dB respectively, as the temperature changes from 18 °C to 44 °C. A change in the surrounding RI from 1.334 to 1.395 results in the spectral redshift of 8 nm using a 5.6 μm fiber waist diameter. By functionalizing the surface of the MFC with various materials, the structure could potentially be used for sensing of other parameters.

  13. Breaking bad: R-loops and genome integrity.

    PubMed

    Sollier, Julie; Cimprich, Karlene A

    2015-09-01

    R-loops, nucleic acid structures consisting of an RNA-DNA hybrid and displaced single-stranded (ss) DNA, are ubiquitous in organisms from bacteria to mammals. First described in bacteria where they initiate DNA replication, it now appears that R-loops regulate diverse cellular processes such as gene expression, immunoglobulin (Ig) class switching, and DNA repair. Changes in R-loop regulation induce DNA damage and genome instability, and recently it was shown that R-loops are associated with neurodegenerative disorders. We discuss recent developments in the field; in particular, the regulation and effects of R-loops in cells, their effect on genomic and epigenomic stability, and their potential contribution to the origin of diseases including cancer and neurodegenerative disorders. PMID:26045257

  14. Induced toroid structures and toroid polarizabilities

    SciTech Connect

    Costescu, A.; Radescu, E.E.

    1987-06-01

    The frequency-dependent toroid dipole polarizability ..gamma..(..omega..) of a (nonrelativistic, spinless) hydrogenlike atom in its ground state is calculated analytically in terms of two Gauss hypergeometric functions. The static result reads ..gamma..(..omega.. = 0) = (23/60)..cap alpha../sup 2/Z/sup -4/a/sub 0/ /sup 5/(..cap alpha.. = fine-structure constant, Z = nucleus charge number, a/sub 0/ = Bohr radius). Comparing the present evaluations for atoms with previous ones for pions, one sees that the role of the induced toroid moments (as against that of the usual electric ones) increases considerably towards smaller distances (or higher characteristic excitation energies). It might become dramatic at the subhadronic level.

  15. Assembly induced delaminations in composite structures

    NASA Technical Reports Server (NTRS)

    Goering, J.; Bohlmann, R.; Wanthal, S.; Kautz, E.; Neri, Lawrence M.

    1992-01-01

    Experimental and analytical studies of the development of delaminations around fastener holes in composite structures are presented. This type of delamination is known to occur in composite skins that are mechanically fastened to a poorly mating substructure. Results of an experimental study to determine the resistance of laminates to the initiation of assembly induced delaminations and the residual strength of assembly damaged coupons are presented for AS4/3501-6, IM7/8551-7A, and AS4/PEEK material systems. A survey of existing analytical models for predicting the residual strength and stability of delaminations is presented, and the development of a new model for predicting the initiation of delaminations around a fastener hole is outlined. The fastener hole damage initiation model utilizes a finite element based Fourier series solution, and is validated through comparisons of analytical and experimental results.

  16. Magnetic loops, downflows, and convection in the solar corona

    NASA Technical Reports Server (NTRS)

    Foukal, P.

    1978-01-01

    Optical and extreme-ultraviolet observations of solar loop structures show that flows of cool plasma from condensations near the loop apex are a common property of loops associated with radiations whose maximum temperature is greater than approximately 7000 K and less than approximately 3,000,000 K. It is suggested that the mass balance of these structures indicates reconnection by means of plasma motion across field lines under rather general circumstances (not only after flares). It is shown that the cool material has lower gas pressure than the surrounding coronal medium. The density structure of the bright extreme ultraviolet loops suggests that downflows of cool gas result from isobaric condensation of plasma that is either out of thermal equilibrium with the local energy deposition rate into the corona, or is thermally unstable. The evidence is thought to indicate that magnetic fields act to induce a pattern of forced convection.

  17. Closed coronal structures. V - Gasdynamic models of flaring loops and comparison with SMM observations

    NASA Technical Reports Server (NTRS)

    Peres, G.; Serio, S.; Vaiana, G.; Acton, L.; Leibacher, J.; Rosner, R.; Pallavicini, R.

    1983-01-01

    A time-dependent one-dimensional code incorporating energy, momentum and mass conservation equations, and taking the entire solar atmospheric structure into account, is used to investigate the hydrodynamic response of confined magnetic structures to strong heating perturbations. Model calculation results are compared with flare observations which include the light curves of spectral lines formed over a wide range of coronal flare temperatures, as well as determinations of Doppler shifts for the high temperature plasma. It is shown that the numerical simulation predictions are in good overall agreement with the observed flare coronal plasma evolution, correctly reproducing the temporal profile of X-ray spectral lines and their relative intensities. The predicted upflow velocities support the interpretation of the blueshifts as due to evaporation of chromospheric material.

  18. Large-scale structure from cosmic-string loops in a baryon-dominated universe

    NASA Technical Reports Server (NTRS)

    Melott, Adrian L.; Scherrer, Robert J.

    1988-01-01

    The results are presented of a numerical simulation of the formation of large-scale structure in a universe with Omega(0) = 0.2 and h = 0.5 dominated by baryons in which cosmic strings provide the initial density perturbations. The numerical model yields a power spectrum. Nonlinear evolution confirms that the model can account for 700 km/s bulk flows and a strong cluster-cluster correlation, but does rather poorly on smaller scales. There is no visual 'filamentary' structure, and the two-point correlation has too steep a logarithmic slope. The value of G mu = 4 x 10 to the -6th is significantly lower than previous estimates for the value of G mu in baryon-dominated cosmic string models.

  19. Fragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis.

    PubMed

    Edink, Ewald; Rucktooa, Prakash; Retra, Kim; Akdemir, Atilla; Nahar, Tariq; Zuiderveld, Obbe; van Elk, René; Janssen, Elwin; van Nierop, Pim; van Muijlwijk-Koezen, Jacqueline; Smit, August B; Sixma, Titia K; Leurs, Rob; de Esch, Iwan J P

    2011-04-13

    Optimization of fragment hits toward high-affinity lead compounds is a crucial aspect of fragment-based drug discovery (FBDD). In the current study, we have successfully optimized a fragment by growing into a ligand-inducible subpocket of the binding site of acetylcholine-binding protein (AChBP). This protein is a soluble homologue of the ligand binding domain (LBD) of Cys-loop receptors. The fragment optimization was monitored with X-ray structures of ligand complexes and systematic thermodynamic analyses using surface plasmon resonance (SPR) biosensor analysis and isothermal titration calorimetry (ITC). Using site-directed mutagenesis and AChBP from different species, we find that specific changes in thermodynamic binding profiles, are indicative of interactions with the ligand-inducible subpocket of AChBP. This study illustrates that thermodynamic analysis provides valuable information on ligand binding modes and is complementary to affinity data when guiding rational structure- and fragment-based discovery approaches. PMID:21322593

  20. A new crystal form of human tear lipocalin reveals high flexibility in the loop region and induced fit in the ligand cavity

    PubMed Central

    Breustedt, Daniel A.; Chatwell, Lorenz; Skerra, Arne

    2009-01-01

    Tear lipocalin (TLC) with the bound artificial ligand 1,4-butanediol has been crystallized in space group P21 with four protein molecules in the asymmetric unit and its X-ray structure has been solved at 2.6 Å resolution. TLC is a member of the lipocalin family that binds ligands with diverse chemical structures, such as fatty acids, phospholipids and cholesterol as well as microbial siderophores and the antibiotic rifampin. Previous X-ray structural analysis of apo TLC crystallized in space group C2 revealed a rather large bifurcated ligand pocket and a partially disordered loop region at the entrace to the cavity. Analysis of the P21 crystal form uncovered major conformational changes (i) in β-strands B, C and D, (ii) in loops 1, 2 and 4 at the open end of the β-­barrel and (iii) in the extended C-terminal segment, which is attached to the β-­barrel via a disulfide bridge. The structural comparison indicates high conformational plasticity of the loop region as well as of deeper parts of the ligand pocket, thus allowing adaptation to ligands that differ vastly in size and shape. This illustrates a mechanism for promiscuity in ligand recognition which may also be relevant for some other physiologically important members of the lipocalin protein family. PMID:19770509

  1. Solution structure of stem-loop α of the hepatitis B virus post-transcriptional regulatory element

    PubMed Central

    Schwalbe, Martin; Ohlenschläger, Oliver; Marchanka, Aliaksandr; Ramachandran, Ramadurai; Häfner, Sabine; Heise, Tilman; Görlach, Matthias

    2008-01-01

    Chronic hepatitis B virus (HBV) infections may lead to severe diseases like liver cirrhosis or hepatocellular carcinoma (HCC). The HBV post-transcriptional regulatory element (HPRE) facilitates the nuclear export of unspliced viral mRNAs, contains a splicing regulatory element and resides in the 3′-region of all viral transcripts. The HPRE consists of three sub-elements α (nucleotides 1151–1346), β1 (nucleotides 1347–1457) and β2 (nucleotides 1458–1582), which confer together full export competence. Here, we present the NMR solution structure (pdb 2JYM) of the stem-loop α (SLα, nucleotides 1292–1321) located in the sub-element α. The SLα contains a CAGGC pentaloop highly conserved in hepatoviruses, which essentially adopts a CUNG-like tetraloop conformation. Furthermore, the SLα harbours a single bulged G residue flanked by A-helical regions. The structure is highly suggestive of serving two functions in the context of export of unspliced viral RNA: binding sterile alpha motif (SAM-) domain containing proteins and/or preventing the utilization of a 3′-splice site contained within SLα. PMID:18263618

  2. Viscosity-dependent structural fluctuation of the M80-containing Ω-loop of horse ferrocytochrome c

    NASA Astrophysics Data System (ADS)

    Kumar, Rajesh; Jain, Rishu; Kumar, Rajesh

    2013-06-01

    To determine the effect of solvent viscosity on low-frequency local motions that control the slow changes in structural dynamics of proteins, we have studied the effects of solvent viscosity on the structural fluctuation of presumably the M80-containing Ω-loop by measuring the rate of thermally-driven CO-dissociation from a natively-folded carbonmonoxycytochrome c (NCO-state) in the 0.65-92.5 cP range of viscosity at pH 7.0. At low viscosities (⩽8 cP), the rate coefficient, kdiss for dissociation of CO from the NCO-state varies inversely with the viscosity, but saturates at high viscosities, suggesting that CO-dissociation reaction involves sequential stages that depend differently on solvent friction, i.e., solvent coupled and nonsolvent-coupled stages of the process. In the low viscosity regime (0.65 ⩽ ηs ⩽ 8.0 cP), the rate-viscosity data were fitted to modified Kramers model, kdiss = [A'/(σ + ηs)n]exp(-ΔG/RT), which produced internal friction, σ = 1.35 cP (±0.88), which suggests that the speed of CO-dissociation from NCO at ηs ⩽ 8.0 cP is controlled by internal friction.

  3. Impaired Acid Catalysis by Mutation of a Protein Loop Hinge Residue in a YopH Mutant Revealed by Crystal Structures

    SciTech Connect

    Brandao, T.; Robinson, H; Johnson, S; Hengge, A

    2009-01-01

    Catalysis by the Yersinia protein-tyrosine phosphatase YopH is significantly impaired by the mutation of the conserved Trp354 residue to Phe. Though not a catalytic residue, this Trp is a hinge residue in a conserved flexible loop (the WPD-loop) that must close during catalysis. To learn why this seemingly conservative mutation reduces catalysis by 2 orders of magnitude, we have solved high-resolution crystal structures for the W354F YopH in the absence and in the presence of tungstate and vanadate. Oxyanion binding to the P-loop in W354F is analogous to that observed in the native enzyme. However, the WPD-loop in the presence of oxyanions assumes a half-closed conformation, in contrast to the fully closed state observed in structures of the native enzyme. This observation provides an explanation for the impaired general acid catalysis observed in kinetic experiments with Trp mutants. A 1.4 Angstroms structure of the W354F mutant obtained in the presence of vanadate reveals an unusual divanadate species with a cyclic [VO]2 core, which has precedent in small molecules but has not been previously reported in a protein crystal structure.

  4. Electrically induced structure formation and pattern transfer

    NASA Astrophysics Data System (ADS)

    Schäffer, Erik; Thurn-Albrecht, Thomas; Russell, Thomas P.; Steiner, Ullrich

    2000-02-01

    The wavelength of light represents a fundamental technological barrier to the production of increasingly smaller features on integrated circuits. New technologies that allow the replication of patterns on scales less than 100nm need to be developed if increases in computing power are to continue at the present rate. Here we report a simple electrostatic technique that creates and replicates lateral structures in polymer films on a submicrometre length scale. Our method is based on the fact that dielectric media experience a force in an electric field gradient. Strong field gradients can produce forces that overcome the surface tension in thin liquid films, inducing an instability that features a characteristic hexagonal order. In our experiments, pattern formation takes place in polymer films at elevated temperatures, and is fixed by cooling the sample to room temperature. The application of a laterally varying electric field causes the instability to be focused in the direction of the highest electric field. This results in the replication of a topographically structured electrode. We report patterns with lateral dimensions of 140nm, but the extension of the technique to pattern replication on scales smaller than 100nm seems feasible.

  5. Effects of Flow on Structure and Abundances in Multispecies Solar Coronal Loops

    NASA Astrophysics Data System (ADS)

    Lenz, Dawn D.

    2004-03-01

    We investigate the effects of large-scale bulk flows on coronal abundances using a multispecies numerical model. The model assumes that electrons, protons, and helium are in thermal equilibrium and constitute the bulk of the coronal plasma. Thermal diffusion and Coulomb friction are included. Temperature profiles for the bulk component and for each ion species are assumed, so the model reduces to a solution of mass and force balance for each component. We further assume that the bulk component has an upward bulk velocity at the base, and that ion flow speeds along field lines are negligible relative to the bulk flow. Coulomb coupling of the electrons and ions induces drag that counteracts the tendency of the ions to gravitationally settle. In regions of small ∇T, such as the outer regions of the corona, Coulomb drag is the only significant force counteracting gravitational settling in this model. We find that relatively modest bulk flows of tens of km s-1 can enhance ion abundances by 2-3 orders of magnitude over their values in low- or no-flow cases.

  6. Performance Comparison of BPL, EtherLoop and SHDSL technology performance on existing pilot cable circuits under the presence of induced voltage

    NASA Astrophysics Data System (ADS)

    Che, Y. X.; Ong, H. S.; Lai, L. C.; Karuppiah, S.; Ong, X. J.; Do, N. Q.

    2013-06-01

    Pilot cable is originally used for utility protection. Then, pilot cable is further utilized for SCADA communication with low frequency PSK modem in the early 1990. However, the quality of pilot cable communication drops recently. Pilot cable starts to deteriorate due to aging and other unknown factors. It is also believed that the presence of induced voltage causes interference to existing modem communication which operates at low frequency channel. Therefore, BPL (Broadband Power Line), EtherLoop and SHDSL (Symmetrical High-speed Digital Subscriber Line) modem technology are proposed as alternative communication solutions for pilot cable communication. The performance of the 3 selected technologies on existing pilot cable circuits under the presence of induced voltage are measured and compared. Total of 11 pilot circuits with different length and level of induced voltage influence are selected for modem testing. The performance of BPL, EtherLoop and SHDSL modem technology are measured by the delay, bandwidth, packet loss and the long term usability SCADA (Supervisory Control and Data Acquisition) application. The testing results are presented and discussed in this paper. The results show that the 3 selected technologies are dependent on distance and independent on the level of induced voltage.

  7. Constant cross section of loops in the solar corona

    NASA Astrophysics Data System (ADS)

    Peter, H.; Bingert, S.

    2012-12-01

    Context. The corona of the Sun is dominated by emission from loop-like structures. When observed in X-ray or extreme ultraviolet emission, these million K hot coronal loops show a more or less constant cross section. Aims: In this study we show how the interplay of heating, radiative cooling, and heat conduction in an expanding magnetic structure can explain the observed constant cross section. Methods: We employ a three-dimensional magnetohydrodynamics (3D MHD) model of the corona. The heating of the coronal plasma is the result of braiding of the magnetic field lines through footpoint motions and subsequent dissipation of the induced currents. From the model we synthesize the coronal emission, which is directly comparable to observations from, e.g., the Atmospheric Imaging Assembly on the Solar Dynamics Observatory (AIA/SDO). Results: We find that the synthesized observation of a coronal loop seen in the 3D data cube does match actually observed loops in count rate and that the cross section is roughly constant, as observed. The magnetic field in the loop is expanding and the plasma density is concentrated in this expanding loop; however, the temperature is not constant perpendicular to the plasma loop. The higher temperature in the upper outer parts of the loop is so high that this part of the loop is outside the contribution function of the respective emission line(s). In effect, the upper part of the plasma loop is not bright and thus the loop actually seen in coronal emission appears to have a constant width. Conclusions: From this we can conclude that the underlying field-line-braiding heating mechanism provides the proper spatial and temporal distribution of the energy input into the corona - at least on the observable scales. Movies associated to Figs. 1 and 2 are available in electronic form at http://www.aanda.org

  8. Sequential Closure of Loop Structures Forms the Folding Nucleus during the Refolding Transition of the Escherichia coli Adenylate Kinase Molecule.

    PubMed

    Orevi, Tomer; Rahamim, Gil; Amir, Dan; Kathuria, Sagar; Bilsel, Osman; Matthews, C Robert; Haas, Elisha

    2016-01-12

    The ensemble of conformers of globular protein molecules immediately following transfer from unfolding to folding conditions is assumed to be collapsed though still disordered, as the first steps of the folding pathway are initiated. In order to test the hypothesis that long loop closure transitions are part of the initiation of the folding pathway, our groups are studying the initiation of the folding transition of a model protein by time-resolved excitation energy transfer (trFRET) detected fast kinetics experiments. Site-specific double labeling is used to study the timing of conformational transitions of individual loop forming chain segments at the microsecond time regime. Previously, it was shown that at least three long loops in the Escherichia coli adenylate kinase (AK) molecule close within the first 5 ms of folding of AK, while the main global folding transition occurs in a time regime of seconds. In order to enhance the time resolution of the kinetics experiments to the microsecond time regime and determine the rate of closure of the two N terminal loops (loop I residues 1-26 and loop II residues 29-72), we applied a continuous flow based double kinetics experiment. These measurements enabled us to obtain a microsecond series of transient time dependent distributions of distances between the ends of the labeled loops. Analysis of the trFRET experiments show that the N terminal loop (loop I) is closed within less than 60 μs after the initiation of refolding. Loop II is also mostly closed within that time step but shows an additional small reduction of the mean end-to-end distance in a second phase at a rate of 0.005 μs(-1). This second phase can either reflect tightening of a loosely closed loop in the ensemble of conformers or may reflect two subpopulations in the ensemble, which differ in the rate of closure of loop II, but not in the rate of closure of loop I. This study shows the very fast closure of long loops in the otherwise disordered backbone

  9. Observational Evidence for Loop-Loop Interaction

    NASA Astrophysics Data System (ADS)

    Guiping, W.; Guangli, H.; Yuhua, T.; Aoao, X.

    2004-01-01

    Through analysis of the data including the hard x-ray(BASTE) microwave(NoRP) and magnetogram(MDI from SOHO) as well as the images of soft x-ray(YHKOH) and EIT(SOHO) on Apr. 151998 solar flare in the active region 8203(N30W12) we found: (1) there are similar quasi period oscillation in the profile of hard x-ray flux (25-5050-100keV) and microwave flux(1GHz) with duration of 85+/-25s every peak includes two sub-peak structures; (2) in the preheat phase of the flare active magnetic field changes apparently and a s-pole spot emerges ; (3) several EIT and soft x-ray loops exist and turn into bright . All of these may suggest that loop-loop interaction indeed exist. Through reconnection the electrons may be accelerated and the hard x-ray and microwave emission take place.

  10. Natively Unstructured Loops Differ from Other Loops

    PubMed Central

    Schlessinger, Avner; Liu, Jinfeng; Rost, Burkhard

    2007-01-01

    Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%–70% of all worm proteins observed to have more than seven protein–protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long