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Sample records for factors evolution domain

  1. Evolution of a protein domain interaction network

    International Nuclear Information System (INIS)

    Li-Feng, Gao; Jian-Jun, Shi; Shan, Guan

    2010-01-01

    In this paper, we attempt to understand complex network evolution from the underlying evolutionary relationship between biological organisms. Firstly, we construct a Pfam domain interaction network for each of the 470 completely sequenced organisms, and therefore each organism is correlated with a specific Pfam domain interaction network; secondly, we infer the evolutionary relationship of these organisms with the nearest neighbour joining method; thirdly, we use the evolutionary relationship between organisms constructed in the second step as the evolutionary course of the Pfam domain interaction network constructed in the first step. This analysis of the evolutionary course shows: (i) there is a conserved sub-network structure in network evolution; in this sub-network, nodes with lower degree prefer to maintain their connectivity invariant, and hubs tend to maintain their role as a hub is attached preferentially to new added nodes; (ii) few nodes are conserved as hubs; most of the other nodes are conserved as one with very low degree; (iii) in the course of network evolution, new nodes are added to the network either individually in most cases or as clusters with relative high clustering coefficients in a very few cases. (general)

  2. Evolution based on domain combinations: the case of glutaredoxins

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    Herrero Enrique

    2009-03-01

    Full Text Available Abstract Background Protein domains represent the basic units in the evolution of proteins. Domain duplication and shuffling by recombination and fusion, followed by divergence are the most common mechanisms in this process. Such domain fusion and recombination events are predicted to occur only once for a given multidomain architecture. However, other scenarios may be relevant in the evolution of specific proteins, such as convergent evolution of multidomain architectures. With this in mind, we study glutaredoxin (GRX domains, because these domains of approximately one hundred amino acids are widespread in archaea, bacteria and eukaryotes and participate in fusion proteins. GRXs are responsible for the reduction of protein disulfides or glutathione-protein mixed disulfides and are involved in cellular redox regulation, although their specific roles and targets are often unclear. Results In this work we analyze the distribution and evolution of GRX proteins in archaea, bacteria and eukaryotes. We study over one thousand GRX proteins, each containing at least one GRX domain, from hundreds of different organisms and trace the origin and evolution of the GRX domain within the tree of life. Conclusion Our results suggest that single domain GRX proteins of the CGFS and CPYC classes have, each, evolved through duplication and divergence from one initial gene that was present in the last common ancestor of all organisms. Remarkably, we identify a case of convergent evolution in domain architecture that involves the GRX domain. Two independent recombination events of a TRX domain to a GRX domain are likely to have occurred, which is an exception to the dominant mechanism of domain architecture evolution.

  3. Domain Wall Evolution in Phase Transforming Oxides

    Science.gov (United States)

    2015-01-14

    Chemically Derived PZT Thin Films on Pt Substrates, Journal of the American Ceramic Society, (09 2014): 2973. doi: 10.1111/jace.13007 Jacob L. Jones...Mari-Ann Einarsrud, D. Johnson. Piezoelectric K0.5Na0.5NbO3 ceramics textured using needle-like K0.5Na0.5NbO3 templates, Journal of the American...Jones. Quantitative comparison between the degree of domain orientation and nonlinear properties of a PZT ceramic during electrical and mechanical

  4. Factorizing the time evolution operator

    International Nuclear Information System (INIS)

    Garcia Quijas, P C; Arevalo Aguilar, L M

    2007-01-01

    There is a widespread belief in the quantum physical community, and textbooks used to teach quantum mechanics, that it is a difficult task to apply the time evolution operator e itH-hat/h on an initial wavefunction. Because the Hamiltonian operator is, generally, the sum of two operators, then it is not possible to apply the time evolution operator on an initial wavefunction ψ(x, 0), for it implies using terms like (a-hat + b-hat). A possible solution is to factorize the time evolution operator and then apply successively the individual exponential operator on the initial wavefunction. However, the exponential operator does not directly factorize, i.e. e a-hat+b-hat ≠ e a-hat e b-hat . In this study we present a useful procedure for factorizing the time evolution operator when the argument of the exponential is a sum of two operators, which obey specific commutation relations. Then, we apply the exponential operator as an evolution operator for the case of elementary unidimensional potentials, like a particle subject to a constant force and a harmonic oscillator. Also, we discuss an apparent paradox concerning the time evolution operator and non-spreading wave packets addressed previously in the literature

  5. The evolution of WRKY transcription factors.

    Science.gov (United States)

    Rinerson, Charles I; Rabara, Roel C; Tripathi, Prateek; Shen, Qingxi J; Rushton, Paul J

    2015-02-27

    The availability of increasing numbers of sequenced genomes has necessitated a re-evaluation of the evolution of the WRKY transcription factor family. Modern day plants descended from a charophyte green alga that colonized the land between 430 and 470 million years ago. The first charophyte genome sequence from Klebsormidium flaccidum filled a gap in the available genome sequences in the plant kingdom between unicellular green algae that typically have 1-3 WRKY genes and mosses that contain 30-40. WRKY genes have been previously found in non-plant species but their occurrence has been difficult to explain. Only two WRKY genes are present in the Klebsormidium flaccidum genome and the presence of a Group IIb gene was unexpected because it had previously been thought that Group IIb WRKY genes first appeared in mosses. We found WRKY transcription factor genes outside of the plant lineage in some diplomonads, social amoebae, fungi incertae sedis, and amoebozoa. This patchy distribution suggests that lateral gene transfer is responsible. These lateral gene transfer events appear to pre-date the formation of the WRKY groups in flowering plants. Flowering plants contain proteins with domains typical for both resistance (R) proteins and WRKY transcription factors. R protein-WRKY genes have evolved numerous times in flowering plants, each type being restricted to specific flowering plant lineages. These chimeric proteins contain not only novel combinations of protein domains but also novel combinations and numbers of WRKY domains. Once formed, R protein WRKY genes may combine different components of signalling pathways that may either create new diversity in signalling or accelerate signalling by short circuiting signalling pathways. We propose that the evolution of WRKY transcription factors includes early lateral gene transfers to non-plant organisms and the occurrence of algal WRKY genes that have no counterparts in flowering plants. We propose two alternative hypotheses

  6. Evolution of SH2 domains and phosphotyrosine signalling networks

    Science.gov (United States)

    Liu, Bernard A.; Nash, Piers D.

    2012-01-01

    Src homology 2 (SH2) domains mediate selective protein–protein interactions with tyrosine phosphorylated proteins, and in doing so define specificity of phosphotyrosine (pTyr) signalling networks. SH2 domains and protein-tyrosine phosphatases expand alongside protein-tyrosine kinases (PTKs) to coordinate cellular and organismal complexity in the evolution of the unikont branch of the eukaryotes. Examination of conserved families of PTKs and SH2 domain proteins provides fiduciary marks that trace the evolutionary landscape for the development of complex cellular systems in the proto-metazoan and metazoan lineages. The evolutionary provenance of conserved SH2 and PTK families reveals the mechanisms by which diversity is achieved through adaptations in tissue-specific gene transcription, altered ligand binding, insertions of linear motifs and the gain or loss of domains following gene duplication. We discuss mechanisms by which pTyr-mediated signalling networks evolve through the development of novel and expanded families of SH2 domain proteins and the elaboration of connections between pTyr-signalling proteins. These changes underlie the variety of general and specific signalling networks that give rise to tissue-specific functions and increasingly complex developmental programmes. Examination of SH2 domains from an evolutionary perspective provides insight into the process by which evolutionary expansion and modification of molecular protein interaction domain proteins permits the development of novel protein-interaction networks and accommodates adaptation of signalling networks. PMID:22889907

  7. Domain organizations of modular extracellular matrix proteins and their evolution.

    Science.gov (United States)

    Engel, J

    1996-11-01

    Multidomain proteins which are composed of modular units are a rather recent invention of evolution. Domains are defined as autonomously folding regions of a protein, and many of them are similar in sequence and structure, indicating common ancestry. Their modular nature is emphasized by frequent repetitions in identical or in different proteins and by a large number of different combinations with other domains. The extracellular matrix is perhaps the largest biological system composed of modular mosaic proteins, and its astonishing complexity and diversity are based on them. A cluster of minireviews on modular proteins is being published in Matrix Biology. These deal with the evolution of modular proteins, the three-dimensional structure of domains and the ways in which these interact in a multidomain protein. They discuss structure-function relationships in calcium binding domains, collagen helices, alpha-helical coiled-coil domains and C-lectins. The present minireview is focused on some general aspects and serves as an introduction to the cluster.

  8. Characterization of Inclusions in Evolution of Sodium Sulfate Using Terahertz Time-domain Spectroscopy.

    Science.gov (United States)

    Bao, Rima; Wu, Zhikui; Li, Hao; Wang, Fang; Miao, Xinyang; Feng, Chengjing

    2017-01-01

    The study of fluid inclusion is one of the important means to understanding the evolution of mineral crystals, and can therefore provide original information of mineral evolution. In the process of evolution, outside factors such as temperature and pressure, directly affect the number and size of inclusions, and thus are related to the properties of crystals. In this paper, terahertz time-domain spectroscopy (THz-TDS) was used to detect sodium sulfate crystals with different growth temperatures, and absorption coefficient spectra of the samples were obtained. It is suggested that the evolution of sodium sulfate could be divided into two stages, and 80°C was the turning point. X-ray diffraction (XRD) and polarizing microscopy were used to support this conclusion. The research showed that THz-TDS could characterize the evolution of mineral crystals, and it had a unique advantage in terms of crystal evolution.

  9. Dynamical evolution of domain walls in an expanding universe

    Science.gov (United States)

    Press, William H.; Ryden, Barbara S.; Spergel, David N.

    1989-01-01

    Whenever the potential of a scalar field has two or more separated, degenerate minima, domain walls form as the universe cools. The evolution of the resulting network of domain walls is calculated for the case of two potential minima in two and three dimensions, including wall annihilation, crossing, and reconnection effects. The nature of the evolution is found to be largely independent of the rate at which the universe expands. Wall annihilation and reconnection occur almost as fast as causality allows, so that the horizon volume is 'swept clean' and contains, at any time, only about one, fairly smooth, wall. Quantitative statistics are given. The total area of wall per volume decreases as the first power of time. The relative slowness of the decrease and the smoothness of the wall on the horizon scale make it impossible for walls to both generate large-scale structure and be consistent with quadrupole microwave background anisotropy limits.

  10. Conserved domains and SINE diversity during animal evolution.

    Science.gov (United States)

    Luchetti, Andrea; Mantovani, Barbara

    2013-10-01

    Eukaryotic genomes harbour a number of mobile genetic elements (MGEs); moving from one genomic location to another, they are known to impact on the host genome. Short interspersed elements (SINEs) are well-represented, non-autonomous retroelements and they are likely the most diversified MGEs. In some instances, sequence domains conserved across unrelated SINEs have been identified; remarkably, one of these, called Nin, has been conserved since the Radiata-Bilateria splitting. Here we report on two new domains: Inv, derived from Nin, identified in insects and in deuterostomes, and Pln, restricted to polyneopteran insects. The identification of Inv and Pln sequences allowed us to retrieve new SINEs, two in insects and one in a hemichordate. The diverse structural combination of the different domains in different SINE families, during metazoan evolution, offers a clearer view of SINE diversity and their frequent de novo emergence through module exchange, possibly underlying the high evolutionary success of SINEs. © 2013 Elsevier Inc. All rights reserved.

  11. Differential evolution and neofunctionalization of snake venom metalloprotease domains.

    Science.gov (United States)

    Brust, Andreas; Sunagar, Kartik; Undheim, Eivind A B; Vetter, Irina; Yang, Daryl C; Yang, Dary C; Casewell, Nicholas R; Jackson, Timothy N W; Koludarov, Ivan; Alewood, Paul F; Hodgson, Wayne C; Lewis, Richard J; King, Glenn F; Antunes, Agostinho; Hendrikx, Iwan; Fry, Bryan G

    2013-03-01

    Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteine-rich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands.

  12. Stress induced magnetic-domain evolution in magnetoelectric composites

    Science.gov (United States)

    Trivedi, Harsh; Shvartsman, Vladimir V.; Lupascu, Doru C.; Medeiros, Marco S. A.; Pullar, Robert C.

    2018-06-01

    Local observation of the stress mediated magnetoelectric (ME) effect in composites has gained a great deal of interest over the last decades. However, there is an apparent lack of rigorous methods for a quantitative characterization of the ME effect at the local scale, especially in polycrystalline microstructures. In the present work, we address this issue by locally probing the surface magnetic state of barium titante–hexagonal barium ferrite (BaTiO3–BaFe12O19) ceramic composites using magnetic force microscopy (MFM). The effect of the piezoelectrically induced local stress on the magnetostrictive component (BaFe12O19, BaM) was observed in the form of the evolution of the magnetic domains. The local piezoelectric stress was induced by applying a voltage to the neighboring BaTiO3 grains, using a conductive atomic force microscopy tip. The resulting stochastic evolution of magnetic domains was studied in the context of the induced magnetoelastic anisotropy. In order to overcome the ambiguity in the domain changes observed by MFM, certain generalizations about the observed MFM contrast are put forward, followed by application of an algorithm for extracting the average micromagnetic changes. An average change in domain wall thickness of 50 nm was extracted, giving a lower limit on the corresponding induced magnetoelastic anisotropy energy. Furthermore, we demonstrate that this induced magnetomechanical energy is approximately equal to the K1 magnetocrystalline anisotropy constant of BaM, and compare it with a modeled value of applied elastic energy density. The comparison allowed us to judge the quality of the interfaces in the composite system, by roughly gauging the energy conversion ratio.

  13. Molecular Evolution of the Oxygen-Binding Hemerythrin Domain.

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    Claudia Alvarez-Carreño

    Full Text Available The evolution of oxygenic photosynthesis during Precambrian times entailed the diversification of strategies minimizing reactive oxygen species-associated damage. Four families of oxygen-carrier proteins (hemoglobin, hemerythrin and the two non-homologous families of arthropodan and molluscan hemocyanins are known to have evolved independently the capacity to bind oxygen reversibly, providing cells with strategies to cope with the evolutionary pressure of oxygen accumulation. Oxygen-binding hemerythrin was first studied in marine invertebrates but further research has made it clear that it is present in the three domains of life, strongly suggesting that its origin predated the emergence of eukaryotes.Oxygen-binding hemerythrins are a monophyletic sub-group of the hemerythrin/HHE (histidine, histidine, glutamic acid cation-binding domain. Oxygen-binding hemerythrin homologs were unambiguously identified in 367/2236 bacterial, 21/150 archaeal and 4/135 eukaryotic genomes. Overall, oxygen-binding hemerythrin homologues were found in the same proportion as single-domain and as long protein sequences. The associated functions of protein domains in long hemerythrin sequences can be classified in three major groups: signal transduction, phosphorelay response regulation, and protein binding. This suggests that in many organisms the reversible oxygen-binding capacity was incorporated in signaling pathways. A maximum-likelihood tree of oxygen-binding hemerythrin homologues revealed a complex evolutionary history in which lateral gene transfer, duplications and gene losses appear to have played an important role.Hemerythrin is an ancient protein domain with a complex evolutionary history. The distinctive iron-binding coordination site of oxygen-binding hemerythrins evolved first in prokaryotes, very likely prior to the divergence of Firmicutes and Proteobacteria, and spread into many bacterial, archaeal and eukaryotic species. The later evolution of the

  14. Structure and evolution of N-domains in AAA metalloproteases.

    Science.gov (United States)

    Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

    2015-02-27

    Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

  15. Evolution of function in the "two dinucleotide binding domains" flavoproteins.

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    Sunil Ojha

    2007-07-01

    Full Text Available Structural and biochemical constraints force some segments of proteins to evolve more slowly than others, often allowing identification of conserved structural or sequence motifs that can be associated with substrate binding properties, chemical mechanisms, and molecular functions. We have assessed the functional and structural constraints imposed by cofactors on the evolution of new functions in a superfamily of flavoproteins characterized by two-dinucleotide binding domains, the "two dinucleotide binding domains" flavoproteins (tDBDF superfamily. Although these enzymes catalyze many different types of oxidation/reduction reactions, each is initiated by a stereospecific hydride transfer reaction between two cofactors, a pyridine nucleotide and flavin adenine dinucleotide (FAD. Sequence and structural analysis of more than 1,600 members of the superfamily reveals new members and identifies details of the evolutionary connections among them. Our analysis shows that in all of the highly divergent families within the superfamily, these cofactors adopt a conserved configuration optimal for stereospecific hydride transfer that is stabilized by specific interactions with amino acids from several motifs distributed among both dinucleotide binding domains. The conservation of cofactor configuration in the active site restricts the pyridine nucleotide to interact with FAD from the re-side, limiting the flow of electrons from the re-side to the si-side. This directionality of electron flow constrains interactions with the different partner proteins of different families to occur on the same face of the cofactor binding domains. As a result, superimposing the structures of tDBDFs aligns not only these interacting proteins, but also their constituent electron acceptors, including heme and iron-sulfur clusters. Thus, not only are specific aspects of the cofactor-directed chemical mechanism conserved across the superfamily, the constraints they impose are

  16. Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

    KAUST Repository

    Wang, Jim Jing-Yan; Gao, Xin

    2014-01-01

    Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

  17. Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-02-01

    Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

  18. Domain-General Factors Influencing Numerical and Arithmetic Processing

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    André Knops

    2017-12-01

    Full Text Available This special issue contains 18 articles that address the question how numerical processes interact with domain-general factors. We start the editorial with a discussion of how to define domain-general versus domain-specific factors and then discuss the contributions to this special issue grouped into two core numerical domains that are subject to domain-general influences (see Figure 1. The first group of contributions addresses the question how numbers interact with spatial factors. The second group of contributions is concerned with factors that determine and predict arithmetic understanding, performance and development. This special issue shows that domain-general (Table 1a as well as domain-specific (Table 1b abilities influence numerical and arithmetic performance virtually at all levels and make it clear that for the field of numerical cognition a sole focus on one or several domain-specific factors like the approximate number system or spatial-numerical associations is not sufficient. Vice versa, in most studies that included domain-general and domain-specific variables, domain-specific numerical variables predicted arithmetic performance above and beyond domain-general variables. Therefore, a sole focus on domain-general aspects such as, for example, working memory, to explain, predict and foster arithmetic learning is also not sufficient. Based on the articles in this special issue we conclude that both domain-general and domain-specific factors contribute to numerical cognition. But the how, why and when of their contribution still needs to be better understood. We hope that this special issue may be helpful to readers in constraining future theory and model building about the interplay of domain-specific and domain-general factors.

  19. Time-Domain Studies as a Probe of Stellar Evolution

    Science.gov (United States)

    Miller, Adam Andrew

    This dissertation focuses on the use of time-domain techniques to discover and characterize these rare astrophysical gems, while also addressing some gaps in our understanding of the earliest and latest stages of stellar evolution. The observational studies presented herein can be grouped into three parts: (i) the study of stellar death (supernovae); (ii) the study of stellar birth; and (iii) the use of modern machine-learning algorithms to discover and classify variable sources. I present observations of supernova (SN) 2006gy, the most luminous SN ever at the time of discovery, and the even-more luminous SN 2008es. Together, these two supernovae (SNe) demonstrate that core-collapse SNe can be significantly more luminous than thermonuclear type Ia SNe, and that there are multiple channels for producing these brilliant core-collapse explosions. For SN 2006gy I show that the progenitor star experienced violent, eruptive mass loss on multiple occasions during the centuries prior to explosion, a scenario that was completely unexpected within the cannon of massive-star evolution theory. I also present observations of SN 2008iy, one of the most unusual SNe ever discovered. Typical SNe take ≲3 weeks to reach peak luminosity; SN 2008iy exhibited a slow and steady rise for ˜400 days before reaching maximum brightness. The best explanation for such behavior is that the progenitor of SN 2008iy experienced an episodic phase of mass loss ˜100 yr prior to explosion. The three SNe detailed in this dissertation have altered our understanding of massive-star mass loss, namely, these SNe provide distinct evidence that post-main sequence mass loss, for at least some massive stars, occurs in sporatic fits, rather than being steady. They also demonstrate that core collapse is not restricted to the red supergiant and Wolf-Rayet stages of stellar evolution as theory predicted. Instead, some massive stars explode while in a luminous blue variable-like state. I also present

  20. SH3 domain tyrosine phosphorylation--sites, role and evolution.

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    Zuzana Tatárová

    Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

  1. Rank-dependant factorization of entanglement evolution

    International Nuclear Information System (INIS)

    Siomau, Michael

    2016-01-01

    Highlights: • In some cases the complex entanglement evolution can be factorized on simple terms. • We suggest factorization equations for multiqubit entanglement evolution. • The factorization is solely defined by the rank of the final state density matrices. • The factorization is independent on the local noisy channels and initial pure states. - Abstract: The description of the entanglement evolution of a complex quantum system can be significantly simplified due to the symmetries of the initial state and the quantum channels, which simultaneously affect parts of the system. Using concurrence as the entanglement measure, we study the entanglement evolution of few qubit systems, when each of the qubits is affected by a local unital channel independently on the others. We found that for low-rank density matrices of the final quantum state, such complex entanglement dynamics can be completely described by a combination of independent factors representing the evolution of entanglement of the initial state, when just one of the qubits is affected by a local channel. We suggest necessary conditions for the rank of the density matrices to represent the entanglement evolution through the factors. Our finding is supported with analytical examples and numerical simulations.

  2. FACTORS INFLUENCING THE EVOLUTION OF YOUTH TRAVEL

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    Student Claudia MOISĂ

    2010-01-01

    Full Text Available Youth travel is an important part of global tourism, consequently, getting to know the evolution of this form of tourism requires an approach of the aspects regarding the permissive and restrictive factors that influence the youth travel dynamic worldwide. In terms of the factors that influence youth travel, we highlighted these two categories of factors (permissive and restrictive and, within each category, we tried to singularize the influence of every factor over youth travel.

  3. Homogenization of the evolution Stokes equation in a perforated domain with a stochastic Fourier boundary condition

    KAUST Repository

    Bessaih, Hakima; Efendiev, Yalchin; Maris, Florin

    2015-01-01

    The evolution Stokes equation in a domain containing periodically distributed obstacles subject to Fourier boundary condition on the boundaries is considered. We assume that the dynamic is driven by a stochastic perturbation on the interior

  4. Birth and upgrowth of the Hox topological domains during evolution

    NARCIS (Netherlands)

    Deschamps, Jacqueline

    The recently discovered chromatin compartments called topologically associating domains (TADs) are essential for the three-dimensional organization of regulatory interactions driving gene expression. A new study documents the emergence of a TAD flanking the amphioxus Hox cluster, prefiguring the

  5. Birth and upgrowth of the Hox topological domains during evolution

    NARCIS (Netherlands)

    Deschamps, J.

    2016-01-01

    The recently discovered chromatin compartments called topologically associating domains (TADs) are essential for the three-dimensional organization of regulatory interactions driving gene expression. A new study documents the emergence of a TAD flanking the amphioxus Hox cluster, prefiguring the

  6. Adaptive evolution of transcription factor binding sites

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    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  7. The diversity and evolution of Wolbachia ankyrin repeat domain genes.

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    Stefanos Siozios

    Full Text Available Ankyrin repeat domain-encoding genes are common in the eukaryotic and viral domains of life, but they are rare in bacteria, the exception being a few obligate or facultative intracellular Proteobacteria species. Despite having a reduced genome, the arthropod strains of the alphaproteobacterium Wolbachia contain an unusually high number of ankyrin repeat domain-encoding genes ranging from 23 in wMel to 60 in wPip strain. This group of genes has attracted considerable attention for their astonishing large number as well as for the fact that ankyrin proteins are known to participate in protein-protein interactions, suggesting that they play a critical role in the molecular mechanism that determines host-Wolbachia symbiotic interactions. We present a comparative evolutionary analysis of the wMel-related ankyrin repeat domain-encoding genes present in different Drosophila-Wolbachia associations. Our results show that the ankyrin repeat domain-encoding genes change in size by expansion and contraction mediated by short directly repeated sequences. We provide examples of intra-genic recombination events and show that these genes are likely to be horizontally transferred between strains with the aid of bacteriophages. These results confirm previous findings that the Wolbachia genomes are evolutionary mosaics and illustrate the potential that these bacteria have to generate diversity in proteins potentially involved in the symbiotic interactions.

  8. Time evolution of one-dimensional gapless models from a domain wall initial state: stochastic Loewner evolution continued?

    International Nuclear Information System (INIS)

    Calabrese, Pasquale; Hagendorf, Christian; Doussal, Pierre Le

    2008-01-01

    We study the time evolution of quantum one-dimensional gapless systems evolving from initial states with a domain wall. We generalize the path integral imaginary time approach that together with boundary conformal field theory allows us to derive the time and space dependence of general correlation functions. The latter are explicitly obtained for the Ising universality class, and the typical behavior of one- and two-point functions is derived for the general case. Possible connections with the stochastic Loewner evolution are discussed and explicit results for one-point time dependent averages are obtained for generic κ for boundary conditions corresponding to stochastic Loewner evolution. We use this set of results to predict the time evolution of the entanglement entropy and obtain the universal constant shift due to the presence of a domain wall in the initial state

  9. Untangling spider silk evolution with spidroin terminal domains

    Directory of Open Access Journals (Sweden)

    Garb Jessica E

    2010-08-01

    Full Text Available Abstract Background Spidroins are a unique family of large, structural proteins that make up the bulk of spider silk fibers. Due to the highly variable nature of their repetitive sequences, spidroin evolutionary relationships have principally been determined from their non-repetitive carboxy (C-terminal domains, though they offer limited character data. The few known spidroin amino (N-terminal domains have been difficult to obtain, but potentially contain critical phylogenetic information for reconstructing the diversification of spider silks. Here we used silk gland expression data (ESTs from highly divergent species to evaluate the functional significance and phylogenetic utility of spidroin N-terminal domains. Results We report 11 additional spidroin N-termini found by sequencing ~1,900 silk gland cDNAs from nine spider species that shared a common ancestor > 240 million years ago. In contrast to their hyper-variable repetitive regions, spidroin N-terminal domains have retained striking similarities in sequence identity, predicted secondary structure, and hydrophobicity. Through separate and combined phylogenetic analyses of N-terminal domains and their corresponding C-termini, we find that combined analysis produces the most resolved trees and that N-termini contribute more support and less conflict than the C-termini. These analyses show that paralogs largely group by silk gland type, except for the major ampullate spidroins. Moreover, spidroin structural motifs associated with superior tensile strength arose early in the history of this gene family, whereas a motif conferring greater extensibility convergently evolved in two distantly related paralogs. Conclusions A non-repetitive N-terminal domain appears to be a universal attribute of spidroin proteins, likely retained from the origin of spider silk production. Since this time, spidroin N-termini have maintained several features, consistent with this domain playing a key role in silk

  10. Evolution of the PWWP-domain encoding genes in the plant and animal lineages

    Directory of Open Access Journals (Sweden)

    Alvarez-Venegas Raúl

    2012-06-01

    Full Text Available Abstract Background Conserved domains are recognized as the building blocks of eukaryotic proteins. Domains showing a tendency to occur in diverse combinations (‘promiscuous’ domains are involved in versatile architectures in proteins with different functions. Current models, based on global-level analyses of domain combinations in multiple genomes, have suggested that the propensity of some domains to associate with other domains in high-level architectures increases with organismal complexity. Alternative models using domain-based phylogenetic trees propose that domains have become promiscuous independently in different lineages through convergent evolution and are, thus, random with no functional or structural preferences. Here we test whether complex protein architectures have occurred by accretion from simpler systems and whether the appearance of multidomain combinations parallels organismal complexity. As a model, we analyze the modular evolution of the PWWP domain and ask whether its appearance in combinations with other domains into multidomain architectures is linked with the occurrence of more complex life-forms. Whether high-level combinations of domains are conserved and transmitted as stable units (cassettes through evolution is examined in the genomes of plant or metazoan species selected for their established position in the evolution of the respective lineages. Results Using the domain-tree approach, we analyze the evolutionary origins and distribution patterns of the promiscuous PWWP domain to understand the principles of its modular evolution and its existence in combination with other domains in higher-level protein architectures. We found that as a single module the PWWP domain occurs only in proteins with a limited, mainly, species-specific distribution. Earlier, it was suggested that domain promiscuity is a fast-changing (volatile feature shaped by natural selection and that only a few domains retain their promiscuity

  11. Reassessing Domain Architecture Evolution of Metazoan Proteins: The Contribution of Different Evolutionary Mechanisms

    Directory of Open Access Journals (Sweden)

    Laszlo Patthy

    2011-08-01

    Full Text Available In the accompanying papers we have shown that sequence errors of public databases and confusion of paralogs and epaktologs (proteins that are related only through the independent acquisition of the same domain types significantly distort the picture that emerges from comparison of the domain architecture (DA of multidomain Metazoan proteins since they introduce a strong bias in favor of terminal over internal DA change. The issue of whether terminal or internal DA changes occur with greater probability has very important implications for the DA evolution of multidomain proteins since gene fusion can add domains only at terminal positions, whereas domain-shuffling is capable of inserting domains both at internal and terminal positions. As a corollary, overestimation of terminal DA changes may be misinterpreted as evidence for a dominant role of gene fusion in DA evolution. In this manuscript we show that in several recent studies of DA evolution of Metazoa the authors used databases that are significantly contaminated with incomplete, abnormal and mispredicted sequences (e.g., UniProtKB/TrEMBL, EnsEMBL and/or the authors failed to separate paralogs and epaktologs, explaining why these studies concluded that the major mechanism for gains of new domains in metazoan proteins is gene fusion. In contrast with the latter conclusion, our studies on high quality orthologous and paralogous Swiss-Prot sequences confirm that shuffling of mobile domains had a major role in the evolution of multidomain proteins of Metazoa and especially those formed in early vertebrates.

  12. Possible description of domain walls in two-dimensional spin glasses by stochastic Loewner evolutions

    International Nuclear Information System (INIS)

    Bernard, Denis; Le Doussal, Pierre; Middleton, A. Alan

    2007-01-01

    Domain walls for spin glasses are believed to be scale invariant; a stronger symmetry, conformal invariance, has the potential to hold. The statistics of zero-temperature Ising spin glass domain walls in two dimensions are used to test the hypothesis that these domain walls are described by a Schramm-Loewner evolution SLE κ . Multiple tests are consistent with SLE κ , where κ=2.32±0.08. Both conformal invariance and the domain Markov property are tested. The latter does not hold in small systems, but detailed numerical evidence suggests that it holds in the continuum limit

  13. Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

    International Nuclear Information System (INIS)

    Cohen-Gihon, Inbar; Nussinov, Ruth; Sharan, Roded

    2011-01-01

    During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

  14. Magnetic bubbles and domain evolution in Fe/Gd multilayer nanodots

    Science.gov (United States)

    Wang, T. T.; Liu, W.; Dai, Z. M.; Zhao, X. T.; Zhao, X. G.; Zhang, Z. D.

    2018-04-01

    The formation of magnetic bubbles and the domain-evolution processes, induced by a perpendicular magnetic field in Fe/Gd multilayer films and nanodots, have been investigated. At room temperature, the stripe domains in a continuous film transform into magnetic bubbles in an external field, while bubbles form spontaneously in nanodots due to the existence of shape anisotropy. When the temperature decreases to 20 K, the enhancement of the perpendicular magnetic anisotropy of the samples results in an increase of the domain size in the continuous film and the magnetization-reversal behavior of each nanodot becomes independent, and most reversed dots do not depend on each other, indicating the magnetic characteristics of a single domain. The present research provides further understanding of the evolution of magnetic bubbles in the Fe/Gd system and suggests their promising applications in patterned recording materials.

  15. Protein domain evolution is associated with reproductive diversification and adaptive radiation in the genus Eucalyptus.

    Science.gov (United States)

    Kersting, Anna R; Mizrachi, Eshchar; Bornberg-Bauer, Erich; Myburg, Alexander A

    2015-06-01

    Eucalyptus is a pivotal genus within the rosid order Myrtales with distinct geographic history and adaptations. Comparative analysis of protein domain evolution in the newly sequenced Eucalyptus grandis genome and other rosid lineages sheds light on the adaptive mechanisms integral to the success of this genus of woody perennials. We reconstructed the ancestral domain content to elucidate the gain, loss and expansion of protein domains and domain arrangements in Eucalyptus in the context of rosid phylogeny. We used functional gene ontology (GO) annotation of genes to investigate the possible biological and evolutionary consequences of protein domain expansion. We found that protein modulation within the angiosperms occurred primarily on the level of expansion of certain domains and arrangements. Using RNA-Seq data from E. grandis, we showed that domain expansions have contributed to tissue-specific expression of tandemly duplicated genes. Our results indicate that tandem duplication of genes, a key feature of the Eucalyptus genome, has played an important role in the expansion of domains, particularly in proteins related to the specialization of reproduction and biotic and abiotic interactions affecting root and floral biology, and that tissue-specific expression of proteins with expanded domains has facilitated subfunctionalization in domain families. © 2014 University of Pretoria New Phytologist © 2014 New Phytologist Trust.

  16. Perturbative evolution of particle orbits around Kerr black holes: time-domain calculation

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Aleman, Ramon [Physical Sciences Department, University of Puerto Rico-Rio Piedras, San Juan, PR 00931 (Puerto Rico); Khanna, Gaurav [Natural Science Division, Long Island University, Southampton, NY 11968 (United States); Pullin, Jorge [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States)

    2003-07-21

    We consider the problem of the gravitational waves produced by a particle of negligible mass orbiting a Kerr black hole. We treat the Teukolsky perturbation equation in the time domain numerically as a 2 + 1 partial differential equation. We model the particle by smearing the singularities in the source term by the use of narrow Gaussian distributions. We have been able to reproduce earlier results for equatorial circular orbits that were computed using the frequency-domain formalism. The time-domain approach is however geared for a more general evolution, for instance of nearly geodesic orbits under the effects of radiation reaction.

  17. Perturbative evolution of particle orbits around Kerr black holes: time-domain calculation

    International Nuclear Information System (INIS)

    Lopez-Aleman, Ramon; Khanna, Gaurav; Pullin, Jorge

    2003-01-01

    We consider the problem of the gravitational waves produced by a particle of negligible mass orbiting a Kerr black hole. We treat the Teukolsky perturbation equation in the time domain numerically as a 2 + 1 partial differential equation. We model the particle by smearing the singularities in the source term by the use of narrow Gaussian distributions. We have been able to reproduce earlier results for equatorial circular orbits that were computed using the frequency-domain formalism. The time-domain approach is however geared for a more general evolution, for instance of nearly geodesic orbits under the effects of radiation reaction

  18. Molecular representation of molar domain (volume), evolution equations, and linear constitutive relations for volume transport.

    Science.gov (United States)

    Eu, Byung Chan

    2008-09-07

    In the traditional theories of irreversible thermodynamics and fluid mechanics, the specific volume and molar volume have been interchangeably used for pure fluids, but in this work we show that they should be distinguished from each other and given distinctive statistical mechanical representations. In this paper, we present a general formula for the statistical mechanical representation of molecular domain (volume or space) by using the Voronoi volume and its mean value that may be regarded as molar domain (volume) and also the statistical mechanical representation of volume flux. By using their statistical mechanical formulas, the evolution equations of volume transport are derived from the generalized Boltzmann equation of fluids. Approximate solutions of the evolution equations of volume transport provides kinetic theory formulas for the molecular domain, the constitutive equations for molar domain (volume) and volume flux, and the dissipation of energy associated with volume transport. Together with the constitutive equation for the mean velocity of the fluid obtained in a previous paper, the evolution equations for volume transport not only shed a fresh light on, and insight into, irreversible phenomena in fluids but also can be applied to study fluid flow problems in a manner hitherto unavailable in fluid dynamics and irreversible thermodynamics. Their roles in the generalized hydrodynamics will be considered in the sequel.

  19. Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture

    Directory of Open Access Journals (Sweden)

    Matteo Vietri Rudan

    2015-03-01

    Full Text Available Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics are not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C in four mammals and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, are enriched at strong topological domain borders, and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Conversely, divergent CTCF binding between species is correlated with divergence of internal domain structure, likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked to a continuous flux of local conformation changes. We also show that large-scale domains are reorganized during genome evolution as intact modules.

  20. Universal features in the genome-level evolution of protein domains.

    Science.gov (United States)

    Cosentino Lagomarsino, Marco; Sellerio, Alessandro L; Heijning, Philip D; Bassetti, Bruno

    2009-01-01

    Protein domains can be used to study proteome evolution at a coarse scale. In particular, they are found on genomes with notable statistical distributions. It is known that the distribution of domains with a given topology follows a power law. We focus on a further aspect: these distributions, and the number of distinct topologies, follow collective trends, or scaling laws, depending on the total number of domains only, and not on genome-specific features. We present a stochastic duplication/innovation model, in the class of the so-called 'Chinese restaurant processes', that explains this observation with two universal parameters, representing a minimal number of domains and the relative weight of innovation to duplication. Furthermore, we study a model variant where new topologies are related to occurrence in genomic data, accounting for fold specificity. Both models have general quantitative agreement with data from hundreds of genomes, which indicates that the domains of a genome are built with a combination of specificity and robust self-organizing phenomena. The latter are related to the basic evolutionary 'moves' of duplication and innovation, and give rise to the observed scaling laws, a priori of the specific evolutionary history of a genome. We interpret this as the concurrent effect of neutral and selective drives, which increase duplication and decrease innovation in larger and more complex genomes. The validity of our model would imply that the empirical observation of a small number of folds in nature may be a consequence of their evolution.

  1. Birth and death of protein domains: A simple model of evolution explains power law behavior

    Directory of Open Access Journals (Sweden)

    Berezovskaya Faina S

    2002-10-01

    Full Text Available Abstract Background Power distributions appear in numerous biological, physical and other contexts, which appear to be fundamentally different. In biology, power laws have been claimed to describe the distributions of the connections of enzymes and metabolites in metabolic networks, the number of interactions partners of a given protein, the number of members in paralogous families, and other quantities. In network analysis, power laws imply evolution of the network with preferential attachment, i.e. a greater likelihood of nodes being added to pre-existing hubs. Exploration of different types of evolutionary models in an attempt to determine which of them lead to power law distributions has the potential of revealing non-trivial aspects of genome evolution. Results A simple model of evolution of the domain composition of proteomes was developed, with the following elementary processes: i domain birth (duplication with divergence, ii death (inactivation and/or deletion, and iii innovation (emergence from non-coding or non-globular sequences or acquisition via horizontal gene transfer. This formalism can be described as a birth, death and innovation model (BDIM. The formulas for equilibrium frequencies of domain families of different size and the total number of families at equilibrium are derived for a general BDIM. All asymptotics of equilibrium frequencies of domain families possible for the given type of models are found and their appearance depending on model parameters is investigated. It is proved that the power law asymptotics appears if, and only if, the model is balanced, i.e. domain duplication and deletion rates are asymptotically equal up to the second order. It is further proved that any power asymptotic with the degree not equal to -1 can appear only if the hypothesis of independence of the duplication/deletion rates on the size of a domain family is rejected. Specific cases of BDIMs, namely simple, linear, polynomial and rational

  2. Effects of biases in domain wall network evolution. II. Quantitative analysis

    Science.gov (United States)

    Correia, J. R. C. C. C.; Leite, I. S. C. R.; Martins, C. J. A. P.

    2018-04-01

    Domain walls form at phase transitions which break discrete symmetries. In a cosmological context, they often overclose the Universe (contrary to observational evidence), although one may prevent this by introducing biases or forcing anisotropic evolution of the walls. In a previous work [Correia et al., Phys. Rev. D 90, 023521 (2014), 10.1103/PhysRevD.90.023521], we numerically studied the evolution of various types of biased domain wall networks in the early Universe, confirming that anisotropic networks ultimately reach scaling while those with a biased potential or biased initial conditions decay. We also found that the analytic decay law obtained by Hindmarsh was in good agreement with simulations of biased potentials, but not of biased initial conditions, and suggested that the difference was related to the Gaussian approximation underlying the analytic law. Here, we extend our previous work in several ways. For the cases of biased potential and biased initial conditions, we study in detail the field distributions in the simulations, confirming that the validity (or not) of the Gaussian approximation is the key difference between the two cases. For anisotropic walls, we carry out a more extensive set of numerical simulations and compare them to the canonical velocity-dependent one-scale model for domain walls, finding that the model accurately predicts the linear scaling regime after isotropization. Overall, our analysis provides a quantitative description of the cosmological evolution of these networks.

  3. Homogenization of the evolution Stokes equation in a perforated domain with a stochastic Fourier boundary condition

    KAUST Repository

    Bessaih, Hakima

    2015-04-01

    The evolution Stokes equation in a domain containing periodically distributed obstacles subject to Fourier boundary condition on the boundaries is considered. We assume that the dynamic is driven by a stochastic perturbation on the interior of the domain and another stochastic perturbation on the boundaries of the obstacles. We represent the solid obstacles by holes in the fluid domain. The macroscopic (homogenized) equation is derived as another stochastic partial differential equation, defined in the whole non perforated domain. Here, the initial stochastic perturbation on the boundary becomes part of the homogenized equation as another stochastic force. We use the twoscale convergence method after extending the solution with 0 in the holes to pass to the limit. By Itô stochastic calculus, we get uniform estimates on the solution in appropriate spaces. In order to pass to the limit on the boundary integrals, we rewrite them in terms of integrals in the whole domain. In particular, for the stochastic integral on the boundary, we combine the previous idea of rewriting it on the whole domain with the assumption that the Brownian motion is of trace class. Due to the particular boundary condition dealt with, we get that the solution of the stochastic homogenized equation is not divergence free. However, it is coupled with the cell problem that has a divergence free solution. This paper represents an extension of the results of Duan and Wang (Comm. Math. Phys. 275:1508-1527, 2007), where a reaction diffusion equation with a dynamical boundary condition with a noise source term on both the interior of the domain and on the boundary was studied, and through a tightness argument and a pointwise two scale convergence method the homogenized equation was derived. © American Institute of Mathematical Sciences.

  4. Evolution of Parallel Spindles Like genes in plants and highlight of unique domain architecture#

    Directory of Open Access Journals (Sweden)

    Consiglio Federica M

    2011-03-01

    Full Text Available Abstract Background Polyploidy has long been recognized as playing an important role in plant evolution. In flowering plants, the major route of polyploidization is suggested to be sexual through gametes with somatic chromosome number (2n. Parallel Spindle1 gene in Arabidopsis thaliana (AtPS1 was recently demonstrated to control spindle orientation in the 2nd division of meiosis and, when mutated, to induce 2n pollen. Interestingly, AtPS1 encodes a protein with a FHA domain and PINc domain putatively involved in RNA decay (i.e. Nonsense Mediated mRNA Decay. In potato, 2n pollen depending on parallel spindles was described long time ago but the responsible gene has never been isolated. The knowledge derived from AtPS1 as well as the availability of genome sequences makes it possible to isolate potato PSLike (PSL and to highlight the evolution of PSL family in plants. Results Our work leading to the first characterization of PSLs in potato showed a greater PSL complexity in this species respect to Arabidopsis thaliana. Indeed, a genomic PSL locus and seven cDNAs affected by alternative splicing have been cloned. In addition, the occurrence of at least two other PSL loci in potato was suggested by the sequence comparison of alternatively spliced transcripts. Phylogenetic analysis on 20 Viridaeplantae showed the wide distribution of PSLs throughout the species and the occurrence of multiple copies only in potato and soybean. The analysis of PSLFHA and PSLPINc domains evidenced that, in terms of secondary structure, a major degree of variability occurred in PINc domain respect to FHA. In terms of specific active sites, both domains showed diversification among plant species that could be related to a functional diversification among PSL genes. In addition, some specific active sites were strongly conserved among plants as supported by sequence alignment and by evidence of negative selection evaluated as difference between non-synonymous and

  5. General purpose graphics-processing-unit implementation of cosmological domain wall network evolution.

    Science.gov (United States)

    Correia, J R C C C; Martins, C J A P

    2017-10-01

    Topological defects unavoidably form at symmetry breaking phase transitions in the early universe. To probe the parameter space of theoretical models and set tighter experimental constraints (exploiting the recent advances in astrophysical observations), one requires more and more demanding simulations, and therefore more hardware resources and computation time. Improving the speed and efficiency of existing codes is essential. Here we present a general purpose graphics-processing-unit implementation of the canonical Press-Ryden-Spergel algorithm for the evolution of cosmological domain wall networks. This is ported to the Open Computing Language standard, and as a consequence significant speedups are achieved both in two-dimensional (2D) and 3D simulations.

  6. General purpose graphics-processing-unit implementation of cosmological domain wall network evolution

    Science.gov (United States)

    Correia, J. R. C. C. C.; Martins, C. J. A. P.

    2017-10-01

    Topological defects unavoidably form at symmetry breaking phase transitions in the early universe. To probe the parameter space of theoretical models and set tighter experimental constraints (exploiting the recent advances in astrophysical observations), one requires more and more demanding simulations, and therefore more hardware resources and computation time. Improving the speed and efficiency of existing codes is essential. Here we present a general purpose graphics-processing-unit implementation of the canonical Press-Ryden-Spergel algorithm for the evolution of cosmological domain wall networks. This is ported to the Open Computing Language standard, and as a consequence significant speedups are achieved both in two-dimensional (2D) and 3D simulations.

  7. Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases

    Science.gov (United States)

    Lamb, Brian M.; Mercer, Andrew C.; Barbas, Carlos F.

    2013-01-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5′-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5′ T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5′ T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes. PMID:23980031

  8. Directed evolution of the TALE N-terminal domain for recognition of all 5' bases.

    Science.gov (United States)

    Lamb, Brian M; Mercer, Andrew C; Barbas, Carlos F

    2013-11-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5' T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5' T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes.

  9. Factors Potentially Influencing Student Acceptance of Biological Evolution

    Science.gov (United States)

    Wiles, Jason R.

    This investigation explored scientific, religious, and otherwise nonscientific factors that may influence student acceptance of biological evolution and related concepts, how students perceived these factors to have influenced their levels of acceptance of evolution and changes therein, and what patterns arose among students' articulations of how their levels of acceptance of evolution may have changed. This exploration also measured the extent to which students' levels of acceptance changed following a treatment designed to address factors identified as potentially affecting student acceptance of evolution. Acceptance of evolution was measured using the MATE instrument (Rutledge and Warden, 1999; Rutledge and Sadler, 2007) among participants enrolled in a secondary-level academic program during the summer prior to their final year of high school and as they transitioned to the post-secondary level. Student acceptance of evolution was measured to be significantly higher than pre-treatment levels both immediately following and slightly over one year after treatment. Qualitative data from informal questionnaires, from formal course evaluations, and from semi-structured interviews of students engaged in secondary level education and former students at various stages of post-secondary education confirmed that the suspected factors were perceived by participants to have influenced their levels of acceptance of evolution. Furthermore, participant reports provided insight regarding the relative effects they perceived these factors to have had on their evolution acceptance levels. Additionally, many participants reported that their science teachers in public schools had avoided, omitted, or denigrated evolution during instruction, and several of these students expressed frustration regarding what they perceived to have been a lack of education of an important scientific principle. Finally, no students expressed feelings of being offended by having been taught about

  10. Wavelength Selection Method Based on Differential Evolution for Precise Quantitative Analysis Using Terahertz Time-Domain Spectroscopy.

    Science.gov (United States)

    Li, Zhi; Chen, Weidong; Lian, Feiyu; Ge, Hongyi; Guan, Aihong

    2017-12-01

    Quantitative analysis of component mixtures is an important application of terahertz time-domain spectroscopy (THz-TDS) and has attracted broad interest in recent research. Although the accuracy of quantitative analysis using THz-TDS is affected by a host of factors, wavelength selection from the sample's THz absorption spectrum is the most crucial component. The raw spectrum consists of signals from the sample and scattering and other random disturbances that can critically influence the quantitative accuracy. For precise quantitative analysis using THz-TDS, the signal from the sample needs to be retained while the scattering and other noise sources are eliminated. In this paper, a novel wavelength selection method based on differential evolution (DE) is investigated. By performing quantitative experiments on a series of binary amino acid mixtures using THz-TDS, we demonstrate the efficacy of the DE-based wavelength selection method, which yields an error rate below 5%.

  11. Multipass forging of Inconel 718 in the delta-Supersolvus domain: assessing and modeling microstructure evolution

    Directory of Open Access Journals (Sweden)

    Zouari Meriem

    2014-01-01

    Full Text Available This work is focused on the evolution of the microstructure of Inconel 718 during multi-pass forging processes. During the forming process, the material is subjected to several physical phenomena such as work-hardening, recovery, recrystallization and grain growth. In this work, transformation kinetics are modeled in the δ-Supersolvus domain (T>Tsolvus where the alloy is single-phase, all the alloying elements being dissolved into the FCC matrix. Torsion tests were used to simulate the forging process and recrystallization kinetics was modeled using a discontinuous dynamic recrystallization (DDRX two-site mean field model. The microstructure evolution under hot forging conditions is predicted in both dynamic and post-dynamic regimes based on the initial distribution of grain size and the evolution of dislocation density distribution during each step of the process. The model predicts recrystallization kinetics, recrystallized grain size distribution and stress–strain curve for different thermo-mechanical conditions and makes the connection between dynamic and post-dynamic regimes.

  12. Probing the Role of Loops & Domains in Regulating Coagulation Factor VIIa Allostery and Specificity

    DEFF Research Database (Denmark)

    Sørensen, Anders Bundgård

    2016-01-01

    The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo).......The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo)....

  13. Study of magnetic domain evolution in an auxetic plane of Galfenol using Kerr microscopy

    Science.gov (United States)

    Raghunath, Ganesh; Flatau, Alison B.

    2015-05-01

    Galfenol (FexGa100-x), a magnetostrictive alloy (3/2λ 110-400 ppm) of Iron and Gallium exhibits an in-plane auxetic response in the ⟨110⟩ crystallographic direction. Negative Poisson's ratios have been observed in response to application of stress fields, where values of as low as -0.7 have been reported for compositions of greater than roughly 20% Ga [Zhang et al., J. Appl. Phys. 108(2), 023513 (2010)] and in response to application of magnetic fields, where values of as low as -2.5 have been reported to be expected for compositions of less than roughly 20% Ga [G. Raghunath and A. B. Flatau, IEEE Trans. Magn. (in press)]. Several models have been proposed to understand these two distinct phenomena. Galfenol samples with less than 20% Ga also exhibit an unusual response to an increasing magnetic field applied along the ⟨110⟩ direction. The longitudinal strain which increases initially with applied field experiences a dip (until ˜10 mT) before increasing again to reach saturation. The transverse strain increases and reaches a maximum value (at the same field of ˜10 mT) and then drops from the maximum by 5%-10% as magnetic saturation is approached [G. Raghunath and A. B. Flatau, IEEE Trans. Magn. (in press)].This work deals with discussing the evolution of magnetic domains in a 16 at. % Ga single crystal Galfenol sample when subjected to magnetic fields in the ⟨110⟩ direction in the (100) plane. The magnetic domains on the surface of mechanically polished Galfenol samples were imaged using Magneto-Optic Kerr Effect microscopy. Simultaneously, the strains along the longitudinal and transverse ⟨110⟩ directions were recorded using a bi-directional strain gauge rosette mounted on the unpolished bottom surface of the planar samples. The energy from the applied magnetic field is expected to grow the ⟨110⟩ oriented domains at the expense of domains oriented along all other directions. But since the plane has an easy ⟨100⟩ axis, we expect the

  14. Neogene palaeogeography and basin evolution of the Western Carpathians, Northern Pannonian domain and adjoining areas

    Science.gov (United States)

    Kováč, Michal; Márton, Emő; Oszczypko, Nestor; Vojtko, Rastislav; Hók, Jozef; Králiková, Silvia; Plašienka, Dušan; Klučiar, Tomáš; Hudáčková, Natália; Oszczypko-Clowes, Marta

    2017-08-01

    The data on the Neogene geodynamics, palaeogeography, and basin evolution of the Western Carpathians, Northern Pannonian domain and adjoining areas (ALCAPA Mega-unit) are summarized, re-evaluated, supplemented, and newly interpreted. The proposed concept is illustrated by a series of palinspastic and palaeotopographic maps. The Miocene development of the Outer Carpathians reflects the vanishing subduction of the residual oceanic and/or thinned continental crust. A compression perpendicular to the front of the orogenic system led to the closing of residual flysch troughs and to accretionary wedge growth, as well as to the development of a foredeep on the margin of the European Platform. Docking of the Outer Western Carpathians accretionary wedge, together with the Central Western Carpathians and Northern Pannonian domain, was accompanied by stretching of the overriding microplate. An orogen parallel and perpendicular extension was associated with the opening and subsidence of the Early and Middle Miocene hinterland (back-arc) basin system that compensated counter-clockwise rotations of the individual crustal fragments of ALCAPA. The Late Miocene development relates to the opening of the Pannonian Basin System. This process was coupled with common stretching of both ALCAPA and Tisza-Dacia Mega-units due to the pull exerted by subduction rollback in front of the Eastern Carpathians. The filling up of the hinterland basin system was associated with thermal subsidence and was followed by the Pliocene tectonic inversion and consequent erosion of the basin system margins, as well as part of the interior.

  15. Characterization and Evolution of the Cell Cycle-Associated Mob Domain-Containing Proteins in Eukaryotes

    Directory of Open Access Journals (Sweden)

    Nicola Vitulo

    2007-01-01

    Full Text Available The MOB family includes a group of cell cycle-associated proteins highly conserved throughout eukaryotes, whose founding members are implicated in mitotic exit and co-ordination of cell cycle progression with cell polarity and morphogenesis. Here we report the characterization and evolution of the MOB domain-containing proteins as inferred from the 43 eukaryotic genomes so far sequenced. We show that genes for Mob-like proteins are present in at least 41 of these genomes, confi rming the universal distribution of this protein family and suggesting its prominent biological function. The phylogenetic analysis reveals fi ve distinct MOB domain classes, showing a progressive expansion of this family from unicellular to multicellular organisms, reaching the highest number in mammals. Plant Mob genes appear to have evolved from a single ancestor, most likely after the loss of one or more genes during the early stage of Viridiplantae evolutionary history. Three of the Mob classes are widespread among most of the analyzed organisms. The possible biological and molecular function of Mob proteins and their role in conserved signaling pathways related to cell proliferation, cell death and cell polarity are also presented and critically discussed.

  16. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    A review is given of the factors determining placental oxygen transfer and the oxygen supply to the fetus. In the case of continuous variables, such as the rate of placental blood flow, it is not possible to trace evolutionary trends. Discontinuous variables, for which we can define character sta......, where fetal and adult haemoglobin are not different, developmental regulation of 2, 3-diphosphoglycerate ensures the high oxygen affinity of fetal blood. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the type of interhaemal barrier. It has been shown...

  17. An optimized digital watermarking algorithm in wavelet domain based on differential evolution for color image.

    Science.gov (United States)

    Cui, Xinchun; Niu, Yuying; Zheng, Xiangwei; Han, Yingshuai

    2018-01-01

    In this paper, a new color watermarking algorithm based on differential evolution is proposed. A color host image is first converted from RGB space to YIQ space, which is more suitable for the human visual system. Then, apply three-level discrete wavelet transformation to luminance component Y and generate four different frequency sub-bands. After that, perform singular value decomposition on these sub-bands. In the watermark embedding process, apply discrete wavelet transformation to a watermark image after the scrambling encryption processing. Our new algorithm uses differential evolution algorithm with adaptive optimization to choose the right scaling factors. Experimental results show that the proposed algorithm has a better performance in terms of invisibility and robustness.

  18. Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

    Science.gov (United States)

    Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

    2013-12-01

    AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

  19. Thermal-driven evolution of magnetic domain structures in ultrathin films

    Czech Academy of Sciences Publication Activity Database

    Zablotskyy, Vitaliy A.; Maziewski, A.; Polyakova, T.

    2006-01-01

    Roč. 112, - (2006), s. 101-108 ISSN 1012-0394. [International School on Physics and Chemistry of Condensed Matter /17./ and International Symposium on Physics in Material Science /5./. Bialoweza, 21.06.2005-29.06.2005] EU Projects: European Commission(XE) 3177 - NANOMAG- LAB Grant - others:PSCSR(PL) 4T11B00624 Institutional research plan: CEZ:AV0Z10100520 Keywords : ultrathin magnetic films * magnetic domain * phase transitions Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.493, year: 2005

  20. Molecular evolution of the primate antiviral restriction factor tetherin.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available BACKGROUND: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu. It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red-queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implying that the primate Tetherin may retain broad spectrum of antiviral activity by maintaining structure stability. CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of Tetherin may be attributed to the host-virus arms race, supporting the Red Queen hypothesis, and Tetherin may be in an intermediate stage in transition from neutral to pervasive

  1. Evolution effects of the copper surface morphology on the nucleation density and growth of graphene domains at different growth pressures

    Energy Technology Data Exchange (ETDEWEB)

    Hedayat, Seyed Mahdi [Transport Phenomena & Nanotechnology Lab., School of Chemical Engineering, College of Engineering, University of Tehran (Iran, Islamic Republic of); Karimi-Sabet, Javad, E-mail: j_karimi@alum.sharif.edu [NFCRS, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Shariaty-Niassar, Mojtaba, E-mail: mshariat@ut.ac.ir [Transport Phenomena & Nanotechnology Lab., School of Chemical Engineering, College of Engineering, University of Tehran (Iran, Islamic Republic of)

    2017-03-31

    Highlights: • Manipulation of the Cu surface morphology in a wide range by electropolishing treatment. • Comparison of the nucleation density of graphene at low pressure and atmospheric pressure CVD processes. • Controlling the evolution of the Cu surface morphology inside a novel confined space. • Growth of large-size graphene domains. - Abstract: In this work, we study the influence of the surface morphology of the catalytic copper substrate on the nucleation density and the growth rate of graphene domains at low and atmospheric pressure chemical vapor deposition (LPCVD and APCVD) processes. In order to obtain a wide range of initial surface morphology, precisely controlled electropolishing methods were developed to manipulate the roughntreess value of the as-received Cu substrate (RMS = 30 nm) to ultra-rough (RMS = 130 nm) and ultra-smooth (RMS = 2 nm) surfaces. The nucleation and growth of graphene domains show obviously different trends at LPCVD and APCVD conditions. In contrast to APCVD condition, the nucleation density of graphene domains is almost equal in substrates with different initial roughness values at LPCVD condition. We show that this is due to the evolution of the surface morphology of the Cu substrate during the graphene growth steps. By stopping the surface sublimation of copper substrate in a confined space saturated with Cu atoms, the evolution of the Cu surface was impeded. This results in the reduction of the nucleation density of graphene domains up to 24 times in the pre-smoothed Cu substrates at LPCVD condition.

  2. Evolution effects of the copper surface morphology on the nucleation density and growth of graphene domains at different growth pressures

    International Nuclear Information System (INIS)

    Hedayat, Seyed Mahdi; Karimi-Sabet, Javad; Shariaty-Niassar, Mojtaba

    2017-01-01

    Highlights: • Manipulation of the Cu surface morphology in a wide range by electropolishing treatment. • Comparison of the nucleation density of graphene at low pressure and atmospheric pressure CVD processes. • Controlling the evolution of the Cu surface morphology inside a novel confined space. • Growth of large-size graphene domains. - Abstract: In this work, we study the influence of the surface morphology of the catalytic copper substrate on the nucleation density and the growth rate of graphene domains at low and atmospheric pressure chemical vapor deposition (LPCVD and APCVD) processes. In order to obtain a wide range of initial surface morphology, precisely controlled electropolishing methods were developed to manipulate the roughntreess value of the as-received Cu substrate (RMS = 30 nm) to ultra-rough (RMS = 130 nm) and ultra-smooth (RMS = 2 nm) surfaces. The nucleation and growth of graphene domains show obviously different trends at LPCVD and APCVD conditions. In contrast to APCVD condition, the nucleation density of graphene domains is almost equal in substrates with different initial roughness values at LPCVD condition. We show that this is due to the evolution of the surface morphology of the Cu substrate during the graphene growth steps. By stopping the surface sublimation of copper substrate in a confined space saturated with Cu atoms, the evolution of the Cu surface was impeded. This results in the reduction of the nucleation density of graphene domains up to 24 times in the pre-smoothed Cu substrates at LPCVD condition.

  3. Incorporating evolution of transcription factor binding sites into ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Identifying transcription factor binding sites (TFBSs) is essential to elucidate ... alignments with parts annotated as gap lessly aligned TFBSs (pair-profile hits) are generated. Moreover, the pair- profile related parameters are derived in a sound statistical framework. ... Much research has gone into the study of the evolution of.

  4. Heavy quarkonium production at collider energies: Factorization and evolution

    Science.gov (United States)

    Kang, Zhong-Bo; Ma, Yan-Qing; Qiu, Jian-Wei; Sterman, George

    2014-08-01

    We present a perturbative QCD factorization formalism for inclusive production of heavy quarkonia of large transverse momentum, pT at collider energies, including both leading power (LP) and next-to-leading power (NLP) behavior in pT. We demonstrate that both LP and NLP contributions can be factorized in terms of perturbatively calculable short-distance partonic coefficient functions and universal nonperturbative fragmentation functions, and derive the evolution equations that are implied by the factorization. We identify projection operators for all channels of the factorized LP and NLP infrared safe short-distance partonic hard parts, and corresponding operator definitions of fragmentation functions. For the NLP, we focus on the contributions involving the production of a heavy quark pair, a necessary condition for producing a heavy quarkonium. We evaluate the first nontrivial order of evolution kernels for all relevant fragmentation functions, and discuss the role of NLP contributions.

  5. Structural organization and chromosomal assignment of the mouse embryonic TEA domain-containing factor (ETF) gene.

    Science.gov (United States)

    Suzuki, K; Yasunami, M; Matsuda, Y; Maeda, T; Kobayashi, H; Terasaki, H; Ohkubo, H

    1996-09-01

    Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and characterization of the cosmid clones encoding the mouse ETF gene (Etdf) revealed that Etdf spans approximately 17.9 kb and consists of 12 exons. The exon-intron structure of Etdf closely resembles that of the Drosophila scalloped gene, indicating that these genes may have evolved from a common ancestor. The multiple transcription initiation sites revealed by S1 protection and primer extension analyses are consistent with the absence of the canonical TATA and CAAT boxes in the 5'-flanking region, which contains many potential regulatory sequences, such as the E-box, N-box, Sp1 element, GATA-1 element, TAATGARAT element, and B2 short interspersed element (SINE) as well as several direct and inverted repeat sequences. The Etdf locus was assigned to the proximal region of mouse chromosome 7 using fluorescence in situ hybridization and linkage mapping analyses. These results provide the molecular basis for studying the regulation, in vivo function, and evolution of Etdf.

  6. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  7. The carboxy-terminal domain of Dictyostelium C-module-binding factor is an independent gene regulatory entity.

    Directory of Open Access Journals (Sweden)

    Jörg Lucas

    Full Text Available The C-module-binding factor (CbfA is a multidomain protein that belongs to the family of jumonji-type (JmjC transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD. An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo.

  8. [Risk factors for malignant evolution of gastrointestinal stromal tumors].

    Science.gov (United States)

    Andrei, S; Andrei, Adriana; Tonea, A; Andronesi, D; Becheanu, G; Dumbravă, Mona; Pechianu, C; Herlea, V; Popescu, I

    2007-01-01

    Gastrointestinal stromal tumors are the most frequent non-epithelial digestive tumors, being classified in the group of primitive mesenchymal tumors of the digestive tract. These tumors have a non predictable evolution and where stratified regarding the risk for malignant behavior in 4 categories: very low risk, low risk, intermediate risk and high risk. We performed a retrospective non randomised study including the patients with gastrointestinal stromal tumors treated in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute in the period January 2002 - June 2007, to define the epidemiological, clinico-paraclinical, histological and especially evolutive features of the gastrointestinal stromal tumors from this group, with a special regard to the risk factors for their malignant behavior. The most important risk factors in gastrointestinal stromal tumors are the tumor size and the mitotic index, based on them being realised the classification of Fletcher in the 4 risk categories mentioned above. In our group all the local advanced or metastatic gastrointestinal stromal tumors, regardless of their location, were classified in the group of high risk for the malignant behavior. The gastric location and the epithelioid type were positive prognostic factors, and the complete resection of the tumor, an other important positive prognostic feature, was possible in about 80% of the cases, probably because the gastrointestinal stromal tumors in our study were diagnosed in less advanced evolutive situations, only about one third being metastatic and about 14% being locally advanced at the time of diagnose. The association with other neoplasias was in our cases insignificant, only 5% of the patients presenting concomitant malignant digestive tumors and 7.6% intraabdominal benign tumors. Gastrointestinal stromal tumors remain a challenge for the medical staff, regarding their diagnose and therapeutical management, the stratification of the

  9. Origin and Evolution of Protein Fold Designs Inferred from Phylogenomic Analysis of CATH Domain Structures in Proteomes

    Science.gov (United States)

    Bukhari, Syed Abbas; Caetano-Anollés, Gustavo

    2013-01-01

    The spatial arrangements of secondary structures in proteins, irrespective of their connectivity, depict the overall shape and organization of protein domains. These features have been used in the CATH and SCOP classifications to hierarchically partition fold space and define the architectural make up of proteins. Here we use phylogenomic methods and a census of CATH structures in hundreds of genomes to study the origin and diversification of protein architectures (A) and their associated topologies (T) and superfamilies (H). Phylogenies that describe the evolution of domain structures and proteomes were reconstructed from the structural census and used to generate timelines of domain discovery. Phylogenies of CATH domains at T and H levels of structural abstraction and associated chronologies revealed patterns of reductive evolution, the early rise of Archaea, three epochs in the evolution of the protein world, and patterns of structural sharing between superkingdoms. Phylogenies of proteomes confirmed the early appearance of Archaea. While these findings are in agreement with previous phylogenomic studies based on the SCOP classification, phylogenies unveiled sharing patterns between Archaea and Eukarya that are recent and can explain the canonical bacterial rooting typically recovered from sequence analysis. Phylogenies of CATH domains at A level uncovered general patterns of architectural origin and diversification. The tree of A structures showed that ancient structural designs such as the 3-layer (αβα) sandwich (3.40) or the orthogonal bundle (1.10) are comparatively simpler in their makeup and are involved in basic cellular functions. In contrast, modern structural designs such as prisms, propellers, 2-solenoid, super-roll, clam, trefoil and box are not widely distributed and were probably adopted to perform specialized functions. Our timelines therefore uncover a universal tendency towards protein structural complexity that is remarkable. PMID:23555236

  10. INFLUENCE OF DOMAIN SHIFT FACTORS ON DEEP SEGMENTATION OF THE DRIVABLE PATH OF AN AUTONOMOUS VEHICLE

    Directory of Open Access Journals (Sweden)

    R. P. A. Bormans

    2018-05-01

    Full Text Available One of the biggest challenges for an autonomous vehicle (and hence the WEpod is to see the world as humans would see it. This understanding is the base for a successful and reliable future of autonomous vehicles. Real-world data and semantic segmentation generally are used to achieve full understanding of its surroundings. However, deploying a pretrained segmentation network to a new, previously unseen domain will not attain similar performance as it would on the domain where it is trained on due to the differences between the domains. Although research is done concerning the mitigation of this domain shift, the factors that cause these differences are not yet fully explored. We filled this gap with the investigation of several factors. A base network was created by a two-step finetuning procedure on a convolutional neural network (SegNet which is pretrained on CityScapes (a dataset for semantic segmentation. The first tuning step is based on RobotCar (road scenery dataset recorded in Oxford, UK while afterwards this network is fine-tuned for a second time but now on the KITTI (road scenery dataset recorded in Germany dataset. With this base, experiments are used to obtain the importance of factors such as horizon line, colour and training order for a successful domain adaptation. In this case the domain adaptation is from the KITTI and RobotCar domain to the WEpod domain. For evaluation, groundtruth labels are created in a weakly-supervised setting. Negative influence was obtained for training on greyscale images instead of RGB images. This resulted in drops of IoU values up to 23.9 % for WEpod test images. The training order is a main contributor for domain adaptation with an increase in IoU of 4.7 %. This shows that the target domain (WEpod is more closely related to RobotCar than to KITTI.

  11. Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event.

    Science.gov (United States)

    Kyndt, Tina; Haegeman, Annelies; Gheysen, Godelieve

    2008-11-03

    Endo-1,4-beta-glucanases or cellulases from the glycosyl hydrolase family 5 (GHF5) have been found in numerous bacteria and fungi, and recently also in higher eukaryotes, particularly in plant-parasitic nematodes (PPN). The origin of these genes has been attributed to horizontal gene transfer from bacteria, although there still is a lot of uncertainty about the origin and structure of the ancestral GHF5 PPN endoglucanase. It is not clear whether this ancestral endoglucanase consisted of the whole gene cassette, containing a catalytic domain and a carbohydrate-binding module (CBM, type 2 in PPN and bacteria) or only of the catalytic domain while the CBM2 was retrieved by domain shuffling later in evolution. Previous studies on the evolution of these genes have focused primarily on data of sedentary nematodes, while in this study, extra data from migratory nematodes were included. Two new endoglucanases from the migratory nematodes Pratylenchus coffeae and Ditylenchus africanus were included in this study. The latter one is the first gene isolated from a PPN of a different superfamily (Sphaerularioidea); all previously known nematode endoglucanases belong to the superfamily Tylenchoidea (order Rhabditida). Phylogenetic analyses were conducted with the PPN GHF5 endoglucanases and homologous endoglucanases from bacterial and other eukaryotic lineages such as beetles, fungi and plants. No statistical incongruence between the phylogenetic trees deduced from the catalytic domain and the CBM2 was found, which could suggest that both domains have evolved together. Furthermore, based on gene structure data, we inferred a model for the evolution of the GHF5 endoglucanase gene structure in plant-parasitic nematodes. Our data confirm a close relationship between Pratylenchus spp. and the root knot nematodes, while some Radopholus similis endoglucanases are more similar to cyst nematode genes. We conclude that the ancestral PPN GHF5 endoglucanase gene most probably consisted of

  12. Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event

    Directory of Open Access Journals (Sweden)

    Gheysen Godelieve

    2008-11-01

    Full Text Available Abstract Background Endo-1,4-beta-glucanases or cellulases from the glycosyl hydrolase family 5 (GHF5 have been found in numerous bacteria and fungi, and recently also in higher eukaryotes, particularly in plant-parasitic nematodes (PPN. The origin of these genes has been attributed to horizontal gene transfer from bacteria, although there still is a lot of uncertainty about the origin and structure of the ancestral GHF5 PPN endoglucanase. It is not clear whether this ancestral endoglucanase consisted of the whole gene cassette, containing a catalytic domain and a carbohydrate-binding module (CBM, type 2 in PPN and bacteria or only of the catalytic domain while the CBM2 was retrieved by domain shuffling later in evolution. Previous studies on the evolution of these genes have focused primarily on data of sedentary nematodes, while in this study, extra data from migratory nematodes were included. Results Two new endoglucanases from the migratory nematodes Pratylenchus coffeae and Ditylenchus africanus were included in this study. The latter one is the first gene isolated from a PPN of a different superfamily (Sphaerularioidea; all previously known nematode endoglucanases belong to the superfamily Tylenchoidea (order Rhabditida. Phylogenetic analyses were conducted with the PPN GHF5 endoglucanases and homologous endoglucanases from bacterial and other eukaryotic lineages such as beetles, fungi and plants. No statistical incongruence between the phylogenetic trees deduced from the catalytic domain and the CBM2 was found, which could suggest that both domains have evolved together. Furthermore, based on gene structure data, we inferred a model for the evolution of the GHF5 endoglucanase gene structure in plant-parasitic nematodes. Our data confirm a close relationship between Pratylenchus spp. and the root knot nematodes, while some Radopholus similis endoglucanases are more similar to cyst nematode genes. Conclusion We conclude that the ancestral

  13. Distribution and evolution of stable single α-helices (SAH domains in myosin motor proteins.

    Directory of Open Access Journals (Sweden)

    Dominic Simm

    Full Text Available Stable single-alpha helices (SAHs are versatile structural elements in many prokaryotic and eukaryotic proteins acting as semi-flexible linkers and constant force springs. This way SAH-domains function as part of the lever of many different myosins. Canonical myosin levers consist of one or several IQ-motifs to which light chains such as calmodulin bind. SAH-domains provide flexibility in length and stiffness to the myosin levers, and may be particularly suited for myosins working in crowded cellular environments. Although the function of the SAH-domains in human class-6 and class-10 myosins has well been characterised, the distribution of the SAH-domain in all myosin subfamilies and across the eukaryotic tree of life remained elusive. Here, we analysed the largest available myosin sequence dataset consisting of 7919 manually annotated myosin sequences from 938 species representing all major eukaryotic branches using the SAH-prediction algorithm of Waggawagga, a recently developed tool for the identification of SAH-domains. With this approach we identified SAH-domains in more than one third of the supposed 79 myosin subfamilies. Depending on the myosin class, the presence of SAH-domains can range from a few to almost all class members indicating complex patterns of independent and taxon-specific SAH-domain gain and loss.

  14. SmPL: A Domain-Specific Language for Specifying Collateral Evolutions in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Muller, Gilles

    2007-01-01

    identifying the affected files and modifying all of the code fragments in these files that in some way depend on the changed interface. We have studied the collateral evolution problem in the context of Linux device drivers. Currently, collateral evolutions in Linux are mostly done manually using a text...

  15. Evolution of the global energy system: technology and other factors

    Energy Technology Data Exchange (ETDEWEB)

    de Leone, R.

    Future directions in government energy policies are assessed in light of the energy evolution following the 1973 oil crisis and the impacts created by technology transfer and other factors. In particular, the paper examines changes which are occurring in global marketing and commercialization trends, and in public opinion, especially in response to the techniques employed by planners in assessing new energy sources and technologies designed to lessen dependency on oil imports. It is noted that greater consideration must be given by scientists and engineers to the socio-economic impacts of their research efforts.

  16. Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

    KAUST Repository

    Liang, Yu; Huimei Hong, Felicia; Ganesan, Pugalenthi; Jiang, Sizun; Jauch, Ralf; Stanton, Lawrence W.; Kolatkar, Prasanna R.

    2012-01-01

    Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

  17. Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

    KAUST Repository

    Liang, Yu

    2012-06-26

    Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

  18. [Detection of the functionally active domains in the molecule of the lethal factor of the anthrax exotoxin].

    Science.gov (United States)

    Noskov, A N; Kravchenko, T B; Noskova, V P

    1996-01-01

    Three functional domains were revealed in the molecule of the lethal factor of B. anthracis. They are located in the linear structure of the molecula as follows: the associative domain occupies the area from Lys39 to Met242, the stabilizing domain from Leu517 to Lys614, and the effector domain still further to the COOH-terminal Lys mino acid.

  19. The Evolution of the Scavenger Receptor Cysteine-Rich Domain of the Class A Scavenger Receptors

    Directory of Open Access Journals (Sweden)

    Nicholas eYap

    2015-07-01

    Full Text Available The class A Scavenger Receptor (cA-SR family is a group of five evolutionarily related innate immune receptors. The cA-SRs are known for their promiscuous ligand binding; as they have been shown to bind bacteria such as Streptococcus pneumoniae, and Escherichia coli, as well as different modified forms of low-density lipoprotein. Three of the five family members possess a Scavenger Receptor Cysteine Rich (SRCR domain while the remaining two receptors lack the domain. Previous work has suggested that the Macrophage Associated Receptor with COllagenous structure (MARCO shares a recent common ancestor with the non-SRCR-containing receptors; however the origin of the SRCR domain within the cA-SRs remains unknown. We hypothesize that the SRCR domains of the cA-SRs have a common origin that predates teleost fish. Using the newly available sequence data from sea lamprey and ghost shark genome projects, we have shown that MARCO shares a common ancestor with the SRCR-containing proteins. In addition, we explored the evolutionary relationships within the SRCR domain by reconstructing the ancestral SRCR domains of the cA-SRs. We identified a motif that is highly conserved between the cA-SR SRCR domains and the ancestral SRCR domain that consist of WGTVCDD. We also show that the GRAEVYY motif, a functionally important motif within MARCO, is poorly conserved in the other cA-SRs and in the reconstructed ancestral domain. Further, we identified three sites within MARCO’s SRCR domain which are under positive selection. Two of these sites lie adjacent to the conserved WGTVCDD motif, and may indicate a potential biological function for these sites. Together these findings indicate a common origin of the SRCR domain within the cA-SRs; however different selective pressures between the proteins may have caused MARCOs SRCR domain to evolve to contain different functional motifs when compared to the other SRCR-containing cA-SRs.

  20. Dynamic factor analysis in the frequency domain: causal modeling of multivariate psychophysiological time series

    NARCIS (Netherlands)

    Molenaar, P.C.M.

    1987-01-01

    Outlines a frequency domain analysis of the dynamic factor model and proposes a solution to the problem of constructing a causal filter of lagged factor loadings. The method is illustrated with applications to simulated and real multivariate time series. The latter applications involve topographic

  1. Exact diagonalization study of domain structures in integer filling factor quantum Hall ferromagnets

    Czech Academy of Sciences Publication Activity Database

    Rezayi, E. H.; Jungwirth, Tomáš; MacDonald, A. H.; Haldane, F. D. M.

    2003-01-01

    Roč. 67, č. 20 (2003), s. 201305-1 - 201305-4 ISSN 0163-1829 R&D Projects: GA ČR GA202/01/0754 Institutional research plan: CEZ:AV0Z1010914 Keywords : domain structure * integer filling factor * quantum Hall ferromagnets Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.962, year: 2003

  2. MADS interactomics : towards understanding the molecular mechanisms of plant MADS-domain transcription factor function

    NARCIS (Netherlands)

    Smaczniak, C.D.

    2013-01-01

    Protein-protein and protein-DNA interactions are essential for the molecular action of transcription factors. By combinatorial binding to target gene promoters, transcription factors are able to up- or down-regulate the expression of these genes. MADS-domain proteins comprise a large family of

  3. Structure discrimination for the C-terminal domain of Escherichia coli trigger factor in solution

    International Nuclear Information System (INIS)

    Yao Yong; Bhabha, Gira; Kroon, Gerard; Landes, Mindy; Dyson, H. Jane

    2008-01-01

    NMR measurements can give important information on solution structure, without the necessity for a full-scale solution structure determination. The C-terminal protein binding domain of the ribosome-associated chaperone protein trigger factor is composed of non-contiguous parts of the polypeptide chain, with an interpolated prolyl isomerase domain. A construct of the C-terminal domain of Escherichia coli trigger factor containing residues 113-149 and 247-432, joined by a Gly-Ser-Gly-Ser linker, is well folded and gives excellent NMR spectra in solution. We have used NMR measurements on this construct, and on a longer construct that includes the prolyl isomerase domain, to distinguish between two possible structures for the C-terminal domain of trigger factor, and to assess the behavior of the trigger factor C-terminal domain in solution. Two X-ray crystal structures, of intact trigger factor from E. coli (Ferbitz et al., Nature 431:590-596, 2004), and of a truncated trigger factor from Vibrio cholerae (Ludlam et al., Proc Natl Acad Sci USA 101:13436-13441, 2004) showed significant differences in the structure of the C-terminal domain, such that the two structures could not be superimposed. We show using NMR chemical shifts and long range nuclear Overhauser effects that the secondary and tertiary structure of the E. coli C-terminal domain in solution is consistent with the crystal structure of the E. coli trigger factor and not with the V. cholerae protein. Given the similarity of the amino acid sequences of the E. coli and V. cholerae proteins, it appears likely that the structure of the V. cholerae protein has been distorted as a result of truncation of a 44-amino acid segment at the C-terminus. Analysis of residual dipolar coupling measurements shows that the overall topology of the solution structure is completely inconsistent with both structures. Dynamics analysis of the C-terminal domain using T 1 , T 2 and heteronuclear NOE parameters show that the protein is

  4. Almost Automorphic and Pseudo-Almost Automorphic Solutions to Semilinear Evolution Equations with Nondense Domain

    Directory of Open Access Journals (Sweden)

    Bruno de Andrade

    2009-01-01

    Full Text Available We study the existence and uniqueness of almost automorphic (resp., pseudo-almost automorphic solutions to a first-order differential equation with linear part dominated by a Hille-Yosida type operator with nondense domain.

  5. Co-evolution of affinity and stability of grafted amyloid-motif domain antibodies.

    Science.gov (United States)

    Julian, Mark C; Lee, Christine C; Tiller, Kathryn E; Rabia, Lilia A; Day, Evan K; Schick, Arthur J; Tessier, Peter M

    2015-10-01

    An attractive approach for designing lead antibody candidates is to mimic natural protein interactions by grafting peptide recognition motifs into the complementarity-determining regions (CDRs). We are using this approach to generate single-domain (VH) antibodies specific for amyloid-forming proteins such as the Alzheimer's Aβ peptide. Here, we use random mutagenesis and yeast surface display to improve the binding affinity of a lead VH domain grafted with Aβ residues 33-42 in CDR3. Interestingly, co-selection for improved Aβ binding and VH display on the surface of yeast yields antibody domains with improved affinity and reduced stability. The highest affinity VH domains were strongly destabilized on the surface of yeast as well as unfolded when isolated as autonomous domains. In contrast, stable VH domains with improved affinity were reliably identified using yeast surface display by replacing the display antibody that recognizes a linear epitope tag at the terminus of both folded and unfolded VH domains with a conformational ligand (Protein A) that recognizes a discontinuous epitope on the framework of folded VH domains. Importantly, we find that selection for improved stability using Protein A without simultaneous co-selection for improved Aβ binding leads to strong enrichment for stabilizing mutations that reduce antigen binding. Our findings highlight the importance of simultaneously optimizing affinity and stability to improve the rapid isolation of well-folded and specific antibody fragments. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine.

    Science.gov (United States)

    Ju, Tong; Niu, Wei; Guo, Jiantao

    2016-09-16

    Protein tyrosine O-sulfation is considered as the most common type of post-translational tyrosine modification in nature and plays important roles in extracellular biomolecular interactions. To facilitate the mapping, biological study, and medicinal application of this type of post-translational modification, we seek to evolve a small protein scaffold that recognizes sulfotyrosine with high affinity. We focused our efforts on the engineering of the Src Homology 2 (SH2) domain, which represents the largest class of known phosphotyrosine-recognition domain in nature and has a highly evolvable binding pocket. By using phage display, we successfully engineered the SH2 domain to recognize sulfotyrosine with high affinity. The best mutant, SH2-60.1, displayed more than 1700 fold higher sulfotyrosine-binding affinity than that of the wild-type SH2 domain. We also demonstrated that the evolved SH2 domain mutants could be used to detect sulfoprotein levels on the cell surface. These evolved SH2 domain mutants can be potentially applied to the study of protein tyrosine O-sulfation with proper experimental designs.

  7. Co-evolution of intelligent socio-technical systems modelling and applications in large scale emergency and transport domains

    CERN Document Server

    2013-01-01

    As the interconnectivity between humans through technical devices is becoming ubiquitous, the next step is already in the making: ambient intelligence, i.e. smart (technical) environments, which will eventually play the same active role in communication as the human players, leading to a co-evolution in all domains where real-time communication is essential. This topical volume, based on the findings of the Socionical European research project, gives equal attention to two highly relevant domains of applications: transport, specifically traffic, dynamics from the viewpoint of a socio-technical interaction and evacuation scenarios for large-scale emergency situations. Care was taken to investigate as much as possible the limits of scalability and to combine the modeling using complex systems science approaches with relevant data analysis.

  8. Tracking the Evolution of the Internet of Things Concept Across Different Application Domains.

    Science.gov (United States)

    Ibarra-Esquer, Jorge E; González-Navarro, Félix F; Flores-Rios, Brenda L; Burtseva, Larysa; Astorga-Vargas, María A

    2017-06-14

    Both the idea and technology for connecting sensors and actuators to a network to remotely monitor and control physical systems have been known for many years and developed accordingly. However, a little more than a decade ago the concept of the Internet of Things (IoT) was coined and used to integrate such approaches into a common framework. Technology has been constantly evolving and so has the concept of the Internet of Things, incorporating new terminology appropriate to technological advances and different application domains. This paper presents the changes that the IoT has undertaken since its conception and research on how technological advances have shaped it and fostered the arising of derived names suitable to specific domains. A two-step literature review through major publishers and indexing databases was conducted; first by searching for proposals on the Internet of Things concept and analyzing them to find similarities, differences, and technological features that allow us to create a timeline showing its development; in the second step the most mentioned names given to the IoT for specific domains, as well as closely related concepts were identified and briefly analyzed. The study confirms the claim that a consensus on the IoT definition has not yet been reached, as enabling technology keeps evolving and new application domains are being proposed. However, recent changes have been relatively moderated, and its variations on application domains are clearly differentiated, with data and data technologies playing an important role in the IoT landscape.

  9. Vacuum tension effects on the evolution of domain walls in the early universe

    International Nuclear Information System (INIS)

    Aurilia, A.

    1984-06-01

    The ''vacuum pressure'' mechanism of the hadronic bag model is taken as a guide to formulate the dynamics of closed domain walls in the cosmological case. The effective action functional suggested by this analogy is a straightforward generalization of the Einstein-Maxwell action: it involves a 3-index antisymmetric potential whose coupling to matter generates two effective cosmological constants, one inside and one outside the domain wall. It is suggested that this mechanism, which is alternative to the introduction of a Higgs potential, is the source of the bubble nucleation process envisaged in the New Inflationary Cosmology. The dynamics of a spherical domain in a de Sitter phase is analyzed and is consistent with the geometrical formulation of shell dynamics proposed long ago by Israel. (author)

  10. Membrane association of the Arabidopsis ARF exchange factor GNOM involves interaction of conserved domains

    DEFF Research Database (Denmark)

    Anders, Nadine; Nielsen, Michael M.; Keicher, Jutta

    2008-01-01

    vesicle formation by activating ARF GTPases on specific membranes in animals, plants, and fungi. However, apart from the catalytic exchange activity of the SEC7 domain, the functional significance of other conserved domains is virtually unknown. Here, we show that a distinct N-terminal domain of GNOM......The GNOM protein plays a fundamental role in Arabidopsis thaliana development by regulating endosome-to-plasma membrane trafficking required for polar localization of the auxin efflux carrier PIN1. GNOM is a family member of large ARF guanine nucleotide exchange factors (ARF-GEFs), which regulate...... mediates dimerization and in addition interacts heterotypically with two other conserved domains in vivo. In contrast with N-terminal dimerization, the heterotypic interaction is essential for GNOM function, as mutations abolishing this interaction inactivate the GNOM protein and compromise its membrane...

  11. The evolution of the DLK1-DIO3 imprinted domain in mammals.

    Directory of Open Access Journals (Sweden)

    Carol A Edwards

    2008-06-01

    Full Text Available A comprehensive, domain-wide comparative analysis of genomic imprinting between mammals that imprint and those that do not can provide valuable information about how and why imprinting evolved. The imprinting status, DNA methylation, and genomic landscape of the Dlk1-Dio3 cluster were determined in eutherian, metatherian, and prototherian mammals including tammar wallaby and platypus. Imprinting across the whole domain evolved after the divergence of eutherian from marsupial mammals and in eutherians is under strong purifying selection. The marsupial locus at 1.6 megabases, is double that of eutherians due to the accumulation of LINE repeats. Comparative sequence analysis of the domain in seven vertebrates determined evolutionary conserved regions common to particular sub-groups and to all vertebrates. The emergence of Dlk1-Dio3 imprinting in eutherians has occurred on the maternally inherited chromosome and is associated with region-specific resistance to expansion by repetitive elements and the local introduction of noncoding transcripts including microRNAs and C/D small nucleolar RNAs. A recent mammal-specific retrotransposition event led to the formation of a completely new gene only in the eutherian domain, which may have driven imprinting at the cluster.

  12. Evolution of the RNase P RNA structural domain in Leptospira spp

    NARCIS (Netherlands)

    Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A.; Devendran, Ajay; Hartskeerl, Rudy A.; Raj, Stephen M. L.

    2014-01-01

    We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along

  13. Social Factors of the Evolution of State Institutions

    Directory of Open Access Journals (Sweden)

    Zhukova Larysa M.

    2017-06-01

    Full Text Available The aim of the article is a comprehensive study of social factors in the evolution of state institutions. By analyzing, systematizing and summarizing the scientific works of many scientists, the process of transformation of state institutions is considered in view of the features of Ukraine’s social and economic development and the impact of institutional changes on the social needs of society. As a result of the research, it is revealed that one of the main factors of social evolution is the culture of relations between the state, business and society. The logical and contradictory interaction of these subjects is analyzed, since based on them there formed an economy aimed at reviving social resources and ensuring both the stability of the social system and the dynamism of its development. It is determined that Ukraine requires urgent development of an integrated socio-economic development strategy that would include specific measures that can ensure improvement of the living standards of citizens, creation of a competitive economy, successful integration into the world and European space. It is substantiated that the system of relations “state – business – society” should be revised from the position of strengthening the importance of both social values and the business community facing the challenges of globalization. Prospects for further research in this area are justification of the strategic goals of the state social policy as a multi-level and multifunctional system that can ensure the country’s social and economic development by activating human capital and maximizing its innovative potential.

  14. Tracking the Evolution of the Internet of Things Concept Across Different Application Domains

    Directory of Open Access Journals (Sweden)

    Jorge E. Ibarra-Esquer

    2017-06-01

    Full Text Available Both the idea and technology for connecting sensors and actuators to a network to remotely monitor and control physical systems have been known for many years and developed accordingly. However, a little more than a decade ago the concept of the Internet of Things (IoT was coined and used to integrate such approaches into a common framework. Technology has been constantly evolving and so has the concept of the Internet of Things, incorporating new terminology appropriate to technological advances and different application domains. This paper presents the changes that the IoT has undertaken since its conception and research on how technological advances have shaped it and fostered the arising of derived names suitable to specific domains. A two-step literature review through major publishers and indexing databases was conducted; first by searching for proposals on the Internet of Things concept and analyzing them to find similarities, differences, and technological features that allow us to create a timeline showing its development; in the second step the most mentioned names given to the IoT for specific domains, as well as closely related concepts were identified and briefly analyzed. The study confirms the claim that a consensus on the IoT definition has not yet been reached, as enabling technology keeps evolving and new application domains are being proposed. However, recent changes have been relatively moderated, and its variations on application domains are clearly differentiated, with data and data technologies playing an important role in the IoT landscape.

  15. Tracking the Evolution of the Internet of Things Concept Across Different Application Domains

    Science.gov (United States)

    Ibarra-Esquer, Jorge E.; González-Navarro, Félix F.; Flores-Rios, Brenda L.; Burtseva, Larysa; Astorga-Vargas, María A.

    2017-01-01

    Both the idea and technology for connecting sensors and actuators to a network to remotely monitor and control physical systems have been known for many years and developed accordingly. However, a little more than a decade ago the concept of the Internet of Things (IoT) was coined and used to integrate such approaches into a common framework. Technology has been constantly evolving and so has the concept of the Internet of Things, incorporating new terminology appropriate to technological advances and different application domains. This paper presents the changes that the IoT has undertaken since its conception and research on how technological advances have shaped it and fostered the arising of derived names suitable to specific domains. A two-step literature review through major publishers and indexing databases was conducted; first by searching for proposals on the Internet of Things concept and analyzing them to find similarities, differences, and technological features that allow us to create a timeline showing its development; in the second step the most mentioned names given to the IoT for specific domains, as well as closely related concepts were identified and briefly analyzed. The study confirms the claim that a consensus on the IoT definition has not yet been reached, as enabling technology keeps evolving and new application domains are being proposed. However, recent changes have been relatively moderated, and its variations on application domains are clearly differentiated, with data and data technologies playing an important role in the IoT landscape. PMID:28613238

  16. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

    International Nuclear Information System (INIS)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-01-01

    The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal

  17. Kinematic evolution of the Mbakop Pan-African granitoids (western Cameroon domain): An integrated AMS and EBSD approach

    Science.gov (United States)

    Bella Nké, B. E.; Njanko, T.; Mamtani, M. A.; Njonfang, E.; Rochette, P.

    2018-06-01

    This study integrates anisotropy of magnetic susceptibility, microstructural and crystallographic preferred orientation (CPO) data from the Mbakop granitic pluton (MGP; Pan-African age) in order to decipher its kinematic evolution. The MGP lies close to NE-SW branch of Central Cameroon Shear Zone (CCSZ) and is emplaced in gneissic basement. High mean magnetic susceptibility and presence of multi-domain magnetite are recorded. Quartz CPO measured using Electron Backscatter diffraction reveals dominance of rhomb , prism and prism slip in different samples, which is consistent with microstructures developed under upper greenschist/amphibolite facies conditions. Quartz CPO along with other kinematic indicators (feldspar porphyroclasts/mineral fish) indicate non-coaxial deformation was important during tectonic evolution of the MGP. Contrasting sense of shear is recorded implying multi-stage mylonitization in the Western Cameroon Domain. Top-towards-south sense of shear is related to regional D2 deformation (613-585 Ma), while top-towards-north is related to D3 (585-540 Ma). The magnetic fabric in MGP records D3. The obliquity between mean orientation of magnetic foliation (N12°E) and the NE-SW CCSZ branch (N48°E) gives kinematic vorticity number of 0.95. This indicates dominantly simple shear with a minor pure shear component. It is concluded that regional transpression was important during MGP emplacement.

  18. Relationship Domain of Form Six Teachers Thinking in Teaching with External Factors of Form Six Teachers

    Science.gov (United States)

    bin Pet, Mokhtar; Sihes, Ahmad Johari Hj

    2015-01-01

    This study aims to examine the external factors of form six teachers who can influence thinking domain form six teachers in their teaching. This study was conducted using a quantitative approach using questionnaires. A total of 300 form six teacher schools in Johor were chosen as respondents. The findings were obtained as student background…

  19. Late replicating domains are highly recombining in females but have low male recombination rates: implications for isochore evolution.

    Directory of Open Access Journals (Sweden)

    Catherine J Pink

    Full Text Available In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in

  20. Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

    Science.gov (United States)

    Dong, Zheng; Zhou, Hongyu; Tao, Peng

    2018-02-01

    PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

  1. Extrapolation of π-meson form factor, zeros in the analyticity domain

    International Nuclear Information System (INIS)

    Morozov, P.T.

    1978-01-01

    The problem of a stable extrapolation from the cut to an arbitrary interior of the analyticity domain for the pion form factor is formulated and solved. As it is shown a stable solution can be derived if module representations with the Karleman weight function are used as the analyticity conditions. The case when the form factor has zeros is discussed. If there are zeros in the complex plane they must be taken into account when determining the extrapolation function

  2. Bacterial elongation factors EF-Tu, their mutants, chimeric forms, and domains: isolation and purification

    Czech Academy of Sciences Publication Activity Database

    Jonák, Jiří

    2007-01-01

    Roč. 849, 1-2 (2007), s. 141-153 ISSN 1570-0232 R&D Projects: GA AV ČR IAA5052206; GA AV ČR KJB500520503; GA MŠk 2B06065 Institutional research plan: CEZ:AV0Z50520514 Keywords : bacterial elongation factors EF-Tu, , G-domain * recombinant EF-Tus * preparation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.935, year: 2007

  3. Evolution of the vertebrate neurocranium : problems of the premandibular domain and the origin of the trabecula

    OpenAIRE

    Kuratani, Shigeru; Ahlberg, Per E.

    2018-01-01

    The subdivision of the gnathostome neurocranium into an anterior neural crest-derived moiety and a posterior mesodermal moiety has attracted the interest of researchers for nearly two centuries. We present a synthetic scenario for the evolution of this structure, uniting developmental data from living cyclostomes and gnathostomes with morphological data from fossil stem gnathostomes in a common phylogenetic framework. Ancestrally, vertebrates had an anteroposteriorly short forebrain, and the ...

  4. Factors that determine the evolution of high-growth businesses

    Directory of Open Access Journals (Sweden)

    Oriol Amat

    2013-09-01

    Full Text Available Objective: The study herein discusses research aimed at elucidating the factors that contribute to a business’ ability to maintain high growth. Design/Methodology/Perspective: The database from the Iberian Balance Sheet Analysis System (SABI, from its initials in Spanish was used to identify 250 industrial Catalonian businesses with high growth during 2004-2007. These companies participated in a survey on strategies and management practices; in 2013, they were re-analyzed to investigate the factors that contributed to continued growth for certain companies. Contributions: Through diverse statistical techniques, business policies related to quality, innovation, internationalization and finance were shown to influence business growth and sustainability over time. Limitations of the Research: This study focuses on industrial businesses at least ten years old in Catalonia; thus, the conclusions may differ in other geographic locations and economic sectors, as well as for smaller businesses. Practical Implications: Because growth is a measure of business success, identifying variables that contribute to high growth and its sustainability is helpful for businesses that seek to adopt effective policies. Social Implications: Generating employment is one of the primary contributions by high-growth businesses. For years with high unemployment, authorities may be interested in corporate policies that strengthen high-growth businesses. Originality/Added Value: High-growth businesses have been studied throughout the world, but this is the first study to investigate the evolution of businesses after a high-growth phase.

  5. Performance of Downlink Frequency Domain Packet Scheduling for the UTRAN Long Term Evolution

    DEFF Research Database (Denmark)

    Pokhariyal, Akhilesh; Kolding, Troels E.; Mogensen, Preben

    2006-01-01

    -blind, but time-opportunistic scheduling, FDPS shows gain in both average system capacity and cell-edge data rates on the order of 40%. However, FDPS performance is shown to depend significantly on the frequency-domain scheduling resolution as well as the accuracy of the channel state reports. Assuming Typical...... Urban channel profile, studies show that the scheduling resolution should preferably be as low as 375 kHz to yield significant FDPS gain and the std. of the error of radio state reports need to be kept within 1.5-2 dB....

  6. Evolution of the RNase P RNA structural domain in Leptospira spp.

    Science.gov (United States)

    Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A; Devendran, Ajay; Hartskeerl, Rudy A; Raj, Stephen M L

    2014-12-01

    We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along with sequences determined from 8 reference strains were examined to fathom strain specific structural differences present in leptospiral RPR. Sequence variations in the RPR gene impacted on the configuration of loops, stems and bulges found in the RPR highlighting species and strain specific structural motifs. In vitro transcribed leptospiral RPR ribozymes are demonstrated to process pre-tRNA into mature tRNA in consonance with the positioning of Leptospira in the taxonomic domain of bacteria. RPR sequence datasets used to construct a phylogenetic tree exemplified the segregation of strains into their respective lineages with a (re)speciation of strain SH 9 to Leptospira borgpetersenii, strains Fiocruz LV 3954 and Fiocruz LV 4135 to Leptospira santarosai, strain CBC 613 to Leptospira kirschneri and strain HAI 1536 to Leptospira noguchii. Furthermore, it allowed characterization of an isolate P2653, presumptively characterized as either serovar Hebdomadis, Kremastos or Longnan to Leptospira weilii, serovar Longnan. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  7. Correlating structure and function during the evolution of fibrinogen-related domains

    Science.gov (United States)

    Doolittle, Russell F; McNamara, Kyle; Lin, Kevin

    2012-01-01

    Fibrinogen-related domains (FReDs) are found in a variety of animal proteins with widely different functions, ranging from non-self recognition to clot formation. All appear to have a common surface where binding of one sort or other occurs. An examination of 19 completed animal genomes—including a sponge and sea anemone, six protostomes, and 11 deuterostomes—has allowed phylogenies to be constructed that show where various types of FReP (proteins containing FReDs) first made their appearance. Comparisons of sequences and structures also reveal particular features that correlate with function, including the influence of neighbor-domains. A particular set of insertions in the carboxyl-terminal subdomain was involved in the transition from structures known to bind sugars to those known to bind amino-terminal peptides. Perhaps not unexpectedly, FReDs with different functions have changed at different rates, with ficolins by far the fastest changing group. Significantly, the greatest amount of change in ficolin FReDs occurs in the third subdomain (“P domain”), the very opposite of the situation in most other vertebrate FReDs. The unbalanced style of change was also observed in FReDs from non-chordates, many of which have been implicated in innate immunity. PMID:23076991

  8. Identification of defect distribution at ferroelectric domain walls from evolution of nonlinear dielectric response during the aging process

    Czech Academy of Sciences Publication Activity Database

    Mokrý, Pavel; Sluka, T.

    2016-01-01

    Roč. 93, č. 6 (2016), č. článku 064114. ISSN 2469-9950 R&D Projects: GA ČR(CZ) GA14-32228S Institutional support: RVO:61389021 Keywords : Nonlinear dielectric response * ferroelectric domain walls * aging process * phase field simulations Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.836, year: 2016 http://journals.aps.org/prb/abstract/10.1103/PhysRevB.93.064114

  9. GNBP domain of Anopheles darlingi: are polymorphic inversions and gene variation related to adaptive evolution?

    Science.gov (United States)

    Bridi, L C; Rafael, M S

    2016-02-01

    Anopheles darlingi is the main malaria vector in humans in South America. In the Amazon basin, it lives along the banks of rivers and lakes, which responds to the annual hydrological cycle (dry season and rainy season). In these breeding sites, the larvae of this mosquito feed on decomposing organic and microorganisms, which can be pathogenic and trigger the activation of innate immune system pathways, such as proteins Gram-negative binding protein (GNBP). Such environmental changes affect the occurrence of polymorphic inversions especially at the heterozygote frequency, which confer adaptative advantage compared to homozygous inversions. We mapped the GNBP probe to the An. darlingi 2Rd inversion by fluorescent in situ hybridization (FISH), which was a good indicator of the GNBP immune response related to the chromosomal polymorphic inversions and adaptative evolution. To better understand the evolutionary relations and time of divergence of the GNBP of An. darlingi, we compared it with nine other mosquito GNBPs. The results of the phylogenetic analysis of the GNBP sequence between the species of mosquitoes demonstrated three clades. Clade I and II included the GNBPB5 sequence, and clade III the sequence of GNBPB1. Most of these sequences of GNBP analyzed were homologous with that of subfamily B, including that of An. gambiae (87 %), therefore suggesting that GNBP of An. darling belongs to subfamily B. This work helps us understand the role of inversion polymorphism in evolution of An. darlingi.

  10. Ferroelectric domains and phase evolution in (Fe:) KTa{sub 1−x}Nb{sub x}O{sub 3} crystals

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hongyang; Cai, Kang; Fan, Ziran; Huang, Zhideng [Hubei Key Laboratory of Plasma Chemistry and Advanced Materials, Department of Materials Science and Engineering, Wuhan Institute of Technology, 693 Xiongchu Road, Wuhan 430073 (China); Ma, Zhibin, E-mail: mazb@wit.edu.cn [Hubei Key Laboratory of Plasma Chemistry and Advanced Materials, Department of Materials Science and Engineering, Wuhan Institute of Technology, 693 Xiongchu Road, Wuhan 430073 (China); Jia, Tingting; Kimura, Hideo [National Institute for Materials Science, Sengen 1-2-1, Tsukuba 305-0047 (Japan); Yang, Yuguo [New Materials Research Institute, Shandong Academy of Sciences, No. 19, Keyuan Road, Jinan 250014 (China); Matsumoto, Takao; Tohei, Tetsuya; Shibata, Naoya; Ikuhara, Yuichi [Institute of Engineering Innovation, School of Engineering, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-8656 (Japan)

    2017-08-15

    Highlights: • Three phase transitions were observed: the R–O, O–T, T–C evolutions. • KTN ferroelectric domain switching is because of the nano-polar-regions. • The domain evolution showed KTN has triangle shape, but Fe: KTN has straight line. - Abstract: The domain structures and phase evolution in mixed ferroelectric (Fe): KTa{sub 1−x}Nb{sub x}O{sub 3} (KTN) crystals were investigated. Temperature dependent Raman spectra show that Curie temperatures of KTN and Fe: KTN are far below room temperature, but the ferroelectric domain switching was still visualized by scanning probe microscopy at room temperature. These observed domains origin from the nano-regions near the grain boundaries. In addition, the intrinsic domains (triangle for KTN and straight line/stripe for Fe: KTN) could only be observed at low temperature by transmission electron microscopy. Three phase transitions in Fe: KTN crystals were found by Raman spectroscopy and dielectric testing: 175 K for Rhombohedral-to-Orthorhombic (R–O), 210 K for Orthorhombic-to-Tetragonal (O–T) and 250 K for Tetragonal-to-Cubic (T–C), which is consistent with the domain behavior.

  11. Edge morphology evolution of graphene domains during chemical vapor deposition cooling revealed through hydrogen etching.

    Science.gov (United States)

    Zhang, Haoran; Zhang, Yanhui; Zhang, Yaqian; Chen, Zhiying; Sui, Yanping; Ge, Xiaoming; Yu, Guanghui; Jin, Zhi; Liu, Xinyu

    2016-02-21

    During cooling, considerable changes such as wrinkle formation and edge passivation occur in graphene synthesized on the Cu substrate. Wrinkle formation is caused by the difference in the thermal expansion coefficients of graphene and its substrate. This work emphasizes the cooling-induced edge passivation. The graphene-edge passivation can limit the regrowth of graphene at the domain edge. Our work shows that silicon-containing particles tend to accumulate at the graphene edge, and the formation of these particles is related to cooling. Furthermore, a clear curvature can be observed at the graphene edge on the Cu substrate, indicating the sinking of the graphene edge into the Cu substrate. Both the sinking of the graphene edge and the accumulation of silicon-containing particles are responsible for edge passivation. In addition, two kinds of graphene edge morphologies are observed after etching, which were explained by different etching mechanisms that illustrate the changes of the graphene edge during cooling.

  12. Divergent evolution in the cytoplasmic domains of PRLR and GHR genes in Artiodactyla

    Directory of Open Access Journals (Sweden)

    Li Meng-Hua

    2009-07-01

    Full Text Available Abstract Background Prolactin receptor (PRLR and growth hormone receptor (GHR belong to the large superfamily of class 1 cytokine receptors. Both of them have been identified as candidate genes affecting key quantitative traits, like growth and reproduction in livestock. We have previously studied the molecular anatomy of the cytoplasmic domain of GHR in different cattle breeds and artiodactyl species. In this study we have analysed the corresponding cytoplasmic signalling region of PRLR. Results We sequenced PRLR gene exon 10, coding for the major part of the cytoplasmic domain, from cattle, American bison, European bison, yak, sheep, pig and wild boar individuals. We found different patterns of variation in the two receptors within and between ruminants and pigs. Pigs and bison species have no variation within GHR exon 10, but show high haplotype diversity for the PRLR exon 10. In cattle, PRLR shows lower diversity than GHR. The Bovinae PRLR haplotype network fits better the known phylogenetic relationships between the species than that of the GHR, where differences within cattle breeds are larger than between the different species in the subfamily. By comparison with the wild boar haplotypes, a high number of subsequent nonsynonymous substitutions seem to have accumulated in the pig PRLR exon 10 after domestication. Conclusion Both genes affect a multitude of traits that have been targets of selection after domestication. The genes seem to have responded differently to different selection pressures imposed by human artificial selection. The results suggest possible effects of selective sweeps in GHR before domestication in the pig lineage or species divergence in the Bison lineage. The PRLR results may be explained by strong directional selection in pigs or functional switching.

  13. Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

    DEFF Research Database (Denmark)

    Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

    1999-01-01

    We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the factor...

  14. Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD.

    Science.gov (United States)

    Grande-García, Araceli; Lallous, Nada; Díaz-Tejada, Celsa; Ramón-Maiques, Santiago

    2014-02-04

    Upregulation of CAD, the multifunctional protein that initiates and controls the de novo biosynthesis of pyrimidines in animals, is essential for cell proliferation. Deciphering the architecture and functioning of CAD is of interest for its potential usage as an antitumoral target. However, there is no detailed structural information about CAD other than that it self-assembles into hexamers of ∼1.5 MDa. Here we report the crystal structure and functional characterization of the dihydroorotase domain of human CAD. Contradicting all assumptions, the structure reveals an active site enclosed by a flexible loop with two Zn²⁺ ions bridged by a carboxylated lysine and a third Zn coordinating a rare histidinate ion. Site-directed mutagenesis and functional assays prove the involvement of the Zn and flexible loop in catalysis. Comparison with homologous bacterial enzymes supports a reclassification of the DHOase family and provides strong evidence against current models of the architecture of CAD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Both Epistasis and Diversifying Selection Drive the Structural Evolution of the Ebola Virus Glycoprotein Mucin-Like Domain.

    Science.gov (United States)

    Ibeh, Neke; Nshogozabahizi, Jean Claude; Aris-Brosou, Stéphane

    2016-06-01

    Throughout the last 3 decades, Ebola virus (EBOV) outbreaks have been confined to isolated areas within Central Africa; however, the 2014 variant reached unprecedented transmission and mortality rates. While the outbreak was still under way, it was reported that the variant leading up to this outbreak evolved faster than previous EBOV variants, but evidence for diversifying selection was undetermined. Here, we test this selection hypothesis and show that while previous EBOV outbreaks were preceded by bursts of diversification, evidence for site-specific diversifying selection during the emergence of the 2014 EBOV clade is weak. However, we show strong evidence supporting an interplay between selection and correlated evolution (epistasis), particularly in the mucin-like domain (MLD) of the EBOV glycoprotein. By reconstructing ancestral structures of the MLD, we further propose a structural mechanism explaining how the substitutions that accumulated between 1918 and 1969 distorted the MLD, while more recent epistatic substitutions restored part of the structure, with the most recent substitution being adaptive. We suggest that it is this complex interplay between weak selection, epistasis, and structural constraints that has shaped the evolution of the 2014 EBOV variant. The role that selection plays in the emergence of viral epidemics remains debated, particularly in the context of the 2014 EBOV outbreak. Most critically, should such evidence exist, it is generally unclear how this relates to function and increased virulence. Here, we show that the viral lineage leading up to the 2014 outbreak underwent a complex interplay between selection and correlated evolution (epistasis) in a protein region that is critical for immune evasion. We then reconstructed the three-dimensional structure of this domain and showed that the initial mutations in this lineage deformed the structure, while subsequent mutations restored part of the structure. Along this mutational path, the

  16. Evolution of Industry Knowledge in the Public Domain: Prior Art Searching for Software Patents

    Directory of Open Access Journals (Sweden)

    Jinseok Park

    2005-03-01

    Full Text Available Searching prior art is a key part of the patent application and examination processes. A comprehensive prior art search gives the inventor ideas as to how he can improve or circumvent existing technology by providing up to date knowledge on the state of the art. It also enables the patent applicant to minimise the likelihood of an objection from the patent office. This article explores the characteristics of prior art associated with software patents, dealing with difficulties in searching prior art due to the lack of resources, and considers public contribution to the formation of prior art databases. It addresses the evolution of electronic prior art in line with technological development, and discusses laws and practices in the EPO, USPTO, and the JPO in relation to the validity of prior art resources on the Internet. This article also investigates the main features of searching sources and tools in the three patent offices as well as non-patent literature databases. Based on the analysis of various searching databases, it provides some strategies of efficient prior art searching that should be considered for software-related inventions.

  17. Structuring and evolution of Neogene transcurrent basins in the Tellian foreland domain, north-eastern Tunisia

    Science.gov (United States)

    Melki, Fetheddine; Zouaghi, Taher; Harrab, Salah; Sainz, Antonio Casas; Bédir, Mourad; Zargouni, Fouad

    2011-07-01

    The Neogene sedimentary basins (Serravallian to Quaternary) of the Tellian tectonic foreland in north-eastern Tunisia formed within the overall NE-SW sinistral strike-slip tectonic framework of the Ras El Korane-Thibar and El Alia-Teboursouk fault systems. From stratigraphic logs, structural cross sections and interpretation of 2D seismic lines and boreholes, the pre-Neogene basement can be interpreted to be structured according to Eocene (NW-SE) compressional and Oligocene extensional phases. This basement comprises structural highs (anticlines and horsts) and subsiding areas (synclines, half-grabens and grabens) formed during the Neogene. The subsiding areas are delineated by faults striking N030E, N-S and N140E, defining (i) narrow, strongly subsiding synclines, (ii) lozenge-shaped basins and (iii) trapezoidal basins. The architecture of their fill results from the sedimentary balance between tectonics and eustatism. Halokinesis and clay diapirism (driven by Triassic and Neogene evaporites and clays) also played an important role in basin evolution, contributing to the formation of domes and diapirs along active faults.

  18. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  19. Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.

    Science.gov (United States)

    McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad

    2013-01-01

    Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  1. Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

    2012-12-13

    The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

  2. Porphyromonas gingivalis Uses Specific Domain Rearrangements and Allelic Exchange to Generate Diversity in Surface Virulence Factors.

    Science.gov (United States)

    Dashper, Stuart G; Mitchell, Helen L; Seers, Christine A; Gladman, Simon L; Seemann, Torsten; Bulach, Dieter M; Chandry, P Scott; Cross, Keith J; Cleal, Steven M; Reynolds, Eric C

    2017-01-01

    Porphyromonas gingivalis is a keystone pathogen of chronic periodontitis. The virulence of P. gingivalis is reported to be strain related and there are currently a number of strain typing schemes based on variation in capsular polysaccharide, the major and minor fimbriae and adhesin domains of Lys-gingipain (Kgp), amongst other surface proteins. P. gingivalis can exchange chromosomal DNA between strains by natural competence and conjugation. The aim of this study was to determine the genetic variability of P. gingivalis strains sourced from international locations over a 25-year period and to determine if variability in surface virulence factors has a phylogenetic basis. Whole genome sequencing was performed on 13 strains and comparison made to 10 previously sequenced strains. A single nucleotide polymorphism-based phylogenetic analysis demonstrated a shallow tri-lobed phylogeny. There was a high level of reticulation in the phylogenetic network, demonstrating extensive horizontal gene transfer between the strains. Two highly conserved variants of the catalytic domain of the major virulence factor the Kgp proteinase (Kgp cat I and Kgp cat II) were found. There were three variants of the fourth Kgp C-terminal cleaved adhesin domain. Specific variants of the cell surface proteins FimA, FimCDE, MfaI, RagAB, Tpr, and PrtT were also identified. The occurrence of all these variants in the P. gingivalis strains formed a mosaic that was not related to the SNP-based phylogeny. In conclusion P. gingivalis uses domain rearrangements and genetic exchange to generate diversity in specific surface virulence factors.

  3. Evolution-guided adaptation of an adenylation domain substrate specificity to an unusual amino acid

    Czech Academy of Sciences Publication Activity Database

    Vobruba, Šimon; Kadlčík, Stanislav; Gažák, Radek; Janata, Jiří

    2017-01-01

    Roč. 12, č. 12 (2017), č. článku e0189684. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GJ17-13436Y; GA MŠk(CZ) LQ1604 Institutional support: RVO:61388971 Keywords : NONRIBOSOMAL PEPTIDE SYNTHETASES * BIOSYNTHETIC GENE-CLUSTER * LINCOSAMIDE ANTIBIOTICS Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.806, year: 2016

  4. Phylogeny of the TRAF/MATH domain.

    Science.gov (United States)

    Zapata, Juan M; Martínez-García, Vanesa; Lefebvre, Sophie

    2007-01-01

    The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel p-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes. The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.

  5. Lithospheric mantle evolution in the Afro-Arabian domain: Insights from Bir Ali mantle xenoliths (Yemen)

    Science.gov (United States)

    Sgualdo, P.; Aviado, K.; Beccaluva, L.; Bianchini, G.; Blichert-Toft, J.; Bryce, J. G.; Graham, D. W.; Natali, C.; Siena, F.

    2015-05-01

    Detailed petrological and geochemical investigations of an extensive sampling of mantle xenoliths from the Neogene-Quaternary Bir Ali diatreme (southern Yemen) indicate that the underlying lithospheric mantle consists predominantly of medium- to fine-grained (often foliated) spinel-peridotites (85-90%) and spinel-pyroxenites (10-15%) showing thermobarometric estimates in the P-T range of 0.9-2.0 GPa and 900-1150 °C. Peridotites, including lherzolites, harzburgites and dunites delineate continuous chemical, modal and mineralogical variations compatible with large extractions of basic melts occurring since the late Proterozoic (~ 2 Ga, according to Lu-Hf model ages). Pyroxenites may represent intrusions of subalkaline basic melts interacting and equilibrated with the host peridotite. Subsequent metasomatism has led to modal changes, with evidence of reaction patches and clinopyroxene and spinel destabilization, as well as formation of new phases (glass, amphibole and feldspar). These changes are accompanied by enrichment of the most incompatible elements and isotopic compositions. 143Nd/144Nd ranges from 0.51419 to 0.51209 (εNd from + 30.3 to - 10.5), 176Hf/177Hf from 0.28459 to 0.28239 (εHf from + 64.4 to - 13.6), and 208Pb/204Pb from 36.85 to 41.56, thus extending from the depleted mantle (DM) towards the enriched OIB mantle (EM and HIMU) components. 3He/4He (R/RA) ratios vary from 7.2 to 7.9 with He concentrations co-varying with the most incompatible element enrichment, in parallel with metasomatic effects. These metasomatic events, particularly effective in harzburgites and dunites, are attributable to the variable interaction with alkaline basic melts related to the general extensional and rifting regime affecting the East Africa-Arabian domain during the Cenozoic. In this respect, Bir Ali mantle xenoliths resemble those occurring along the Arabian margins and the East Africa Rift system, similarly affected by alkaline metasomatism, whereas they are

  6. Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs.

    Science.gov (United States)

    Stinson, Julie; Inoue, Toshiaki; Yates, Paula; Clancy, Anne; Norton, John D; Sharrocks, Andrew D

    2003-08-15

    DNA binding by the ternary complex factor (TCF) subfamily of ETS-domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix-loop-helix (HLH)-containing Id proteins are trans-acting negative regulators of DNA binding by the TCFs. In the TCF, SAP-2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis-acting NID region that also contains an HLH-like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP-1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin-Cdk complexes results in reduction in protein-protein interactions between the Ids and TCFs and relief of their DNA-binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans-acting Id HLH proteins are themselves regulated by phosphorylation.

  7. SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

    Science.gov (United States)

    McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

    1992-01-01

    The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

  8. Membrane re-modelling by BAR domain superfamily proteins via molecular and non-molecular factors.

    Science.gov (United States)

    Nishimura, Tamako; Morone, Nobuhiro; Suetsugu, Shiro

    2018-04-17

    Lipid membranes are structural components of cell surfaces and intracellular organelles. Alterations in lipid membrane shape are accompanied by numerous cellular functions, including endocytosis, intracellular transport, and cell migration. Proteins containing Bin-Amphiphysin-Rvs (BAR) domains (BAR proteins) are unique, because their structures correspond to the membrane curvature, that is, the shape of the lipid membrane. BAR proteins present at high concentration determine the shape of the membrane, because BAR domain oligomers function as scaffolds that mould the membrane. BAR proteins co-operate with various molecular and non-molecular factors. The molecular factors include cytoskeletal proteins such as the regulators of actin filaments and the membrane scission protein dynamin. Lipid composition, including saturated or unsaturated fatty acid tails of phospholipids, also affects the ability of BAR proteins to mould the membrane. Non-molecular factors include the external physical forces applied to the membrane, such as tension and friction. In this mini-review, we will discuss how the BAR proteins orchestrate membrane dynamics together with various molecular and non-molecular factors. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  9. Diversification, phylogeny and evolution of auxin response factor (ARF) family: insights gained from analyzing maize ARF genes.

    Science.gov (United States)

    Wang, Yijun; Deng, Dexiang; Shi, Yating; Miao, Nan; Bian, Yunlong; Yin, Zhitong

    2012-03-01

    Auxin response factors (ARFs), member of the plant-specific B3 DNA binding superfamily, target specifically to auxin response elements (AuxREs) in promoters of primary auxin-responsive genes and heterodimerize with Aux/IAA proteins in auxin signaling transduction cascade. In previous research, we have isolated and characterized maize Aux/IAA genes in whole-genome scale. Here, we report the comprehensive analysis of ARF genes in maize. A total of 36 ARF genes were identified and validated from the B73 maize genome through an iterative strategy. Thirty-six maize ARF genes are distributed in all maize chromosomes except chromosome 7. Maize ARF genes expansion is mainly due to recent segmental duplications. Maize ARF proteins share one B3 DNA binding domain which consists of seven-stranded β sheets and two short α helixes. Twelve maize ARFs with glutamine-rich middle regions could be as activators in modulating expression of auxin-responsive genes. Eleven maize ARF proteins are lack of homo- and heterodimerization domains. Putative cis-elements involved in phytohormones and light signaling responses, biotic and abiotic stress adaption locate in promoters of maize ARF genes. Expression patterns vary greatly between clades and sister pairs of maize ARF genes. The B3 DNA binding and auxin response factor domains of maize ARF proteins are primarily subjected to negative selection during selective sweep. The mixed selective forces drive the diversification and evolution of genomic regions outside of B3 and ARF domains. Additionally, the dicot-specific proliferation of ARF genes was detected. Comparative genomics analysis indicated that maize, sorghum and rice duplicate chromosomal blocks containing ARF homologs are highly syntenic. This study provides insights into the distribution, phylogeny and evolution of ARF gene family.

  10. Ultrafast carrier dynamics unravel role of surface ligands and metal domain size on the photocatalytic hydrogen evolution efficiency of Au-tipped CdS nanorods: an ultrafast transient absorption spectroscopy study

    Science.gov (United States)

    Ben-Shahar, Yuval; Kriegel, Ilka; Scotognella, Francesco; Waiskopf, Nir; Dal Conte, Stefano; Moretti, Luca; Cerullo, Giulio; Rabani, Eran; Banin, Uri

    2017-02-01

    Semiconductor-metal hybrid nanostructures are interesting materials for photocatalysis. Their tunable properties offer a highly controllable platform to design light-induced charge separation, a key to their function in photocatalytic water splitting. Hydrogen evolution quantum yields are influenced by factors as size, shape, material and morphology of the system, additionally the surface coating or the metal domain size play a dominant role. In this paper we present a study on a well-defined model system of Au-tipped CdS nanorods. We use transient absorption spectroscopy to get insights into the charge carrier dynamics after photoexcitation of the bandgap of CdS nanorods. The study of charge transfer processes combined with the hydrogen evolution efficiency unravels the effects of surface coating and the gold tip size on the photocatalytic efficiency. Differences in efficiency with various surface ligands are primarily ascribed to the effects of surface passivation. Surface trapping of charge carriers is competing with effective charge separation, a prerequisite for photocatalysis, leading to the observed lower hydrogen production quantum yields. Interestingly, non-monotonic hydrogen evolution efficiency with size of the gold tip is observed, resulting in an optimal metal domain size for the most efficient photocatalysis. These results are explained by the sizedependent interplay of the metal domain charging and the relative band-alignments. Taken together our findings are of major importance for the potential application of hybrid nanoparticles as photocatalysts.

  11. Shapes of isolated domains and field induced evolution of regular and random 2D domain structures in LiNbO3 and LiTaO3

    International Nuclear Information System (INIS)

    Chernykh, A.; Shur, V.; Nikolaeva, E.; Shishkin, E.; Shur, A.; Terabe, K.; Kurimura, S.; Kitamura, K.; Gallo, K.

    2005-01-01

    The variety of the shapes of isolated domains, revealed in congruent and stoichiometric LiTaO 3 and LiNbO 3 by chemical etching and visualized by optical and scanning probe microscopy, was obtained by computer simulation. The kinetic nature of the domain shape was clearly demonstrated. The kinetics of domain structure with the dominance of the growth of the steps formed at the domain walls as a result of domain merging was investigated experimentally in slightly distorted artificial regular two-dimensional (2D) hexagonal domain structure and random natural one. The artificial structure has been realized in congruent LiNbO 3 by 2D electrode pattern produced by photolithography. The polarization reversal in congruent LiTaO 3 was investigated as an example of natural domain growth limited by merging. The switching process defined by domain merging was studied by computer simulation. The crucial dependence of the switching kinetics on the nuclei concentration has been revealed

  12. Binding of von Willebrand factor to collagen type III: role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains

    NARCIS (Netherlands)

    van der Plas, R. M.; Gomes, L.; Marquart, J. A.; Vink, T.; Meijers, J. C.; de Groot, P. G.; Sixma, J. J.; Huizinga, E. G.

    2000-01-01

    Binding of von Willebrand Factor (vWF) to sites of vascular injury is the first step of hemostasis. Collagen types I and III are important binding sites for vWF. We have previously determined the three-dimensional structure of the collagen binding A3 domain of vWF (Huizinga et al., Structure 1997;

  13. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC) SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    OpenAIRE

    Karim MAMDOUH ABBAS

    2014-01-01

    The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC) system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms) in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC) in Eg...

  14. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  15. An Operator-Integration-Factor Splitting (OIFS) method for Incompressible Flows in Moving Domains

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Saumil S. [Argonne National Lab. (ANL), Argonne, IL (United States); Fischer, Paul F. [Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Illinois, Urbana-Champaign, IL (United States); Min, Misun [Argonne National Lab. (ANL), Argonne, IL (United States); Tomboulides, Ananias G [Argonne National Lab. (ANL), Argonne, IL (United States); Aristotle Univ., Thessaloniki (Greece)

    2017-10-21

    In this paper, we present a characteristic-based numerical procedure for simulating incompressible flows in domains with moving boundaries. Our approach utilizes an operator-integration-factor splitting technique to help produce an effcient and stable numerical scheme. Using the spectral element method and an arbitrary Lagrangian-Eulerian formulation, we investigate flows where the convective acceleration effects are non-negligible. Several examples, ranging from laminar to turbulent flows, are considered. Comparisons with a standard, semi-implicit time-stepping procedure illustrate the improved performance of the scheme.

  16. Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution

    International Nuclear Information System (INIS)

    Chen, Liqing; Wang, Yujun; Wells, David; Toh, Diana; Harold, Hunt; Zhou, Jing; DiGiammarino, Enrico; Meehan, Edward J.

    2006-01-01

    The crystal structure of the SH3 domain of human osteoclast-stimulating factor has been determined and refined to the ultrahigh resolution of 1.07 Å. The structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors. Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in protein–protein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 12–72, yielded crystals that diffracted to the ultrahigh resolution of 1.07 Å. The overall structure shows a characteristic SH3 fold consisting of two perpendicular β-sheets that form a β-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors

  17. Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation

    Directory of Open Access Journals (Sweden)

    Adam Z. Blatt

    2017-11-01

    Full Text Available Platelet/granulocyte aggregates (PGAs increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP negative regulator, Factor H (FH. Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS, yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism. Utilizing recombinant fragments of FH spanning the entire length of the protein, we mapped the regions of FH most critical for limiting AP activity on the surface of isolated human platelets and neutrophils, as well as the regions most critical for regulating PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP. FH domains 19–20 were the most critical for limiting AP activity on platelets, neutrophils, and at the platelet/granulocyte interface. The role of FH in PGA formation was attributed to its ability to regulate AP-mediated C5a generation. AHUS-related mutations in domains 19–20 caused differential effects on control of PGA formation and AP activity on platelets and neutrophils. Our data indicate FH C-terminal domains are key for regulating PGA formation, thus increased FH protection may have a beneficial impact on diseases characterized by increased PGA formation, such as cardiovascular disease. Additionally, aHUS-related mutations in domains 19–20 have varying effects on control of TRAP-mediated PGA formation, suggesting that some, but not all, aHUS-related mutations may cause increased PGA formation that contributes to excessive thrombosis in patients with aHUS.

  18. Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

    DEFF Research Database (Denmark)

    Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

    1999-01-01

    We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the fact...

  19. Thermochronometrically constrained anatomy and evolution of a Miocene extensional accommodation zone and tilt domain boundary: The southern Wassuk Range, Nevada

    Science.gov (United States)

    Gorynski, Kyle E.; Stockli, Daniel F.; Douglas Walker, J.

    2013-06-01

    (AHe) and Zircon (ZHe) (U-Th)/He thermochronometric data from the southern Wassuk Range (WR) coupled with 40Ar/39Ar age data from the overlying tilted Tertiary section are used to constrain the thermal evolution of an extensional accommodation zone and tilt-domain boundary. AHe and ZHe data record two episodes of rapid cooling related to the tectonic exhumation of the WR fault block beginning at ~15 and ~4 Ma. Extension was accommodated through fault-block rotation and variably tilted the southern WR to the west from ~60°-70° in the central WR to ~15°-35° in the southernmost WR and Pine Grove Hills, and minimal tilting in the Anchorite Hills and along the Mina Deflection to the south. Middle Miocene geothermal gradient estimates record heating immediately prior to large-magnitude extension that was likely coeval with the extrusion of the Lincoln Flat andesite at ~14.8 Ma. Geothermal gradients increase from ~19° ± 4°C/km to ≥ 65° ± 20°C/km toward the Mina Deflection, suggesting that it was the focus of Middle Miocene arc magmatism in the upper crust. The decreasing thickness of tilt blocks toward the south resulted from a shallowing brittle/ductile transition zone. Postmagmatic Middle Miocene extension and fault-block advection were focused in the northern and central WR and coincidentally moderated the large lateral thermal gradient within the uppermost crust.

  20. Epitope mapping of functional domains of human factor V with human and mouse monoclonal antibodies

    International Nuclear Information System (INIS)

    Annamalai, A.E.; Rao, A.K.; Chiu, H.C.; Wang, D.; Dutta-Roy, A.K.; Colman, R.W.

    1986-01-01

    The authors previously described two human monoclonal antibodies (MAbs) which inactivated factor V. The authors have now purified the predominant antibody (H2) on protein A Sepharose using a pH gradient and typed it as IgG 1 ,. Immunoprecipitation of 125 I-human factor Va with H2 demonstrated specificity for the heavy chain (D), Mr = 105,000. The authors compared using ELISA the competitive binding to factor Va, of H2, H1 and two mouse MAbs, B38 (directed to E) and B10 (to activation peptide, Cl). All four antibodies recognized distinct epitopes in factor V with steric overlap in some cases. Factor Xa showed a concentration dependent competition for binding of H1, H2 and B38 but not B10 to factor V/Va in ELISA. All MAbs bound to factor V/Va in the absence of Ca ++ . However, Ca ++ at 8 mM increased the binding of H1 and H2 to 165% and 360% and did not have any effect on the binding of either mouse MAbs. Prothrombin at a concentration of up to 400 μg/ml did not inhibit binding of any of these antibodies. Thus, both the light (E) and heavy (D) chains of factor Va but not the activation peptide (Cl) interact with factor Xa as defined by the MAbs. In addition, sites on both chains for Ca ++ are recognized by particular MAbs (H1 and H2). These studies increase their knowledge of the interactions of factor V domains in the formation of prothrombinase complex

  1. Thickness-dependent a_1/a_2 domain evolution in ferroelectric PbTiO_3 films

    International Nuclear Information System (INIS)

    Li, S.; Zhu, Y.L.; Tang, Y.L.; Liu, Y.; Zhang, S.R.; Wang, Y.J.; Ma, X.L.

    2017-01-01

    Ferroelectric a_1/a_2 domain structure has great potentials in high dielectric capacitors and tunable microwave devices. Understanding its structure is crucial to better control the domain configurations for future applications. In this paper, PbTiO_3 thin films with variant thicknesses are deposited on (110)-oriented GdScO_3 substrates by Pulsed Laser Deposition (PLD) and investigated by using conventional transmission electron microscopy (TEM) and Cs-corrected Scanning TEM. Contrast analysis and electron diffractions reveal that PbTiO_3 films are domain oriented consisting of a_1/a_2 and a/c domain structure. The a_1/a_2 domains are found to distribute periodically and its width increases with increasing film thickness following square root rule. Cs-corrected STEM imaging demonstrates that the domain walls of a_1/a_2 domain structure have the rotation characteristic of 90° ferroelastic domain wall. The interchange of a_1/a_2 domains induces the formation of vertex domains composed of two 90° and one 180° domain walls. Strains are mainly concentrated on the domain walls. The formation of this complex domain configuration is discussed in terms of the effect of the misfit strain, film thickness and cooling rate. These results provide novel information about a_1/a_2 domain structures and are expected to shed some light on modulating a_1/a_2 ferroelectric domain patterns in the design of ferroelectric-based devices.

  2. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Sara Garamszegi

    Full Text Available A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1 domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2 domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral

  3. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    Science.gov (United States)

    Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

    2013-01-01

    A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are

  4. RLS Channel Estimation with Adaptive Forgetting Factor for DS-CDMA Frequency-Domain Equalization

    Science.gov (United States)

    Kojima, Yohei; Tomeba, Hiromichi; Takeda, Kazuaki; Adachi, Fumiyuki

    Frequency-domain equalization (FDE) based on the minimum mean square error (MMSE) criterion can increase the downlink bit error rate (BER) performance of DS-CDMA beyond that possible with conventional rake combining in a frequency-selective fading channel. FDE requires accurate channel estimation. Recently, we proposed a pilot-assisted channel estimation (CE) based on the MMSE criterion. Using MMSE-CE, the channel estimation accuracy is almost insensitive to the pilot chip sequence, and a good BER performance is achieved. In this paper, we propose a channel estimation scheme using one-tap recursive least square (RLS) algorithm, where the forgetting factor is adapted to the changing channel condition by the least mean square (LMS)algorithm, for DS-CDMA with FDE. We evaluate the BER performance using RLS-CE with adaptive forgetting factor in a frequency-selective fast Rayleigh fading channel by computer simulation.

  5. Observation on the transformation domains of super-elastic NiTi shape memory alloy and their evolutions during cyclic loading

    International Nuclear Information System (INIS)

    Xie, Xi; Kan, Qianhua; Kang, Guozheng; Li, Jian; Qiu, Bo; Yu, Chao

    2016-01-01

    The strain field of a super-elastic NiTi shape memory alloy (SMA) and its variation during uniaxial cyclic tension-unloading were observed by a non-contact digital image correlation method, and then the transformation domains and their evolutions were indirectly investigated and discussed. It is seen that the super-elastic NiTi (SMA) exhibits a remarkable localized deformation and the transformation domains evolve periodically with the repeated cyclic tension-unloading within the first several cycles. However, the evolutions of transformation domains at the stage of stable cyclic transformation depend on applied peak stress: when the peak stress is low, no obvious transformation band is observed and the strain field is nearly uniform; when the peak stress is large enough, obvious transformation bands occur due to the residual martensite caused by the prevention of enriched dislocations to the reverse transformation from induced martensite to austenite. Temperature variations measured by an infrared thermal imaging method further verifies the formation and evolution of transformation domains. (paper)

  6. Observation on the transformation domains of super-elastic NiTi shape memory alloy and their evolutions during cyclic loading

    Science.gov (United States)

    Xie, Xi; Kan, Qianhua; Kang, Guozheng; Li, Jian; Qiu, Bo; Yu, Chao

    2016-04-01

    The strain field of a super-elastic NiTi shape memory alloy (SMA) and its variation during uniaxial cyclic tension-unloading were observed by a non-contact digital image correlation method, and then the transformation domains and their evolutions were indirectly investigated and discussed. It is seen that the super-elastic NiTi (SMA) exhibits a remarkable localized deformation and the transformation domains evolve periodically with the repeated cyclic tension-unloading within the first several cycles. However, the evolutions of transformation domains at the stage of stable cyclic transformation depend on applied peak stress: when the peak stress is low, no obvious transformation band is observed and the strain field is nearly uniform; when the peak stress is large enough, obvious transformation bands occur due to the residual martensite caused by the prevention of enriched dislocations to the reverse transformation from induced martensite to austenite. Temperature variations measured by an infrared thermal imaging method further verifies the formation and evolution of transformation domains.

  7. Position specific variation in the rate of evolution intranscription factor binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Moses, Alan M.; Chiang, Derek Y.; Kellis, Manolis; Lander, EricS.; Eisen, Michael B.

    2003-08-28

    The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Here we analyze the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikataeto study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artifacts of computational motif finding algorithms. As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative

  8. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Lee

    2006-12-01

    Full Text Available Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy.Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132 of glioblastomas and 12.5% (1/8 of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors.Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

  9. Evolution of trefoil factor(s: genetic and spatio-temporal expression of trefoil factor 2 in the chicken (Gallus gallus domesticus.

    Directory of Open Access Journals (Sweden)

    Zhengyu Jiang

    Full Text Available Trefoil factors are essential healing initiators participating in mucosal reconstitution and tissue morphogenesis, especially on the surfaces of the gastrointestinal tract. This family has been cloned and characterized predominantly from mammals and amphibians. Avian species ingest stone and grit to help digest food, which may expose their gut to severe physical conditions. To further the understanding of the function of the TFF gene family across species, we undertook this research to clone, sequence, and characterize the spatio-temporal expression patterns of chicken TFF2 (ChTFF2 cDNA. Bioinformatics analysis of the promoter region and deduced amino acid sequence demonstrated that ChTFF2 contained unique characteristics; specifically the chicken promoter has multiple start sites and the protein contains a series of Lys-Lys-Val repeats. Unlike mammals, where TFF2 is detected primarily in the stomach, and occasionally in the proximal duodenum, chicken TFF2 transcripts are found throughout the gastrointestinal tract, with major expression sites in the glandular and muscular stomach as well as evident expression in the colon, small intestine, cecal tonsil and crop. Temporal analysis of intestinal ChTFF2 transcripts by quantitative RT-PCR showed high levels in embryos and a trend of constant expression during embryonic and post-hatch development, with a reduction occurring around hatch. Phylogenetic analysis highlighted the conservation of TFF proteins and functional divergence of trefoil domains, which suggest a transitional role in the bird during evolution.

  10. Predicting Homophobic Behavior among Heterosexual Youth: Domain General and Sexual Orientation-Specific Factors at the Individual and Contextual Level

    Science.gov (United States)

    Poteat, V. Paul; DiGiovanni, Craig D.; Scheer, Jillian R.

    2013-01-01

    As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual…

  11. The Contributions of Domain-General and Numerical Factors to Third-Grade Arithmetic Skills and Mathematical Learning Disability

    Science.gov (United States)

    Cowan, Richard; Powell, Daisy

    2014-01-01

    Explanations of the marked individual differences in elementary school mathematical achievement and mathematical learning disability (MLD or dyscalculia) have involved domain-general factors (working memory, reasoning, processing speed, and oral language) and numerical factors that include single-digit processing efficiency and multidigit skills…

  12. [Expression in E.coli and bioactivity assay of Micrococcus luteus resuscitation promoting factor domain and its mutants].

    Science.gov (United States)

    Yue, Chen-Li; Shi, Jie-Ran; Shi, Chang-Hong; Zhang, Hai; Zhao, Lei; Zhang, Ting-Fen; Zhao, Yong; Xi, Li

    2008-10-01

    To express Micrococcus luteus resuscitation promoting factor (Rpf) domain and its mutants in prokaryotic cells, and to investigate their bioactivity. The gene of Rpf domain and its mutants (E54K, E54A) were amplified by polymerase chain reaction (PCR) from the genome of Micrococcus luteus and cloned into pMD18-T vector. After sequenced, the Rpf domain and its mutant gene were subcloned into expression vector PGEX-4T-1, and transfected into E. coli DH5alpha. The expressed product was purified by affinity chromatography using GST Fusion Protein Purification bead. The aim proteins were identified by SDS-PAGE analysis and by Western blot with monoclonal antibodies against Rpf domain (mAb). The bioactivity of the proteins was analyzed by stimulating the resuscitation of Mycobacterium smegmatis. The sequences of the PCR products were identical to those of the Rpf domain and its mutant gene in GenBank. The relative molecular mass identified by SDS-PAGE analysis was consistent with that had been reported, which was also confirmed by Western blot analysis that there were specific bindings at 32 000 with Rpf domain mAb. The purified GST-Rpf domain could stimulate resuscitation of Mycobacterium smegmatis. Replacements E54A and especially E54K resulted in inhibition of Rpf resuscitation activity. Rpf domain and two kinds of its mutant protein were obtained, and its effects on the resuscitation of dormant Mycobacterium smegmatis were clarified.

  13. Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

    Science.gov (United States)

    Johnson, Bryce G; Ren, Shuyu; Karaca, Gamze; Gomez, Ivan G; Fligny, Cécile; Smith, Benjamin; Ergun, Ayla; Locke, George; Gao, Benbo; Hayes, Sebastian; MacDonnell, Scott; Duffield, Jeremy S

    2017-06-01

    Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ β -catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis. Copyright © 2017 by the American Society of Nephrology.

  14. Measuring implementation behaviour of menu guidelines in the childcare setting: confirmatory factor analysis of a theoretical domains framework questionnaire (TDFQ).

    Science.gov (United States)

    Seward, Kirsty; Wolfenden, Luke; Wiggers, John; Finch, Meghan; Wyse, Rebecca; Oldmeadow, Christopher; Presseau, Justin; Clinton-McHarg, Tara; Yoong, Sze Lin

    2017-04-04

    While there are number of frameworks which focus on supporting the implementation of evidence based approaches, few psychometrically valid measures exist to assess constructs within these frameworks. This study aimed to develop and psychometrically assess a scale measuring each domain of the Theoretical Domains Framework for use in assessing the implementation of dietary guidelines within a non-health care setting (childcare services). A 75 item 14-domain Theoretical Domains Framework Questionnaire (TDFQ) was developed and administered via telephone interview to 202 centre based childcare service cooks who had a role in planning the service menu. Confirmatory factor analysis (CFA) was undertaken to assess the reliability, discriminant validity and goodness of fit of the 14-domain theoretical domain framework measure. For the CFA, five iterative processes of adjustment were undertaken where 14 items were removed, resulting in a final measure consisting of 14 domains and 61 items. For the final measure: the Chi-Square goodness of fit statistic was 3447.19; the Standardized Root Mean Square Residual (SRMR) was 0.070; the Root Mean Square Error of Approximation (RMSEA) was 0.072; and the Comparative Fit Index (CFI) had a value of 0.78. While only one of the three indices support goodness of fit of the measurement model tested, a 14-domain model with 61 items showed good discriminant validity and internally consistent items. Future research should aim to assess the psychometric properties of the developed TDFQ in other community-based settings.

  15. A non-catalytic N-terminal domain negatively influences the nucleotide exchange activity of translation elongation factor 1Bα.

    Science.gov (United States)

    Trosiuk, Tetiana V; Shalak, Vyacheslav F; Szczepanowski, Roman H; Negrutskii, Boris S; El'skaya, Anna V

    2016-02-01

    Eukaryotic translation elongation factor 1Bα (eEF1Bα) is a functional homolog of the bacterial factor EF-Ts, and is a component of the macromolecular eEF1B complex. eEF1Bα functions as a catalyst of guanine nucleotide exchange on translation elongation factor 1A (eEF1A). The C-terminal domain of eEF1Bα is necessary and sufficient for its catalytic activity, whereas the N-terminal domain interacts with eukaryotic translation elongation factor 1Bγ (eEF1Bγ) to form a tight complex. However, eEF1Bγ has been shown to enhance the catalytic activity of eEF1Bα attributed to the C-terminal domain of eEF1Bα. This suggests that the N-terminal domain of eEF1Bα may in some way influence the guanine nucleotide exchange process. We have shown that full-length recombinant eEF1Bα and its truncated forms are non-globular proteins with elongated shapes. Truncation of the N-terminal domain of eEF1Bα, which is dispensable for catalytic activity, resulted in acceleration of the rate of guanine nucleotide exchange on eEF1A compared to full-length eEF1Bα. A similar effect on the catalytic activity of eEF1Bα was observed after its interaction with eEF1Bγ. We suggest that the non-catalytic N-terminal domain of eEF1Bα may interfere with eEF1A binding to the C-terminal catalytic domain, resulting in a decrease in the overall rate of the guanine nucleotide exchange reaction. Formation of a tight complex between the eEF1Bγ and eEF1Bα N-terminal domains abolishes this inhibitory effect. © 2015 FEBS.

  16. Factors which influence Texas biology teachers' decisions to emphasize fundamental concepts of evolution

    Science.gov (United States)

    Bilica, Kimberly Lynn

    emphasis that Texas biology teachers currently as well as prefer to place on fundamental evolution concepts in relationship to specific belief factors which influence biology teachers' curricular decisions.

  17. Evolution of defect signatures at ferroelectric domain walls in Mg-doped LiNbO3

    International Nuclear Information System (INIS)

    Nataf, Guillaume F.; Guennou, Mael; Haussmann, Alexander; Barrett, Nick; Kreisel, Jens

    2016-01-01

    The domain structure of uniaxial ferroelectric lithium niobate single crystals is investigated using Raman spectroscopy mapping. The influence of doping with magnesium and poling at room temperature is studied by analysing frequency shifts at domain walls and their variations with dopant concentration and annealing conditions. It is shown that defects are stabilized at domain walls and that changes in the defect structures with Mg concentration can be probed by the shift of Raman modes. We show that the signatures of polar defects in the bulk and at the domain walls differ. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. Evolution of defect signatures at ferroelectric domain walls in Mg-doped LiNbO{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Nataf, Guillaume F. [Materials, Research and Technology Department, Luxembourg Institute of Science and Technology, 41 Rue du Brill, 4422, Belvaux (Luxembourg); Service de Physique de l' Etat Condense, DSM/IRAMIS/SPEC, CNRS UMR 3680, CEA Saclay, 91191, Gif sur Yvette cedex (France); Guennou, Mael [Materials, Research and Technology Department, Luxembourg Institute of Science and Technology, 41 Rue du Brill, 4422, Belvaux (Luxembourg); Haussmann, Alexander [Institut fuer Angewandte Photophysik, Technische Universitaet Dresden, George-Baehr-Str. 1, 01069, Dresden (Germany); Barrett, Nick [Service de Physique de l' Etat Condense, DSM/IRAMIS/SPEC, CNRS UMR 3680, CEA Saclay, 91191, Gif sur Yvette cedex (France); Kreisel, Jens [Materials, Research and Technology Department, Luxembourg Institute of Science and Technology, 41 Rue du Brill, 4422, Belvaux (Luxembourg); Physics and Materials Science Research Unit, University of Luxembourg, 41 Rue du Brill, 4422, Belvaux (Luxembourg)

    2016-03-15

    The domain structure of uniaxial ferroelectric lithium niobate single crystals is investigated using Raman spectroscopy mapping. The influence of doping with magnesium and poling at room temperature is studied by analysing frequency shifts at domain walls and their variations with dopant concentration and annealing conditions. It is shown that defects are stabilized at domain walls and that changes in the defect structures with Mg concentration can be probed by the shift of Raman modes. We show that the signatures of polar defects in the bulk and at the domain walls differ. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Heavy Quark Production at HERA in KT Factorization Supplemented With CCFM Evolution

    International Nuclear Information System (INIS)

    Jung, H.

    2001-01-01

    The application of k t - factorization, supplemented with the CCFM small-x evolution equation, to heavy quark production is discussed. Differential cross sections of bb production and also inelastic J/ψ production as measured at HERA are compared to the hadron level CCFM Monte Carlo generator Cascade, using the unintegrated gluon density obtained within the CCFM evolution approach from a fit to HERA F 2 data. (author)

  20. APETALA 2-domain-containing transcription factors: focusing on abscisic acid and gibberellins antagonism.

    Science.gov (United States)

    Shu, Kai; Zhou, Wenguan; Yang, Wenyu

    2018-02-01

    The phytohormones abscisic acid (ABA) and gibberellin (GA) antagonistically mediate diverse plant developmental processes including seed dormancy and germination, root development, and flowering time control, and thus the optimal balance between ABA and GA is essential for plant growth and development. Although more than a half and one century have passed since the initial discoveries of ABA and GA, respectively, the precise mechanisms underlying ABA-GA antagonism still need further investigation. Emerging evidence indicates that two APETALA 2 (AP2)-domain-containing transcription factors (ATFs), ABI4 in Arabidopsis and OsAP2-39 in rice, play key roles in ABA and GA antagonism. These two transcription factors precisely regulate the transcription pattern of ABA and GA biosynthesis or inactivation genes, mediating ABA and GA levels. In this Viewpoint article, we try to shed light on the effects of ATFs on ABA-GA antagonism, and summarize the overlapping but distinct biological functions of these ATFs in the antagonism between ABA and GA. Finally, we strongly propose that further research is needed into the detailed roles of additional numerous ATFs in ABA and GA crosstalk, which will improve our understanding of the antagonism between these two phytohormones. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  1. CNF1-like deamidase domains: common Lego bricks among cancer-promoting immunomodulatory bacterial virulence factors.

    Science.gov (United States)

    Ho, Mengfei; Mettouchi, Amel; Wilson, Brenda A; Lemichez, Emmanuel

    2018-05-03

    Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic E. coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer. In particular, through in silico analysis of the distribution of the CNF1-like deamidase active site Gly-Cys-(Xaa)n-His sequence motif in bacterial genomes, we unveil the wide distribution of the super-family of CNF-like toxins and CNF-like deamidase domains among members of the enterobacteriacae and in association with a large variety of toxin delivery systems. We extent our discussion with recent findings concerning cellular systems that control activated Rac1 GTPase stability and provide protection against cancer. These findings point to the urgency for developing holistic approaches toward personalized medicine that include monitoring for asymptomatic carriage of pathogenic toxin-producing bacteria and that ultimately might lead to improved public health and increased lifespans.

  2. A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution

    DEFF Research Database (Denmark)

    Wong, W T; Schumacher, C; Salcini, A E

    1995-01-01

    In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heteroge......In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several...... heterogeneous proteins of yeast and nematode. The EH domain spans about 70 amino acids and shows approximately 60% overall amino acid conservation. We demonstrated the ability of the EH domain to specifically bind cytosolic proteins in normal and malignant cells of mesenchymal, epithelial, and hematopoietic...... (for Eps15-related). Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins....

  3. Evolution of psychosocial factors at work in a French region.

    Science.gov (United States)

    Bègue, C; Fouquet, N; Bodin, J; Ramond-Roquin, A; Huez, J-F; Bouton, C; Roquelaure, Y

    2016-03-01

    Psychosocial factors at work (PFW) can be defined as all non-physicochemical occupational risks. Several epidemiological models have been proposed to measure PFW, but one of the most widely used is Karasek's model. To determine whether psychosocial factors, evaluated by Karasek's questionnaire, had increased in a cohort of workers. A random sample of workers in the Pays de la Loire region of France, who could be considered representative of the region's population of salaried workers, filled in a self-administered questionnaire, including Karasek's self-administered questionnaire, in 2002-05 and 2007-09. Karasek's questionnaire can be used to study three psychosocial dimensions (psychological demand, decision latitude and social support in the workplace) in workers in order to define two high-risk situations for their health: 'Job Strain' and 'Iso Strain'. Changes in job strain and iso strain among workers were studied according to the workers' sociodemographic characteristics and their working conditions. In this sample of 2049 workers, the proportion with iso strain increased between the two periods from 12 to 16%, P workers. Deterioration of Karasek indicators was mainly explained by an increase of the 'low social support' dimension (38 versus 49%, P workers in recent years. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. 1H, 15N and 13C assignments of domain 5 of Dictyostelium discoideum gelation factor (ABP-120) in its native and 8M urea-denatured states.

    Science.gov (United States)

    Hsu, Shang-Te Danny; Cabrita, Lisa D; Christodoulou, John; Dobson, Christopher M

    2009-06-01

    The gelation factor from Dictyostelium discoideum (ABP-120) is an actin binding protein consisting of six immunoglobulin (Ig) domains in the C-terminal rod domain. We have recently used the pair of domains 5 and 6 of ABP-120 as a model system for studying multi-domain nascent chain folding on the ribosome. Here we present the NMR assignments of domain 5 in its native and 8M urea-denatured states.

  5. Impact factor evolution of nursing research journals: 2009 to 2014.

    Science.gov (United States)

    Cáceres, Macarena C; Guerrero-Martín, Jorge; González-Morales, Borja; Pérez-Civantos, Demetrio V; Carreto-Lemus, Maria A; Durán-Gómez, Noelia

    The use of bibliometric indicators (impact factor [IF], impact index, h-index, etc.) is now believed to be a fundamental measure of the quality of scientific research output. In this context, the presence of scientific nursing journals in international databases and the factors influencing their impact ratings is being widely analyzed. The aim of this study was to analyze the presence of scientific nursing journals in international databases and track the changes in their IF. A secondary analysis was carried out on data for the years 2009 to 2014 held in the JCR database (subject category: nursing). Additionally, the presence of scientific nursing journals in Medline, CINAHL, Scopus, and SJR was analyzed. During the period studied, the number of journals indexed in the JCR under the nursing subject category increased from 70 in 2009 (mean IF: 0.99, standard deviation: 0.53) to 115 in 2014 (mean IF: 1.04, standard deviation: 0.42), of which only 70 were listed for the full six years. Although mean IF showed an upward trend throughout this time, no statistically significant differences were found in the variations to this figure. Although IF and other bibliometric indicators have their limitations, it is nonetheless true that bibliometry is now the most widely used tool for evaluating scientific output in all disciplines, including nursing, highlighting the importance of being familiar with how they are calculated and their significance when deciding the journal or journals in which to publish the results of our research. That said, it is also necessary to consider other possible alternative ways of assessing the quality and impact of scientific contributions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The B-domain of factor VIII reduces cell membrane attachement to host cells in serum free conditions

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Flintegaard, Thomas Veje

    2010-01-01

    engineered extensively throughout the years to increase the low production yields that initially were obtained from mammalian cell cultures. The scope of this work was to investigate the interaction of rFVIII with the cell membrane surface of the producing cells in serum free medium. We wondered whether...... binding of rFVIII to the cell membrane could be a factor diminishing the production yield. We studied the contribution of the rFVIII B-domain to membrane attachment by transfecting several constructs containing increasing lengths of the B-domain into cells under serum free conditions. We found that 90......% of rFVIII is attached to the cell membrane of the producing cell when the rFVIII variant contains a short B-domain (21 aa). By increasing the length of the B-domain the membrane attached fraction can be reduced to 50% of the total expressed rFVIII. Further, our studies show that the N...

  7. Heavy quark production at the TEVATRON and HERA using kt-factorization with CCFM evolution

    International Nuclear Information System (INIS)

    Jung, H.

    2001-10-01

    The application of k t -factorization supplemented with the CCFM small-x evolution equation to heavy quark production at the TEVATRON and at HERA is discussed. The bb production cross sections at the TEVATRON can be consistently described using the k t -factorization formalism together with the unintegrated gluon density obtained within the CCFM evolution approach from a fit to HERA F 2 data. Special attention is drawn to the comparison with measured visible cross sections, which are compared to the hadron level Monte Carlo generator Cascade. (orig.)

  8. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  9. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors.

    Science.gov (United States)

    Yoshimura, Shin-ichiro; Gerondopoulos, Andreas; Linford, Andrea; Rigden, Daniel J; Barr, Francis A

    2010-10-18

    A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activate Rab35 in an endocytic pathway trafficking Shiga toxin to the trans-Golgi network. DENND2 GEFs target to actin filaments and control Rab9-dependent trafficking of mannose-6-phosphate receptor to lysosomes. DENND4 GEFs target to a tubular membrane compartment adjacent to the Golgi, where they activate Rab10, which suggests a function in basolateral polarized sorting in epithelial cells that compliments the non-DENN GEF Sec2 acting on Rab8 in apical sorting. DENND1C, DENND3, DENND5A/5B, MTMR5/13, and MADD activate Rab13, Rab12, Rab39, Rab28, and Rab27A/27B, respectively. Together, these findings provide a basis for future studies on Rab regulation and function.

  10. A novel firmicute protein family related to the actinobacterial resuscitation-promoting factors by non-orthologous domain displacement

    Directory of Open Access Journals (Sweden)

    Finan Christopher L

    2005-03-01

    Full Text Available Abstract Background In Micrococcus luteus growth and resuscitation from starvation-induced dormancy is controlled by the production of a secreted growth factor. This autocrine resuscitation-promoting factor (Rpf is the founder member of a family of proteins found throughout and confined to the actinobacteria (high G + C Gram-positive bacteria. The aim of this work was to search for and characterise a cognate gene family in the firmicutes (low G + C Gram-positive bacteria and obtain information about how they may control bacterial growth and resuscitation. Results In silico analysis of the accessory domains of the Rpf proteins permitted their classification into several subfamilies. The RpfB subfamily is related to a group of firmicute proteins of unknown function, represented by YabE of Bacillus subtilis. The actinobacterial RpfB and firmicute YabE proteins have very similar domain structures and genomic contexts, except that in YabE, the actinobacterial Rpf domain is replaced by another domain, which we have called Sps. Although totally unrelated in both sequence and secondary structure, the Rpf and Sps domains fulfil the same function. We propose that these proteins have undergone "non-orthologous domain displacement", a phenomenon akin to "non-orthologous gene displacement" that has been described previously. Proteins containing the Sps domain are widely distributed throughout the firmicutes and they too fall into a number of distinct subfamilies. Comparative analysis of the accessory domains in the Rpf and Sps proteins, together with their weak similarity to lytic transglycosylases, provide clear evidence that they are muralytic enzymes. Conclusions The results indicate that the firmicute Sps proteins and the actinobacterial Rpf proteins are cognate and that they control bacterial culturability via enzymatic modification of the bacterial cell envelope.

  11. The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf

    Directory of Open Access Journals (Sweden)

    Geldner Niko

    2005-02-01

    Full Text Available Abstract Background Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. Results Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7. Conclusion Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains.

  12. The Role of Factor XIa (FXIa) Catalytic Domain Exosite Residues in Substrate Catalysis and Inhibition by the Kunitz Protease Inhibitor Domain of Protease Nexin 2*

    Science.gov (United States)

    Su, Ya-Chi; Miller, Tara N.; Navaneetham, Duraiswamy; Schoonmaker, Robert T.; Sinha, Dipali; Walsh, Peter N.

    2011-01-01

    To select residues in coagulation factor XIa (FXIa) potentially important for substrate and inhibitor interactions, we examined the crystal structure of the complex between the catalytic domain of FXIa and the Kunitz protease inhibitor (KPI) domain of a physiologically relevant FXIa inhibitor, protease nexin 2 (PN2). Six FXIa catalytic domain residues (Glu98, Tyr143, Ile151, Arg3704, Lys192, and Tyr5901) were subjected to mutational analysis to investigate the molecular interactions between FXIa and the small synthetic substrate (S-2366), the macromolecular substrate (factor IX (FIX)) and inhibitor PN2KPI. Analysis of all six Ala mutants demonstrated normal Km values for S-2366 hydrolysis, indicating normal substrate binding compared with plasma FXIa; however, all except E98A and K192A had impaired values of kcat for S-2366 hydrolysis. All six Ala mutants displayed deficient kcat values for FIX hydrolysis, and all were inhibited by PN2KPI with normal values of Ki except for K192A, and Y5901A, which displayed increased values of Ki. The integrity of the S1 binding site residue, Asp189, utilizing p-aminobenzamidine, was intact for all FXIa mutants. Thus, whereas all six residues are essential for catalysis of the macromolecular substrate (FIX), only four (Tyr143, Ile151, Arg3704, and Tyr5901) are important for S-2366 hydrolysis; Glu98 and Lys192 are essential for FIX but not S-2366 hydrolysis; and Lys192 and Tyr5901 are required for both inhibitor and macromolecular substrate interactions. PMID:21778227

  13. Elucidating the Molecular Factors Implicated in the Persistence and Evolution of Transferable Antibiotic Resistance

    DEFF Research Database (Denmark)

    Porse, Andreas

    Being the most diverse and abundant domain of life, bacteria exemplify the remarkable ability of evolution to fit organisms into almost any imaginable niche on the planet. Although the capacity of bacteria to diversify and adapt is fundamental to natural ecosystems and modern biotechnology...... natural environment, we looked into the genomes of Escherichia coli longitudinally sampled from the infant gut over the first year of life. Sequence analysis revealed a high degree of genomic plasticity, with frequent gene acquisition and loss events. While the acquisition of new genetic material is often...

  14. Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

    Science.gov (United States)

    Collier, Mary E. W.; Ettelaie, Camille

    2011-01-01

    The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

  15. Allostery Is an Intrinsic Property of the Protease Domain of DegS Implications for Enzyme Function and Evolution

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jungsan; Grant, Robert A.; Sauer, Robert T. (MIT)

    2010-12-02

    DegS is a periplasmic Escherichia coli protease, which functions as a trimer to catalyze the initial rate-limiting step in a proteolytic cascade that ultimately activates transcription of stress response genes in the cytoplasm. Each DegS subunit consists of a protease domain and a PDZ domain. During protein folding stress, DegS is allosterically activated by peptides exposed in misfolded outer membrane porins, which bind to the PDZ domain and stabilize the active protease. It is not known whether allostery is conferred by the PDZ domains or is an intrinsic feature of the trimeric protease domain. Here, we demonstrate that free DegS{sup {Delta}PDZ} equilibrates between active and inactive trimers with the latter species predominating. Substrate binding stabilizes active DegS{sup {Delta}PDZ} in a positively cooperative fashion. Mutations can also stabilize active DegS{sup {Delta}PDZ} and produce an enzyme that displays hyperbolic kinetics and degrades substrate with a maximal velocity within error of that for fully activated, intact DegS. Crystal structures of multiple DegS{sup {Delta}PDZ} variants, in functional and non-functional conformations, support a two-state model in which allosteric switching is mediated by changes in specific elements of tertiary structure in the context of an invariant trimeric base. Overall, our results indicate that protein substrates must bind sufficiently tightly and specifically to the functional conformation of DegS{sup {Delta}PDZ} to assist their own degradation. Thus, substrate binding alone may have regulated the activities of ancestral DegS trimers with subsequent fusion of the protease domain to a PDZ domain, resulting in ligand-mediated regulation.

  16. An analysis of factors influencing the teaching of biological evolution in Louisiana public secondary schools

    Science.gov (United States)

    Aguillard, Donald Wayne

    Louisiana public school biology teachers were surveyed to investigate their attitudes toward biological evolution. A mixed method investigation was employed using a questionnaire and open-ended interviews. Results obtained from 64 percent of the sample receiving the questionnaire indicate that although teachers endorse the study of evolution as important, instructional time allocated to evolution is disproportionate with its status as a unifying concept of science. Two variables, number of college courses specifically devoted to evolution and number of semester credit hours in biology, produced a significant correlation with emphasis placed on evolution. The data suggest that teachers' knowledge base emerged as the most significant factor in determining degree of classroom emphasis on evolution. The data suggest a need for substantive changes in the training of biology teachers. Thirty-five percent of teachers reported pursuing fewer than 20 semester credit hours in biology and 68 percent reported fewer than three college courses in which evolution was specifically discussed. Fifty percent reported a willingness to undergo additional training about evolution. In spite of the fact that evolution has been identified as a major conceptual theme across all of the sciences, there is strong evidence that Louisiana biology teachers de-emphasize evolutionary theory. Even when biology teachers allocate instructional time to evolutionary theory, many avoid discussion of human evolution. The research data show that only ten percent of teachers reported allocating more than sixty minutes of instructional time to human evolution. Louisiana biology teachers were found to hold extreme views on the subject of creationism as a component of the biology curriculum. Twenty-nine percent indicated that creationism should be taught in high school biology and 25--35 percent allocated instructional time to discussions of creationism. Contributing to the de-emphasis of evolutionary theory

  17. Structure, dynamics and RNA binding of the multi-domain splicing factor TIA-1

    Science.gov (United States)

    Wang, Iren; Hennig, Janosch; Jagtap, Pravin Kumar Ankush; Sonntag, Miriam; Valcárcel, Juan; Sattler, Michael

    2014-01-01

    Alternative pre-messenger ribonucleic acid (pre-mRNA) splicing is an essential process in eukaryotic gene regulation. The T-cell intracellular antigen-1 (TIA-1) is an apoptosis-promoting factor that modulates alternative splicing of transcripts, including the pre-mRNA encoding the membrane receptor Fas. TIA-1 is a multi-domain ribonucleic acid (RNA) binding protein that recognizes poly-uridine tract RNA sequences to facilitate 5′ splice site recognition by the U1 small nuclear ribonucleoprotein (snRNP). Here, we characterize the RNA interaction and conformational dynamics of TIA-1 by nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC) and small angle X-ray scattering (SAXS). Our NMR-derived solution structure of TIA-1 RRM2–RRM3 (RRM2,3) reveals that RRM2 adopts a canonical RNA recognition motif (RRM) fold, while RRM3 is preceded by an non-canonical helix α0. NMR and SAXS data show that all three RRMs are largely independent structural modules in the absence of RNA, while RNA binding induces a compact arrangement. RRM2,3 binds to pyrimidine-rich FAS pre-mRNA or poly-uridine (U9) RNA with nanomolar affinities. RRM1 has little intrinsic RNA binding affinity and does not strongly contribute to RNA binding in the context of RRM1,2,3. Our data unravel the role of binding avidity and the contributions of the TIA-1 RRMs for recognition of pyrimidine-rich RNAs. PMID:24682828

  18. Factors regulating nitrogenase activity and hydrogen evolution in Azolla-Anabaena symbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, M.; Kumar, A.; Kumar, H.D. (Banaras Hindu Univ., Varanasi (India). Dept. of Botany)

    1989-01-01

    Nitrogenase activity and H{sub 2} production capacity have been studied in intact Azolla plants. Under aerobic conditions the plants showed a C{sub 2}H{sub 2} reduction rate of 6.65 nmoles C{sub 2}H{sub 4} mg {sup -1} fresh weight in light at 48 h. Considerable activity was also present in the dark. Though H{sub 2} evolution was detected under aerobic conditions there was multifold stimulation under anaerobic conditions. There was no significant change in nitrogenase activity under anaerobic conditions. Increasing concentrations of O{sub 2} inhibited nitrogenase activity but 5% O{sub 2} proved stimulatory for H{sub 2} evolution in light. In the dark, there was a gradual stimulation in H{sub 2} evolution even up to 20% O{sub 2}. The addition of combined nitrogen sources, namely NH{sub 4}Cl or KNO{sub 3} (10 mM), resulted in complete inhibition of the C{sub 2}H{sub 2}-reduction activity within 48 h, but H{sub 2} evolution was not inhibited. Indeed, these combined nitrogen sources stimulated H{sub 2} evolution. Though nitrogenase activity was affected, the heterocyst frequency remained unaltered. Phosphate addition resulted in significant stimulation of nitrogenase and H{sub 2} evolution activity. These results suggest that nitrogenase and H{sub 2} evolution activity in Azolla are affected by a number of factors which show a differential effect on nitrogenase and H{sub 2} evolution. Furthermore, our results indicate the presence of a soluble reversible hydrogenase in Azolla. (author).

  19. The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals

    Directory of Open Access Journals (Sweden)

    Dunham Ian

    2007-09-01

    Full Text Available Abstract Background The evolution of genomic imprinting, the parental-origin specific expression of genes, is the subject of much debate. There are several theories to account for how the mechanism evolved including the hypothesis that it was driven by the evolution of X-inactivation, or that it arose from an ancestrally imprinted chromosome. Results Here we demonstrate that mammalian orthologues of imprinted genes are dispersed amongst autosomes in both monotreme and marsupial karyotypes. Conclusion These data, along with the similar distribution seen in birds, suggest that imprinted genes were not located on an ancestrally imprinted chromosome or associated with a sex chromosome. Our results suggest imprinting evolution was a stepwise, adaptive process, with each gene/cluster independently becoming imprinted as the need arose.

  20. The secondary structure of large-subunit rRNA divergent domains, a marker for protist evolution

    DEFF Research Database (Denmark)

    Lenaers, G; Nielsen, Henrik; Engberg, J

    1988-01-01

    The secondary structure of the large-subunit ribosomal RNA (24-26S rRNA) has been studied with emphasis on comparative analysis of the folding patterns of the divergent domains in the available protist sequences, that is Prorocentrum micans (dinoflagellate), Saccharomyces carlsbergensis (yeast......), Tetrahymena thermophila (ciliate), Physarum polycephalum and Dictyostelium discoideum (slime moulds), Crithidia fasciculata and Giardia lamblia (parasitic flagellates). The folding for the D3, D7a and D10 divergent domains has been refined and a consensus model for the protist 24-26S rRNA structure...

  1. Crystal Structure of the HEAT Domain from the Pre-mRNA Processing Factor Symplekin

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, Sarah A.; Frazier, Monica L.; Steiniger, Mindy; Mast, Ann M.; Marzluff, William F.; Redinbo, Matthew R.; (UNC)

    2010-09-30

    The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and polyadenylation, although in metazoa the replication-dependent histone mRNAs are processed by 3'-end cleavage but not polyadenylation. The macromolecular complex responsible for processing both canonical and histone pre-mRNAs contains the {approx} 1160-residue protein Symplekin. Secondary-structural prediction algorithms identified putative HEAT domains in the 300 N-terminal residues of all Symplekins of known sequence. The structure and dynamics of this domain were investigated to begin elucidating the role Symplekin plays in mRNA maturation. The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was determined to 2.4 {angstrom} resolution with single-wavelength anomalous dispersion phasing methods. The structure exhibits five canonical HEAT repeats along with an extended 31-amino-acid loop (loop 8) between the fourth and fifth repeat that is conserved within closely related Symplekin sequences. Molecular dynamics simulations of this domain show that the presence of loop 8 dampens correlated and anticorrelated motion in the HEAT domain, therefore providing a neutral surface for potential protein-protein interactions. HEAT domains are often employed for such macromolecular contacts. The Symplekin HEAT region not only structurally aligns with several established scaffolding proteins, but also has been reported to contact proteins essential for regulating 3'-end processing. Together, these data support the conclusion that the Symplekin HEAT domain serves as a scaffold for protein-protein interactions essential to the mRNA maturation process.

  2. Evolution of vacuolar proton pyrophosphatase domains and volutin granules: clues into the early evolutionary origin of the acidocalcisome

    Directory of Open Access Journals (Sweden)

    Valerio Alejandro

    2011-10-01

    Full Text Available Abstract Background Volutin granules appear to be universally distributed and are morphologically and chemically identical to acidocalcisomes, which are electron-dense granular organelles rich in calcium and phosphate, whose functions include storage of phosphorus and various metal ions, metabolism of polyphosphate, maintenance of intracellular pH, osmoregulation and calcium homeostasis. Prokaryotes are thought to differ from eukaryotes in that they lack membrane-bounded organelles. However, it has been demonstrated that as in acidocalcisomes, the calcium and polyphosphate-rich intracellular "volutin granules (polyphosphate bodies" in two bacterial species, Agrobacterium tumefaciens, and Rhodospirillum rubrum, are membrane bound and that the vacuolar proton-translocating pyrophosphatases (V-H+PPases are present in their surrounding membranes. Volutin granules and acidocalcisomes have been found in organisms as diverse as bacteria and humans. Results Here, we show volutin granules also occur in Archaea and are, therefore, present in the three superkingdoms of life (Archaea, Bacteria and Eukarya. Molecular analyses of V-H+PPase pumps, which acidify the acidocalcisome lumen and are diagnostic proteins of the organelle, also reveal the presence of this enzyme in all three superkingdoms suggesting it is ancient and universal. Since V-H+PPase sequences contained limited phylogenetic signal to fully resolve the ancestral nodes of the tree, we investigated the divergence of protein domains in the V-H+PPase molecules. Using Protein family (Pfam database, we found a domain in the protein, PF03030. The domain is shared by 31 species in Eukarya, 231 in Bacteria, and 17 in Archaea. The universal distribution of the V-H+PPase PF03030 domain, which is associated with the V-H+PPase function, suggests the domain and the enzyme were already present in the Last Universal Common Ancestor (LUCA. Conclusion The importance of the V-H+PPase function and the

  3. Structure and function of the Juxta membrane domain of the human epidermal growth factor receptor by NMR spectroscopy

    International Nuclear Information System (INIS)

    Choowongkomon, Kiattawee; Carlin, Cathleen; Sonnichsen, Frank D.

    2005-10-01

    The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family involved in the regulation of cellular proliferation and differentiation. Its juxta membrane domain (JX), the region located between the transmembrane and kinase domains, plays important roles in receptor trafficking since both basolateral sorting in polarized epithelial cells and lysosomal sorting signals are identified in this region. In order to understand the regulation of these signals, we characterized the structural properties of recombinant JX domain in dodecyl phosphocholine detergent (DPC) by nuclear magnetic resonance (NMR) spectroscopy. In DPC micelles, structures derived from NMR data showed three amphipathic, helical segments. Two equivalent average structural models on the surface of micelles were obtained that differ only in the relative orientation between the first and second helices. Our data suggests that the activity of sorting signals may be regulated by their membrane association and restricted accessibility in the intact receptor

  4. The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation.

    Directory of Open Access Journals (Sweden)

    Sarah V Consonni

    Full Text Available PDZGEF is a guanine nucleotide exchange factor for the small G protein Rap. It was recently found that PDZGEF contributes to establishment of intestinal epithelial polarity downstream of the kinase Lkb1. By binding to phosphatidic acid enriched at the apical membrane, PDZGEF locally activates Rap2a resulting in induction of brush border formation via a pathway that includes the polarity players TNIK, Mst4 and Ezrin. Here we show that the PDZ domain of PDZGEF is essential and sufficient for targeting PDZGEF to the apical membrane of polarized intestinal epithelial cells. Inhibition of PLD and consequently production of phosphatidic acid inhibitis targeting of PDZGEF to the plasma membrane. Furthermore, localization requires specific positively charged residues within the PDZ domain. We conclude that local accumulation of PDZGEF at the apical membrane during establishment of epithelial polarity is mediated by electrostatic interactions between positively charged side chains in the PDZ domain and negatively charged phosphatidic acid.

  5. Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins

    Science.gov (United States)

    Kretsinger, R. H.; Nakayama, S.

    1993-01-01

    In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences.

  6. Factors that influence effective perioperative temperature management by anesthesiologists: a qualitative study using the Theoretical Domains Framework.

    Science.gov (United States)

    Boet, Sylvain; Patey, Andrea M; Baron, Justine S; Mohamed, Karim; Pigford, Ashlee-Ann E; Bryson, Gregory L; Brehaut, Jamie C; Grimshaw, Jeremy M

    2017-06-01

    Inadvertent perioperative hypothermia (IPH) is associated with a range of adverse outcomes. Safe and effective warming techniques exist to prevent IPH; however, IPH remains common. This study aimed to identify factors that anesthesiologists perceive may influence temperature management during the perioperative period. After Research Ethics Board approval, semi-structured interviews were conducted with staff anesthesiologists at a Canadian academic hospital. An interview guide based on the Theoretical Domains Framework (TDF) was used to capture 14 theoretical domains that may influence temperature management. The interview transcripts were coded using direct content analysis to generate specific beliefs and to identify relevant TDF domains perceived to influence temperature management behaviour. Data saturation was achieved after 15 interviews. The following nine theoretical domains were identified as relevant to designing an intervention for practices in perioperative temperature management: knowledge, beliefs about capabilities, beliefs about consequences, reinforcement, memory/attention/decision-making, environmental context and resources, social/professional role/identity, social influences, and behavioural regulation. Potential target areas to improve temperature management practices include interventions that address information needs about individual temperature management behaviour as well as patient outcome (feedback), increasing awareness of possible temperature management strategies and guidelines, and a range of equipment and surgical team dynamics that influence temperature management. This study identified several potential target areas for future interventions from nine of the TDF behavioural domains that anesthesiologists perceive to drive their temperature management practices. Future interventions that aim to close the evidence-practice gap in perioperative temperature management may include these targets.

  7. The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs

    International Nuclear Information System (INIS)

    Takagaki, Yoshio; Manley, J.L.; MacDonald, C.C.; Shenk, T.

    1992-01-01

    Cleavage stimulation factor is one of the multiple factors required for 3'-end cleavage of mammalian pre-mRNAs. The authors have shown previously that this factor is composed of three subunits with estimated molecular masses of 77, 64, and 50 kDa and that the 64-kDa subunit can be UV-cross linked to RNA in a polyadenylylation signal (AAUAAA)-dependent manner. They have now isolated cDNAs encoding the 64-kDa subunit of human cleavage stimulation factor. The 64-kDa subunit contains a ribonucleoprotein-type RNA binding domain in the N-terminal region and a repeat structure in the C-terminal region in which a pentapeptide sequence (consensus MEARA/G) is repeated 12 times and the formation of a long α-helix stabilized by salt bridges is predicted. An ∼270-amino acid segment surrounding this repeat structure is highly enriched in proline and glycine residues (∼20% for each). When cloned 64-kDa subunit was expressed in Escherichia coli, an N-terminal fragment containing the RNA binding domain bound to RNAs in a polyadenylylation-signal-independent manner, suggesting that the RNA binding domain is directly involved in the binding of the 64-kDa subunit to pre-mRNAs

  8. Mechanism of Dynamic Recrystallization and Evolution of Texture in the Hot Working Domains of the Processing Map for Mg-4Al-2Ba-2Ca Alloy

    Directory of Open Access Journals (Sweden)

    Kalidass Suresh

    2017-12-01

    Full Text Available The occurrence of dynamic recrystallization (DRX and its effect on the evolution of texture during uniaxial compression of a creep-resistant cast Mg-4Al-2Ba-2Ca alloy in the temperature range of 260–500 °C and strain rate range of 0.0003–10 s−1 has been studied using transmission electron microscopy and electron backscatter diffraction techniques with a view to understand its mechanism. For this purpose, a processing map has been developed for this alloy, which revealed two domains of DRX in the temperature and strain rate ranges of: (1 300–390 °C/0.0003–0.001 s−1 and (2 400–500 °C/0.0003–0.5 s−1. In Domain 1, DRX occurs by basal slip and recovery by dislocation climb, as indicated by the presence of planar slip bands and high dislocation density leading to tilt boundary formation and a low-intensity basal texture. On the other hand, DRX in Domain 2 occurs by second order pyramidal slip and recovery by cross-slip since the microstructure revealed tangled dislocation structure with twist boundaries and randomized texture. The high volume content of intermetallic phases Mg21Al3Ba2 and (Al,Mg2Ca eutectic phase is considered to be responsible for the observed hot deformation behavior.

  9. Identification of the kinase that activates a nonmetazoan STAT gives insights into the evolution of phosphotyrosine-SH2 domain signaling.

    Science.gov (United States)

    Araki, Tsuyoshi; Kawata, Takefumi; Williams, Jeffrey G

    2012-07-10

    SH2 domains are integral to many animal signaling pathways. By interacting with specific phosphotyrosine residues, they provide regulatable protein-protein interaction domains. Dictyostelium is the only nonmetazoan with functionally characterized SH2 domains, but the cognate tyrosine kinases are unknown. There are no orthologs of the animal tyrosine kinases, but there are very many tyrosine kinase-like kinases (TKLs), a group of kinases which, despite their family name, are classified mainly as serine-threonine kinases. STATs are transcription factors that dimerize via phosphotyrosine-SH2 domain interactions. STATc is activated by phosphorylation on Tyr922 when cells are exposed to the prestalk inducer differentiation inducing factor (DIF-1), a chlorinated hexaphenone. We show that in a null mutant for Pyk2, a tyrosine-specific TKL, exposure to DIF-1 does not activate STATc. Conversely, overexpression of Pyk2 causes constitutive STATc activation. Pyk2 phosphorylates STATc on Tyr922 in vitro and complexes with STATc both in vitro and in vivo. This demonstration that a TKL directly activates a STAT has significant implications for understanding the evolutionary origins of SH2 domain-phosphotyrosine signaling. It also has mechanistic implications. Our previous work suggested that a predicted constitutive STATc tyrosine kinase activity is counterbalanced in vivo by the DIF-1-regulated activity of PTP3, a Tyr922 phosphatase. Here we show that the STATc-Pyk2 complex is formed constitutively by an interaction between the STATc SH2 domain and phosphotyrosine residues on Pyk2 that are generated by autophosphorylation. Also, as predicted, Pyk2 is constitutively active as a STATc kinase. This observation provides further evidence for this highly atypical, possibly ancestral, STAT regulation mechanism.

  10. Evolution of the vertebrate neurocranium: problems of the premandibular domain and the origin of the trabecula

    OpenAIRE

    Kuratani, Shigeru; Ahlberg, Per. E.

    2018-01-01

    The subdivision of the gnathostome neurocranium into an anterior neural crest-derived moiety and a posterior mesodermal moiety has attracted the interest of researchers for nearly two centuries. We present a synthetic scenario for the evolution of this structure, uniting developmental data from living cyclostomes and gnathostomes with morphological data from fossil stem gnathostomes in a common phylogenetic framework. Ancestrally, vertebrates had an anteroposteriorly short forebrain, and the ...

  11. Predicting homophobic behavior among heterosexual youth: domain general and sexual orientation-specific factors at the individual and contextual level.

    Science.gov (United States)

    Poteat, V Paul; DiGiovanni, Craig D; Scheer, Jillian R

    2013-03-01

    As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual orientation identity importance, number of sexual minority friends, parents' sexual minority attitudes, media messages). We documented support for a model in which these sets of factors converged to predict homophobic behavior, mediated through bullying and prejudice, among 581 students in grades 9-12 (55 % female). The structural equation model indicated that, with the exception of media messages, these additional factors predicted levels of prejudice and bullying, which in turn predicted the likelihood of students to engage in homophobic behavior. These findings highlight the importance of addressing multiple interrelated factors in efforts to reduce bullying, prejudice, and discrimination among youth.

  12. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  13. Assembly of the intrinsic factor domains and oligomerization of the protein in the presence of cobalamin

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars

    2004-01-01

    oligomerized. A mixture of two fragments IF(30) + IF(20) and Cbl produced a firm complex, IF(30+20).Cbl, which could not associate to dimers. In contrast to IF(30+20).Cbl, the saturated full-length monomers IF(50).Cbl dimerized with K(d) approximately 1 microM. We suggest a two-domain organization of the full......-length protein, where two distant units, IF(30) and IF(20), can be assembled only by Cbl. They are connected by a protease-sensitive link, whose native structure is likely to be important for dimerization. However, linkage between two domains is not compulsory for Cbl binding. Advantages of the two...

  14. Motivated Cognition: Effects of Reward, Emotion, and Other Motivational Factors Across a Variety of Cognitive Domains

    OpenAIRE

    Christopher R. Madan

    2017-01-01

    A growing body of literature has demonstrated that motivation influences cognitive processing. The breadth of these effects is extensive and span influences of reward, emotion, and other motivational processes across all cognitive domains. As examples, this scope includes studies of emotional memory, value-based attentional capture, emotion effects on semantic processing, reward-related biases in decision making, and the role of approach/avoidance motivation on cognitive scope. Additionally, ...

  15. The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.

    Science.gov (United States)

    Arsenault, Patrick R; Song, Daisheng; Chung, Yu Jin; Khurana, Tejvir S; Lee, Frank S

    2016-09-15

    Prolyl hydroxylase domain protein 2 (PHD2) (also known as EGLN1) is a key oxygen sensor in mammals that posttranslationally modifies hypoxia-inducible factor α (HIF-α) and targets it for degradation. In addition to its catalytic domain, PHD2 contains an evolutionarily conserved zinc finger domain, which we have previously proposed recruits PHD2 to the HSP90 pathway to promote HIF-α hydroxylation. Here, we provide evidence that this recruitment is critical both in vitro and in vivo We show that in vitro, the zinc finger can function as an autonomous recruitment domain to facilitate interaction with HIF-α. In vivo, ablation of zinc finger function by a C36S/C42S Egln1 knock-in mutation results in upregulation of the erythropoietin gene, erythrocytosis, and augmented hypoxic ventilatory response, all hallmarks of Egln1 loss of function and HIF stabilization. Hence, the zinc finger ordinarily performs a critical positive regulatory function. Intriguingly, the function of this zinc finger is impaired in high-altitude-adapted Tibetans, suggesting that their adaptation to high altitude may, in part, be due to a loss-of-function EGLN1 allele. Thus, these findings have important implications for understanding both the molecular mechanism of the hypoxic response and human adaptation to high altitude. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Evolution of the vertebrate neurocranium: problems of the premandibular domain and the origin of the trabecula.

    Science.gov (United States)

    Kuratani, Shigeru; Ahlberg, Per E

    2018-01-01

    The subdivision of the gnathostome neurocranium into an anterior neural crest-derived moiety and a posterior mesodermal moiety has attracted the interest of researchers for nearly two centuries. We present a synthetic scenario for the evolution of this structure, uniting developmental data from living cyclostomes and gnathostomes with morphological data from fossil stem gnathostomes in a common phylogenetic framework. Ancestrally, vertebrates had an anteroposteriorly short forebrain, and the neurocranium was essentially mesodermal; skeletal structures derived from premandibular ectomesenchyme were mostly anterior to the brain and formed part of the visceral arch skeleton. The evolution of a one-piece neurocranial 'head shield' in jawless stem gnathostomes, such as galeaspids and osteostracans, caused this mesenchyme to become incorporated into the neurocranium, but its position relative to the brain and nasohypophyseal duct remained unchanged. Basically similar distribution of the premandibular ectomesenchyme is inferred, even in placoderms, the earliest jawed vertebrates, in which the separation of hypophyseal and nasal placodes obliterated the nasohypophyseal duct, leading to redeployment of this ectomesenchyme between the separate placodes and permitting differentiation of the crown gnathostome trabecula that floored the forebrain. Initially this region was very short, and the bulk of the premandibular cranial part projected anteroventral to the nasal capsule, as in jawless stem gnathostomes. Due to the lengthening of the forebrain, the anteriorly projecting 'upper lip' was lost, resulting in the modern gnathostome neurocranium with a long forebrain cavity floored by the trabeculae.

  17. Cryo-EM Structure of the Archaeal 50S Ribosomal Subunit in Complex with Initiation Factor 6 and Implications for Ribosome Evolution

    Science.gov (United States)

    Greber, Basil J.; Boehringer, Daniel; Godinic-Mikulcic, Vlatka; Crnkovic, Ana; Ibba, Michael; Weygand-Durasevic, Ivana; Ban, Nenad

    2013-01-01

    Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The structure provides detailed architectural insights into the 50S ribosomal subunit from a methanogenic archaeon through identification of the rRNA expansion segments and ribosomal proteins that are shared between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea. PMID:22306461

  18. First measurements of the temporal evolution of the plasma density in HiPIMS discharges using THz time domain spectroscopy

    Science.gov (United States)

    Meier, Steffen M.; Hecimovic, Ante; Tsankov, Tsanko V.; Luggenhölscher, Dirk; Czarnetzki, Uwe

    2018-03-01

    In this paper, the novel technique of THz time domain spectroscopy has been applied to obtain time-resolved measurements of the plasma density in the active zone of a HiPIMS discharge with a titanium target. The obtained peak values are in the range of 1012-1013 cm-3 for discharge current densities of 1-4 A cm-2 at 0.5 and 2 Pa argon pressure. The measured densities show good correlation with the discharge current and voltage and the intensity of various atomic and ionic lines. The well known phases of the discharge have been identified and related to the variation of the electron density. The measurement results show that the plasma density remains nearly constant during the runaway/self-sputtering phase. Based on that, it is conjectured that singly charged titanium ions are the dominant ion species during this phase.

  19. Pathophysiologic Domains Underlying the Metabolic Syndrome: An Alternative Factor Analytic Strategy

    NARCIS (Netherlands)

    Peeters, C. F. W.; Dziura, J.; van Wesel, F.; Peeters, C.F.W.

    2014-01-01

    Factor analysis (FA) has become part and parcel in metabolic syndrome (MBS) research. Both exploration- and confirmation-driven factor analyzes are rampant. However, factor analytic results on MBS differ widely. A situation that is at least in part attributable to misapplication of FA. Here, our

  20. The 1.7 Å X-ray crystal structure of the porcine factor VIII C2 domain and binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.

    Directory of Open Access Journals (Sweden)

    Caileen M Brison

    Full Text Available The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the "non-classical" antibody epitopes. Furthermore, antibody-binding results illustrate that the "classical" 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.

  1. Euglena in time: Evolution, control of central metabolic processes and multi-domain proteins in carbohydrate and natural product biochemistry

    Directory of Open Access Journals (Sweden)

    Ellis C. O’Neill

    2015-12-01

    Full Text Available Euglena gracilis is a eukaryotic microalgae that has been the subject of scientific study for hundreds of years. It has a complex evolutionary history, with traces of at least four endosymbiotic genomes and extensive horizontal gene transfer. Given the importance of Euglena in terms of evolutionary cell biology and its unique taxonomic position, we initiated a de novo transcriptome sequencing project in order to understand this intriguing organism. By analysing the proteins encoded in this transcriptome, we can identify an extremely complex metabolic capacity, rivalling that of multicellular organisms. Many genes have been acquired from what are now very distantly related species. Herein we consider the biology of Euglena in different time frames, from evolution through control of cell biology to metabolic processes associated with carbohydrate and natural products biochemistry.

  2. Convergent evolution of RFX transcription factors and ciliary genes predated the origin of metazoans

    Directory of Open Access Journals (Sweden)

    Chen Nansheng

    2010-05-01

    Full Text Available Abstract Background Intraflagellar transport (IFT genes, which are critical for the development and function of cilia and flagella in metazoans, are tightly regulated by the Regulatory Factor X (RFX transcription factors (TFs. However, how and when their evolutionary relationship was established remains unknown. Results We have identified evidence suggesting that RFX TFs and IFT genes evolved independently and their evolution converged before the first appearance of metazoans. Both ciliary genes and RFX TFs exist in all metazoans as well as some unicellular eukaryotes. However, while RFX TFs and IFT genes are found simultaneously in all sequenced metazoan genomes, RFX TFs do not co-exist with IFT genes in most pre-metazoans and thus do not regulate them in these organisms. For example, neither the budding yeast nor the fission yeast possesses cilia although both have well-defined RFX TFs. Conversely, most unicellular eukaryotes, including the green alga Chlamydomonas reinhardtii, have typical cilia and well conserved IFT genes but lack RFX TFs. Outside of metazoans, RFX TFs and IFT genes co-exist only in choanoflagellates including M. brevicollis, and only one fungus Allomyces macrogynus of the 51 sequenced fungus genomes. M. brevicollis has two putative RFX genes and a full complement of ciliary genes. Conclusions The evolution of RFX TFs and IFT genes were independent in pre-metazoans. We propose that their convergence in evolution, or the acquired transcriptional regulation of IFT genes by RFX TFs, played a pivotal role in the establishment of metazoan.

  3. Asymmetric Evolution and Expansion of the NAC Transcription Factor in Polyploidized Cotton

    Directory of Open Access Journals (Sweden)

    Kai Fan

    2018-01-01

    Full Text Available Polyploidy in Gossypium hirsutum conferred different properties from its diploid ancestors under the regulation of transcription factors. The NAC transcription factor is a plant-specific family that can be related to plant growth and development. So far, little is known about the NAC family in cotton. This study identified 495 NAC genes in three cotton species and investigated the evolution and expansion of different genome-derived NAC genes in cotton. We revealed 15 distinct NAC subfamilies in cotton. Different subfamilies had different gene proportions, expansion rate, gene loss rate, and orthologous exchange rate. Paleohexaploidization (35% and cotton-specific decaploidy (32% might have primarily led to the expansion of the NAC family in cotton. Half of duplication events in G. hirsutum were inherited from its diploid ancestor, and others might have occurred after interspecific hybridization. In addition, NAC genes in the At and Dt subgenomes displayed asymmetric molecular evolution, as evidenced by their different gene loss rates, orthologous exchange, evolutionary rates, and expression levels. The dominant duplication event was different during the cotton evolutionary history. Different genome-derived NACs might have interacted with each other, which ultimately resulted in morphogenetic evolution. This study delineated the expansion and evolutionary history of the NAC family in cotton and illustrated the different fates of NAC genes during polyploidization.

  4. THE EVOLUTION OF PRIVATE LOANS IN ROMANIA AND EXAMINATION OF SOME FACTORS OF INFLUENCE

    Directory of Open Access Journals (Sweden)

    MIHAI MIEILĂ

    2017-08-01

    Full Text Available The paper analyzes the evolution of Romanian private loans, in national currency (lei, granted to households and non-financial corporations in the period between July 2005 and April 2017. In this context, after reviewing the importance of credit within the context of national economy is presented the evolution of some factors considered as influential upon the evolution of credit. These factors are, namely: the average interest rate of outstanding private loans granted by credit institutions, the average interest rate of outstanding amount of deposits received by credit institutions, the ratio of minimum (or reserve requirements, the interest rate on required reserves and the monetary policy rate. The database was built using the available data from the Statistical Section of the monthly bulletins released by the National Bank of Romania (herein after, referred to as NBR and published on the institution’s website. Every series of data is subject of testing for stationarity, using both the Augmented Dickey-Fuller and Pillips-Perron tests (herein after, referred to as ADF and PP, respectively, and the reported results are presented within the paper. In order to avoid spurious regression, following the stationarization of the data series, an analysis model is put in place and the significant results are subject to further interpretation.

  5. Exposure to simultaneous sedentary behavior domains and sociodemographic factors associated in public servants

    Directory of Open Access Journals (Sweden)

    Fernanda Cerveira Fronza

    2017-11-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2017v19n4p469   Exposure to sedentary behavior may contribute to health problems. This study aimed to estimate the prevalence of exposure to simultaneous sedentary behavior domains and verify associated sociodemographic characteristics among technical and administrative servers of a Brazilian university. This is a cross-sectional epidemiological study carried out with 623 technical and administrative servers. Sedentary behavior was identified through a questionnaire in the following domains: commuting (active / passive, sitting time at work, daily time spent watching television and computer use (≥3 hours / day. Sociodemographic variables were age, sex and educational level. The prevalence of servers that had one, two, three and four simultaneous sedentary behavior was 28.4%, 43.2%, 22.5% and 4.3%, respectively. Women were more likely to have three sedentary behavior simultaneously (OR = 1.61, CI 95% = 1.02, 2.56. Servers with 9-11 years of schooling were less exposed to two (OR = 0.27, CI 95% = 0.17, 0.44, three (OR = 0.39, CI 95% = 0.23, 0.66 and four (OR = 0.22, CI 95% = 0.07; 0.69 sedentary behavior simultaneously and those over 12 years of schooling were less likely of having two (OR = 0.22, CI 95% = 0.10; 0.49 and three (OR = 0.15, CI 95% = 0.05, 0.46 sedentary behavior simultaneously. More than half of servers have two sedentary behavior during the week. Having sedentary behavior in more than one domain simultaneously was associated with sex and educational level.

  6. Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

    Science.gov (United States)

    Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

    2017-02-01

    Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis

  7. Genome-wide analysis of WRKY transcription factors in white pear (Pyrus bretschneideri) reveals evolution and patterns under drought stress.

    Science.gov (United States)

    Huang, Xiaosan; Li, Kongqing; Xu, Xiaoyong; Yao, Zhenghong; Jin, Cong; Zhang, Shaoling

    2015-12-24

    WRKY transcription factors (TFs) constitute one of the largest protein families in higher plants, and its members contain one or two conserved WRKY domains, about 60 amino acid residues with the WRKYGQK sequence followed by a C2H2 or C2HC zinc finger motif. WRKY proteins play significant roles in plant development, and in responses to biotic and abiotic stresses. Pear (Pyrus bretschneideri) is one of the most important fruit crops in the world and is frequently threatened by abiotic stress, such as drought, affecting growth, development and productivity. Although the pear genome sequence has been released, little is known about the WRKY TFs in pear, especially in respond to drought stress at the genome-wide level. We identified a total of 103 WRKY TFs in the pear genome. Based on the structural features of WRKY proteins and topology of the phylogenetic tree, the pear WRKY (PbWRKY) family was classified into seven groups (Groups 1, 2a-e, and 3). The microsyteny analysis indicated that 33 (32%) PbWRKY genes were tandemly duplicated and 57 genes (55.3%) were segmentally duplicated. RNA-seq experiment data and quantitative real-time reverse transcription PCR revealed that PbWRKY genes in different groups were induced by drought stress, and Group 2a and 3 were mainly involved in the biological pathways in response to drought stress. Furthermore, adaptive evolution analysis detected a significant positive selection for Pbr001425 in Group 3, and its expression pattern differed from that of other members in this group. The present study provides a solid foundation for further functional dissection and molecular evolution of WRKY TFs in pear, especially for improving the water-deficient resistance of pear through manipulation of the PbWRKYs.

  8. Cloning, purification and structure determination of the HIV integrase-binding domain of lens epithelium-derived growth factor.

    Science.gov (United States)

    Hannon, Clare; Cruz-Migoni, Abimael; Platonova, Olga; Owen, Robin L; Nettleship, Joanne E; Miller, Ami; Carr, Stephen B; Harris, Gemma; Rabbitts, Terence H; Phillips, Simon E V

    2018-03-01

    Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase in human cells. The crystal structure of the HIV integrase-binding domain (IBD) of LEDGF has been determined in the absence of ligand. IBD was overexpressed in Escherichia coli, purified and crystallized by sitting-drop vapour diffusion. X-ray diffraction data were collected at Diamond Light Source to a resolution of 2.05 Å. The crystals belonged to space group P2 1 , with eight polypeptide chains in the asymmetric unit arranged as an unusual octamer composed of four domain-swapped IBD dimers. IBD exists as a mixture of monomers and dimers in concentrated solutions, but the dimers are unlikely to be biologically relevant.

  9. The central domain of yeast transcription factor Rpn4 facilitates degradation of reporter protein in human cells.

    Science.gov (United States)

    Morozov, A V; Spasskaya, D S; Karpov, D S; Karpov, V L

    2014-10-16

    Despite high interest in the cellular degradation machinery and protein degradation signals (degrons), few degrons with universal activity along species have been identified. It has been shown that fusion of a target protein with a degradation signal from mammalian ornithine decarboxylase (ODC) induces fast proteasomal degradation of the chimera in both mammalian and yeast cells. However, no degrons from yeast-encoded proteins capable to function in mammalian cells were identified so far. Here, we demonstrate that the yeast transcription factor Rpn4 undergoes fast proteasomal degradation and its central domain can destabilize green fluorescent protein and Alpha-fetoprotein in human HEK 293T cells. Furthermore, we confirm the activity of this degron in yeast. Thus, the Rpn4 central domain is an effective interspecies degradation signal. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. The assessment of Big Five Personality Factors and Temperament Domains as modifiers of cardiovascular response to occupational stress.

    Science.gov (United States)

    Merecz, D; Makowska, Z; Makowiec-Dabrowska, T

    1999-01-01

    The aim of the study was to explore the role of Big Five Personality Factors and Temperament Domains as the factors influencing cardiovascular response to work, and their moderating effect on the relationship between occupational stress and cardiovascular reactivity. The self-reported data on occupational stress and filled in NEO-Five Factor Inventory by Costa, and McCrae and Pavlovian Temperament Survey by Strelau et al. were collected from 97 bank clerks employed in large bank branches. The subjects also responded to the questionnaire on personal and professional background factors. A 24 hour monitoring of cardiovascular reactivity (heart rate and blood pressure) was also provided. Conscientiousness was found to be the only modifier of cardiovascular response to occupational stress reflected by systolic blood pressure. Several main, independent of stress effects of personality and temperament domains were also found. The ratio of heart rate at work to heart rate during sleep was associated with the strength of excitatory process, the percentage of maximum heart rate index with Conscientiousness, and systolic blood pressure at work was influenced by the strength of inhibitory process. However, generally speaking, physiological indicators of the cardiovascular system functioning were not very sensitive to changes in values of personality and temperament variables at the level of occupational stress reported by the bank clerks who participated in the study.

  11. The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

    Science.gov (United States)

    Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

    2013-09-01

    Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

  12. Characterization of a baculovirus nuclear localization signal domain in the late expression factor 3 protein

    International Nuclear Information System (INIS)

    Au, Victoria; Yu Mei; Carstens, Eric B.

    2009-01-01

    The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) single-stranded DNA binding protein LEF-3 is a multi-functional protein that is required to transport the helicase protein P143 into the nucleus of infected cells where they function to replicate viral DNA. The N-terminal 56 amino acid region of LEF-3 is required for nuclear transport. In this report, we analyzed the effect of site-specific mutagenesis of LEF-3 on its intracellular distribution. Fluorescence microscopy of expression plasmid-transfected cells demonstrated that the residues 28 to 32 formed the core nuclear localization signal, but other adjacent positively-charged residues augmented these sequences. Comparison with other group I Alphabaculoviruses suggested that this core region functionally duplicated residues including 18 and 19. This was demonstrated by the loss of nuclear localization when the equivalent residues (18 to 20) in Choristoneura fumiferana nucleopolyhedrovirus (CfMNPV) LEF-3 were mutated. The AcMNPV LEF-3 nuclear localization domain was also shown to drive nuclear transport in mammalian cells indicating that the protein nuclear import systems in insect and mammalian cells are conserved. We also demonstrated by mutagenesis that two conserved cysteine residues located at 82 and 106 were not essential for nuclear localization or for interaction with P143. However, by using a modified construct of P143 that localized on its own to the nucleus, we demonstrated that a functional nuclear localization domain on LEF-3 was required for interaction between LEF-3 and P143

  13. The effects of heavy meteorite bombardment on the early evolution — The emergence of the three Domains of life

    Science.gov (United States)

    Gogarten-Boekels, Maria; Hilario, Elena; Gogarten, J. Peter

    1995-06-01

    A characteristic of many molecular phylogenies is that the three domains of life (Bacteria, Archaea, Eucarya) are clearly separated from each other. The analyses of ancient duplicated genes suggest that the last common ancestor of all presently known life forms already had been a sophisticated cellular prokaryote. These findings are in conflict with theories that have been proposed to explain the absence of deep branching lineages. In this paper we propose an alternative scenario, namely, a large meteorite impact that wiped out almost all life forms present on the early Earth. Following this nearly complete frustation of life on Earth, two surviving extreme thermophilic species gave rise to the now existing major groups of living organisms, the Bacteria and Archaea. [The latter also contributed the major portion to the nucleo-cytoplasmic component of the Eucarya]. An exact calibration of the molecular record with regard to time is not yet possible. The emergence of Eucarya in fossil and molecular records suggests that the proposed late impact should have occurred before 2100 million years before present (BP). If the 3500 million year old microfossils [Schopf, J. W. 1993: Science 260: 640 646] are interpreted as representatives of present day existing groups of bacteria (i.e., as cyanobacteria), then the impact is dated to around 3700 million years BP. The analysis of molecular sequences suggests that the separation between the Eucarya and the two prokaryotic domains is less deep then the separation between Bacteria and Archaea. The fundamental cell biological differences between Archaea and Eucarya were obtained over a comparatively short evolutionary distance (as measured in number of substitution events in biological macromolecules). Our interpretation of the molecular record suggests that life emerged early in Earth's history even before the time of the heavy bombardment was over. Early life forms already had colonized extreme habitats which allowed at least two

  14. Analysis of chitin-binding proteins from Manduca sexta provides new insights into evolution of peritrophin A-type chitin-binding domains in insects.

    Science.gov (United States)

    Tetreau, Guillaume; Dittmer, Neal T; Cao, Xiaolong; Agrawal, Sinu; Chen, Yun-Ru; Muthukrishnan, Subbaratnam; Haobo, Jiang; Blissard, Gary W; Kanost, Michael R; Wang, Ping

    2015-07-01

    together in the phylogenetic tree. For chitinases and chitin deacetylases, most of phylogenetic analysis performed with the CBD sequences resulted in similar clustering to the one obtained by using catalytic domain sequences alone, suggesting that CBDs were incorporated into these enzymes and evolved in tandem with the catalytic domains before the diversification of different insect orders. Based on these results, the evolution of CBDs in insect CBPs is discussed to provide a new insight into the CBD sequence structure and diversity, and their evolution and expression in insects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The evolution of groundwater flow and mass transport in Canadian shield flow domains: a methodology for numerical simulation

    International Nuclear Information System (INIS)

    Sykes, J.F.; Sudicky, E.A.; Normani, S.D.; Park, Y.J.; Cornaton, F.; McLaren, R.G.

    2007-01-01

    The Deep Geologic Repository Technology Programme (DGRTP) of Ontario Power Generation (OPG) is developing numerous approaches and methodologies for integrated and multidisciplinary site characterisation. A principal element involves the use and further development of state-of-the-art numerical simulators, and immersive visualisation technologies, while fully honouring multi-disciplinary litho-structural, hydrogeologic, paleo-hydrogeologic, geophysical, hydrogeochemical and geomechanical field data. Paleo-climate reconstructions provide surface boundary conditions for numerical models of the subsurface, furthering the understanding of groundwater flow in deep geologic systems and quantifying the effects of glaciation and deglaciation events. The use of geo-statistically plausible fracture networks conditioned on surface lineaments within the numerical models results in more physically representative and realistic characterizations of the repository site. Finally, immersive three-dimensional visualisation technology is used to query, investigate, explore and understand both the raw data, and simulation results in a spatially and temporally consistent framework. This environment allows multi-disciplinary teams of geoscience professionals to explore each other's work and can significantly enhance understanding and knowledge, thereby creating stronger linkages between the geo-scientific disciplines. The use of more physically representative and realistic conceptual models, coupled with immersive visualisation, contributes to an overall integrated approach to site characterisation, instilling further confidence in the understanding of flow system evolution. (authors)

  16. Motivated Cognition: Effects of Reward, Emotion, and Other Motivational Factors Across a Variety of Cognitive Domains

    Directory of Open Access Journals (Sweden)

    Christopher R. Madan

    2017-10-01

    Full Text Available A growing body of literature has demonstrated that motivation influences cognitive processing. The breadth of these effects is extensive and span influences of reward, emotion, and other motivational processes across all cognitive domains. As examples, this scope includes studies of emotional memory, value-based attentional capture, emotion effects on semantic processing, reward-related biases in decision making, and the role of approach/avoidance motivation on cognitive scope. Additionally, other less common forms of motivation–cognition interactions, such as self-referential and motoric processing can also be considered instances of motivated cognition. Here I outline some of the evidence indicating the generality and pervasiveness of these motivation influences on cognition, and introduce the associated ‘research nexus’ at 'Collabra: Psychology'.

  17. Phylogenetic utility of the AP3/DEF K-domain and its molecular evolution in Impatiens (Balsaminaceae)

    NARCIS (Netherlands)

    Janssens, S.; Geuten, K.; Viaene, T.; Yong-Ming, Y.; Yi, S.; Smets, E.

    2007-01-01

    APETALA3 (AP3)/DEFICIENS (DEF) is a MADS-box transcription factor that is involved in establishing the identity of petal and stamen floral organs. The AP3/DEF gene lineage has been extensively examined throughout the angiosperms in order to better understand its role in floral diversity and

  18. Factors across home, work, and school domains influence nutrition and physical activity behaviors of nontraditional college students.

    Science.gov (United States)

    Quintiliani, Lisa M; Bishop, Hillary L; Greaney, Mary L; Whiteley, Jessica A

    2012-10-01

    Nontraditional college students (older, part-time, and/or working) have less healthful nutrition and physical activity behaviors compared to traditional students, yet few health promotion efforts focus on nontraditional students. The purpose of this study was to use qualitative methods to explore factors affecting nutrition and physical activity behaviors of nontraditional students. Fourteen semi-structured individual interviews were conducted with nontraditional undergraduate students attending a large university. The sample had a median age of 25 (range, 21-64), 57% were men, 43% were racial/ethnic minorities, and 57% were employed (mean 22 hours/week). Data were coded using a systematic team-based approach. Consistent themes (mentioned by 4+ students) were identified and categorized into three domains: home, work, and school. Home (themes: neighborhood characteristics, family, partners), work (theme: work environment), and school (themes: cafeteria, vending machines) factors consistently influenced positive nutrition behaviors. Similarly, home (themes: neighborhood including safety, friends from home, partner,), work (theme: work environment), and school (themes: not having a car, campus structure, campus gym, friends at school) factors consistently influenced positive physical activity. Financial resources and perceptions of autonomy had influence across domains. Results indicate consistent influences on nutrition and physical activity behaviors across home, work, and school domains for nontraditional college students. Study findings suggest possible, and sometimes unconventional, intervention strategies to promote healthful eating and physical activity. For example, when cafeteria meal plans are not offered and financial constraints limit eating at the cafeteria, encouraging healthful choices from vending machines could be preferable to not eating at all. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The Rho Termination Factor of Clostridium botulinum contains a Prion-Like Domain with a highly Amyloidogenic Core

    Directory of Open Access Journals (Sweden)

    Irantzu ePallares

    2016-01-01

    Full Text Available Prion-like proteins can switch between a soluble intrinsically disordered conformation and a highly ordered amyloid assembly. This conformational promiscuity is encoded in specific sequence regions, known as prion domains (PrDs. Prions are best known as the causative factors of neurological diseases in mammals. However, bioinformatics analyses reveal that proteins bearing PrDs are present in all kingdoms of life, including bacteria, thus supporting the idea that they serve conserved beneficial cellular functions. Despite the proportion of predicted prion-like proteins in bacterial proteomes is generally low, pathogenic species seem to have a higher prionic load, suggesting that these malleable proteins may favor pathogenic traits. In the present work, we performed a stringent computational analysis of the Clostridium botulinum pathogen proteome in the search for prion-like proteins. A total of 54 candidates were predicted for this anaerobic bacterium, including the transcription termination Rho factor. This RNA-binding protein has been shown to play a crucial role in bacterial adaptation to changing environments. We show here that the predicted disordered PrD domain of this RNA-binding protein contains an inner, highly polar, asparagine-rich short sequence able to spontaneously self-assemble into amyloid-like structures, bearing thus the potential to induce a Rho factor conformational switch that might rewire gene expression in response to environmental conditions.

  20. A Staphylococcus aureus TIR domain protein virulence factor blocks TLR2-mediated NF-κB signaling.

    Science.gov (United States)

    Askarian, Fatemeh; van Sorge, Nina M; Sangvik, Maria; Beasley, Federico C; Henriksen, Jørn R; Sollid, Johanna U E; van Strijp, Jos A G; Nizet, Victor; Johannessen, Mona

    2014-01-01

    Signaling through Toll-like receptors (TLRs), crucial molecules in the induction of host defense responses, requires adaptor proteins that contain a Toll/interleukin-1 receptor (TIR) domain. The pathogen Staphylococcus aureus produces several innate immune-evasion molecules that interfere with the host's innate immune response. A database search analysis suggested the presence of a gene encoding a homologue of the human TIR domain in S. aureus MSSA476 which was named staphylococcal TIR domain protein (TirS). Ectopic expression of TirS in human embryonic kidney, macrophage and keratinocyte cell lines interfered with signaling through TLR2, including MyD88 and TIRAP, NF-κB and/or mitogen-activated protein kinase pathways. Moreover, the presence of TirS reduced the levels of cytokines MCP-1 and G-CSF secreted in response to S. aureus. The effects on NF-κB pathway were confirmed using S. aureus MSSA476 wild type, an isogenic mutant MSSA476ΔtirS, and complemented MSSA476ΔtirS +pTirS in a Transwell system where bacteria and host cells were physically separated. Finally, in a systematic mouse infection model, TirS promoted bacterial accumulation in several organs 4 days postinfection. The results of this study reveal a new S. aureus virulence factor that can interfere with PAMP-induced innate immune signaling in vitro and bacterial survival in vivo. © 2014 S. Karger AG, Basel.

  1. Switching Operation Simulations in a Large Offshore Wind Farm with Use of Parametric Variation and Frequency Domain Severity Factor

    DEFF Research Database (Denmark)

    Holdyk, Andrzej; Holbøll, Joachim; Arana, Ivan

    2012-01-01

    Transient voltages resulting from switching operations depend on an interaction between the breaker, the transformer, cables and a neighbourhood grid and imply a risk for the transformer and other components. In this paper the Frequency Domain Severity Factor (FDSF) is used to assess the severity...... of electrical stress imposed on wind turbine transformers by voltage waveforms produced during switching operations. The method is implemented in Matlab together with automatic and systematic variation of parameters. Simulations of a radial energization are performed on a 90MVA offshore wind farm model...

  2. Effects of environmental factor on gas evolution behavior from Al in simulating mortar environments

    International Nuclear Information System (INIS)

    Hashizume, Shuji; Matsumoto, Junko; Banba, Tsunetaka

    1998-01-01

    Dry Low-Level Radioactive Wastes (LLW) which mean incombustible solid LLW generated from nuclear power stations are scheduled to be packed in steel drums followed by solidification with mortar. The solidified dry LLW is then to be disposed to shallow under-ground at Rokkasho LLW Disposal Center. Dry LLW includes some amphoteric metals among which aluminum is the most corrosive with gas evolution in high alkaline media such as mortar. The evolved gas may accelerate the leaching of solidified dry LLW with mortar. Despite the planned removal of aluminum from dry LLW, small inclusion of aluminum is unavoidable. The present study focuses on the effect of environmental factors such as pH and temperature on gas evolution behavior caused by aluminum corrosion. Large effects of pH and temperature on corrosion rate of aluminum and gas evolution were recognized. Principal corrosion product of aluminum was calcium aluminate compound when it was immersed in simulated mortar environments. It is demonstrated that 1.5 mol hydrogen gas evolves with the corrosion of 1 mol aluminum in environments of 12 < pH < 13 at temperatures below 60degC. (author)

  3. Factors Affecting the Binding of a Recombinant Heavy Metal-Binding Domain (CXXC motif Protein to Heavy Metals

    Directory of Open Access Journals (Sweden)

    Kamala Boonyodying

    2012-06-01

    Full Text Available A number of heavy metal-binding proteins have been used to study bioremediation. CXXC motif, a metal binding domain containing Cys-X-X-Cys motif, has been identified in various organisms. These proteins are capable of binding various types of heavy metals. In this study, heavy metal binding domain (CXXC motif recombinant protein encoded from mcsA gene of S. aureus were cloned and overexpressed in Escherichia coli. The factors involved in the metal-binding activity were determined in order to analyze the potential of recombinant protein for bioremediation. A recombinant protein can be bound to Cd2+, Co2+, Cu2+ and Zn2+. The thermal stability of a recombinant protein was tested, and the results showed that the metal binding activity to Cu2+ and Zn2+ still exist after treating the protein at 85ºC for 30 min. The temperature and pH that affected the metal binding activity was tested and the results showed that recombinant protein was still bound to Cu2+ at 65ºC, whereas a pH of 3-7 did not affect the metal binding E. coli harboring a pRset with a heavy metal-binding domain CXXC motif increased the resistance of heavy metals against CuCl2 and CdCl2. This study shows that metal binding domain (CXXC motif recombinant protein can be effectively bound to various types of heavy metals and may be used as a potential tool for studying bioremediation.

  4. Intermittent auscultation versus continuous fetal monitoring: exploring factors that influence birthing unit nurses' fetal surveillance practice using theoretical domains framework.

    Science.gov (United States)

    Patey, Andrea M; Curran, Janet A; Sprague, Ann E; Francis, Jill J; Driedger, S Michelle; Légaré, France; Lemyre, Louise; Pomey, Marie-Pascale A; Grimshaw, Jeremy M

    2017-09-25

    Intermittent Auscultation (IA) is the recommended method of fetal surveillance for healthy women in labour. However, the majority of women receive continuous electronic monitoring. We used the Theoretical Domains Framework (TDF) to explore the views of Birthing Unit nurses about using IA as their primary method of fetal surveillance for healthy women in labour. Using a semi-structured interview guide, we interviewed a convenience sample of birthing unit nurses throughout Ontario, Canada to elicit their views about fetal surveillance. Interviews were recorded and transcribed verbatim. Transcripts were content analysed using the TDF and themes were framed as belief statements. Domains potentially key to changing fetal surveillance behaviour and informing intervention design were identified by noting the frequencies of beliefs, content, and their reported influence on the use of IA. We interviewed 12 birthing unit nurses. Seven of the 12 TDF domains were perceived to be key to changing birthing unit nurses' behaviour The nurses reported that competing tasks, time constraints and the necessity to multitask often limit their ability to perform IA (domains Beliefs about capabilities; Environmental context and resources). Some nurses noted the decision to use IA was something that they consciously thought about with every patient while others stated it their default decision as long as there were no risk factors (Memory, attention and decision processes, Nature of behaviour). They identified positive consequences (e.g. avoid unnecessary interventions, mother-centered care) and negative consequences of using IA (e.g. legal concerns) and reported that the negative consequences can often outweigh positive consequences (Beliefs about consequences). Some reported that hospital policies and varying support from care teams inhibited their use of IA (Social influences), and that support from the entire team and hospital management would likely increase their use (Social

  5. Domain wall magnetoresistance in nanowires: Dependence on geometrical factors and material parameters

    International Nuclear Information System (INIS)

    Allende, S.; Retamal, J.C.; Altbir, D.; D'Albuquerque e Castro, J.

    2014-01-01

    The magnetoresistance associated with the presence of domain walls in metallic nanowires is investigated as a function of geometrical parameters, corresponding to the wall thickness and the nanowire width, as well as of material parameters, such as the band filling and the exchange interaction. Transport across the structure is described within Landauer formalism. Both cases of saturated and non-saturated ferromagnets are considered, and in all of them the contributions from spin-flip and non-spin-flip are separately analyzed. It has been found that for certain range of parameters deviations in the normalized magnetoresistance as high as 20% may be achieved. In addition, it has been shown that the spin-flip process is dependent on the wall thickness. - Highlights: • We identify thickness regions within which transport across the wall is dominated by either spin-flip or non-spin-flip process. • We analyze the dependence of the magnetoresistance on both the material's band filling and strength of the exchange interaction. • We identify parameter ranges within which magnetoresistance ratios as high as 20% or even more might be achieved

  6. Domain wall magnetoresistance in nanowires: Dependence on geometrical factors and material parameters

    Energy Technology Data Exchange (ETDEWEB)

    Allende, S.; Retamal, J.C. [Departamento de Física, CEDENNA, Universidad de Santiago de Chile, USACH, Avenida Ecuador 3493, 917-0124 Santiago (Chile); Altbir, D., E-mail: dora.altbir@usach.cl [Departamento de Física, CEDENNA, Universidad de Santiago de Chile, USACH, Avenida Ecuador 3493, 917-0124 Santiago (Chile); D' Albuquerque e Castro, J. [Instituto de Física, Universidade Federal do Rio de Janeiro, Caixa Postal 68528, Rio de Janeiro 21941-972 (Brazil)

    2014-04-15

    The magnetoresistance associated with the presence of domain walls in metallic nanowires is investigated as a function of geometrical parameters, corresponding to the wall thickness and the nanowire width, as well as of material parameters, such as the band filling and the exchange interaction. Transport across the structure is described within Landauer formalism. Both cases of saturated and non-saturated ferromagnets are considered, and in all of them the contributions from spin-flip and non-spin-flip are separately analyzed. It has been found that for certain range of parameters deviations in the normalized magnetoresistance as high as 20% may be achieved. In addition, it has been shown that the spin-flip process is dependent on the wall thickness. - Highlights: • We identify thickness regions within which transport across the wall is dominated by either spin-flip or non-spin-flip process. • We analyze the dependence of the magnetoresistance on both the material's band filling and strength of the exchange interaction. • We identify parameter ranges within which magnetoresistance ratios as high as 20% or even more might be achieved.

  7. Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging.

    Science.gov (United States)

    Liu, Heng; Chen, Xiao; Xue, Wei; Chu, Chengchao; Liu, Yu; Tong, Haipeng; Du, Xuesong; Xie, Tian; Liu, Gang; Zhang, Weiguo

    The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma.

  8. Inhibition of tumor metastasis by a growth factor receptor bound protein 2 Src homology 2 domain-binding antagonist.

    Science.gov (United States)

    Giubellino, Alessio; Gao, Yang; Lee, Sunmin; Lee, Min-Jung; Vasselli, James R; Medepalli, Sampath; Trepel, Jane B; Burke, Terrence R; Bottaro, Donald P

    2007-07-01

    Metastasis, the primary cause of death in most forms of cancer, is a multistep process whereby cells from the primary tumor spread systemically and colonize distant new sites. Blocking critical steps in this process could potentially inhibit tumor metastasis and dramatically improve cancer survival rates; however, our understanding of metastasis at the molecular level is still rudimentary. Growth factor receptor binding protein 2 (Grb2) is a widely expressed adapter protein with roles in epithelial cell growth and morphogenesis, as well as angiogenesis, making it a logical target for anticancer drug development. We have previously shown that a potent antagonist of Grb2 Src homology-2 domain-binding, C90, blocks growth factor-driven cell motility in vitro and angiogenesis in vivo. We now report that C90 inhibits metastasis in vivo in two aggressive tumor models, without affecting primary tumor growth rate. These results support the potential efficacy of this compound in reducing the metastatic spread of primary solid tumors and establish a critical role for Grb2 Src homology-2 domain-mediated interactions in this process.

  9. Role of multiprotein bridging factor 1 in archaea: bridging the domains?

    NARCIS (Netherlands)

    Koning, de B.; Blombach, F.; Wu Hao,; Brouns, S.J.J.; Oost, van der J.

    2009-01-01

    MBF1 (multiprotein bridging factor 1) is a highly conserved protein in archaea and eukaryotes. It was originally identified as a mediator of the eukaryotic transcription regulator BmFTZ-F1 (Bombyx mori regulator of fushi tarazu). MBF1 was demonstrated to enhance transcription by forming a bridge

  10. Imitative and Direct Learning as Interacting Factors in Life History Evolution.

    Science.gov (United States)

    Bullinaria, John A

    2017-01-01

    The idea that lifetime learning can have a significant effect on life history evolution has recently been explored using a series of artificial life simulations. These involved populations of competing individuals evolving by natural selection to learn to perform well on simplified abstract tasks, with the learning consisting of identifying regularities in their environment. In reality, there is more to learning than that type of direct individual experience, because it often includes a substantial degree of social learning that involves various forms of imitation of what other individuals have learned before them. This article rectifies that omission by incorporating memes and imitative learning into revised versions of the previous approach. To do this reliably requires formulating and testing a general framework for meme-based simulations that will enable more complete investigations of learning as a factor in any life history evolution scenarios. It does that by simulating imitative information transfer in terms of memes being passed between individuals, and developing a process for merging that information with the (possibly inconsistent) information acquired by direct experience, leading to a consistent overall body of learning. The proposed framework is tested on a range of learning variations and a representative set of life history factors to confirm the robustness of the approach. The simulations presented illustrate the types of interactions and tradeoffs that can emerge, and indicate the kinds of species-specific models that could be developed with this approach in the future.

  11. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.

    Science.gov (United States)

    Ogimi, Chikara; Greninger, Alexander L; Waghmare, Alpana A; Kuypers, Jane M; Shean, Ryan C; Xie, Hu; Leisenring, Wendy M; Stevens-Ayers, Terry L; Jerome, Keith R; Englund, Janet A; Boeckh, Michael

    2017-07-15

    Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of Genome changes were consistent with the expected molecular clock of HCoV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Tectono-thermal Evolution of a Distal Rifted Margin: Constraints From the Calizzano Massif (Prepiedmont-Briançonnais Domain, Ligurian Alps)

    Science.gov (United States)

    Decarlis, Alessandro; Fellin, Maria Giuditta; Maino, Matteo; Ferrando, Simona; Manatschal, Gianreto; Gaggero, Laura; Seno, Silvio; Stuart, Finlay M.; Beltrando, Marco

    2017-12-01

    The thermal evolution of distal domains along rifted margins is at present poorly constrained. In this study, we show that a thermal pulse, most likely triggered by lithospheric thinning and asthenospheric rise, is recorded at upper crustal levels and may also influence the diagenetic processes in the overlying sediments, thus representing a critical aspect for the evaluation of hydrocarbon systems. The thermal history of a distal sector of the Alpine Tethys rifted margin preserved in the Ligurian Alps (Case Tuberto-Calizzano unit) is investigated with thermochronological methods and petrologic observations. The studied unit is composed of a polymetamorphic basement and a sedimentary cover, providing a complete section through the prerift, synrift, and postrift system. Zircon fission track analyses on basement rocks samples suggest that temperatures exceeding 240 ± 25°C were reached before 150-160 Ma (Upper Jurassic) at few kilometer depth. Neoformation of green biotite, stable at temperatures of 350 to 450°C, was synkinematic with this event. The tectonic setting of the studied unit suggests that the heating-cooling cycle took place during the formation of the distal rifted margin and terminated during Late Jurassic (150-160 Ma). Major crustal and lithospheric thinning likely promoted high geothermal gradients ( 60-90°C/km) and triggered the circulation of hot, deep-seated fluids along brittle faults, causing the observed thermal anomaly. Our results suggest that rifting can generate thermal perturbations at relatively high temperatures (between 240 and 450°C) at less than 3 km depth in the distal domains during major crustal thinning preceding breakup and onset of seafloor spreading.

  13. RRM domain of Arabidopsis splicing factor SF1 is important for pre-mRNA splicing of a specific set of genes

    KAUST Repository

    Lee, Keh Chien

    2017-04-11

    The RNA recognition motif of Arabidopsis splicing factor SF1 affects the alternative splicing of FLOWERING LOCUS M pre-mRNA and a heat shock transcription factor HsfA2 pre-mRNA. Splicing factor 1 (SF1) plays a crucial role in 3\\' splice site recognition by binding directly to the intron branch point. Although plant SF1 proteins possess an RNA recognition motif (RRM) domain that is absent in its fungal and metazoan counterparts, the role of the RRM domain in SF1 function has not been characterized. Here, we show that the RRM domain differentially affects the full function of the Arabidopsis thaliana AtSF1 protein under different experimental conditions. For example, the deletion of RRM domain influences AtSF1-mediated control of flowering time, but not the abscisic acid sensitivity response during seed germination. The alternative splicing of FLOWERING LOCUS M (FLM) pre-mRNA is involved in flowering time control. We found that the RRM domain of AtSF1 protein alters the production of alternatively spliced FLM-β transcripts. We also found that the RRM domain affects the alternative splicing of a heat shock transcription factor HsfA2 pre-mRNA, thereby mediating the heat stress response. Taken together, our results suggest the importance of RRM domain for AtSF1-mediated alternative splicing of a subset of genes involved in the regulation of flowering and adaptation to heat stress.

  14. Structure, dynamics and folding of an immunoglobulin domain of the gelation factor (ABP-120) from Dictyostelium discoideum.

    Science.gov (United States)

    Hsu, Shang-Te Danny; Cabrita, Lisa D; Fucini, Paola; Dobson, Christopher M; Christodoulou, John

    2009-05-15

    We have carried out a detailed structural and dynamical characterisation of the isolated fifth repeat of the gelation factor (ABP-120) from Dictyostelium discoideum (ddFLN5) by NMR spectroscopy to provide a basis for studies of co-translational folding on the ribosome of this immunoglobulin-like domain. The isolated ddFLN5 can fold autonomously in solution into a structure that resembles very closely the crystal structure of the domain in a construct in which the adjacent sixth repeat (ddFLN6) is covalently linked to its C-terminus in tandem but deviates locally from a second crystal structure in which ddFLN5 is flanked by ddFLN4 and ddFLN6 at both N- and C-termini. Conformational fluctuations were observed via (15)N relaxation methods and are primarily localised in the interstrand loops that encompass the C-terminal hemisphere. These fluctuations are distinct in location from the region where line broadening is observed in ddFLN5 when attached to the ribosome as part of a nascent chain. This observation supports the conclusion that the broadening is associated with interactions with the ribosome surface [Hsu, S. T. D., Fucini, P., Cabrita, L. D., Launay, H., Dobson, C. M. & Christodoulou, J. (2007). Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy. Proc. Natl. Acad. Sci. USA, 104, 16516-16521]. The unfolding of ddFLN5 induced by high concentrations of urea shows a low population of a folding intermediate, as inferred from an intensity-based analysis, a finding that differs from that of ddFLN5 as a ribosome-bound nascent chain. These results suggest that interesting differences in detail may exist between the structure of the domain in isolation and when linked to the ribosome and between protein folding in vitro and the folding of a nascent chain as it emerges from the ribosome.

  15. The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis.

    Science.gov (United States)

    Liou, M L; Liou, H C

    1999-04-09

    The tumor necrosis factor receptor, p60 (TNF-R1), transduces death signals via the association of its cytoplasmic domain with several intracellular proteins. By screening a mammalian cDNA library using the yeast two-hybrid cloning technique, we isolated a ubiquitin-homology protein, DAP-1, which specifically interacts with the cytoplasmic death domain of TNF-R1. Sequence analysis reveals that DAP-1 shares striking sequence homology with the yeast SMT3 protein that is essential for the maintenance of chromosome integrity during mitosis (Meluh, P. B., and Koshland, D. (1995) Mol. Biol. Cell 6, 793-807). DAP-1 is nearly identical to PIC1, a protein that interacts with the PML tumor suppressor implicated in acute promyelocytic leukemia (Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., and Freemont, P. S. (1996) Oncogene 13, 971-982), and the sentrin protein, which associates with the Fas death receptor (Okura, T., Gong, L., Kamitani, T., Wada, T., Okura, I., Wei, C. F., Chang, H. M., and Yeh, E. T. (1996) J. Immunol. 157, 4277-4281). The in vivo interaction between DAP-1 and TNF-R1 was further confirmed in mammalian cells. In transient transfection assays, overexpression of DAP-1 suppresses NF-kappaB/Rel activity in 293T cells, a human kidney embryonic carcinoma cell line. Overexpression of either DAP-1 or sentrin causes apoptosis of TNF-sensitive L929 fibroblast cell line, as well as TNF-resistant osteosarcoma cell line, U2OS. Furthermore, the dominant negative Fas-associated death domain protein (FADD) protein blocks the cell death induced by either DAP-1 or FADD. Collectively, these observations highly suggest a role for DAP-1 in mediating TNF-induced cell death signaling pathways, presumably through the recruitment of FADD death effector.

  16. Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

    International Nuclear Information System (INIS)

    Huang, L.H.; Cheng, H.; Sweeney, W.V.; Pardi, A.; Tam, J.P.

    1991-01-01

    Factor IX is a blood clotting protein that contains three regions, including a γ-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel β-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp 28 , with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the β-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself

  17. Domains of reciprocity beyond monetary compensation: How do non-pecuniary factors affect effort and shirking?

    Directory of Open Access Journals (Sweden)

    Akinori Tomohara

    2016-12-01

    Full Text Available This empirical study examines how sources of reciprocity are related to work motivation by distinguishing positive and negative work attitudes in practical working environments. We move away from the unidimensional perspective of monetary compensation and investigate employees’ reciprocal behaviors, together with non-pecuniary aspects of work relations such as human relationships and company management. The results show that positive reciprocity, represented by effort, is fundamentally distinct from negative reciprocity, represented by shirking, when examining the multi-dimensional sources of reciprocity. Additionally, our analyses reveal that non-pecuniary factors in the working environment have a relatively large degree of association with work motivation, even when compared to monetary compensation. Our results complement those from controlled laboratory experiments.

  18. Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance.

    Science.gov (United States)

    Hishiki, Asami; Hara, Kodai; Ikegaya, Yuzu; Yokoyama, Hideshi; Shimizu, Toshiyuki; Sato, Mamoru; Hashimoto, Hiroshi

    2015-05-22

    HLTF (helicase-like transcription factor) is a yeast RAD5 homolog found in mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. HLTF has an N-terminal domain that has been designated the HIRAN (HIP116 and RAD5 N-terminal) domain. The HIRAN domain has been hypothesized to play a role in DNA binding; however, the structural basis of, and functional evidence for, the HIRAN domain in DNA binding has remained unclear. Here we show for the first time the crystal structure of the HIRAN domain of human HLTF in complex with DNA. The HIRAN domain is composed of six β-strands and two α-helices, forming an OB-fold structure frequently found in ssDNA-binding proteins, including in replication factor A (RPA). Interestingly, this study reveals that the HIRAN domain interacts with not only with a single-stranded DNA but also with a duplex DNA. Furthermore, the structure unexpectedly clarifies that the HIRAN domain specifically recognizes the 3'-end of DNA. These results suggest that the HIRAN domain functions as a sensor to the 3'-end of the primer strand at the stalled replication fork and that the domain facilitates fork regression. HLTF is recruited to a damaged site through the HIRAN domain at the stalled replication fork. Furthermore, our results have implications for the mechanism of template switching. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The WRKY57 Transcription Factor Affects the Expression of Jasmonate ZIM-Domain Genes Transcriptionally to Compromise Botrytis cinerea Resistance.

    Science.gov (United States)

    Jiang, Yanjuan; Yu, Diqiu

    2016-08-01

    Although necrotrophic pathogens cause many devastating plant diseases, our understanding of the plant defense response to them is limited. Here, we found that loss of function of WRKY57 enhanced the resistance of Arabidopsis (Arabidopsis thaliana) against Botrytis cinerea infection. Further investigation suggested that the negative regulation of WRKY57 against B cinerea depends on the jasmonic acid (JA) signaling pathway. Chromatin immunoprecipitation experiments revealed that WRKY57 directly binds to the promoters of JASMONATE ZIM-DOMAIN1 (JAZ1) and JAZ5, encoding two important repressors of the JA signaling pathway, and activates their transcription. In vivo and in vitro experiments demonstrated that WRKY57 interacts with nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2. Further experiments display that the same domain, the VQ motif, of SIB1 and SIB2 interact with WRKY33 and WRKY57. Moreover, transient transcriptional activity assays confirmed that WRKY57 and WRKY33 competitively regulate JAZ1 and JAZ5, SIB1 and SIB2 further enhance these competitions of WRKY57 to WRKY33. Therefore, coordinated regulation of Arabidopsis against B cinerea by transcription activators and repressors would benefit plants by allowing fine regulation of defense. © 2016 American Society of Plant Biologists. All Rights Reserved.

  20. Arg156 in the AP2-domain exhibits the highest binding activity among the 20 individuals to the GCC box in BnaERF-B3-hy15, a mutant ERF transcription factor from Brassica napus

    Directory of Open Access Journals (Sweden)

    Jing Zhuang

    2016-10-01

    Full Text Available To develop mutants of the ERF factor with more binding activities to the GCC box, we performed in vitro directed evolution by using DNA shuffling and screened mutants through yeast one-hybrid assay. Here, a series of mutants were obtained and used to reveal key amino acids that induce changes in the DNA binding activity of the BnaERF-B3 protein. With the BnaERF-B3-hy15 as the template, we produced 12 mutants which host individual mutation of potential key residues. We found that amino acid 156 is the key site, and the other 18 mutants host the 18 corresponding individual amino acid residues at site 156. Among the 20 individuals comprising WT (Gly156, Mu3 (Arg156, and 18 mutants with other 18 amino acid residues, Arg156 in the AP2-domain is the amino acid residue with the highest binding activity to the GCC box. The structure of the α-helix in the AP2-domain affects the binding activity. Other residues within AP2-domain modulated binding activity of ERF protein, suggesting that these positions are important for binding activity. Comparison of the mutant and wild-type transcription factors revealed the relationship of protein function and sequence modification. Our result provides a potential useful resource for understanding the trans-activation of ERF proteins.

  1. Factors controlling the geochemical evolution of fumarolic encrustations, Valley of Ten Thousand Smokes, Alaska

    Science.gov (United States)

    Kodosky, L.G.; Keith, T.E.C.

    1993-01-01

    Factor and canonical correlation analysis of geochemical data from eight fossil fumaroles suggest that six major factors controlled the formation and evolution of fumarolic encrustations on the 1912 ash-flow sheet in the Valley of Ten Thousand Smokes (VTTS). The six-factor solution model explains a large proportion (low of 74% for Ni to high of 99% for Si) of the individual element data variance. Although the primary fumarolic deposits have been degraded by secondary alteration reactions and up to 75 years of weathering, the relict encrustations still preserve a signature of vapor-phase element transport. This vapor-phase transport probably occurred as halide or oxyhalide species and was significant for As, Sb and Br. At least three, and possibly four, varied temperature leaching events affected the fumarolic deposits. High-temperature gases/liquids heavily altered the ejecta glass and mineral phases adjacent to the fumarolic conduit. As the fumaroles cooled. Fe-rich acidic condensate leached the ejecta and primary fumarolic deposits and resulted in the subsequent precipitation of Fe-hydroxides and/or Fe-oxides. Low- to ambient-temperature leaching and hydration reactions generated abundant hydrated amorphous phases. Up to 87% of the individual element data variance is apparently controlled by the chemistry of the ejecta on which the relict encrustations are found. This matrix chemistry factor illustrates that the primary fumarolic minerals surrounding the active VTTS vents observed by earlier workers have been effectively removed by the dissolution reactions. Element enrichment factors calculated for the VTTS relict encrustations support the statistical factor interpretations. On the average, the relict encrustations are enriched, relative to visibly unaltered matrix protolith, in As, Br, Cr, Sb, Cu, Ni, Pb, Fe, and LOI (an indirect measure of sample H2O content). ?? 1993.

  2. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells

    Energy Technology Data Exchange (ETDEWEB)

    Noah, Taeko K.; Kazanjian, Avedis [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Whitsett, Jeffrey [Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Neonatology and Pulmonary Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Shroyer, Noah F., E-mail: noah.shroyer@cchmc.org [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2010-02-01

    Background and Aims: SPDEF (also termed PDEF or PSE) is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation. Methods: SPDEF expression was inhibited in colon cancer cells to determine its ability to control goblet cell gene activation. The effects of transgenic expression of Spdef on intestinal differentiation and homeostasis were determined. Results: In LS174T colon cancer cells treated with Notch/{gamma}-secretase inhibitor to activate goblet cell gene expression, shRNAs that inhibited SPDEF also repressed expression of goblet cell genes AGR2, MUC2, RETLNB, and SPINK4. Transgenic expression of Spdef caused the expansion of intestinal goblet cells and corresponding reduction in Paneth, enteroendocrine, and absorptive enterocytes. Spdef inhibited proliferation of intestinal crypt cells without induction of apoptosis. Prolonged expression of the Spdef transgene caused a progressive reduction in the number of crypts that expressed Spdef, consistent with its inhibitory effects on cell proliferation. Conclusions: Spdef was sufficient to inhibit proliferation of intestinal progenitors and induce differentiation into goblet cells; SPDEF was required for activation of goblet cell associated genes in vitro. These data support a model in which Spdef promotes terminal differentiation into goblet cells of a common goblet/Paneth progenitor.

  3. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

    politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

  4. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    Science.gov (United States)

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  5. Modeling risk evolution of digestive tract functional violations when exposed to chemical environmental factors

    Directory of Open Access Journals (Sweden)

    M.R. Kamaltdinov

    2015-06-01

    Full Text Available Modern methods of health risk assessment are based on the representation of individual and public health as a dynamic process of “evolution”, which describes a continuous course of negative (and positive changes in the condition of the body. The article presents a conceptual diagram of multilevel health risk evolution modeling under the influence of environmental factors. The main aspects associated with the simulation of digestive processes in the “meso level” are considered. Some results of solving the problem of the flow in the digestive tract antroduodenal area taken into account tract motility. Further development ways of the model are outlines – account of biochemical reactions, secretory and absorptive functions tract. The proposed approach will enable not only to predict the risk of digestive system functional disorders, but also take into account basic physiological processes, mechanisms of income, distribution, excretion of chemicals.

  6. Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains.

    Science.gov (United States)

    Chigira, Yuko; Oka, Takuji; Okajima, Tetsuya; Jigami, Yoshifumi

    2008-04-01

    Development of a heterologous system for the production of homogeneous sugar structures has the potential to elucidate structure-function relationships of glycoproteins. In the current study, we used an artificial O-glycosylation pathway to produce an O-fucosylated epidermal growth factor (EGF) domain in Saccharomyces cerevisiae. The in vivo O-fucosylation system was constructed via expression of genes that encode protein O-fucosyltransferase 1 and the EGF domain, along with genes whose protein products convert cytoplasmic GDP-mannose to GDP-fucose. This system allowed identification of an endogenous ability of S. cerevisiae to transport GDP-fucose. Moreover, expression of EGF domain mutants in this system revealed the different contribution of three disulfide bonds to in vivo O-fucosylation. In addition, lectin blotting revealed differences in the ability of fucose-specific lectin to bind the O-fucosylated structure of EGF domains from human factors VII and IX. Further introduction of the human fringe gene into yeast equipped with the in vivo O-fucosylation system facilitated the addition of N-acetylglucosamine to the EGF domain from factor IX but not from factor VII. The results suggest that engineering of an O-fucosylation system in yeast provides a powerful tool for producing proteins with homogenous carbohydrate chains. Such proteins can be used for the analysis of substrate specificity and the production of antibodies that recognize O-glycosylated EGF domains.

  7. A Computational Study of the Oligosaccharide Binding Sites in the Lectin-Like Domain of Tumor Necrosis Factor and the TNF-derived TIP Peptide

    Czech Academy of Sciences Publication Activity Database

    Dulebo, A.; Ettrich, Rüdiger; Lucas, R.; Kaftan, D.

    2012-01-01

    Roč. 18, č. 27 (2012), s. 4236-4243 ISSN 1381-6128 Institutional support: RVO:67179843 Keywords : lectin-like domain * tumor necrosis factor * TIP peptide * oligosaccharides * molecular docking * molecular dynamics simulation * alveolar liquid clearance Subject RIV: CE - Biochemistry Impact factor: 3.311, year: 2012

  8. Multiple native-like conformations trapped via self-association-induced hydrophobic collapse of the 33-residue beta-sheet domain from platelet factor 4.

    OpenAIRE

    Ilyina, E; Mayo, K H

    1995-01-01

    Native platelet factor 4 (PF4) (70 residues) has a hydrophobic three-stranded anti-parallel beta-sheet domain on to which is folded an amphipathic C-terminal alpha-helix and an aperiodic N-terminal domain. The 33-amino acid beta-sheet domain from PF4 (residues 23-55) has been synthesized and studied by c.d. and n.m.r. At 10 degrees C and low concentration, peptide 23-55 appears to exist in aqueous solution in a random-coil distribution of highly flexible conformational states. Some preferred ...

  9. The leucine zipper domains of the transcription factors GCN4 and c-Jun have ribonuclease activity.

    Directory of Open Access Journals (Sweden)

    Yaroslav Nikolaev

    Full Text Available Basic-region leucine zipper (bZIP proteins are one of the largest transcription factor families that regulate a wide range of cellular functions. Owing to the stability of their coiled coil structure leucine zipper (LZ domains of bZIP factors are widely employed as dimerization motifs in protein engineering studies. In the course of one such study, the X-ray structure of the retro-version of the LZ moiety of yeast transcriptional activator GCN4 suggested that this retro-LZ may have ribonuclease activity. Here we show that not only the retro-LZ but also the authentic LZ of GCN4 has weak but distinct ribonuclease activity. The observed cleavage of RNA is unspecific, it is not suppressed by the ribonuclease A inhibitor RNasin and involves the breakage of 3',5'-phosphodiester bonds with formation of 2',3'-cyclic phosphates as the final products as demonstrated by HPLC/electrospray ionization mass spectrometry. Several mutants of the GCN4 leucine zipper are catalytically inactive, providing important negative controls and unequivocally associating the enzymatic activity with the peptide under study. The leucine zipper moiety of the human factor c-Jun as well as the entire c-Jun protein are also shown to catalyze degradation of RNA. The presented data, which was obtained in the test-tube experiments, adds GCN4 and c-Jun to the pool of proteins with multiple functions (also known as moonlighting proteins. If expressed in vivo, the endoribonuclease activity of these bZIP-containing factors may represent a direct coupling between transcription activation and controlled RNA turnover. As an additional result of this work, the retro-leucine zipper of GCN4 can be added to the list of functional retro-peptides.

  10. Correlations between risk factors and functional evolution in patients with spastic quadriplegia.

    Science.gov (United States)

    Rogoveanu, O C; Tuțescu, N C; Kamal, D; Alexandru, D O; Kamal, C; Streba, L; Trăistaru, M R

    2016-01-01

    Cerebral palsy is the most common cause of developing neuro-motor disability in children, in many cases, the triggering cause remaining unknown. Quadriplegia is the most severe spastic cerebral palsy, characterized by severe mental retardation and bi-pyramidal syndrome. The purpose of this paper was to demonstrate the importance of knowing the risk factors and the psychosomatic ones, determining to what extent they influence the functional evolution in patients diagnosed with spastic quadriplegia. 23 children diagnosed with spastic quadriplegia were included in the study, being aged between 1 year and half and 12 years. Patients were assessed at baseline (T1), at one year (T2) and after two years at the end of the study (T3). Patients received a comprehensive rehabilitation program for the motor and sensory deficits throughout the study. Initially, a comprehensive evaluation (etiopathogenic, clinical and functional) that started from a thorough medical history of children (the older ones), was conducted but chose parents to identify the risk factors, and a complete physical exam. At each assessment, joint and muscle balance was conducted. To assess functionality, the gross motor function classification systems (GMFCS) and manual ability (MACS) were used. Many risk factors that were classified according to the timeline in prenatal factors, perinatal and postnatal, were identified from a thorough history. A direct correlation was noticed between the decrease of coarse functionality and manual ability, both initially and in dynamic and low APGAR scores, low gestational age, low birth weight and a higher body mass index of the mother. A direct link was observed between the gross motor function and the manual ability. A significant improvement in the MACS score was noticed in patients with a better GMFCS score.

  11. Azadirachtin Interacts with the Tumor Necrosis Factor (TNF) Binding Domain of Its Receptors and Inhibits TNF-induced Biological Responses*

    Science.gov (United States)

    Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A.; Manna, Sunil K.

    2010-01-01

    The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor κB (NF-κB) and also expression of NF-κB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-κB (IκBα) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IκBα kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-κB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy. PMID:20018848

  12. Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses.

    Science.gov (United States)

    Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A; Manna, Sunil K

    2010-02-19

    The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor kappaB (NF-kappaB) and also expression of NF-kappaB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-kappaB (IkappaB alpha) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IkappaB alpha kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-kappaB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy.

  13. Evolved α-factor prepro-leaders for directed laccase evolution in Saccharomyces cerevisiae.

    Science.gov (United States)

    Mateljak, Ivan; Tron, Thierry; Alcalde, Miguel

    2017-11-01

    Although the functional expression of fungal laccases in Saccharomyces cerevisiae has proven to be complicated, the replacement of signal peptides appears to be a suitable approach to enhance secretion in directed evolution experiments. In this study, twelve constructs were prepared by fusing native and evolved α-factor prepro-leaders from S. cerevisiae to four different laccases with low-, medium- and high-redox potential (PM1L from basidiomycete PM1; PcL from Pycnoporus cinnabarinus; TspC30L from Trametes sp. strain C30; and MtL from Myceliophthora thermophila). Microcultures of the prepro-leader:laccase fusions were grown in selective expression medium that used galactose as both the sole carbon source and as the inducer of expression so that the secretion and activity were assessed with low- and high-redox potential mediators in a high-throughput screening context. With total activity improvements as high as sevenfold over those obtained with the native α-factor prepro-leader, the evolved prepro-leader from PcL (α PcL ) most strongly enhanced secretion of the high- and medium-redox potential laccases PcL, PM1L and TspC30L in the microtiter format with an expression pattern driven by prepro-leaders in the order α PcL  > α PM 1L  ~ α native . By contrast, the pattern of the low-redox potential MtL was α native  > α PcL  > α PM 1L . When produced in flask with rich medium, the evolved prepro-leaders outperformed the α native signal peptide irrespective of the laccase attached, enhancing secretion over 50-fold. Together, these results highlight the importance of using evolved α-factor prepro-leaders for functional expression of fungal laccases in directed evolution campaigns. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  14. Genetic Variation of Goat Interferon Regulatory Factor 3 Gene and Its Implication in Goat Evolution.

    Science.gov (United States)

    Okpeku, Moses; Esmailizadeh, Ali; Adeola, Adeniyi C; Shu, Liping; Zhang, Yesheng; Wang, Yangzi; Sanni, Timothy M; Imumorin, Ikhide G; Peters, Sunday O; Zhang, Jiajin; Dong, Yang; Wang, Wen

    2016-01-01

    The immune systems are fundamentally vital for evolution and survival of species; as such, selection patterns in innate immune loci are of special interest in molecular evolutionary research. The interferon regulatory factor (IRF) gene family control many different aspects of the innate and adaptive immune responses in vertebrates. Among these, IRF3 is known to take active part in very many biological processes. We assembled and evaluated 1356 base pairs of the IRF3 gene coding region in domesticated goats from Africa (Nigeria, Ethiopia and South Africa) and Asia (Iran and China) and the wild goat (Capra aegagrus). Five segregating sites with θ value of 0.0009 for this gene demonstrated a low diversity across the goats' populations. Fu and Li tests were significantly positive but Tajima's D test was significantly negative, suggesting its deviation from neutrality. Neighbor joining tree of IRF3 gene in domesticated goats, wild goat and sheep showed that all domesticated goats have a closer relationship than with the wild goat and sheep. Maximum likelihood tree of the gene showed that different domesticated goats share a common ancestor and suggest single origin. Four unique haplotypes were observed across all the sequences, of which, one was particularly common to African goats (MOCH-K14-0425, Poitou and WAD). In assessing the evolution mode of the gene, we found that the codon model dN/dS ratio for all goats was greater than one. Phylogenetic Analysis by Maximum Likelihood (PAML) gave a ω0 (dN/dS) value of 0.067 with LnL value of -6900.3 for the first Model (M1) while ω2 = 1.667 in model M2 with LnL value of -6900.3 with positive selection inferred in 3 codon sites. Mechanistic empirical combination (MEC) model for evaluating adaptive selection pressure on particular codons also confirmed adaptive selection pressure in three codons (207, 358 and 408) in IRF3 gene. Positive diversifying selection inferred with recent evolutionary changes in domesticated goat IRF3

  15. Validating Domains of Patient Contextual Factors Essential to Preventing Contextual Errors: A Qualitative Study Conducted at Chicago Area Veterans Health Administration Sites.

    Science.gov (United States)

    Binns-Calvey, Amy E; Malhiot, Alex; Kostovich, Carol T; LaVela, Sherri L; Stroupe, Kevin; Gerber, Ben S; Burkhart, Lisa; Weiner, Saul J; Weaver, Frances M

    2017-09-01

    "Patient context" indicates patient circumstances and characteristics or states that are essential to address when planning patient care. Specific patient "contextual factors," if overlooked, result in an inappropriate plan of care, a medical error termed a "contextual error." The myriad contextual factors that constitute patient context have been grouped into broad domains to create a taxonomy of challenges to consider when planning care. This study sought to validate a previously identified list of contextual domains. This qualitative study used directed content analysis. In 2014, 19 Department of Veterans Affairs (VA) providers (84% female) and 49 patients (86% male) from two VA medical centers and four outpatient clinics in the Chicago area participated in semistructured interviews and focus groups. Topics included patient-specific, community, and resource-related factors that affect patients' abilities to manage their care. Transcripts were analyzed with a previously identified list of contextual domains as a framework. Analysis of responses revealed that patients and providers identified the same 10 domains previously published, plus 3 additional ones. Based on comments made by patients and providers, the authors created a revised list of 12 domains from themes that emerged. Six pertain to patient circumstances such as access to care and financial situation, and 6 to patient characteristics/states including skills, abilities, and knowledge. Contextual factors in patients' lives may be essential to address for effective care planning. The rubric developed can serve as a "contextual differential" for clinicians to consider when addressing challenges patients face when planning their care.

  16. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a

    OpenAIRE

    Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M.; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

    2003-01-01

    The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique...

  17. Time evolution and emission factors of aerosol particles from day and night time savannah fires

    Science.gov (United States)

    Vakkari, Ville; Beukes, Johan Paul; Tiitta, Petri; Venter, Andrew; Jaars, Kerneels; Josipovic, Miroslav; van Zyl, Pieter; Kulmala, Markku; Laakso, Lauri

    2013-04-01

    The largest uncertainties in the current global climate models originate from aerosol particle effects (IPCC, 2007) and at the same time aerosol particles also pose a threat to human health (Pope and Dockery, 2006). In southern Africa wild fires and prescribed burning are one of the most important sources of aerosol particles, especially during the dry season from June to September (e.g. Swap et al., 2003; Vakkari et al., 2012). The aerosol particle emissions from savannah fires in southern Africa have been studied in several intensive campaigns such as SAFARI 1992 and 2000 (Swap et al., 2003). However, all previous measurements have been carried out during the daytime, whereas most of the prescribed fires in southern Africa are lit up only after sunset. Furthermore, the previous campaigns followed the plume evolution for up to one hour after emission only. In this study, combining remote sensing fire observations to ground-based long-term measurements of aerosol particle and trace gas properties at the Welgegund measurement station (www.welgegund.org), we have been able to follow the time evolution of savannah fire plumes up to several hours in the atmosphere. For the first time the aerosol particle size distribution measurements in savannah fire plumes cover both day and night time plumes and also the ultrafine size range below 100 nm. During the period from May 20th 2010 to April 15th 2012 altogether 61 savannah fire plumes were observed at Welgegund. The evolution of the aerosol size distribution remained rapid for at least five hours after the fire: during this period the growth rate of the aerosol particle count mean diameter (size range 12 to 840 nm) was 24 nm h-1 for daytime plumes and 8 nm h-1 for night time plumes. The difference in the day and night time growth rate shows that photochemical reactions significantly increase the condensable vapour concentration in the plume. Furthermore, the condensable vapour concentration was found to affect both the

  18. Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1

    Energy Technology Data Exchange (ETDEWEB)

    Veggiani, Gianluca; Ossolengo, Giuseppe; Aliprandi, Marisa; Cavallaro, Ugo [IFOM-IEO Campus, Via Adamello 16, 20139 Milano (Italy); Marco, Ario de, E-mail: ario.demarco@ung.si [IFOM-IEO Campus, Via Adamello 16, 20139 Milano (Italy); Dept. Environmental Sciences, University of Nova Gorica (UNG), Vipavska 13, P.O. Box 301-SI-5000, Rozna Dolina, Nova Gorica (Slovenia)

    2011-05-20

    Highlights: {yields} Recombinant antibodies for FGFR1 were isolated from a llama naive library in VHH format. {yields} These antibodies compete with the natural ligand FGF-2 for the same epitope on FGFR1. {yields} The antibody competition inhibits the FGF-2-dependent internalization of FGFR1. -- Abstract: Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naive library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications.

  19. Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1

    International Nuclear Information System (INIS)

    Veggiani, Gianluca; Ossolengo, Giuseppe; Aliprandi, Marisa; Cavallaro, Ugo; Marco, Ario de

    2011-01-01

    Highlights: → Recombinant antibodies for FGFR1 were isolated from a llama naive library in VHH format. → These antibodies compete with the natural ligand FGF-2 for the same epitope on FGFR1. → The antibody competition inhibits the FGF-2-dependent internalization of FGFR1. -- Abstract: Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naive library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications.

  20. Bivalent Llama Single-Domain Antibody Fragments against Tumor Necrosis Factor Have Picomolar Potencies due to Intramolecular Interactions

    Directory of Open Access Journals (Sweden)

    Els Beirnaert

    2017-07-01

    Full Text Available The activity of tumor necrosis factor (TNF, a cytokine involved in inflammatory pathologies, can be inhibited by antibodies or trap molecules. Herein, llama-derived variable heavy-chain domains of heavy-chain antibody (VHH, also called Nanobodies™ were generated for the engineering of bivalent constructs, which antagonize the binding of TNF to its receptors with picomolar potencies. Three monomeric VHHs (VHH#1, VHH#2, and VHH#3 were characterized in detail and found to bind TNF with sub-nanomolar affinities. The crystal structures of the TNF–VHH complexes demonstrate that VHH#1 and VHH#2 share the same epitope, at the center of the interaction area of TNF with its TNFRs, while VHH#3 binds to a different, but partially overlapping epitope. These structures rationalize our results obtained with bivalent constructs in which two VHHs were coupled via linkers of different lengths. Contrary to conventional antibodies, these bivalent Nanobody™ constructs can bind to a single trimeric TNF, thus binding with avidity and blocking two of the three receptor binding sites in the cytokine. The different mode of binding to antigen and the engineering into bivalent constructs supports the design of highly potent VHH-based therapeutic entities.

  1. Analysis of von Willebrand factor A domain-related protein (WARP polymorphism in temperate and tropical Plasmodium vivax field isolates

    Directory of Open Access Journals (Sweden)

    Zakeri Sedigheh

    2009-06-01

    Full Text Available Abstract Background The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs, among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP, is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. Methods Clinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991 which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp. Results Amplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT to A (GCT and R (AGA to S (AGT] in comparison with the Sal-I sequence. Conclusion This study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

  2. Molecular Evolution and Expansion Analysis of the NAC Transcription Factor in Zea mays

    Science.gov (United States)

    Fan, Kai; Wang, Ming; Miao, Ying; Ni, Mi; Bibi, Noreen; Yuan, Shuna; Li, Feng; Wang, Xuede

    2014-01-01

    NAC (NAM, ATAF1, 2 and CUC2) family is a plant-specific transcription factor and it controls various plant developmental processes. In the current study, 124 NAC members were identified in Zea mays and were phylogenetically clustered into 13 distinct subfamilies. The whole genome duplication (WGD), especially an additional WGD event, may lead to expanding ZmNAC members. Different subfamily has different expansion rate, and NAC subfamily preference was found during the expansion in maize. Moreover, the duplication events might occur after the divergence of the lineages of Z. mays and S. italica, and segmental duplication seemed to be the dominant pattern for the gene duplication in maize. Furthermore, the expansion of ZmNAC members may be also related to gain and loss of introns. Besides, the restriction of functional divergence was discovered after most of the gene duplication events. These results could provide novel insights into molecular evolution and expansion analysis of NAC family in maize, and advance the NAC researches in other plants, especially polyploid plants. PMID:25369196

  3. Factor VII deficiency: Unveiling the cellular and molecular mechanisms underlying three model alterations of the enzyme catalytic domain.

    Science.gov (United States)

    Chollet, Maria Eugenia; Andersen, Elisabeth; Skarpen, Ellen; Myklebust, Christiane F; Koehler, Christian; Morth, Jens Preben; Chuansumrit, Ampaiwan; Pinotti, Mirko; Bernardi, Francesco; Thiede, Bernd; Sandset, Per Morten; Skretting, Grethe

    2018-03-01

    Activated factor (F) VII is a vitamin K-dependent glycoprotein that initiates blood coagulation upon interaction with tissue factor. FVII deficiency is the most common of the rare congenital bleeding disorders. While the mutational pattern has been extensively characterized, the pathogenic molecular mechanisms of mutations, particularly at the intracellular level, have been poorly defined. Here, we aimed at elucidating the mechanisms underlying altered FVII biosynthesis in the presence of three mutation types in the catalytic domain: a missense change, a microdeletion and a frameshift/elongation, associated with severe or moderate to severe phenotypes. Using CHO-K1 cells transiently transfected with expression vectors containing the wild-type FVII cDNA (FVIIwt) or harboring the p.I289del, p.G420V or p.A354V-p.P464Hfs mutations, we found that the secretion of the FVII mutants was severely decreased compared to FVIIwt. The synthesis rate of the mutants was slower than the FVIIwt and delayed, and no degradation of the FVII mutants by proteasomes, lysosomes or cysteine proteases was observed. Confocal immunofluorescence microscopy studies showed that FVII variants were localized into the endoplasmic reticulum (ER) but were not detectable within the Golgi apparatus. These findings suggested that a common pathogenic mechanism, possibly a defective folding of the mutant proteins, was triggered by the FVII mutations. The misfolded state led to impaired trafficking of these proteins causing ER retention, which would explain the low to very low FVII plasma levels observed in patients carrying these mutations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.

    Science.gov (United States)

    Dorji, Dorji; Mooi, Frits; Yantorno, Osvaldo; Deora, Rajendar; Graham, Ross M; Mukkur, Trilochan K

    2018-02-01

    Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and acellular pertussis (aP) vaccines in 1990s reduced the mortality due to pertussis. Despite induction of both antibody and cell-mediated immune (CMI) responses by aP and wP vaccines, there has been resurgence of pertussis in many countries in recent years. Possible reasons hypothesised for resurgence have ranged from incompliance with the recommended vaccination programmes with the currently used aP vaccine to infection with a resurged clinical isolates characterised by mutations in the virulence factors, resulting in antigenic divergence with vaccine strain, and increased production of pertussis toxin, resulting in dampening of immune responses. While use of these vaccines provide varying degrees of protection against whooping cough, protection against infection and transmission appears to be less effective, warranting continuation of efforts in the development of an improved pertussis vaccine formulations capable of achieving this objective. Major approaches currently under evaluation for the development of an improved pertussis vaccine include identification of novel biofilm-associated antigens for incorporation in current aP vaccine formulations, development of live attenuated vaccines and discovery of novel non-toxic adjuvants capable of inducing both antibody and CMI. In this review, the potential roles of different accredited virulence factors, including novel biofilm-associated antigens, of B. pertussis in the evolution, formulation and delivery of improved pertussis vaccines, with potential to block the transmission of whooping cough in the community, are discussed.

  5. Do DSM-5 Section II personality disorders and Section III personality trait domains reflect the same genetic and environmental risk factors?

    Science.gov (United States)

    Reichborn-Kjennerud, T; Krueger, R F; Ystrom, E; Torvik, F A; Rosenström, T H; Aggen, S H; South, S C; Neale, M C; Knudsen, G P; Kendler, K S; Czajkowski, N O

    2017-09-01

    DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known. We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors. When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91. The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.

  6. Evolution in the Southeastern USA: Factors Influencing Acceptance and Rejection in Pre-Service Science Teachers

    Science.gov (United States)

    Glaze, Amanda L.; Goldston, M. Jenice; Dantzler, John

    2015-01-01

    Evolution continues to be a controversial topic around the world but nowhere is this more apparent locally than in the Southeastern region of the USA. In this study, we explored acceptance and rejection of evolution among pre-service science teachers in a teaching college in the rural Southeast and sought to determine (1) what relationships exist…

  7. In situ X-ray study of the structural evolution of gold nano-domains by spray deposition on thin conductive P3HT films.

    Science.gov (United States)

    Al-Hussein, M; Schindler, M; Ruderer, M A; Perlich, J; Schwartzkopf, M; Herzog, G; Heidmann, B; Buffet, A; Roth, S V; Müller-Buschbaum, P

    2013-02-26

    Gold (Au) nanoparticles are deposited from aqueous solution onto one of the most used conductive polymers, namely poly(3-hexylthiophene) (P3HT), using airbrush deposition. We report on the structure formation and packing of the Au nanoparticles after a 5 s spray cycle. In situ grazing incidence small-angle X-ray scattering (GISAXS) measurements with 20 ms time resolution allow a real-time observation of the emergence and evolution of the microstructure during a spray cycle and subsequent solvent evaporation. The results reveal multistage nanoscale ordering of the Au nanoparticles during the spray cycle. Further ex situ atomic force microscopy measurements of the sprayed films showed the formation of Au monolayer islands on top of the polymer film. Our study suggests that the solvent-substrate interaction as well as solvent evaporation kinetics are important factors that need to be taken into consideration in order to grow a compact uniform monolayer film for the fabrication of ultrathin films using airbrush deposition.

  8. Development and Characterization of a Camelid Single Domain Antibody-Urease Conjugate That Targets Vascular Endothelial Growth Factor Receptor 2.

    Science.gov (United States)

    Tian, Baomin; Wong, Wah Yau; Uger, Marni D; Wisniewski, Pawel; Chao, Heman

    2017-01-01

    Angiogenesis is the process of new blood vessel formation and is essential for a tumor to grow beyond a certain size. Tumors secrete the pro-angiogenic factor vascular endothelial growth factor, which acts upon local endothelial cells by binding to vascular endothelial growth factor receptors (VEGFRs). In this study, we describe the development and characterization of V21-DOS47, an immunoconjugate that targets VEGFR2. V21-DOS47 is composed of a camelid single domain anti-VEGFR2 antibody (V21) and the enzyme urease. The conjugate specifically binds to VEGFR2 and urease converts endogenous urea into ammonia, which is toxic to tumor cells. Previously, we developed a similar antibody-urease conjugate, L-DOS47, which is currently in clinical trials for non-small cell lung cancer. Although V21-DOS47 was designed from parameters learned from the generation of L-DOS47, additional optimization was required to produce V21-DOS47. In this study, we describe the expression and purification of two versions of the V21 antibody: V21H1 and V21H4. Each was conjugated to urease using a different chemical cross-linker. The conjugates were characterized by a panel of analytical techniques, including SDS-PAGE, size exclusion chromatography, Western blotting, and LC-MS E peptide mapping. Binding characteristics were determined by ELISA and flow cytometry assays. To improve the stability of the conjugates at physiologic pH, the pIs of the V21 antibodies were adjusted by adding several amino acid residues to the C-terminus. For V21H4, a terminal cysteine was also added for use in the conjugation chemistry. The modified V21 antibodies were expressed in the E. coli BL21 (DE3) pT7 system. V21H1 was conjugated to urease using the heterobifunctional cross-linker succinimidyl-[( N -maleimidopropionamido)-diethyleneglycol] ester (SM(PEG) 2 ), which targets lysine resides in the antibody. V21H4 was conjugated to urease using the homobifunctional cross-linker, 1,8-bis(maleimido)diethylene glycol

  9. Development and Characterization of a Camelid Single Domain Antibody–Urease Conjugate That Targets Vascular Endothelial Growth Factor Receptor 2

    Directory of Open Access Journals (Sweden)

    Baomin Tian

    2017-08-01

    Full Text Available Angiogenesis is the process of new blood vessel formation and is essential for a tumor to grow beyond a certain size. Tumors secrete the pro-angiogenic factor vascular endothelial growth factor, which acts upon local endothelial cells by binding to vascular endothelial growth factor receptors (VEGFRs. In this study, we describe the development and characterization of V21-DOS47, an immunoconjugate that targets VEGFR2. V21-DOS47 is composed of a camelid single domain anti-VEGFR2 antibody (V21 and the enzyme urease. The conjugate specifically binds to VEGFR2 and urease converts endogenous urea into ammonia, which is toxic to tumor cells. Previously, we developed a similar antibody–urease conjugate, L-DOS47, which is currently in clinical trials for non-small cell lung cancer. Although V21-DOS47 was designed from parameters learned from the generation of L-DOS47, additional optimization was required to produce V21-DOS47. In this study, we describe the expression and purification of two versions of the V21 antibody: V21H1 and V21H4. Each was conjugated to urease using a different chemical cross-linker. The conjugates were characterized by a panel of analytical techniques, including SDS-PAGE, size exclusion chromatography, Western blotting, and LC-MSE peptide mapping. Binding characteristics were determined by ELISA and flow cytometry assays. To improve the stability of the conjugates at physiologic pH, the pIs of the V21 antibodies were adjusted by adding several amino acid residues to the C-terminus. For V21H4, a terminal cysteine was also added for use in the conjugation chemistry. The modified V21 antibodies were expressed in the E. coli BL21 (DE3 pT7 system. V21H1 was conjugated to urease using the heterobifunctional cross-linker succinimidyl-[(N-maleimidopropionamido-diethyleneglycol] ester (SM(PEG2, which targets lysine resides in the antibody. V21H4 was conjugated to urease using the homobifunctional cross-linker, 1,8-bis

  10. Epidermal Growth Factor-like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Sørensen, Flemming Brandt

    2014-01-01

    The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevaci...

  11. Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Andersen, Rikke Fredslund; Aalund Olsen, Dorte

    2017-01-01

    High tumor expression of epidermal growth factor-like domain 7 (EGFL7) has been associated with a poor prognosis in colorectal cancer. The aim of the current study was to investigate the possible prognostic impact of circulating EGFL7 (cir-EGFL7), combined with single nucleotide polymorphism (SNP...

  12. Mechanism of Diphtheria Toxin Catalytic Domain Delivery to the Eukaryotic Cell Cytosol and the Cellular Factors that Directly Participate in the Process

    Science.gov (United States)

    Murphy, John R.

    2011-01-01

    Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. PMID:22069710

  13. Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

    Science.gov (United States)

    Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

    2005-01-01

    The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

  14. Zinc finger transcription factors displaced SREBP proteins as the major Sterol regulators during Saccharomycotina evolution.

    Directory of Open Access Journals (Sweden)

    Sarah L Maguire

    2014-01-01

    Full Text Available In most eukaryotes, including the majority of fungi, expression of sterol biosynthesis genes is regulated by Sterol-Regulatory Element Binding Proteins (SREBPs, which are basic helix-loop-helix transcription activators. However, in yeasts such as Saccharomyces cerevisiae and Candida albicans sterol synthesis is instead regulated by Upc2, an unrelated transcription factor with a Gal4-type zinc finger. The SREBPs in S. cerevisiae (Hms1 and C. albicans (Cph2 have lost a domain, are not major regulators of sterol synthesis, and instead regulate filamentous growth. We report here that rewiring of the sterol regulon, with Upc2 taking over from SREBP, likely occurred in the common ancestor of all Saccharomycotina. Yarrowia lipolytica, a deep-branching species, is the only genome known to contain intact and full-length orthologs of both SREBP (Sre1 and Upc2. Deleting YlUPC2, but not YlSRE1, confers susceptibility to azole drugs. Sterol levels are significantly reduced in the YlUPC2 deletion. RNA-seq analysis shows that hypoxic regulation of sterol synthesis genes in Y. lipolytica is predominantly mediated by Upc2. However, YlSre1 still retains a role in hypoxic regulation; growth of Y. lipolytica in hypoxic conditions is reduced in a Ylupc2 deletion and is abolished in a Ylsre1/Ylupc2 double deletion, and YlSre1 regulates sterol gene expression during hypoxia adaptation. We show that YlSRE1, and to a lesser extent YlUPC2, are required for switching from yeast to filamentous growth in hypoxia. Sre1 appears to have an ancestral role in the regulation of filamentation, which became decoupled from its role in sterol gene regulation by the arrival of Upc2 in the Saccharomycotina.

  15. Zinc Finger Transcription Factors Displaced SREBP Proteins as the Major Sterol Regulators during Saccharomycotina Evolution

    Science.gov (United States)

    Maguire, Sarah L.; Wang, Can; Holland, Linda M.; Brunel, François; Neuvéglise, Cécile; Nicaud, Jean-Marc; Zavrel, Martin; White, Theodore C.; Wolfe, Kenneth H.; Butler, Geraldine

    2014-01-01

    In most eukaryotes, including the majority of fungi, expression of sterol biosynthesis genes is regulated by Sterol-Regulatory Element Binding Proteins (SREBPs), which are basic helix-loop-helix transcription activators. However, in yeasts such as Saccharomyces cerevisiae and Candida albicans sterol synthesis is instead regulated by Upc2, an unrelated transcription factor with a Gal4-type zinc finger. The SREBPs in S. cerevisiae (Hms1) and C. albicans (Cph2) have lost a domain, are not major regulators of sterol synthesis, and instead regulate filamentous growth. We report here that rewiring of the sterol regulon, with Upc2 taking over from SREBP, likely occurred in the common ancestor of all Saccharomycotina. Yarrowia lipolytica, a deep-branching species, is the only genome known to contain intact and full-length orthologs of both SREBP (Sre1) and Upc2. Deleting YlUPC2, but not YlSRE1, confers susceptibility to azole drugs. Sterol levels are significantly reduced in the YlUPC2 deletion. RNA-seq analysis shows that hypoxic regulation of sterol synthesis genes in Y. lipolytica is predominantly mediated by Upc2. However, YlSre1 still retains a role in hypoxic regulation; growth of Y. lipolytica in hypoxic conditions is reduced in a Ylupc2 deletion and is abolished in a Ylsre1/Ylupc2 double deletion, and YlSre1 regulates sterol gene expression during hypoxia adaptation. We show that YlSRE1, and to a lesser extent YlUPC2, are required for switching from yeast to filamentous growth in hypoxia. Sre1 appears to have an ancestral role in the regulation of filamentation, which became decoupled from its role in sterol gene regulation by the arrival of Upc2 in the Saccharomycotina. PMID:24453983

  16. Interaction of Arabidopsis Trihelix-Domain Transcription Factors VFP3 and VFP5 with Agrobacterium Virulence Protein VirF

    Science.gov (United States)

    García-Cano, Elena; Magori, Shimpei; Sun, Qi; Ding, Zehong; Lazarowitz, Sondra G.; Citovsky, Vitaly

    2015-01-01

    Agrobacterium is a natural genetic engineer of plants that exports several virulence proteins into host cells in order to take advantage of the cell machinery to facilitate transformation and support bacterial growth. One of these effectors is the F-box protein VirF, which presumably uses the host ubiquitin/proteasome system (UPS) to uncoat the packaging proteins from the invading bacterial T-DNA. By analogy to several other bacterial effectors, VirF most likely has several functions in the host cell and, therefore, several interacting partners among host proteins. Here we identify one such interactor, an Arabidopsis trihelix-domain transcription factor VFP3, and further show that its very close homolog VFP5 also interacted with VirF. Interestingly, interactions of VirF with either VFP3 or VFP5 did not activate the host UPS, suggesting that VirF might play other UPS-independent roles in bacterial infection. To better understand the potential scope of VFP3 function, we used RNAi to reduce expression of the VFP3 gene. Transcriptome profiling of these VFP3-silenced plants using high-throughput cDNA sequencing (RNA-seq) revealed that VFP3 substantially affected plant gene expression; specifically, 1,118 genes representing approximately 5% of all expressed genes were significantly either up- or down-regulated in the VFP3 RNAi line compared to wild-type Col-0 plants. Among the 507 up-regulated genes were genes implicated in the regulation of transcription, protein degradation, calcium signaling, and hormone metabolism, whereas the 611 down-regulated genes included those involved in redox regulation, light reactions of photosynthesis, and metabolism of lipids, amino acids, and cell wall. Overall, this pattern of changes in gene expression is characteristic of plants under stress. Thus, VFP3 likely plays an important role in controlling plant homeostasis. PMID:26571494

  17. Interaction of Arabidopsis Trihelix-Domain Transcription Factors VFP3 and VFP5 with Agrobacterium Virulence Protein VirF.

    Directory of Open Access Journals (Sweden)

    Elena García-Cano

    Full Text Available Agrobacterium is a natural genetic engineer of plants that exports several virulence proteins into host cells in order to take advantage of the cell machinery to facilitate transformation and support bacterial growth. One of these effectors is the F-box protein VirF, which presumably uses the host ubiquitin/proteasome system (UPS to uncoat the packaging proteins from the invading bacterial T-DNA. By analogy to several other bacterial effectors, VirF most likely has several functions in the host cell and, therefore, several interacting partners among host proteins. Here we identify one such interactor, an Arabidopsis trihelix-domain transcription factor VFP3, and further show that its very close homolog VFP5 also interacted with VirF. Interestingly, interactions of VirF with either VFP3 or VFP5 did not activate the host UPS, suggesting that VirF might play other UPS-independent roles in bacterial infection. To better understand the potential scope of VFP3 function, we used RNAi to reduce expression of the VFP3 gene. Transcriptome profiling of these VFP3-silenced plants using high-throughput cDNA sequencing (RNA-seq revealed that VFP3 substantially affected plant gene expression; specifically, 1,118 genes representing approximately 5% of all expressed genes were significantly either up- or down-regulated in the VFP3 RNAi line compared to wild-type Col-0 plants. Among the 507 up-regulated genes were genes implicated in the regulation of transcription, protein degradation, calcium signaling, and hormone metabolism, whereas the 611 down-regulated genes included those involved in redox regulation, light reactions of photosynthesis, and metabolism of lipids, amino acids, and cell wall. Overall, this pattern of changes in gene expression is characteristic of plants under stress. Thus, VFP3 likely plays an important role in controlling plant homeostasis.

  18. Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.

    Science.gov (United States)

    Bambino, Kathryn; Lacko, Lauretta A; Hajjar, Katherine A; Stuhlmann, Heidi

    2014-07-01

    Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo is largely restricted to sites of mesodermal progenitors of angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that Egfl7 marks the endothelial lineage during embryonic development, and can be used to define the emergence of endothelial progenitor cells, as well as to visualize newly-forming vasculature in the embryo and during the processes of physiologic and pathologic angiogenesis in the adult. We have generated a transgenic mouse strain that expresses enhanced green fluorescent protein (eGFP) under the control of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene recapitulated that of endogenous Egfl7 at sites of vasculogenesis and angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene was not expressed in the quiescent endothelium of most adult organs. However, the uterus and ovary, which undergo vascular growth and remodeling throughout the estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the Egfl7:eGFP transgene was induced in adult neovasculature. We also found that increased Egfl7 expression contributed to pathologic revascularization in the mouse retina. To our knowledge, this is the first mouse model that enables monitoring of endothelial cells at sites of active vasculogenesis and angiogenesis. This model also facilitated the isolation and characterization of EGFL7(+) endothelial cell populations by fluorescence activated cell sorting (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a valuable tool that can be used to elucidate the mechanisms by which blood vessels form during development and under pathologic circumstances. © 2014 Wiley Periodicals, Inc.

  19. Molecular Evolution and Genetic Variation of G2-Like Transcription Factor Genes in Maize.

    Directory of Open Access Journals (Sweden)

    Fang Liu

    Full Text Available The productivity of maize (Zea mays L. depends on the development of chloroplasts, and G2-like transcription factors play a central role in regulating chloroplast development. In this study, we identified 59 G2-like genes in the B73 maize genome and systematically analyzed these genes at the molecular and evolutionary levels. Based on gene structure character, motif compositions and phylogenetic analysis, maize G2-like genes (ZmG1- ZmG59 were divided into seven groups (I-VII. By synteny analysis, 18 collinear gene pairs and strongly conserved microsyntny among regions hosting G2-like genes across maize and sorghum were found. Here, we showed that the vast majority of ZmG gene duplications resulted from whole genome duplication events rather than tandem duplications. After gene duplication events, some ZmG genes were silenced. The functions of G2-like genes were multifarious and most genes that are expressed in green tissues may relate to maize photosynthesis. The qRT-PCR showed that the expression of these genes was sensitive to low temperature and drought. Furthermore, we analyzed differences of ZmGs specific to cultivars in temperate and tropical regions at the population level. Interestingly, the single nucleotide polymorphism (SNP analysis revealed that nucleotide polymorphism associated with different temperature zones. Above all, G2-like genes were highly conserved during evolution, but polymorphism could be caused due to a different geographical location. Moreover, G2-like genes might be related to cold and drought stresses.

  20. Plutonium isotopes in the atmosphere of Central Europe: Isotopic composition and time evolution vs. circulation factors

    Energy Technology Data Exchange (ETDEWEB)

    Kierepko, Renata, E-mail: Renata.Kierepko@ifj.edu.pl [Institute of Nuclear Physics, Polish Academy of Sciences, Krakow (Poland); Mietelski, Jerzy W. [Institute of Nuclear Physics, Polish Academy of Sciences, Krakow (Poland); Ustrnul, Zbigniew [Jagiellonian University, Krakow (Poland); Institute of Meteorology and Water Management, National Research Institute, Krakow (Poland); Anczkiewicz, Robert [Institute of Geological Sciences, Polish Academy of Sciences, Krakow (Poland); Wershofen, Herbert [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany); Holgye, Zoltan [National Radiation Protection Institute, Prague (Czech Republic); Kapała, Jacek [Medical University of Bialystok (Poland); Isajenko, Krzysztof [Central Laboratory for Radiological Protection, Warsaw (Poland)

    2016-11-01

    This paper reports evidence of Pu isotopes in the lower part of the troposphere of Central Europe. The data were obtained based on atmospheric aerosol fraction samples collected from four places in three countries (participating in the informal European network known as the Ring of Five (Ro5)) forming a cell with a surface area of about 200,000 km{sup 2}. We compared our original data sets from Krakow (Poland, 1990–2007) and Bialystok (Poland, 1991–2007) with the results from two other locations, Prague (Czech Republic; 1997–2004) and Braunschweig (Germany; 1990–2003) to find time evolution of the Pu isotopes. The levels of the activity concentration for {sup 238}Pu and for {sup (239} {sup +} {sup 240)}Pu were estimated to be a few and some tens of nBq m{sup −} {sup 3}, respectively. However, we also noted some results were much higher (even about 70 times higher) than the average concentration of {sup 238}Pu in the atmosphere. The achieved complex data sets were used to test a new approach to the problem of solving mixing isotopic traces from various sources (here up to three) in one sample. Results of our model, supported by mesoscale atmospheric circulation parameters, suggest that Pu from nuclear weapon accidents or tests and nuclear burnt-up fuel are present in the air. - Highlights: • Evidence of Pu isotopes in the lower part of the troposphere of Central Europe • The effective annual doses associated with Pu inhalation • New approach to the problem of solving mixed Pu origins in one sample (3SM) • Relationship between Pu isotopes activity concentration and circulation factors.

  1. The BARD1 C-Terminal Domain Structure and Interactions with Polyadenylation Factor CstF-50

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Ross A.; Lee, Megan S.; Tsutakawa, Susan E.; Williams, R. Scott; Tainer, John A.; Glover, J. N. Mark

    2009-07-13

    The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF- 50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins.Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.

  2. Genomic identification of WRKY transcription factors in carrot (Daucus carota) and analysis of evolution and homologous groups for plants.

    Science.gov (United States)

    Li, Meng-Yao; Xu, Zhi-Sheng; Tian, Chang; Huang, Ying; Wang, Feng; Xiong, Ai-Sheng

    2016-03-15

    WRKY transcription factors belong to one of the largest transcription factor families. These factors possess functions in plant growth and development, signal transduction, and stress response. Here, we identified 95 DcWRKY genes in carrot based on the carrot genomic and transcriptomic data, and divided them into three groups. Phylogenetic analysis of WRKY proteins from carrot and Arabidopsis divided these proteins into seven subgroups. To elucidate the evolution and distribution of WRKY transcription factors in different species, we constructed a schematic of the phylogenetic tree and compared the WRKY family factors among 22 species, which including plants, slime mold and protozoan. An in-depth study was performed to clarify the homologous factor groups of nine divergent taxa in lower and higher plants. Based on the orthologous factors between carrot and Arabidopsis, 38 DcWRKY proteins were calculated to interact with other proteins in the carrot genome. Yeast two-hybrid assay showed that DcWRKY20 can interact with DcMAPK1 and DcMAPK4. The expression patterns of the selected DcWRKY genes based on transcriptome data and qRT-PCR suggested that those selected DcWRKY genes are involved in root development, biotic and abiotic stress response. This comprehensive analysis provides a basis for investigating the evolution and function of WRKY genes.

  3. Using Dynamic Multi-Task Non-Negative Matrix Factorization to Detect the Evolution of User Preferences in Collaborative Filtering.

    Directory of Open Access Journals (Sweden)

    Bin Ju

    Full Text Available Predicting what items will be selected by a target user in the future is an important function for recommendation systems. Matrix factorization techniques have been shown to achieve good performance on temporal rating-type data, but little is known about temporal item selection data. In this paper, we developed a unified model that combines Multi-task Non-negative Matrix Factorization and Linear Dynamical Systems to capture the evolution of user preferences. Specifically, user and item features are projected into latent factor space by factoring co-occurrence matrices into a common basis item-factor matrix and multiple factor-user matrices. Moreover, we represented both within and between relationships of multiple factor-user matrices using a state transition matrix to capture the changes in user preferences over time. The experiments show that our proposed algorithm outperforms the other algorithms on two real datasets, which were extracted from Netflix movies and Last.fm music. Furthermore, our model provides a novel dynamic topic model for tracking the evolution of the behavior of a user over time.

  4. Using Dynamic Multi-Task Non-Negative Matrix Factorization to Detect the Evolution of User Preferences in Collaborative Filtering.

    Science.gov (United States)

    Ju, Bin; Qian, Yuntao; Ye, Minchao; Ni, Rong; Zhu, Chenxi

    2015-01-01

    Predicting what items will be selected by a target user in the future is an important function for recommendation systems. Matrix factorization techniques have been shown to achieve good performance on temporal rating-type data, but little is known about temporal item selection data. In this paper, we developed a unified model that combines Multi-task Non-negative Matrix Factorization and Linear Dynamical Systems to capture the evolution of user preferences. Specifically, user and item features are projected into latent factor space by factoring co-occurrence matrices into a common basis item-factor matrix and multiple factor-user matrices. Moreover, we represented both within and between relationships of multiple factor-user matrices using a state transition matrix to capture the changes in user preferences over time. The experiments show that our proposed algorithm outperforms the other algorithms on two real datasets, which were extracted from Netflix movies and Last.fm music. Furthermore, our model provides a novel dynamic topic model for tracking the evolution of the behavior of a user over time.

  5. Search for scalar-tensor gravity theories with a non-monotonic time evolution of the speed-up factor

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, A [Dept Fisica, Universidad de Murcia, E30071-Murcia (Spain); Serna, A [Dept Fisica, Computacion y Comunicaciones, Universidad Miguel Hernandez, E03202-Elche (Spain); Alimi, J-M [Lab. de l' Univers et de ses Theories (LUTH, CNRS FRE2462), Observatoire de Paris-Meudon, F92195-Meudon (France)

    2002-08-21

    We present a method to detect, in the framework of scalar-tensor gravity theories, the existence of stationary points in the time evolution of the speed-up factor. An attractive aspect of this method is that, once the particular scalar-tensor theory has been specified, the stationary points are found through a simple algebraic equation which does not contain any integration. By applying this method to the three classes of scalar-tensor theories defined by Barrow and Parsons, we have found several new cosmological models with a non-monotonic evolution of the speed-up factor. The physical interest of these models is that, as previously shown by Serna and Alimi, they predict the observed primordial abundance of light elements for a very wide range of baryon density. These models are then consistent with recent CMB and Lyman-{alpha} estimates of the baryon content of the universe.

  6. Personality, posttraumatic stress and trauma type: factors contributing to posttraumatic growth and its domains in a Turkish community sample

    Directory of Open Access Journals (Sweden)

    Ayse Nuray Karanci

    2012-06-01

    Full Text Available Background: Posttraumatic growth (PTG is conceptualized as a positive transformation resulting from coping with and processing traumatic life events. This study examined the contributory roles of personality traits, posttraumatic stress (PTS severity and their interactions on PTG and its domains, as assessed with the Posttraumatic Growth Inventory Turkish form (PTGI-T. The study also examined the differences in PTG domains between survivors of accidents, natural disasters and unexpected loss of a loved one. Methods: The Basic Personality Traits Inventory, Posttraumatic Diagnostic Scale, and PTGI-T were administered to a large stratified cluster community sample of 969 Turkish adults in their home settings. Results: The results showed that conscientiousness, agreeableness, and openness to experience significantly related to the total PTG and most of the domains. The effects of extraversion, neuroticism and openness to experience were moderated by the PTS severity for some domains. PTG in relating to others and appreciation of life domains was lower for the bereaved group. Conclusion: Further research should examine the mediating role of coping between personality and PTG using a longitudinal design.

  7. Efficient fully 3D list-mode TOF PET image reconstruction using a factorized system matrix with an image domain resolution model

    International Nuclear Information System (INIS)

    Zhou, Jian; Qi, Jinyi

    2014-01-01

    A factorized system matrix utilizing an image domain resolution model is attractive in fully 3D time-of-flight PET image reconstruction using list-mode data. In this paper, we study a factored model based on sparse matrix factorization that is comprised primarily of a simplified geometrical projection matrix and an image blurring matrix. Beside the commonly-used Siddon’s ray-tracer, we propose another more simplified geometrical projector based on the Bresenham’s ray-tracer which further reduces the computational cost. We discuss in general how to obtain an image blurring matrix associated with a geometrical projector, and provide theoretical analysis that can be used to inspect the efficiency in model factorization. In simulation studies, we investigate the performance of the proposed sparse factorization model in terms of spatial resolution, noise properties and computational cost. The quantitative results reveal that the factorization model can be as efficient as a non-factored model, while its computational cost can be much lower. In addition we conduct Monte Carlo simulations to identify the conditions under which the image resolution model can become more efficient in terms of image contrast recovery. We verify our observations using the provided theoretical analysis. The result offers a general guide to achieve the optimal reconstruction performance based on a sparse factorization model with an image domain resolution model. (paper)

  8. Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding.

    Science.gov (United States)

    Kibbey, Megan M; Jameson, Mark J; Eaton, Erin M; Rosenzweig, Steven A

    2006-03-01

    Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been implicated in the promotion and aggressiveness of breast, prostate, colorectal, and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them attractive candidates as therapeutics for cancer prevention and control. Recombinant human IGFBP-2 significantly attenuated IGF-1-stimulated MCF-7 cell proliferation with coaddition of 20 or 100 nM IGFBP-2 (50 or 80% inhibition, respectively). We previously identified IGF-1 contact sites both upstream and downstream of the CWCV motif (residues 247-250) in human IGFBP-2 (J Biol Chem 276:2880-2889, 2001). To further test their contributions to IGFBP-2 function, the single tryptophan in human IGFBP-2, Trp-248, was selectively cleaved with 2-(2'nitrophenylsulfenyl)-3-methyl-3 bromoindolenine (BNPS-skatole) and the BNPS-skatole products IGFBP-2(1-248) and IGFBP-2(249-289) as well as IGFBP-2(1-190) were expressed as glutathione S-transferase-fusion proteins and purified. Based on competition binding analysis, deletion of residues 249 to 289 caused an approximately 20-fold decrease in IGF-1 binding affinity (IGFBP-2 EC50 = 0.35 nM and IGFBP-2(1-248) = 7 nM). Removal of the remainder of the C-terminal domain had no further effect on affinity (IGFBP-2(1-190) EC50 = 9.2 nM). In kinetic assays, IGFBP-2(1-248) and IGFBP-2(1-190) exhibited more rapid association and dissociation rates than full-length IGFBP-2. These results confirm that regions upstream and downstream of the CWCV motif participate in IGF-1 binding. They further support the development of full-length IGFBP-2 as a cancer therapeutic.

  9. The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis.

    Science.gov (United States)

    Barbieri, M Alejandro; Kong, Chen; Chen, Pin-I; Horazdovsky, Bruce F; Stahl, Philip D

    2003-08-22

    Activated epidermal growth factor receptors (EGFRs) recruit intracellular proteins that mediate receptor signaling and endocytic trafficking. Rin1, a multifunctional protein, has been shown to regulate EGFR internalization (1). Here we show that EGF stimulation induces a specific, rapid, and transient membrane recruitment of Rin1 and that recruitment is dependent on the Src homology 2 (SH2) domain of Rin1. Immunoprecipitation of EGFR is accompanied by co-immunoprecipitation of Rin1 in a time- and ligand-dependent manner. Association of Rin1 and specifically the SH2 domain of Rin1 with the EGFR was dependent on tyrosine phosphorylation of the intracellular domain of the EGFR. The recruitment of Rin1, observed by light microscopy, indicated that although initially cytosolic, Rin1 was recruited to both plasma membrane and endosomes following EGF addition. Moreover, the expression of the SH2 domain of Rin1 substantially impaired the internalization of EGF without affecting internalization of transferrin. Finally, we found that Rin1 co-immunoprecipitated with a number of tyrosine kinase receptors but not with cargo endocytic receptors. These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a.

  10. Solution structure of the N-terminal domain of a replication restart primosome factor, PriC, in Escherichia coli

    Science.gov (United States)

    Aramaki, Takahiko; Abe, Yoshito; Katayama, Tsutomu; Ueda, Tadashi

    2013-01-01

    In eubacterial organisms, the oriC-independent primosome plays an essential role in replication restart after the dissociation of the replication DNA-protein complex by DNA damage. PriC is a key protein component in the replication restart primosome. Our recent study suggested that PriC is divided into two domains: an N-terminal and a C-terminal domain. In the present study, we determined the solution structure of the N-terminal domain, whose structure and function have remained unknown until now. The revealed structure was composed of three helices and one extended loop. We also observed chemical shift changes in the heteronuclear NMR spectrum and oligomerization in the presence of ssDNA. These abilities may contribute to the PriC-ssDNA complex, which is important for the replication restart primosome. PMID:23868391

  11. Domain analysis

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    The domain-analytic approach to knowledge organization (KO) (and to the broader field of library and information science, LIS) is outlined. The article reviews the discussions and proposals on the definition of domains, and provides an example of a domain-analytic study in the field of art studies....... Varieties of domain analysis as well as criticism and controversies are presented and discussed....

  12. Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

    Science.gov (United States)

    Suzuki, Toru; Muto, Shinsuke; Miyamoto, Saku; Aizawa, Kenichi; Horikoshi, Masami; Nagai, Ryozo

    2003-08-01

    Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.

  13. Arabidopsis thaliana FLA4 functions as a glycan-stabilized soluble factor via its carboxy-proximal Fasciclin 1 domain.

    Science.gov (United States)

    Xue, Hui; Veit, Christiane; Abas, Lindy; Tryfona, Theodora; Maresch, Daniel; Ricardi, Martiniano M; Estevez, José Manuel; Strasser, Richard; Seifert, Georg J

    2017-08-01

    Fasciclin-like arabinogalactan proteins (FLAs) are involved in numerous important functions in plants but the relevance of their complex structure to physiological function and cellular fate is unresolved. Using a fully functional fluorescent version of Arabidopsis thaliana FLA4 we show that this protein is localized at the plasma membrane as well as in endosomes and soluble in the apoplast. FLA4 is likely to be GPI-anchored, is highly N-glycosylated and carries two O-glycan epitopes previously associated with arabinogalactan proteins. The activity of FLA4 was resistant against deletion of the amino-proximal fasciclin 1 domain and was unaffected by removal of the GPI-modification signal, a highly conserved N-glycan or the deletion of predicted O-glycosylation sites. Nonetheless these structural changes dramatically decreased endoplasmic reticulum (ER)-exit and plasma membrane localization of FLA4, with N-glycosylation acting at the level of ER-exit and O-glycosylation influencing post-secretory fate. We show that FLA4 acts predominantly by molecular interactions involving its carboxy-proximal fasciclin 1 domain and that its amino-proximal fasciclin 1 domain is required for stabilization of plasma membrane localization. FLA4 functions as a soluble glycoprotein via its carboxy-proximal Fas1 domain and its normal cellular trafficking depends on N- and O-glycosylation. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  14. Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5.

    Science.gov (United States)

    Blythe, Amanda; Gunasekara, Sanjika; Walshe, James; Mackay, Joel P; Hartzog, Grant A; Vrielink, Alice

    2014-08-01

    Spt4/5 is a hetero-dimeric transcription elongation factor that can both inhibit and promote transcription elongation by RNA polymerase II (RNAPII). However, Spt4/5's mechanism of action remains elusive. Spt5 is an essential protein and the only universally-conserved RNAP-associated transcription elongation factor. The protein contains multiple Kyrpides, Ouzounis and Woese (KOW) domains. These domains, in other proteins, are thought to bind RNA although there is little direct evidence in the literature to support such a function in Spt5. This could be due, at least in part, to difficulties in expressing and purifying recombinant Spt5. When expressed in Escherichia coli (E. coli), Spt5 is innately insoluble. Here we report a new approach for the successful expression and purification of milligram quantities of three different multi-KOW domain complexes of Saccharomyces cerevisiae Spt4/5 for use in future functional studies. Using the E. coli strain Rosetta2 (DE3) we have developed strategies for co-expression of Spt4 and multi-KOW domain Spt5 complexes from the bi-cistronic pET-Duet vector. In a second strategy, Spt4/5 was expressed via co-transformation of Spt4 in the vector pET-M11 with Spt5 ubiquitin fusion constructs in the vector pHUE. We characterized the multi-KOW domain Spt4/5 complexes by Western blot, limited proteolysis, circular dichroism, SDS-PAGE and size exclusion chromatography-multiangle light scattering and found that the proteins are folded with a Spt4:Spt5 hetero-dimeric stoichiometry of 1:1. These expression constructs encompass a larger region of Spt5 than has previously been reported, and will provide the opportunity to elucidate the biological function of the multi-KOW containing Spt5. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Preparation, crystallization and preliminary X-ray diffraction analysis of the DNA-binding domain of the Ets transcription factor in complex with target DNA

    International Nuclear Information System (INIS)

    Suwa, Yoshiaki; Nakamura, Teruya; Toma, Sachiko; Ikemizu, Shinji; Kai, Hirofumi; Yamagata, Yuriko

    2008-01-01

    The complex between the Ets domain of Ets2 and its target DNA has been crystallized. The crystals diffracted to 3.0 Å resolution. The Ets2 transcription factor is a member of the Ets transcription-factor family. Ets2 plays a role in the malignancy of cancer and in Down’s syndrome by regulating the transcription of various genes. The DNA-binding domain of Ets2 (Ets domain; ETSD), which contains residues that are highly conserved among Ets transcription-factor family members, was expressed as a GST-fusion protein. The aggregation of ETSD produced after thrombin cleavage could be prevented by treatment with NDSB-195 (nondetergent sulfobetaine 195). ETSD was crystallized in complex with DNA containing the Ets2 target sequence (GGAA) by the hanging-drop vapour-diffusion method. The best crystals were grown using 25% PEG 3350, 80 mM magnesium acetate, 50 mM sodium cacodylate pH 5.0/5.5 as the reservoir at 293 K. The crystals belonged to space group C2, with unit-cell parameters a = 85.89, b = 95.52, c = 71.89 Å, β = 101.7° and a V M value of 3.56 Å 3 Da −1 . Diffraction data were collected to a resolution of 3.0 Å

  16. Cross-Sectional Associations between Home Environmental Factors and Domain-Specific Sedentary Behaviors in Adults: The Moderating Role of Socio-Demographic Variables and BMI

    Science.gov (United States)

    Busschaert, Cedric; Cardon, Greet; Chastin, Sebastien F. M.; Van Cauwenberg, Jelle; De Cocker, Katrien

    2017-01-01

    Despite the negative health effects of too much sitting, the majority of adults are too sedentary. To develop effective interventions, insight is needed into home environmental correlates of adults’ sedentary behaviors, and into the susceptibility of population subgroups to these home environmental cues. In total, 559 Flemish adults reported socio-demographics, weight and height, home environmental factors and domain-specific sedentary behaviors. Generalized linear modeling was conducted to examine main associations between home environmental factors and domain-specific sedentary behaviors, and to test the moderating role of socio-demographics and BMI on these associations. In case of significant interactions, stratified analyses were performed. Results showed that, among those who did use a computer/laptop during the last week, a one-unit increase in the number of computers or laptops was associated with 17% (OR = 1.17; 95% CI = 1.02, 1.34) and 24% (OR = 1.24; 95% CI = 1.08, 1.43) more minutes computer time per day, respectively. The proximity of the remote controller (p moderated by BMI, with significant positive associations limited to those not overweight. To conclude, home environmental factors were associated with domain-specific sedentary behaviors, especially in healthy weight adults. If confirmed by longitudinal studies, public health professionals should encourage adults to limit the number of indoor entertainment devices and motorized vehicles. PMID:29088089

  17. Preparation, crystallization and preliminary X-ray diffraction analysis of the DNA-binding domain of the Ets transcription factor in complex with target DNA

    Energy Technology Data Exchange (ETDEWEB)

    Suwa, Yoshiaki; Nakamura, Teruya; Toma, Sachiko; Ikemizu, Shinji; Kai, Hirofumi; Yamagata, Yuriko, E-mail: yamagata@gpo.kumamoto-u.ac.jp [Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973 (Japan)

    2008-03-01

    The complex between the Ets domain of Ets2 and its target DNA has been crystallized. The crystals diffracted to 3.0 Å resolution. The Ets2 transcription factor is a member of the Ets transcription-factor family. Ets2 plays a role in the malignancy of cancer and in Down’s syndrome by regulating the transcription of various genes. The DNA-binding domain of Ets2 (Ets domain; ETSD), which contains residues that are highly conserved among Ets transcription-factor family members, was expressed as a GST-fusion protein. The aggregation of ETSD produced after thrombin cleavage could be prevented by treatment with NDSB-195 (nondetergent sulfobetaine 195). ETSD was crystallized in complex with DNA containing the Ets2 target sequence (GGAA) by the hanging-drop vapour-diffusion method. The best crystals were grown using 25% PEG 3350, 80 mM magnesium acetate, 50 mM sodium cacodylate pH 5.0/5.5 as the reservoir at 293 K. The crystals belonged to space group C2, with unit-cell parameters a = 85.89, b = 95.52, c = 71.89 Å, β = 101.7° and a V{sub M} value of 3.56 Å{sup 3} Da{sup −1}. Diffraction data were collected to a resolution of 3.0 Å.

  18. SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains.

    Science.gov (United States)

    Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S E; Prabhakar, Shyam; Jauch, Ralf

    2015-05-27

    The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins.

  19. SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains

    Science.gov (United States)

    Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S. E.; Prabhakar, Shyam; Jauch, Ralf

    2015-01-01

    The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins. PMID:26013289

  20. Use of the Theoretical Domains Framework to evaluate factors driving successful implementation of the Accelerated Chest pain Risk Evaluation (ACRE) project.

    Science.gov (United States)

    Skoien, Wade; Page, Katie; Parsonage, William; Ashover, Sarah; Milburn, Tanya; Cullen, Louise

    2016-10-12

    The translation of healthcare research into practice is typically challenging and limited in effectiveness. The Theoretical Domains Framework (TDF) identifies 12 domains of behaviour determinants which can be used to understand the principles of behavioural change, a key factor influencing implementation. The Accelerated Chest pain Risk Evaluation (ACRE) project has successfully translated research into practice, by implementing an intervention to improve the assessment of low to intermediate risk patients presenting to emergency departments (EDs) with chest pain. The aims of this paper are to describe use of the TDF to determine which factors successfully influenced implementation and to describe use of the TDF as a tool to evaluate implementation efforts and which domains are most relevant to successful implementation. A 30-item questionnaire targeting clinicians was developed using the TDF as a guide. Questions encompassed ten of the domains of the TDF: Knowledge; Skills; Social/professional role and identity; Beliefs about capabilities; Optimism; Beliefs about consequences; Intentions; Memory, attention and decision processes; Environmental context and resources; and Social influences. Sixty-three of 176 stakeholders (36 %) responded to the questionnaire. Responses for all scales showed that respondents were highly favourable to all aspects of the implementation. Scales with the highest mean responses were Intentions, Knowledge, and Optimism, suggesting that initial education and awareness strategies around the ACRE project were effective. Scales with the lowest mean responses were Environmental context and resources, and Social influences, perhaps highlighting that implementation planning could have benefitted from further consideration of the factors underlying these scales. The ACRE project was successful, and therefore, a perfect case study for understanding factors which drive implementation success. The overwhelmingly positive response suggests that it

  1. Time evolution of the energy confinement time, internal inductance and effective edge safety factor on IR-T1 tokamak

    International Nuclear Information System (INIS)

    Salar Elahi, A; Ghoranneviss, M

    2010-01-01

    An attempt is made to investigate the time evolution of the energy confinement time, internal inductance and effective edge safety factor on IR-T1 tokamak. For this purpose, four magnetic pickup coils were designed, constructed and installed on the outer surface of the IR-T1 and then the Shafranov parameter (asymmetry factor) was obtained from them. On the other hand, also a diamagnetic loop was designed and installed on IR-T1 and poloidal beta was determined from it. Therefore, the internal inductance and effective edge safety factor were measured. Also, the time evolution of the energy confinement time was measured using the diamagnetic loop. Experimental results on IR-T1 show that the maximum energy confinement time (which corresponds to minimum collisions, minimum microinstabilities and minimum transport) is at low values of the effective edge safety factor (2.5 eff (a) i <0.72). The results obtained are in agreement with those obtained with the theoretical approach [1-5].

  2. The Amazon Mangrove Coast: The Role of Geological Factors in its Evolution During the Quaternary

    Science.gov (United States)

    Souza-Filho, P. W.; Lara, R.; Silveira, O.; Miranda, F. P.

    2007-05-01

    The Amazon mangrove coast considered in this work includes the northeast Para and northwest Maranhao states. This coast is extremely irregular and jagged with numerous bays and estuaries. The main goal of the present work is to recognize the principal geological factors responsible for the development of the mangrove system. The integration of remote sensing data with other available studies indicates the existence of four main geomorphological sectors along the mangrove coast as described below. Sector 1 extends from Marajo to Pirabas Bay and is developed over the Para platform. The coastal plateau reaches the shoreline forming terraces and active cliffs. Sector 2 extends between the Pirabas and Gurupi bays and is structured over the Bragança- Viseu basin. In this sector, the coastal sedimentary environments widen considerably towards the east from Pirabas Bay and the coastal plateaus stretch out southward to constitute inactive cliffs. Mangroves developed seaward, reaching currently a width of 30 km. Sector 3 extends from Gurupi to Turiaçu Bay and is developed over the Gurupi horst. The latter represents a stratigraphic window where proterozoic rocks outcrop near the coast. Compared with the other sectors, mangrove deposits here reach their maximum extension with up to 40 km wide. Sector 4 extends between the Turiacu and Cuma bays and is structured in the Sao Luis basin. This coastal basin is also developed on land and represents a gravimetric low along a NE-SE direction.Mangroves are narrower, with a maximum width of 26 km. This analysis of the coastal geomorphology by considering neotectonic activity allows the identification of five sectors. Sector 1, with a positive gravimetric anomaly and poorly influenced by peripheral bulge. These characteristics suggest a relative tectonic stability of this sector, where the coastal plateau reaches the shoreline and mangroves are poorly developed. Sector 2 is marked by low gravimetric anomalies and normal faults

  3. The origin of the supernumerary subunits and assembly factors of complex I: A treasure trove of pathway evolution.

    Science.gov (United States)

    Elurbe, Dei M; Huynen, Martijn A

    2016-07-01

    We review and document the evolutionary origin of all complex I assembly factors and nine supernumerary subunits from protein families. Based on experimental data and the conservation of critical residues we identify a spectrum of protein function conservation between the complex I representatives and their non-complex I homologs. This spectrum ranges from proteins that have retained their molecular function but in which the substrate specificity may have changed or have become more specific, like NDUFAF5, to proteins that have lost their original molecular function and critical catalytic residues like NDUFAF6. In between are proteins that have retained their molecular function, which however appears unrelated to complex I, like ACAD9, or proteins in which amino acids of the active site are conserved but for which no enzymatic activity has been reported, like NDUFA10. We interpret complex I evolution against the background of molecular evolution theory. Complex I supernumerary subunits and assembly factors appear to have been recruited from proteins that are mitochondrial and/or that are expressed when complex I is active. Within the evolution of complex I and its assembly there are many cases of neofunctionalization after gene duplication, like ACAD9 and TMEM126B, one case of subfunctionalization: ACPM1 and ACPM2 in Yarrowia lipolytica, and one case in which a complex I protein itself appears to have been the source of a new protein from another complex: NDUFS6 gave rise to cytochrome c oxidase subunit COX4/COX5b. Complex I and its assembly can therewith be regarded as a treasure trove for pathway evolution. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Evolution of and Factors Controlling Eocene Sedimentation in the Darende-Balaban Basin, Malatya (Eastern Turkey)

    OpenAIRE

    GÜL, KEMAL GÜRBÜZ & MURAT

    2005-01-01

    Collision of the Arabian and Anatolian plates affected evolution of basins located along the southern flank of the Anatolian Plate. The Darende-Balaban foreland basin is one such basin – a basin filled with Upper Cretaceous and Eocene sediments, accumulated unconformably and transgressively above ophiolitic and carbonate basement rocks. This basin is locally surrounded, to the north and south, by Late Jurassic–Early Cretaceous structural highs created by tectonic elements during the collision...

  5. Evolution of and Factors Controlling Eocene Sedimentation in the Darende-Balaban Basin, Malatya (Eastern Turkey)

    OpenAIRE

    GÜL, KEMAL GÜRBÜZ & GÜL, MURAT

    2014-01-01

    Collision of the Arabian and Anatolian plates affected evolution of basins located along the southern flank of the Anatolian Plate. The Darende-Balaban foreland basin is one such basin – a basin filled with Upper Cretaceous and Eocene sediments, accumulated unconformably and transgressively above ophiolitic and carbonate basement rocks. This basin is locally surrounded, to the north and south, by Late Jurassic–Early Cretaceous structural highs created by tectonic elements during the collision...

  6. Factors influencing malignant evolution and long-term survival in solitary fibrous tumours of the pleura

    OpenAIRE

    Rodríguez-González, Marta; Novoa, Nuria M.; Gomez, Maria T.; García, Juan L.; Ludeña, María Dolores

    2014-01-01

    Solitary pleuro-pulmonary fibrous tumours are relatively uncommon neoplasms that are difficult to manage therapeutically and which, cytogenetically, have been poorly studied. The aim of the present work was to analyse the characteristics of a series of consecutive operated solitary pleural fibrous tumours in an attempt to discover a malignant pattern of evolution. This was a retrospective observational study of 19 cases. Samples were studied for clinical, histological, immunohistochemical and...

  7. Outcome of patients in acute poisoning with ethylene glycol - factors which may have influence on evolution

    OpenAIRE

    Tanasescu, A; Macovei, RA; Tudosie, MS

    2014-01-01

    Introduction. Intoxication with ethylene glycol occurs as a result of intentional ingestion in suicide attempts or accidentally. Clinical ethylene glycol poisoning is not specific and occurs in many poisoning cases therefore the diagnosis is difficult. Early diagnostic and establishment of therapy are very important for a favorable evolution. The mortality rate of ethylene glycol intoxication ranges between 1 and 22% depending on the amount of alcohol ingestion and the time period between alc...

  8. The role of ecological factors in shaping bat cone opsin evolution.

    Science.gov (United States)

    Gutierrez, Eduardo de A; Schott, Ryan K; Preston, Matthew W; Loureiro, Lívia O; Lim, Burton K; Chang, Belinda S W

    2018-04-11

    Bats represent one of the largest and most striking nocturnal mammalian radiations, exhibiting many visual system specializations for performance in light-limited environments. Despite representing the greatest ecological diversity and species richness in Chiroptera, Neotropical lineages have been undersampled in molecular studies, limiting the potential for identifying signatures of selection on visual genes associated with differences in bat ecology. Here, we investigated how diverse ecological pressures mediate long-term shifts in selection upon long-wavelength ( Lws ) and short-wavelength ( Sws1 ) opsins, photosensitive cone pigments that form the basis of colour vision in most mammals, including bats. We used codon-based likelihood clade models to test whether ecological variables associated with reliance on visual information (e.g. echolocation ability and diet) or exposure to varying light environments (e.g. roosting behaviour and foraging habitat) mediated shifts in evolutionary rates in bat cone opsin genes. Using additional cone opsin sequences from newly sequenced eye transcriptomes of six Neotropical bat species, we found significant evidence for different ecological pressures influencing the evolution of the cone opsins. While Lws is evolving under significantly lower constraint in highly specialized high-duty cycle echolocating lineages, which have enhanced sonar ability to detect and track targets, variation in Sws1 constraint was significantly associated with foraging habitat, exhibiting elevated rates of evolution in species that forage among vegetation. This suggests that increased reliance on echolocation as well as the spectral environment experienced by foraging bats may differentially influence the evolution of different cone opsins. Our study demonstrates that different ecological variables may underlie contrasting evolutionary patterns in bat visual opsins, and highlights the suitability of clade models for testing ecological hypotheses of

  9. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the central zinc-binding domain of the human Mcm10 DNA-replication factor

    International Nuclear Information System (INIS)

    Jung, Nam Young; Bae, Won Jin; Chang, Jeong Ho; Kim, Young Chang; Cho, Yunje

    2008-01-01

    Mcm10 is a highly conserved nuclear protein that plays a key role in the initiation and elongation processes of DNA replication by providing a physical link between the Mcm2–7 complex and DNA polymerases. In this study, the central domain of human Mcm10 was crystallized using the hanging-drop vapour-diffusion method in the presence of PEG 3350. The initiation of eukaryotic DNA replication requires the tightly controlled assembly of a set of replication factors. Mcm10 is a highly conserved nuclear protein that plays a key role in the initiation and elongation processes of DNA replication by providing a physical link between the Mcm2–7 complex and DNA polymerases. The central domain, which contains the CCCH zinc-binding motif, is most conserved within Mcm10 and binds to DNA and several proteins, including proliferative cell nuclear antigen. In this study, the central domain of human Mcm10 was crystallized using the hanging-drop vapour-diffusion method in the presence of PEG 3350. An X-ray diffraction data set was collected to a resolution of 2.6 Å on a synchrotron beamline. The crystals formed belonged to space group R3, with unit-cell parameters a = b = 99.5, c = 133.0 Å. According to Matthews coefficient calculations, the crystals were predicted to contain six MCM10 central domain molecules in the asymmetric unit

  10. Identification of a domain within human TAF(I)48, a subunit of Selectivity Factor 1, that interacts with helix 2 of TBP.

    Science.gov (United States)

    Xu, Shuping; Hori, Roderick T

    2004-09-01

    RNA polymerase I transcription in human cells requires Selectivity Factor 1, a multisubunit complex composed of the TATA-box-binding protein (TBP) and three TBP-associated factors (TAFs) called TAF(I)48, TAF(I)63 and TAF(I)110. Each of the Selectivity Factor 1 subunits binds directly to the other three components, but these interactions have not been characterized. This study is the initial identification and analysis of a TBP-binding domain within a Selectivity Factor 1 TAF. The interaction between human TBP and human TAF(I)48 was initially examined using the yeast two-hybrid assay, and a TBP-binding domain was identified in the carboxyl-terminus of human (h)TAF(I)48. Consistent with this result, the hTAF(I)48 carboxyl-terminus was able to bind directly to TBP in protein-protein interaction assays. When mutations were introduced into the hTAF(I)48 carboxyl-terminus, we identified changes in uncharged and positive residues that affect its interaction with TBP. By examining TBP mutants, residues within and adjacent to helix 2 of TBP, previously demonstrated to interact with subunits of other TBP-containing complexes [Transcription Factor IID (TFIID) and TFIIIB] were also found to diminish its affinity for the carboxyl-terminus of hTAF(I)48. The regions of hTAF(I)48 and TBP that interact are compared to those identified within other complexes containing TBP.

  11. Concrete domains

    OpenAIRE

    Kahn, G.; Plotkin, G.D.

    1993-01-01

    This paper introduces the theory of a particular kind of computation domains called concrete domains. The purpose of this theory is to find a satisfactory framework for the notions of coroutine computation and sequentiality of evaluation.

  12. Domain Engineering

    Science.gov (United States)

    Bjørner, Dines

    Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

  13. Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains.

    Science.gov (United States)

    Zhang, Yiguo; Ren, Yonggang; Li, Shaojun; Hayes, John D

    2014-01-01

    The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap'n'collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Thus after Nrf1 is anchored within ER membranes, its acidic transactivation domains (TADs), including the Asn/Ser/Thr-rich (NST) glycodomain situated between acidic domain 1 (AD1) and AD2, are transiently translocated into the lumen of the ER, where NST is glycosylated in the presence of glucose to yield an inactive 120-kDa Nrf1 glycoprotein. Subsequently, portions of the TADs partially repartition across membranes into the cyto/nucleoplasmic compartments, whereupon an active 95-kDa form of Nrf1 accumulates, a process that is more obvious in glucose-deprived cells and may involve deglycosylation. The repartitioning of Nrf1 out of membranes is monitored within this protein by its acidic-hydrophobic amphipathic glucose-responsive domains, particularly the Neh5L subdomain within AD1. Therefore, the membrane-topological organization of Nrf1 dictates its post-translational modifications (i.e. glycosylation, the putative deglycosylation and selective proteolysis), which together control its ability to transactivate target genes.

  14. Basic processes and factors determining the evolution of collapse sinkholes: a sensitivity study

    Science.gov (United States)

    Romanov, Douchko; Kaufmann, Georg

    2017-04-01

    Collapse sinkholes appear as closed depressions at the surface. The origin of these karst features is related to the continuous dissolution of the soluble rock caused by a focussed sub-surface flow. Water flowing along a preferential pathway through fissures and fractures within the phreatic part of a karst aquifer is able to dissolve the rock (limestone, gypsum, anhydrite). With time, the dissolved void volume increases and part of the ceiling above the stream can become unstable, collapses, and accumulates as debris in the flow path. The debris partially blocks the flow and thus activates new pathways. Because of the low compaction of the debris (high hydraulic conductivity), the flow and the dissolution rates within this crushed zone remain high. This allows a relatively fast dissolutional and erosional removal of the crushed material and the development of new empty voids. The void volume expands upwards towards the surface until a collapse sinkhole is formed. The collapse sinkholes exhibit a large variety of shapes (cylindrical, cone-, bowl-shaped), depths (from few to few hundred meters) and diameters (meters up to hundreds of meters). Two major processes are responsible for this diversity: a) the karst evolution of the aquifer - responsible for the dissolutional and erosional removal of material; b) the mechanical evolution of the host rock and the existence of structural features, faults for example, which determine the stability and the magnitude of the subsequent collapses. In this work we demonstrate the influence of the host rock type, the hydrological and geological boundary conditions, the chemical composition of the flowing water, and the geometry and the scale of the crushed zone, on the location and the evolution of the growing sinkhole. We demonstrate the ability of the karst evolution models to explain, at least qualitatively, the growth and the morphology of the collapse sinkholes and to roughly predict their shape and location. Implementing

  15. Evolution of RLSB, a nuclear-encoded S1 domain RNA binding protein associated with post-transcriptional regulation of plastid-encoded rbcL mRNA in vascular plants.

    Science.gov (United States)

    Yerramsetty, Pradeep; Stata, Matt; Siford, Rebecca; Sage, Tammy L; Sage, Rowan F; Wong, Gane Ka-Shu; Albert, Victor A; Berry, James O

    2016-06-29

    RLSB, an S-1 domain RNA binding protein of Arabidopsis, selectively binds rbcL mRNA and co-localizes with Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within chloroplasts of C3 and C4 plants. Previous studies using both Arabidopsis (C3) and maize (C4) suggest RLSB homologs are post-transcriptional regulators of plastid-encoded rbcL mRNA. While RLSB accumulates in all Arabidopsis leaf chlorenchyma cells, in C4 leaves RLSB-like proteins accumulate only within Rubisco-containing bundle sheath chloroplasts of Kranz-type species, and only within central compartment chloroplasts in the single cell C4 plant Bienertia. Our recent evidence implicates this mRNA binding protein as a primary determinant of rbcL expression, cellular localization/compartmentalization, and photosynthetic function in all multicellular green plants. This study addresses the hypothesis that RLSB is a highly conserved Rubisco regulatory factor that occurs in the chloroplasts all higher plants. Phylogenetic analysis has identified RLSB orthologs and paralogs in all major plant groups, from ancient liverworts to recent angiosperms. RLSB homologs were also identified in algae of the division Charophyta, a lineage closely related to land plants. RLSB-like sequences were not identified in any other algae, suggesting that it may be specific to the evolutionary line leading to land plants. The RLSB family occurs in single copy across most angiosperms, although a few species with two copies were identified, seemingly randomly distributed throughout the various taxa, although perhaps correlating in some cases with known ancient whole genome duplications. Monocots of the order Poales (Poaceae and Cyperaceae) were found to contain two copies, designated here as RLSB-a and RLSB-b, with only RLSB-a implicated in the regulation of rbcL across the maize developmental gradient. Analysis of microsynteny in angiosperms revealed high levels of conservation across eudicot species and for both paralogs in

  16. Genome-Wide Identification, Evolution and Functional Divergence of MYB Transcription Factors in Chinese White Pear (Pyrus bretschneideri).

    Science.gov (United States)

    Li, Xiaolong; Xue, Cheng; Li, Jiaming; Qiao, Xin; Li, Leiting; Yu, Li'ang; Huang, Yuhua; Wu, Jun

    2016-04-01

    The MYB superfamily is large and functionally diverse in plants. To date, MYB family genes have not yet been identified in Chinese white pear (Pyrus bretschneideri), and their functions remain unclear. In this study, we identified 231 genes as candidate MYB genes and divided them into four subfamilies. The R2R3-MYB (PbrMYB) family shared an R2R3 domain with 104 amino acid residues, including five conserved tryptophan residues. The Pbr MYB family was divided into 37 functional subgroups including 33 subgroups which contained both MYB genes of Rosaceae plants and AtMYB genes, and four subgroups which included only Rosaceae MYB genes or AtMYB genes. PbrMYB genes with similar functions clustered into the same subgroup, indicating functional conservation. We also found that whole-genome duplication (WGD) and dispersed duplications played critical roles in the expansion of the MYB family. The 87 Pbr MYB duplicated gene pairs dated back to the two WGD events. Purifying selection was the primary force driving Pbr MYB gene evolution. The 15 gene pairs presented 1-7 codon sites under positive selection. A total of 147 expressed genes were identified from RNA-sequencing data of fruit, and six Pbr MYB members in subgroup C1 were identified as important candidate genes in the regulation of lignin synthesis by quantitative real-time PCR analysis. Further correlation analysis revealed that six PbrMYBs were significantly correlated with five structural gene families (F5H, HCT, CCR, POD and C3'H) in the lignin pathway. The phylogenetic, evolution and expression analyses of the MYB gene family in Chinese white pear establish a solid foundation for future comprehensive functional analysis of Pbr MYB genes. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Non-adiabatic quantum evolution: The S matrix as a geometrical phase factor

    Energy Technology Data Exchange (ETDEWEB)

    Saadi, Y., E-mail: S_yahiadz@yahoo.fr [Laboratoire de Physique Quantique et Systèmes Dynamiques, Faculté des Sciences, Université Ferhat Abbas de Sétif, Sétif 19000 (Algeria); Maamache, M. [Laboratoire de Physique Quantique et Systèmes Dynamiques, Faculté des Sciences, Université Ferhat Abbas de Sétif, Sétif 19000 (Algeria)

    2012-03-19

    We present a complete derivation of the exact evolution of quantum mechanics for the case when the underlying spectrum is continuous. We base our discussion on the use of the Weyl eigendifferentials. We show that a quantum system being in an eigenstate of an invariant will remain in the subspace generated by the eigenstates of the invariant, thereby acquiring a generalized non-adiabatic or Aharonov–Anandan geometric phase linked to the diagonal element of the S matrix. The modified Pöschl–Teller potential and the time-dependent linear potential are worked out as illustrations. -- Highlights: ► In this Letter we study the exact quantum evolution for continuous spectra problems. ► We base our discussion on the use of the Weyl eigendifferentials. ► We give a generalized Lewis and Riesenfeld phase for continuous spectra. ► This generalized phase or Aharonov–Anandan geometric phase is linked to the S matrix. ► The modified Pöschl–Teller and the linear potential are worked out as illustrations.

  18. Plasticity and constraints on social evolution in African mole-rats: ultimate and proximate factors.

    Science.gov (United States)

    Faulkes, Chris G; Bennett, Nigel C

    2013-05-19

    Here, we review comparative studies of African mole-rats (family Bathyergidae) to explain how constraints acting at the ultimate (environmental) and proximate (organismal) levels have led to convergent gains and losses of sociality within this extensive adaptive radiation of subterranean rodents endemic to sub-Saharan Africa. At the ultimate level, living in environments that range from mesic through to arid has led to both variation and flexibility in social organization among species, culminating in the pinnacle of social evolution in the eusocial naked and Damaraland mole-rats (Heterocephalus glaber and Fukomys damarensis). The common mole-rat (Cryptomys hottentotus) provides a model example of how plasticity in social traits exists within a single species inhabiting areas with different ecological constraint. At the proximate level, reproductive strategies and cooperative breeding may be constrained by the correlated evolution of a suite of traits including physiological suppression of reproduction, the development of physiological and morphological castes, and the mode of ovulatory control and seasonality in breeding. Furthermore, recent neurobiological advances indicate that differential patterns of neurotransmitter expression within the forebrain may underpin (and limit) either a solitary or group living/cooperative lifestyle not only in mole-rats, but also more widely among disparate mammalian taxa.

  19. Evolution of hematopoiesis: Three members of the PU.1 transcription factor family in a cartilaginous fish, Raja eglanteria

    Science.gov (United States)

    Anderson, M. K.; Sun, X.; Miracle, A. L.; Litman, G. W.; Rothenberg, E. V.

    2001-01-01

    T lymphocytes and B lymphocytes are present in jawed vertebrates, including cartilaginous fishes, but not in jawless vertebrates or invertebrates. The origins of these lineages may be understood in terms of evolutionary changes in the structure and regulation of transcription factors that control lymphocyte development, such as PU.1. The identification and characterization of three members of the PU.1 family of transcription factors in a cartilaginous fish, Raja eglanteria, are described here. Two of these genes are orthologs of mammalian PU.1 and Spi-C, respectively, whereas the third gene, Spi-D, is a different family member. In addition, a PU.1-like gene has been identified in a jawless vertebrate, Petromyzon marinus (sea lamprey). Both DNA-binding and transactivation domains are highly conserved between mammalian and skate PU.1, in marked contrast to lamprey Spi, in which similarity is evident only in the DNA-binding domain. Phylogenetic analysis of sequence data suggests that the appearance of Spi-C may predate the divergence of the jawed and jawless vertebrates and that Spi-D arose before the divergence of the cartilaginous fish from the lineage leading to the mammals. The tissue-specific expression patterns of skate PU.1 and Spi-C suggest that these genes share regulatory as well as structural properties with their mammalian orthologs.

  20. Boussinesq evolution equations

    DEFF Research Database (Denmark)

    Bredmose, Henrik; Schaffer, H.; Madsen, Per A.

    2004-01-01

    This paper deals with the possibility of using methods and ideas from time domain Boussinesq formulations in the corresponding frequency domain formulations. We term such frequency domain models "evolution equations". First, we demonstrate that the numerical efficiency of the deterministic...... Boussinesq evolution equations of Madsen and Sorensen [Madsen, P.A., Sorensen, O.R., 1993. Bound waves and triad interactions in shallow water. Ocean Eng. 20 359-388] can be improved by using Fast Fourier Transforms to evaluate the nonlinear terms. For a practical example of irregular waves propagating over...... a submerged bar, it is demonstrated that evolution equations utilising FFT can be solved around 100 times faster than the corresponding time domain model. Use of FFT provides an efficient bridge between the frequency domain and the time domain. We utilise this by adapting the surface roller model for wave...

  1. Origin and evolution of group XI secretory phospholipase A2 from flax (Linum usitatissimum) based on phylogenetic analysis of conserved domains.

    Science.gov (United States)

    Gupta, Payal; Saini, Raman; Dash, Prasanta K

    2017-07-01

    Phospholipase A 2 (PLA 2 ) belongs to class of lipolytic enzymes (EC 3.1.1.4). Lysophosphatidic acid (LPA) and free fatty acids (FFAs) are the products of PLA 2 catalyzed hydrolysis of phosphoglycerides at sn-2 position. LPA and FFA that act as second mediators involved in the development and maturation of plants and animals. Mining of flax genome identified two phospholipase A 2 encoding genes, viz., LusPLA 2 I and LusPLA 2 II (Linum usitatissimum secretory phospholipase A 2 ). Molecular simulation of LusPLA 2 s with already characterized plant sPLA 2 s revealed the presence of conserved motifs and signature domains necessary to classify them as secretory phospholipase A 2 . Phylogenetic analysis of flax sPLA 2 with representative sPLA 2 s from other organisms revealed that they evolved rapidly via gene duplication/deletion events and shares a common ancestor. Our study is the first report of detailed phylogenetic analysis for secretory phospholipase A 2 in flax. Comparative genomic analysis of two LusPLA 2 s with earlier reported plant sPLA 2 s, based on their gene architectures, sequence similarities, and domain structures are presented elucidating the uniqueness of flax sPLA 2 .

  2. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a.

    Science.gov (United States)

    Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

    2003-10-28

    The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique C-terminal tail of c-Met (supersite). There is a strong link between aberrant c-Met activity and oncogenesis, which makes this kinase an important cancer drug target. The furanosylated indolocarbazole K-252a belongs to a family of microbial alkaloids that also includes staurosporine. It was recently shown to be a potent inhibitor of c-Met. Here we report the crystal structures of an unphosphorylated c-Met kinase domain harboring a human cancer mutation and its complex with K-252a at 1.8-A resolution. The structure follows the well established architecture of protein kinases. It adopts a unique, inhibitory conformation of the activation loop, a catalytically noncompetent orientation of helix alphaC, and reveals the complete C-terminal docking site. The first SH2-binding motif (1349YVHV) adopts an extended conformation, whereas the second motif (1356YVNV), a binding site for Grb2-SH2, folds as a type II Beta-turn. The intermediate portion of the supersite (1353NATY) assumes a type I Beta-turn conformation as in an Shc-phosphotyrosine binding domain peptide complex. K-252a is bound in the adenosine pocket with an analogous binding mode to those observed in previously reported structures of protein kinases in complex with staurosporine.

  3. Cross-Sectional Associations between Home Environmental Factors and Domain-Specific Sedentary Behaviors in Adults: The Moderating Role of Socio-Demographic Variables and BMI.

    Science.gov (United States)

    Compernolle, Sofie; Busschaert, Cedric; De Bourdeaudhuij, Ilse; Cardon, Greet; Chastin, Sebastien F M; Van Cauwenberg, Jelle; De Cocker, Katrien

    2017-10-31

    Despite the negative health effects of too much sitting, the majority of adults are too sedentary. To develop effective interventions, insight is needed into home environmental correlates of adults' sedentary behaviors, and into the susceptibility of population subgroups to these home environmental cues. In total, 559 Flemish adults reported socio-demographics, weight and height, home environmental factors and domain-specific sedentary behaviors. Generalized linear modeling was conducted to examine main associations between home environmental factors and domain-specific sedentary behaviors, and to test the moderating role of socio-demographics and BMI on these associations. In case of significant interactions, stratified analyses were performed. Results showed that, among those who did use a computer/laptop during the last week, a one-unit increase in the number of computers or laptops was associated with 17% (OR = 1.17; 95% CI = 1.02, 1.34) and 24% (OR = 1.24; 95% CI = 1.08, 1.43) more minutes computer time per day, respectively. The proximity of the remote controller ( p vehicles (95% CI = 0.001, 0.12) was positively associated with the odds of participation in transport-related sitting time. The latter two associations were moderated by BMI, with significant positive associations limited to those not overweight. To conclude, home environmental factors were associated with domain-specific sedentary behaviors, especially in healthy weight adults. If confirmed by longitudinal studies, public health professionals should encourage adults to limit the number of indoor entertainment devices and motorized vehicles.

  4. Activation of phosphatidylinositol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains.

    Science.gov (United States)

    Ohmichi, M; Decker, S J; Saltiel, A R

    1992-10-01

    Growth factor receptor tyrosine kinases can form stable associations with intracellular proteins that contain src homology (SH) 2 domains, including the p85 regulatory subunit of phosphatidylinositol (PI)-3 kinase. The activation of this enzyme by growth factors is evaluated in PC12 pheochromocytoma cells and NIH 3T3 fibroblasts expressing the pp140c-trk nerve growth factor (NGF) receptor (3T3-c-trk). NGF causes the rapid stimulation of PI-3 kinase activity detected in anti-phosphotyrosine, but not in anti-trk, immunoprecipitates. This effect coincides with the tyrosine phosphorylation of two proteins, with molecular masses of of 100 kd and 110 kd, that coimmunoprecipitate with p85. Similar phosphorylation patterns are induced when an immobilized fusion protein containing the amino-terminal SH2 domain of p85 is used to precipitate tyrosine-phosphorylated proteins. Thus, although NGF produces the rapid activation of PI-3 kinase through a mechanism that involves tyrosine phosphorylation, there is no evidence for tyrosine phosphorylation of p85, or for its ligand-dependent association with the NGF receptor. Perhaps another phosphoprotein may link the NGF receptor to this enzyme.

  5. What factors influence uptake of retinal screening among young adults with type 2 diabetes? A qualitative study informed by the theoretical domains framework.

    Science.gov (United States)

    Lake, Amelia J; Browne, Jessica L; Rees, Gwyneth; Speight, Jane

    2017-06-01

    Young adults with type 2 diabetes (T2D, 18-39years) face increased risk of vision loss from diabetic retinopathy (DR). Retinal screening is essential to detect DR, yet screening rates for this group are low and little is known about the underlying factors influencing this important behavior. Using the theoretical domains framework (TDF) to guide data collection and analysis, we explored screening barriers and facilitator, contrasting them with a comparator group of older adults with T2D (40+ years). Thirty semi-structured telephone interviews (10 younger, 20 older adults) were conducted. Data were coded into TDF domains with salience identified by "frequency" of reference. Screening facilitators and barriers were systematically compared between groups. Although many screening facilitators and barriers were shared by younger and older adults, additional factors highly relevant to the former included: social comparison with others ('social influences'); concern for the impact on the family unit, unrealistic optimism and perceived invulnerability ('beliefs about consequences'); lack of time and financial resources ('environmental context and resources'), and DR misconceptions ('knowledge'). This study demonstrated that young adult retinal screening behavior was influenced by additional social cognitive factors compared to older adults, providing a first-step evidence base for clinicians and other health professionals, and potential targets for future eye health and retinal screening interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  7. The Three-Dimensional Solution Structure of the Src Homology Domain-2 of the Growth Factor Receptor-Bound Protein-2

    International Nuclear Information System (INIS)

    Senior, Mary M.; Frederick, Anne F.; Black, Stuart; Murgolo, Nicholas J.; Perkins, Louise M.; Wilson, Oswald; Snow, Mark E.; Wang Yusen

    1998-01-01

    A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central β-sheet. The core structure of the SH2 domain contains an antiparallel β-sheet flanked by two parallel α-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions

  8. N1421K mutation in the glycoprotein Ib binding domain impairs ristocetin- and botrocetin-mediated binding of von Willebrand factor to platelets

    DEFF Research Database (Denmark)

    Lanke, E.; Kristoffersson, A.C.; Isaksson, C.

    2008-01-01

    , moderately decreased plasma factor VIII (FVIII) and VWF levels, and disproportionately low-plasma VWF:RCo levels. The patients were found to be heterozygous for the novel N1421K mutation, caused by a 4263C > G transversion in exon 28 of the VWF gene coding for the A1 domain. Botrocetin- and ristocetin-mediated...... binding of plasma VWF to GPIb were reduced in the patients. In vitro mutagenesis and expression in COS-7 cells confirmed the impairment of the mutant in botrocetin- and ristocetin-mediated VWF binding to GPIb. VWF collagen binding capacity was unaffected in plasma from the heterozygous individuals as well...

  9. E-commerce evolution in Hungary: an investigation of critical succes factor

    OpenAIRE

    Kolos, Krisztina; Gáti, Mirkó; Gyulavári, Tamás

    2011-01-01

    In this paper we highlight how the use of internet has changed from 2004 to 2009 among Hungarian companies, how their expectations about the role of e-commerce as a competitive advantage has evolved and whether perceived benefits of e-commerce show a shift from 2004 to 2009.We investigate the role of environmental factors and market orientation as two relevant types of critical success factors proposed by the management literature and measure their impacts on Internet usage, ex...

  10. Explicit Solutions for the (2 + 1-Dimensional Jaulent–Miodek Equation Using the Integrating Factors Method in an Unbounded Domain

    Directory of Open Access Journals (Sweden)

    Rahma Sadat

    2018-03-01

    Full Text Available In this work, we prove that the integrating factors can be used as a reduction method. Analytical solutions of the Jaulent–Miodek (JM equation are obtained using integrating factors as an extension of a recent work where, through hidden symmetries, the JM was reduced to ordinary differential equations (ODEs. Some of these ODEs had no quadrature. We here derive several new solutions for these non-solvable ODEs.

  11. Evolution to pathogenicity of the parvovirus minute virus of mice in immunodeficient mice involves genetic heterogeneity at the capsid domain that determines tropism.

    Science.gov (United States)

    López-Bueno, Alberto; Segovia, José C; Bueren, Juan A; O'Sullivan, M Gerard; Wang, Feng; Tattersall, Peter; Almendral, José M

    2008-02-01

    Very little is known about the role that evolutionary dynamics plays in diseases caused by mammalian DNA viruses. To address this issue in a natural host model, we compared the pathogenesis and genetics of the attenuated fibrotropic and the virulent lymphohematotropic strains of the parvovirus minute virus of mice (MVM), and of two invasive fibrotropic MVM (MVMp) variants carrying the I362S or K368R change in the VP2 major capsid protein, in the infection of severe combined immunodeficient (SCID) mice. By 14 to 18 weeks after oronasal inoculation, the I362S and K368R viruses caused lethal leukopenia characterized by tissue damage and inclusion bodies in hemopoietic organs, a pattern of disease found by 7 weeks postinfection with the lymphohematotropic MVM (MVMi) strain. The MVMp populations emerging in leukopenic mice showed consensus sequence changes in the MVMi genotype at residues G321E and A551V of VP2 in the I362S virus infections or A551V and V575A changes in the K368R virus infections, as well as a high level of genetic heterogeneity within a capsid domain at the twofold depression where these residues lay. Amino acids forming this capsid domain are important MVM tropism determinants, as exemplified by the switch in MVMi host range toward mouse fibroblasts conferred by coordinated changes of some of these residues and by the essential character of glutamate at residue 321 for maintaining MVMi tropism toward primary hemopoietic precursors. The few viruses within the spectrum of mutants from mice that maintained the respective parental 321G and 575V residues were infectious in a plaque assay, whereas the viruses with the main consensus sequences exhibited low levels of fitness in culture. Consistent with this finding, a recombinant MVMp virus carrying the consensus sequence mutations arising in the K368R virus background in mice failed to initiate infection in cell lines of different tissue origins, even though it caused rapid-course lethal leukopenia in SCID

  12. Interacting mechanism of ID3 HLH domain towards E2A/E12 transcription factor – An Insight through molecular dynamics and docking approach

    Directory of Open Access Journals (Sweden)

    Nishith Saurav Topno

    2016-03-01

    Full Text Available Inhibitor of DNA binding protein 3 (ID3 has long been characterized as an oncogene that implicates its functional role through its Helix–Loop–Helix (HLH domain upon protein–protein interaction. An insight into the dimerization brought by this domain helps in identifying the key residues that favor the mechanism behind it. Molecular dynamics (MD simulations were performed for the HLH proteins ID3 and Transcription factor E2-alpha (E2A/E12 and their ensemble complex (ID3-E2A/E12 to gather information about the HLH domain region and its role in the interaction process. Further evaluation of the results by Principal Component Analysis (PCA and Free Energy Landscape (FEL helped in revealing residues of E2A/E12: Lys570, Ala595, Val598, and Ile599 and ID3: Glu53, Gln63, and Gln66 buried in their HLH motifs imparting key roles in dimerization process. Furthermore the T-pad analysis results helped in identifying the key fluctuations and conformational transitions using the intrinsic properties of the residues present in the domain region of the proteins thus specifying their crucial role towards molecular recognition. The study provides an insight into the interacting mechanism of the ID3-E2A/E12 complex and maps the structural transitions arising in the essential conformational space indicating the key structural changes within the helical regions of the motif. It thereby describes how the internal dynamics of the proteins might regulate their intrinsic structural features and its subsequent functionality.

  13. The Evolution of Early-Stage Entrepreneurial Activity Influencing Factors in Romania

    Directory of Open Access Journals (Sweden)

    Tünde Petra PETRU

    2010-07-01

    Full Text Available The aim of the article is to analyze the main influencing factors of the probability of becoming an early-stage entrepreneur in Romania. The analyzed factors are: gender, age, education, household income, work status, network, opportunity perception, perception regarding the trust in own entrepreneurial skills, perception on the society’s appreciation regarding the principle of equality in life standard, perception on the society’s appreciation regarding the entrepreneurial career, perception on the proper promotion of entrepreneurial successes by mass media. We estimate a logit model for each year of the 2007-2009 period and we study the main influencing perceptional and sociodemographic factors, based on the Global Entrepreneurship Monitor (GEM Adult Population Survey database for Romania.

  14. Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

    2018-01-01

    activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...

  15. Evolution of human factors research and studies of health information technologies: the role of patient safety

    NARCIS (Netherlands)

    Beuscart-Zéphir, M. C.; Borycki, E.; Carayon, P.; Jaspers, M. W. M.; Pelayo, S.

    2013-01-01

    The objective of this survey paper is to present and explain the impact of recent regulations and patient safety initiatives (EU, US and Canada) on Human Factors (HF)/Usability studies and research focusing on Health Information Technology (HIT). The authors have selected the most prominent of these

  16. Acculturation and Adjustment in Latino Adolescents: How Cultural Risk Factors and Assets Influence Multiple Domains of Adolescent Mental Health

    Science.gov (United States)

    Smokowski, Paul; Buchanan, Rachel L.; Bacallao, Martica L.

    2009-01-01

    The purpose of this study was to examine the relationships among risk factors, cultural assets, and Latino adolescent mental health outcomes. We extend past research by using a longitudinal design and evaluating direct and moderated acculturation effects across a range of internalizing, externalizing, and academic engagement outcomes. The sample…

  17. Insulin-like Growth Factor 1 Analogs Clicked in the C Domain: Chemical Synthesis and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Macháčková, Kateřina; Collinsová, Michaela; Chrudinová, Martina; Selicharová, Irena; Pícha, Jan; Buděšínský, Miloš; Vaněk, Václav; Žáková, Lenka; Brzozowski, A. M.; Jiráček, Jiří

    2017-01-01

    Roč. 60, č. 24 (2017), s. 10105-10117 ISSN 0022-2623 Institutional support: RVO:61388963 Keywords : IGF-1 * receptor * synthesis * triazole Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 6.259, year: 2016 http://pubs.acs.org/doi/full/10.1021/acs.jmedchem.7b01331

  18. Evolution of electrical properties and domain configuration of Mn modified Pb(In1/2Nb1/2)O3-PbTiO3 single crystals

    Science.gov (United States)

    Qiao, Huimin; He, Chao; Yuan, Feifei; Wang, Zujian; Li, Xiuzhi; Liu, Ying; Guo, Haiyan; Long, Xifa

    2018-04-01

    The acceptor doped relaxor-based ferroelectric materials are useful for high power applications such as probes in ultrasound-guided high intensity focused ultrasound therapy. In addition, a high Curie temperature is desired because of wider temperature usage and improved temperature stability. Previous investigations have focused on Pb(Mg1/3Nb2/3)O3-PbTiO3 and Pb(Zn1/3Nb2/3)O3-PbTiO3 systems, which have a ultrahigh piezoelectric coefficient and dielectric constant, but a relatively low Curie temperature. It is desirable to study the binary relaxor-based system with a high Curie temperature. Therefore, Pb(In1/2Nb1/2)O3-PbTiO3 (PINT) single crystals were chosen to study the Mn-doped influence on their electrical properties and domain configuration. The evolution of ferroelectric hysteresis loops for doped and virgin samples exhibit the pinning effect in Mn-doped PINT crystals. The relaxation behaviors of doped and virgin samples are studied by fit of the modified Curie-Weiss law and Volgel-Fucher relation. In addition, a short-range correlation length was fitted to study the behavior of polar nanoregions based on the domain configuration obtained by piezoresponse force microscopy. Complex domain structures and smaller short-range correlation lengths (100-150 nm for Mn-doped PINT and >400 nm for pure PINT) were obtained in the Mn-doped PINT single crystals.

  19. Debris cover increase as an essential factor determining evolution of the Djankuat Glacier in the Caucasus

    Science.gov (United States)

    Rezepkin, Alexey; Popovnin, Victor

    2013-04-01

    45-year-long direct monitoring of Djankuat Glacier mass and water balance revealed the continuous increase of its superficial debris cover. Its area was mapped 7 times since 1968 on a basis of photogrammetric surveys, showing more than three-fold increase from 0,104 to 0,344 km2, whereas its share in the entire glacier surface increased more than 4 times (from 3% to 13%); currently supraglacial moraine occupies 61% of the ablation area. Besides, 3 direct and complete areal surveys of debris thickness were carried out in 1983, 1994 and 2010. They consisted of 133-240 measurement points which were distributed either in checkmate order over uniform debris-covered parts of the snout or by transverse profiles across linear morainic ramparts. Procedure of measuring thickness with an accuracy of 1 cm was coming to till piercing down to ice surface with metallic rod or, when impossible, to manual excavations. Maximum detected point values reached 183 cm in 1983, 280 cm in 1994 and 245 cm in 2010, and average debris thickness turned out to increased more than twice during the monitoring period - 26, 39 and 54 cm, for correspondent surveys. Debris cover influence on liquid run-off was estimated by heat balance considerations, based both on records of AWSs, erected on clean and debris-covered ice surface, and on vertical temperature profiles within the lithogenic layer, demonstrating clearly the diurnal cycle attenuation with depth. Sub-debris ablation is higher than clean ice melting rate under a thin debris layer (2025 the debris cover will reduce hypsometrical lowering rate on the snout by 45% in the latter case. This lead to the assumption about the future role of debris mantle development in Djankuat Glacier evolution: it may become comparable with that exerted by climate change.

  20. [Post-therapeutic evolution and prognostic factors of intestinal lymphomas, Retrospective analysis of 42 cases].

    Science.gov (United States)

    Sánchez-Fayos, M P; Hernández Guío, C; Rivas, M C; Outeiriño, J; González-Campos, C; Lobo, F

    1993-12-01

    To evaluate in retrospect the response to therapy and long-term evolution of a series of primitive intestinal lymphomas. The series was comprised of 42 patients diagnosed in our hospital during 1960-1962. The mean age was 34.5 years (range, 3-73), the M/F ratio was 21/21, and the histopathology distributes as follows: high grade (HG), 24 cases, low grade (LG), 12 cases, and mixed (LG/HG), 6 cases. B/T immunophenotype: 40/2. Staging: IE1,29 cases, IIE2-IV, 11 cases. The treatment applied in the series was classified in various types: ample surgical resection (aSR), 21 cases; partial surgical resection (pSR), 9 cases; abdominal radiation therapy (RT), 7 cases; monochemotherapy (MCT), 7 cases, and polychemotherapy (PCT), 28 cases. The correlation of clinicobiological variables with immediate response to treatment was evaluated by means of the chi square test, and the acturial post-therapeutic survival curves in accordance to the life tables, differences being calculated by the log rank test. Small intestine was the commonest site of involvement, 31 cases; ileocecal region, 7 cases; colon, 2 cases, and colon plus small intestine, 2 cases. Regardless of therapy type, complete remission (CR) was attained in 20 patients (47.5%), partial remission in 5; 11 cases were unresponsive (26.5%) and early death occurred in 6 instances (14.2%). The acturial post-therapeutic survival offered an 8-year expectancy of 47%. The correlation between immediate complete response and 16 clinico-biologic variables showed favourable significance for tumoral proliferation index (i.e., Pc10-positive cells studies. 2) Female sex, type of therapy, multifocal involvement, the need of emergency surgery and high LDH levels have significant value in univariate analyses.

  1. [Ecological Footprint Evolution Characteristics and Its Influencing Factors in China from 2000 to 2010].

    Science.gov (United States)

    Huang, Bao-rong; Cui, Shu-hong; Li, Ying-ming

    2016-02-15

    According to global average land productivities in 2000, this study calculated ecological footprint (EF) in China from 2000 to 2010, and analyzed its dynamic characteristics and socio-economic driving forces. The results showed that the total EF in China increased from 1.769 to 3.259 billion global hectares (gha) from 2000 to 2010, and its annual growth rate was 6.30%. Carbon Footprint was the fastest growth type of EF. It increased from 0.742 to 1.805 billion gha, and its annual growth rate was 9.29%. The net increase of cropland Footprint was also large in comparison to other types of Footprint. It increased from 0.678 to 0.891 billion gha. Per capita EF in China increased from 1.40 to 2.43 gha in this period. Although it was still below the world average level, it was far beyond per capita ecological carrying capacity in China, which led to serious ecological deficit and severe ecological crisis in China. The fast growth of per capita EF was the main driving force for the growth of total EF in China during the study period. Further, the growth of per capita EF was positively influenced by the growth of per capita consumption of products and severs, which was driven by economic growth and urbanization. Meanwhile, a large amount of exports of resource-intensive products in international trade was also an important driving force for EF growth. According to the evolution route of per capita EF in developed countries, along with China moving from middle-income to high-income country, per capita EF will maintain rapid growth, and ecological deficit in China will further exacerbate.

  2. Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures

    Directory of Open Access Journals (Sweden)

    Hayes Michael L

    2012-05-01

    Full Text Available Abstract Background Pentatricopeptide repeat (PPR proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82 and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. Results All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3’ UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. Conclusion PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative

  3. Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures.

    Science.gov (United States)

    Hayes, Michael L; Giang, Karolyn; Mulligan, R Michael

    2012-05-14

    Pentatricopeptide repeat (PPR) proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3' UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative selection even in the absence of an editing site target

  4. Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah L. McCarron

    2013-01-01

    Full Text Available A minority of chronic myeloid leukaemia (CML patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2 BCR-ABL1 CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.

  5. Subretinal fibrosis and uveitis: a spectral domain OCT study of its evolution and the minimal therapeutic effect of the off-label treatment with ranibizumab.

    Science.gov (United States)

    Symeonidis, Chrysanthos; Dastiridou, Anna; Konidaris, Vasilis; Brazitikos, Periklis; Androudi, Sofia

    2014-12-01

    The subretinal fibrosis and uveitis (SFU) syndrome is a rare multifocal posterior uveitis characterized by progressive subretinal fibrosis and significant visual loss. Slit-lamp examination, dilated fundoscopy, fluorescein angiography, Spectral Domain-Optical Coherence Tomography (SD-OCT) and laboratory testing were employed. A 52-year-old male presented with bilateral (best-corrected visual acuity: 2/10) visual loss. Clinical examination revealed bilateral anterior uveitis with posterior synechiae and posterior uveitis. Medical workup revealed no pathologic findings. Treatment included 1 gr intravenous prednisone followed by oral prednisone, immunosuppresive therapy and three ranibizumab injections in the right eye with no improvement. One year later, there was significant subretinal fibrosis. In the second year follow-up, the picture was slightly worse, with persisting bilateral macular edema and fibrosis. This is the first SFU syndrome report monitored with SD-OCT. This novel imaging modality can localize the lesion level, guide the therapeutic approach and may prove helpful in assessing disease prognosis.

  6. Disturbance is an important factor in the evolution and distribution of root-sprouting species

    Czech Academy of Sciences Publication Activity Database

    Klimešová, Jitka; Herben, Tomáš; Martínková, Jana

    2017-01-01

    Roč. 31, č. 3 (2017), s. 387-399 ISSN 0269-7653 R&D Projects: GA ČR(CZ) GA16-19245S; GA ČR GB14-36079G Institutional support: RVO:67985939 Keywords : disturbance * root-sprouting species * bud bank Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 1.818, year: 2016

  7. Probing Receptor Specificity by Sampling the Conformational Space of the Insulin-like Growth Factor II C-domain

    Czech Academy of Sciences Publication Activity Database

    Hexnerová, Rozálie; Křížková, Květoslava; Fábry, Milan; Sieglová, Irena; Kedrová, Kateřina; Collinsová, Michaela; Ullrichová, P.; Srb, Pavel; Williams, C.; Crump, M. P.; Tošner, Z.; Jiráček, Jiří; Veverka, Václav; Žáková, Lenka

    2016-01-01

    Roč. 291, č. 40 (2016), s. 21234-21245 ISSN 0021-9258 R&D Projects: GA ČR GA15-19018S; GA MŠk(CZ) LK11205; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : insulin * IGF-2 * receptor Subject RIV: CE - Biochemistry Impact factor: 4.125, year: 2016 http://www.jbc.org/content/291/40/21234.full

  8. Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

    Directory of Open Access Journals (Sweden)

    Bussières André E

    2012-08-01

    Full Text Available Abstract Background The Theoretical Domains Framework (TDF was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without x-rays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine x-rays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences; beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied ( social/professional role & identity; the influence of formal training, colleagues, and patients also appeared to be important factors ( social influences; conflicting comments regarding levels of confidence and comfort in managing patients

  9. Spatial Evolution of Producer Service Sectors and Its Influencing Factors in Cities: A Case Study of Hangzhou, China

    Directory of Open Access Journals (Sweden)

    Yizhou Wu

    2018-03-01

    Full Text Available Producer service industries are an important feature in the current development of a metropolis. Researchers from different countries are increasingly concerned about location changes and the motives of producer service sectors in cities. Given the rapid development of producer service sectors in developing countries, this study examines changes in the distribution of producer service sectors over the past decade and factors influencing them in a case study using the city of Hangzhou in China. Results show that Hangzhou’s producer service sector is still mainly concentrated in the central business district (CBD. However, a distinct trend of diffusion to suburban areas was observed, which formed several secondary clusters on the periphery of the city. Locations of the CBD, sub-centers, and professional clusters of producer service sectors established by the government are the most important factors that affect the spatial distribution of producer service sectors. The main influencing factors for the spatial evolution of producer service sectors are: (1 the high development cost and residential suburbanization of the central areas of the city promote the development of producer service sectors toward the periphery; (2 city planning has guided the clustering of producer service sectors on the city’s CBD and secondary city centers; (3 city renewal has provided personalized and diversified development space for producer service sectors; (4 incentive policies introduced by the government, such as rentals, and taxes have enhanced the orderly aggregation of producer service sectors.

  10. Astrophysics and Weak Form of Panspermia Hypothesis and Exogenous Factors in the Evolution of the Earth

    Science.gov (United States)

    Adushkin, V. V.; Vityazev, A. V.; Glazachev, D. O.; Pechernikova, G. V.

    2014-10-01

    The problems of the origin of Earth and life are fundamental in the modern science. We, relying on the data of resent years, contemplate a new course of research in this old problem. On the base of astrophysical data, obtained during the last 30-50 years, and the resent results of the study of small bodies in the Solar System (comets in particular) it is possible to combine the old idea about panspermia in a comprehensive sense and the search of the basis of life on the early Earth grounded on theoretical and laboratory data on the Earth evolution. Most likely, the Sun and a gas-and-dust disk surrounding it were created in a Giant molecular cloud near young giants - blue O-B-stars which ultraviolet radiation provided a weak chirality (to 15% of EEs) in organics of interstellar dust. Further a part of interstellar dust beyond orbits larger than 3-4 a.u. remained cold and then entered into the first planetesimals. The organics, after melting of interiors of the first planetesimals due to the heating by shortliving 26Al and 60Fe, sank, in the form of kerogens, into the core where formation of the first complex organic compounds began. This occurred in the first 3-4 Myr after the CAI. Apparently, it is necessary to look for anaerobic life in comets. In geosciences obtained various data banks, such as data on the endogenous activity of the Earth, mass extinctions of life and changes in biodiversity, impacts of cosmic bodies, inversions of the magnetic field, climate change, etc. The problem of cyclicity and correlation of all these processes is studied for 50 years. Results of spectral, wavelet and correlation analysis of the data series, representing some of these processes are given. We conclude, that most of them are cyclic, some of the periods are present in all the processes. The mechanisms of the influence of the galaxy on the processes occurring on the Earth are discussed.

  11. Offspring mortality was a determinant factor in the evolution of paternal investment in humans: An evolutionary game approach.

    Science.gov (United States)

    López Alonso, Diego; Ortiz-Rodríguez, Isabel M

    2017-04-21

    Some researchers support the belief that man evolved philandering behavior because of the greater reproductive success of promiscuous males. According to this idea, deserting behavior from the man should be expected along with null paternal involvement in offspring care. Paradoxically however, the average offspring investment in the human male is far higher than that of any other male mammal, including other primates. In our work, we have addressed this conundrum by employing evolutionary game theory, using objective payoffs instead of, as are commonly used, arbitrary payoffs. Payoffs were computed as reproductive successes by a model based on trivial probabilities, implemented within the Barreto's Population Dynamics Toolbox (2014). The evolution of the parent conflict was simulated by a game with two players (the woman and the man). First, a simple game was assayed with two strategies, 'desert-unfaithful' and 'care-faithful'. Then, the game was played with a third mixed strategy, 'care-unfaithful'. The two-strategy game results were mainly determined by the offspring survival rate (s) and the non-paternity rate (z), with remaining factors playing a secondary role. Starting from two empirical estimates for both rates (s = 0.617 and z = 0.033) and decreasing the offspring mortality from near 0.4 to 0.1, the results were consistent with a win for the 'care-faithful' strategy. The 'desert-unfaithful' strategy only won at unrealistically high non-paternity rates (z>0.2). When three-strategy games were played, the mixed strategy of 'care-unfaithful' man could win the game in some less frequent cases. Regardless of the number of game strategies, 'care' fathers always won. These results strongly suggest that offspring mortality was the key factor in the evolution of paternal investment within the Homo branch. The 'care-faithful' strategy would have been the main strategy in human evolution but 'care-unfaithful' men did evolve at a lesser frequency. It can therefore be

  12. Spatial and temporal evolution of climatic factors and its impacts on potential evapotranspiration in Loess Plateau of Northern Shaanxi, China.

    Science.gov (United States)

    Li, C; Wu, P T; Li, X L; Zhou, T W; Sun, S K; Wang, Y B; Luan, X B; Yu, X

    2017-07-01

    Agriculture is very sensitive to climate change, and correct forecasting of climate change is a great help to accurate allocation of irrigation water. The use of irrigation water is influenced by crop water demand and precipitation. Potential evapotranspiration (ET 0 ) is a measure of the ability of the atmosphere to remove water from the surface through the processes of evaporation and transpiration, assuming no control on water supply. It plays an important role in assessing crop water requirements, regional dry-wet conditions, and other factors of water resource management. This study analyzed the spatial and temporal evolution processes and characteristics of major meteorological parameters at 10 stations in the Loess Plateau of northern Shaanxi (LPNS). By using the Mann-Kendall trend test with trend-free pre-whitening and the ArcGIS platform, the potential evapotranspiration of each station was quantified by using the Penman-Monteith equation, and the effects of climatic factors on potential evapotranspiration were assessed by analyzing the contribution rate and sensitivity of the climatic factors. The results showed that the climate in LPNS has become warmer and drier. In terms of the sensitivity of ET 0 to the variation of each climatic factor in LPNS, relative humidity (0.65) had the highest sensitivity, followed by daily maximum temperature, wind speed, sunshine hours, and daily minimum temperature (-0.05). In terms of the contribution rate of each factor to ET 0 , daily maximum temperature (5.16%) had the highest value, followed by daily minimum temperature, sunshine hours, relative humidity, and wind speed (1.14%). This study provides a reference for the management of agricultural water resources and for countermeasures to climate change. According to the climate change and the characteristics of the study area, farmers in the region should increase irrigation to guarantee crop water demand. Copyright © 2017. Published by Elsevier B.V.

  13. Inflationary Regime of the Evolution of the Scale Factor in the Relativistic Theory of Gravitation with a Graviton Mass

    Science.gov (United States)

    Lasukov, V. V.; Lasukova, T. V.; Abdrashitova, M. O.

    2018-05-01

    It is shown that a cosmological medium consisting of a kinetic and a potential component, at the outset of its evolution is vacuum-like and at the end of its evolution asymptotically becomes the quintessence.

  14. Adaptation of an L-proline adenylation domain to use 4-propyl-L-proline in the evolution of lincosamide biosynthesis.

    Directory of Open Access Journals (Sweden)

    Stanislav Kadlčík

    Full Text Available Clinically used lincosamide antibiotic lincomycin incorporates in its structure 4-propyl-L-proline (PPL, an unusual amino acid, while celesticetin, a less efficient related compound, makes use of proteinogenic L-proline. Biochemical characterization, as well as phylogenetic analysis and homology modelling combined with the molecular dynamics simulation were employed for complex comparative analysis of the orthologous protein pair LmbC and CcbC from the biosynthesis of lincomycin and celesticetin, respectively. The analysis proved the compared proteins to be the stand-alone adenylation domains strictly preferring their own natural substrate, PPL or L-proline. The LmbC substrate binding pocket is adapted to accommodate a rare PPL precursor. When compared with L-proline specific ones, several large amino acid residues were replaced by smaller ones opening a channel which allowed the alkyl side chain of PPL to be accommodated. One of the most important differences, that of the residue corresponding to V306 in CcbC changing to G308 in LmbC, was investigated in vitro and in silico. Moreover, the substrate binding pocket rearrangement also allowed LmbC to effectively adenylate 4-butyl-L-proline and 4-pentyl-L-proline, substrates with even longer alkyl side chains, producing more potent lincosamides. A shift of LmbC substrate specificity appears to be an integral part of biosynthetic pathway adaptation to the PPL acquisition. A set of genes presumably coding for the PPL biosynthesis is present in the lincomycin--but not in the celesticetin cluster; their homologs are found in biosynthetic clusters of some pyrrolobenzodiazepines (PBD and hormaomycin. Whereas in the PBD and hormaomycin pathways the arising precursors are condensed to another amino acid moiety, the LmbC protein is the first functionally proved part of a unique condensation enzyme connecting PPL to the specialized amino sugar building unit.

  15. Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2)

    NARCIS (Netherlands)

    C.A. Berrevoets (Cor); P. Doesburg (Paul); K. Steketee (Karine); J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractPrevious studies in yeast and mammalian cells showed a functional interaction between the amino-terminal domain and the carboxy-terminal, ligand-binding domain (LBD) of the human androgen receptor (AR). In the present study, the AR subdomains involved in

  16. Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses.

    OpenAIRE

    Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A.; Manna, Sunil K.

    2013-01-01

    The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor κB (NF-κB) and also expression of NF-κB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-κB (IκBα) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IκBα kinase (IKK...

  17. Penicilliosis and AIDS in Haiphong, Vietnam: evolution and predictive factors of death.

    Science.gov (United States)

    Son, V T; Khue, P M; Strobel, M

    2014-12-01

    The study objective was to assess the lethality rates and the predictive factors for death in AIDS patients infected by Penicillium marneffei (Pm) in Hai Phong, Vietnam. A retrospective cohort study was conducted by reviewing 103 medicals records of confirmed cases from June 2006 to August 2009. Penicilliosis-related mortality was very high (33%). The majors risk factors of death were: (i) patient lacking complete treatment, a regimen with both of secondary prophylaxis by itraconazole and HAART (OR=52.2, P<0.001); (ii) patients having received only secondary prophylaxis (OR=21.2, P<0.001); (iii) patients coinfected by hepatitis C (OR=2.3, P=0.02) and tuberculosis (OR=1.97, P=0.04). Penicilliosis occurred in 28 cases after initiation of ART, probably caused by IRIS, with the same signs and symptoms as "common" penicilliosis. However, the diagnosis of IRIS was ruled out because the viral load could not be assessed. Penicilliosis is very frequent in the North of Vietnam. A good compliance to a complete treatment with healing antifungal (Amphotericin B) then secondary prophylaxis (Itraconazole) associate with ART, prolongs survival, prevents relapse, and also allows discontinuing a secondary prophylaxis in a half of the cases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. The realistic consideration of human factors in model based simulation tools for the air traffic control domain.

    Science.gov (United States)

    Duca, Gabriella; Attaianese, Erminia

    2012-01-01

    Advanced Air Traffic Management (ATM) concepts related to automation, airspace organization and operational procedures are driven by the overall goal to increase ATM system performance. Independently on the nature and/or impact of envisaged changes (e.g. from a short term procedure adjustment to a very long term operational concept or aid tools completion), the preliminary assessment of possible gains in airspace/airport capacity, safety and cost-effectiveness is done by running Model Based Simulations (MBSs, also known as Fast Time Simulations - FTS). Being a not human-in-the-loop technique, the reliability of a MBS results depend on the accuracy and significance of modeled human factors. Despite that, it can be observed in the practice that modeling tools commonly assume a generalized standardization of human behaviors and tasks and consider a very few range of work environment factors that, in the reality, affect the actual human-system performance. The present paper is aimed at opening a discussion about the possibility to keep task description and related weight at a high/general level, suitable for an efficient use of MBSs and, at the same time, increasing simulations reliability adopting some adjustment coming from the elaboration of further variables related to the human aspects of controllers workload.

  19. Adaptation of an L-Proline Adenylation Domain to Use 4-Propyl-L-Proline in the Evolution of Lincosamide Biosynthesis

    Czech Academy of Sciences Publication Activity Database

    Kadlčík, Stanislav; Kučera, Tomáš; Chalupská, Dominika; Gažák, Radek; Koběrská, Markéta; Ulanová, Dana; Kopecký, Jan; Kutejová, Eva; Najmanová, Lucie; Janata, Jiří

    2013-01-01

    Roč. 8, č. 12 (2013) E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) EE2.3.20.0055; GA MŠk(CZ) EE2.3.30.0003; GA MŠk ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : NONRIBOSOMAL PEPTIDE SYNTHETASES * GENE-CLUSTER * BIOCHEMICAL-CHARACTERIZATION Subject RIV: EE - Microbiology, Virology Impact factor: 3.534, year: 2013

  20. Differential evolution of antiretroviral restriction factors in pteropid bats as revealed by APOBEC3 gene complexity.

    Science.gov (United States)

    Hayward, Joshua A; Tachedjian, Mary; Cui, Jie; Cheng, Adam Z; Johnson, Adam; Baker, Michelle; Harris, Reuben S; Wang, Lin-Fa; Tachedjian, Gilda

    2018-03-29

    Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.

  1. [The role of malnutrition and other medical factors in the evolution of patients with hip fracture].

    Science.gov (United States)

    García Lázaro, M; Montero Pérez-Barquero, M; Carpintero Benítez, P

    2004-11-01

    As the population progressively ages, hip fractures have become increasingly common and are associated with high morbidity and mortality and a pronounced decline in functional status. Hip fractures frequently occur in elderly patients with a high rate of comorbidity and polymedication. Patients hospitalised with hip fractures often display signs of protein malnutrition and may develop medical complications requiring intrahospital care. These factors, more than simply surgical ones, unfavourably influence the vital status and functional outcome of these patients. For this reason, it is necessary to improve the management of pre-existing conditions during hospitalisation, assess and treat malnutrition and prevent medical complications to achieve optimal outcomes for these patients. With this objective, we believe that care should be provided by multidisciplinary teams in close partnership with internists.

  2. [Evolution of Asthma Prevalence and Sociodemographic and Health Factors Associated in Madrid Region (1996-2013)].

    Science.gov (United States)

    López Pereira, Patricia; Gandarillas Grande, Ana María; Díez Gañán, Lucía; Ordobás Gavín, María

    2017-05-25

    Asthma is an important public health issue. The goal of this study is to analyse the trends in self-reported asthma prevalence in the Madrid Region and its association with socio-demographic and health factors. Data from the "Non-Communicable Disease Risk Factor Surveillance System" in adult population (SIVFRENT-A) 1996-2013 were used. Prevalences and 95% CI were estimated for: current asthma, cumulative prevalence of asthma and asthma attack in the last 12 months, in five periods. Changes in inter-period prevalence were estimated by calculating prevalence ratios (PR) with 95% CI by Poisson regression. The association between asthma prevalence socio-demographic and health variables was evaluated by multivariate logistic regression. Current prevalence of asthma and cumulative prevalence of asthma increased per study period an average of 14%. Asthma attack prevalence in the last 12 months increased an average of 19%. It was associated (statistically significant) to an increase of current prevalence of asthma, cumulative prevalence of asthma and asthma attack prevalence in the last 12 months: being a woman, ORa: 1.55; ORa: 1.35 and ORa: 1.46 respectively; have poor self-perceived health, ORa: 3.09; ORa: 2.63 and ORa: 2.89; and intense physical activity, ORa: 1.48; ORa: 1.32 and ORa: 1.49. In the case of current prevalence of asthma and cumulative prevalence of asthma also be studying, ORa: 1.34 and ORa: 1.46 respectively. Self-reported asthma prevalence increased in the last decades. The prevalence was higher in woman, persons with poor self-perceived health and adults with intense physical activity.

  3. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual β cell function

    Directory of Open Access Journals (Sweden)

    Dib Sergio A

    2009-12-01

    Full Text Available Abstract Type 1A diabetes mellitus (T1ADM is a progressive autoimmune disease mediated by T lymphocytes with destruction of beta cells. Up to now, we do not have precise methods to assess the beta cell mass, "in vivo" or "ex-vivo". The studies about its genetic susceptibility show strong association with class II antigens of the HLA system (particularly DQ. Others genetics associations are weaker and depend on the population studied. A combination of precipitating events may occur at the beginning of the disease. There is a silent loss of immune-mediated beta cells mass which velocity has an inverse relation with the age, but it is influenced by genetic and metabolic factors. We can predict the development of the disease primarily through the determination of four biochemically islet auto antibodies against antigens like insulin, GAD65, IA2 and Znt8. Beta cell destruction is chronically progressive but at clinical diagnosis of the disease a reserve of these cells still functioning. The goal of secondary disease prevention is halt the autoimmune attack on beta cells by redirecting or dampening the immune system. It is remains one of the foremost therapeutic goals in the T1ADM. Glycemic intensive control and immunotherapeutic agents may preserve beta-cell function in newly diagnosed patients with T1ADM. It may be assessed through C-peptide values, which are important for glycemic stability and for the prevention of chronic complications of this disease. This article will summarize the etiopathogenesis mechanisms of this disease and the factors can influence on residual C-peptide and the strategies to it preservation.

  4. [Investigation of potential toxic factors for fleece-flower root: from perspective of processing methods evolution].

    Science.gov (United States)

    Cui, He-Rong; Bai, Zhao-Fang; Song, Hai-Bo; Jia, Tian-Zhu; Wang, Jia-Bo; Xiao, Xiao-He

    2016-01-01

    In recent years, the rapid growth of reports on fleece-flower root-caused liver damages has drawn wide attention of both at home and abroad, however, there were rare literature on toxicology of fleece-flower root in ancient Chinese medicine. But why there are so many reports on toxicology of fleece-flower root now compared with the ancient literature? As a typical tonic medicine, the clinical utility of fleece-flower root was largely limited by its standardization and reliability of processing methods in ancient Chinese medicine. The ancient processing methods of fleece-flower root emphasized nine times of steaming and nine times of drying, while the modern processes have been simplified into one time of steaming. Whether the differences between ancient and modern processing methods are the potential cause of the increased events of fleece-flower root-caused liver damages. We will make deep analysis and provide new clues and perspectives for the research on its toxicity. This article, therefore, would discuss the affecting factors and key problems in toxicity attenuation of fleece-flower root on the basis of sorting out the processing methods of fleece-flower root in ancient medical books and modern standards, in order to provide the reference for establishing specification for toxicity attenuation of fleece-flower root. Copyright© by the Chinese Pharmaceutical Association.

  5. Site of ADP-ribosylation and the RNA-binding site are situated in different domains of the elongation factor EF-2

    International Nuclear Information System (INIS)

    Davydova, E.K.

    1987-01-01

    One of the proteins participating in the process of elongation of polypeptide chains - elongation factor 2 (EF-2) - can be ADP-ribosylated at a unique amino acid residue - diphthamide. Since the ADP-ribosylation of EF-2 at dipthamide leads to a loss of affinity of the factor for RNA while the presence of RNA inhibits the ADP-ribosylation reaction, it seemed probable to the authors that diphthamide participated directly in the binding of EF-2 to DNA. The experiments presented in this article showed that this was not the case: diphthamide and the RNA-binding site are situated on different domains of EF-2. Thus, ADP-ribosylation of factor EF-2 in one domain leads to a loss of the ability to bind to RNA in the other. The authors investigated the mutual arrangement of diphthamide and the RNA-binding site on the EF-2 molecule by preparing a factor from rabbit reticulocytes and subjecting it to proteolytic digestion with elastase. The factor was incubated with elastase for 15 min at 37 0 C at an enzyme:substrate ratio of 1:100 in buffer solution containing 20 mM Tris-HCl, pH 7.6, 10 mM KCl, 1 mM MgCl 2 , and 2 mM dithiothreitol. The reaction was stopped by adding para-methylsulfonyl fluoride to 50 micro-M. The authors obtained a preparation as a result of proteolysis and applied it on a column with RNA-Sepharose and separated into two fractions: RNA-binding and without affinity for RNA. The initial preparation and its fractions were subjected to exhaustive ADP-ribosylation in the presence of diphtheria toxin and [U- 14 C] nicotinaide adenine dinucleotide ([ 14 C]NAD) (296 mCi/mmole). The samples were analyzed electrophoretically in a polyacrylamide gel gradient in the presence of sodium dodecyl sulfate. For the detection of [ 14 C] ADP-ribosylated components, the gels were dried and exposed with RM-V x-ray film

  6. Directed evolution induces tributyrin hydrolysis in a virulence factor of Xylella fastidiosa using a duplicated gene as a template.

    Science.gov (United States)

    Gouran, Hossein; Chakraborty, Sandeep; Rao, Basuthkar J; Asgeirsson, Bjarni; Dandekar, Abhaya

    2014-01-01

    Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC), implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF). In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.

  7. [Polyadenylated RNA and mRNA export factors in extrachromosomal nuclear domains of vitellogenic oocytes of the insect Tenebrio molitor].

    Science.gov (United States)

    Bogoliubov, D S; Kiselev, A M; Shabel'nikov, S V; Parfenov, V N

    2012-01-01

    The nucleus ofvitellogenic oocytes of the yellow mealworm, Tenebrio molitor, contains a karyosphere that consists of the condensed chromatin embedded in an extrachromosomal fibrogranular material. Numerous nuclear bodies located freely in the nucleoplasm are also observed. Amongst these bodies, counterparts of nuclear speckles (= interchromatin granule clusters, IGCs) can be identified by the presence of the marker protein SC35. Microinjections of fluorescently tagged methyloligoribonucleotide probes 2'-O-Me(U)22, complementary to poly(A) tails of RNAs, revealed poly(A)+ RNA in the vast majority of IGCs. We found that all T. molitor oocyte IGCs contain heterogeneous ribonucleoprotein (hnRNP) core protein Al that localizes to IGCs in an RNA-dependent manner. The extrachromosomal material of the karyosphere and a part of nucleoplasmic IGCs also contain the adapter protein Aly that is known to provide a link between pre-mRNA splicing and mRNA export. The essential mRNA export factor/receptor NXF1 was observed to colocalize with Aly. In nucleoplasmic IGCs, NXF1 was found to localize in an RNA-dependent manner whereas it is RNA-independently located in the extrachromosomal material of the karyosphere. We believe our data suggest on a role of the nucleoplasmic IGCs in mRNA biogenesis and retention in a road to nuclear export.

  8. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, T F; Christensen, René dePont; Andersen, R F

    2013-01-01

    Background:This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC).Methods:A total of 230 patients......-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry.Results:High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95...... on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics....

  9. Mechanism of Retinal Pigment Epithelium Tear Formation Following Intravitreal Anti–Vascular Endothelial Growth Factor Therapy Revealed by Spectral-Domain Optical Coherence Tomography

    DEFF Research Database (Denmark)

    Nagiel, Aaron; Freund, K Bailey; Spaide, Richard F

    2013-01-01

    to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution......PURPOSE: To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT......). DESIGN: Retrospective observational case series. METHODS: OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur...

  10. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  11. Protein domain organisation: adding order.

    Science.gov (United States)

    Kummerfeld, Sarah K; Teichmann, Sarah A

    2009-01-29

    Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and

  12. Controlling factors of turf-banked solifluction lobe evolution in the Turtmann glacier forefield (Switzerland)

    Science.gov (United States)

    Draebing, Daniel; Eichel, Jana

    2016-04-01

    Soil structure and moisture, thermal conditions and vegetation control solifluction movement, however, the spatial distribution of controlling factors and resultant spatial variability of movement are poorly understood. We use a (1) geomorphological and vegetation mapping of solifluction lobe properties, (2) temperature loggers to quantify thermal conditions, (3) 2D Electrical Resistivity Tomography (ERT), Puerkhauer drilling and TDR measurements to evaluate material properties as well as (4) 3D Time-Lapse ERT to quantify spatial variability of material properties. Our results are used to (5) evaluate the influence of potential controlling factors on solifluction movement. Investigations took place on three turf-banked lobes (TBL) located at proximal and distal slopes of Little Ice Age and 1920s lateral moraines in the Turtmann glacier forefield, Swiss Alps. (1) Vegetation is spatially differentiated at TBLs. The treads are mostly covered by the ecosystem engineer Dryas octopetala, while other dwarf shrubs, shrubs and pioneer species were found at the high lobe risers (0.8-1.8 m). In contrast, less vegetated ridge-like features at the upper part of the treads are colonized by frost-tolerant species. Large blocks are located at the lobe fronts, probably impeding the lobe movement. (2) Temperature loggers show a lack of ground cooling due to snow isolation at the vegetated lower tread between 2014 and 2015. Thus, significant ground cooling in winter is reduced to the wind-exposed upper parts (ridges). (3) TBL material consists of sandy silt, thus, lobe material is much finer than subjacent moraine till and indicates former colluviation. As a consequence, 2D ERT demonstrates low-resistant areas until depths equal to riser height, thus, the finer TBL body is higher saturated than the coarser surrounding parent slope and more susceptible to gelifluction. On the contrary, risers show high resistivities indicating dry conditions which are supported by TDR results

  13. The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation.

    Science.gov (United States)

    Zhang, Yufan; Clemens, Adam; Maximova, Siela N; Guiltinan, Mark J

    2014-04-24

    The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm.

  14. Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.

    Science.gov (United States)

    Tahtouh, Muriel; Croq, Françoise; Vizioli, Jacopo; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Daha, Mohamed R; Pestel, Joël; Lefebvre, Christophe

    2009-02-01

    In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.

  15. Brain derived Neurotropic Factor (BDNF) is associated with childhood abuse but not cognitive domains in first episode psychosis.

    Science.gov (United States)

    Theleritis, Christos; Fisher, Helen L; Shäfer, Ingo; Winters, Laura; Stahl, Daniel; Morgan, Craig; Dazzan, Paola; Breedvelt, Josefien; Sambath, Irene; Vitoratou, Silia; Russo, Manuela; Reichenberg, Abraham; Falcone, M Aurora; Mondelli, Valeria; O'Connor, Jennifer; David, Anthony; McGuire, Philip; Pariante, Carmine; Di Forti, Marta; Murray, Robin M; Bonaccorso, Stefania

    2014-10-01

    The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome. We investigated the hypothesis that BDNF is associated with both CT and cognitive deficits in a sample of first-episode psychosis (FEP) cases and unaffected controls. Participants with FEP and healthy controls were recruited between August 2008 and July 2011 from South London, UK. Childhood traumatic events were detected using the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Neuropsychological data were also collected. BDNF plasma levels were measured from fasting blood samples. Data were available on 87 FEP patients and 152 controls. Our results showed a significant effect of separation (F=5.5; df=1,115; p=.02), physical (F=4.7; df=1, 118; p=.03) and sexual abuse (F=5.4; df=1,117; p=.02) on BDNF levels with lower levels among those who experienced the traumatic event compared to those who did not. Physical abuse predicted lower plasma levels of BDNF (β=-.30; p=.03) whereas sexual and/or physical abuse showed a trend (β=-.26; p=.06) in FEP patients but not in unaffected controls. No association between BDNF plasma levels and cognitive functions was found among patients with FEP and controls. Our findings suggest the possible involvement of BDNF in the onset of first-episode psychosis in individuals exposed to early trauma and propose BDNF as a potential clinical biomarker to detect the detrimental effects of CT on human brain plasticity. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  16. Platelet activating factor-induced ceramide micro-domains drive endothelial NOS activation and contribute to barrier dysfunction.

    Directory of Open Access Journals (Sweden)

    Sanda Predescu

    Full Text Available The spatial and functional relationship between platelet activating factor-receptor (PAF-R and nitric oxide synthase (eNOS in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles.

  17. Superbinder SH2 domains act as antagonists of cell signaling.

    Science.gov (United States)

    Kaneko, Tomonori; Huang, Haiming; Cao, Xuan; Li, Xing; Li, Chengjun; Voss, Courtney; Sidhu, Sachdev S; Li, Shawn S C

    2012-09-25

    Protein-ligand interactions mediated by modular domains, which often play important roles in regulating cellular functions, are generally of moderate affinities. We examined the Src homology 2 (SH2) domain, a modular domain that recognizes phosphorylated tyrosine (pTyr) residues, to investigate how the binding affinity of a modular domain for its ligand influences the structure and cellular function of the protein. We used the phage display method to perform directed evolution of the pTyr-binding residues in the SH2 domain of the tyrosine kinase Fyn and identified three amino acid substitutions that critically affected binding. We generated three SH2 domain triple-point mutants that were "superbinders" with much higher affinities for pTyr-containing peptides than the natural domain. Crystallographic analysis of one of these superbinders revealed that the superbinder SH2 domain recognized the pTyr moiety in a bipartite binding mode: A hydrophobic surface encompassed the phenyl ring, and a positively charged site engaged the phosphate. When expressed in mammalian cells, the superbinder SH2 domains blocked epidermal growth factor receptor signaling and inhibited anchorage-independent cell proliferation, suggesting that pTyr superbinders might be explored for therapeutic applications and useful as biological research tools. Although the SH2 domain fold can support much higher affinity for its ligand than is observed in nature, our results suggest that natural SH2 domains are not optimized for ligand binding but for specificity and flexibility, which are likely properties important for their function in signaling and regulatory processes.

  18. Factors Affecting the Development and Evolution of the Teaching Beliefs of Future Geoscience Professors

    Science.gov (United States)

    Chapman, LeeAnna Tiffany Young

    The pedagogical beliefs of university instructors influence how they design their courses and whether they choose to use research-validated teaching methods that have been shown to improve student learning. The next generation of professors will be drawn from today's graduate students and post-doctoral fellows but we know relatively little about their preparation to use research-validated teaching practices. We followed a broad population of geoscience graduate students and post-docs over a three year period to evaluate changes in teaching beliefs. This study employed a longitudinal mixed-methods experimental design including surveys, short interviews, and longer case study interviews to: a) collect information on the teaching beliefs of geoscience graduate students and post-doctoral scholars; and b) identify experiences that contributed to the development of reformed teaching beliefs and their interest in an academic career. We collected initial surveys from more than 600 participants and re-surveyed more than 300 of these participants 12-18 months later. We conducted an initial round of interviews with 61 participants and repeat interviews with 31 of these individuals. The survey utilized was the Beliefs about Reformed Teaching and Learning (BARSTL); the interview tool was the Teacher Belief Interview (TBI). Finally, we conducted detailed case study interviews with a sample of ten participants who were either PhD students, post-doctoral scholars, or beginning professors at the time of the interviews. The data were examined to determine if there was a difference in beliefs about teaching on the basis of factors including number of years in graduate school, teaching assistant (TA) experiences, gender, and participation in professional development. Data from the large initial population were interpreted to show that participation in teaching-related professional development was the experience that was most likely to result in more reformed pedagogical beliefs among

  19. Gifted Students' Self-Perceptions of Ability in Specific Subject Domains: Factor Structure and Relationship with Above-Level Test Scores

    Science.gov (United States)

    Swiatek, Mary Ann

    2005-01-01

    Current self-concept theories suggest a multi-dimensional construct, with domain-specific self-concepts hierarchically related to global self-concept. The academic domain may be comprised of subject-specific domains that are related to performance in corresponding areas. Here, gifted students' responses to questions about how they compare with…

  20. Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

    Science.gov (United States)

    Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

    2018-01-01

    The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  1. Comparative analysis of function and interaction of transcription factors in nematodes: Extensive conservation of orthology coupled to rapid sequence evolution

    Directory of Open Access Journals (Sweden)

    Singh Rama S

    2008-08-01

    Full Text Available Abstract Background Much of the morphological diversity in eukaryotes results from differential regulation of gene expression in which transcription factors (TFs play a central role. The nematode Caenorhabditis elegans is an established model organism for the study of the roles of TFs in controlling the spatiotemporal pattern of gene expression. Using the fully sequenced genomes of three Caenorhabditid nematode species as well as genome information from additional more distantly related organisms (fruit fly, mouse, and human we sought to identify orthologous TFs and characterized their patterns of evolution. Results We identified 988 TF genes in C. elegans, and inferred corresponding sets in C. briggsae and C. remanei, containing 995 and 1093 TF genes, respectively. Analysis of the three gene sets revealed 652 3-way reciprocal 'best hit' orthologs (nematode TF set, approximately half of which are zinc finger (ZF-C2H2 and ZF-C4/NHR types and HOX family members. Examination of the TF genes in C. elegans and C. briggsae identified the presence of significant tandem clustering on chromosome V, the majority of which belong to ZF-C4/NHR family. We also found evidence for lineage-specific duplications and rapid evolution of many of the TF genes in the two species. A search of the TFs conserved among nematodes in Drosophila melanogaster, Mus musculus and Homo sapiens revealed 150 reciprocal orthologs, many of which are associated with important biological processes and human diseases. Finally, a comparison of the sequence, gene interactions and function indicates that nematode TFs conserved across phyla exhibit significantly more interactions and are enriched in genes with annotated mutant phenotypes compared to those that lack orthologs in other species. Conclusion Our study represents the first comprehensive genome-wide analysis of TFs across three nematode species and other organisms. The findings indicate substantial conservation of transcription

  2. Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells.

    Science.gov (United States)

    Wang, Yun-Liang; Dong, Feng-Lin; Yang, Jian; Li, Zhi; Zhi, Qiao-Ming; Zhao, Xin; Yang, Yong; Li, De-Chun; Shen, Xiao-Chun; Zhou, Jin

    2015-01-01

    Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NC- PANC-1, and si-PANC-1 cells, respectively. After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.

  3. Domain crossing

    DEFF Research Database (Denmark)

    Schraefel, M. C.; Rouncefield, Mark; Kellogg, Wendy

    2012-01-01

    In CSCW, how much do we need to know about another domain/culture before we observe, intersect and intervene with designs. What optimally would that other culture need to know about us? Is this a “how long is a piece of string” question, or an inquiry where we can consider a variety of contexts a...

  4. The spatial-temporal evolution of aerosol optical depth and the analysis of influence factors in Bohai Rim

    International Nuclear Information System (INIS)

    Hou, Chunliang; Jiang, Hong; Wang, Xiaoyan; Pei, Huan

    2014-01-01

    Aerosol Optical Depth (AOD) is an important parameter of aerosol optical properties and it is an important physical parameter quantity to understanding the atmospheric environment. Bohai Rim is one of the three major urban agglomeration regions with rapidly developing economy in China. The study of AOD over this region is important to understand the environment and climate in Bohai Rim. Firstly, aerosol product data from 2000 to 2010, published by NASA, were used to analyze the temporal-spatial evolution of AOD in Bohai Rim with precision evaluation. The results showed that the spatial distribution of AOD had an obvious regional characteristic. The spatial distribution characterized that a much high value existed at urban areas and plain areas. On the contrary, the low value data existed in some mountainous regions which had higher percentages of forest coverage. The AOD values fluctuated somewhat each year in the region, from the minimum annual mean in 2003 to the maximum in 2009. Generally, the highest AOD value was in summer, followed by spring, autumn and winter. In terms of monthly variation, the value of AOD reached its peak in June and the lowest value was in December. This study analyzed the relation between AOD and some influence factors such as land use types, elevation, and distribution of urban agglomeration and so on. These results provide an important basic dataset for climate and environmental research

  5. lac repressor is an antivirulence factor of Salmonella enterica: its role in the evolution of virulence in Salmonella.

    Directory of Open Access Journals (Sweden)

    Sandeepa M Eswarappa

    Full Text Available The genus Salmonella includes many pathogens of great medical and veterinary importance. Bacteria belonging to this genus are very closely related to those belonging to the genus Escherichia. lacZYA operon and lacI are present in Escherichia coli, but not in Salmonella enterica. It has been proposed that Salmonella has lost lacZYA operon and lacI during evolution. In this study, we have investigated the physiological and evolutionary significance of the absence of lacI in Salmonella enterica. Using murine model of typhoid fever, we show that the expression of LacI causes a remarkable reduction in the virulence of Salmonella enterica. LacI also suppresses the ability of Salmonella enterica to proliferate inside murine macrophages. Microarray analysis revealed that LacI interferes with the expression of virulence genes of Salmonella pathogenicity island 2. This effect was confirmed by RT-PCR and Western blot analysis. Interestingly, we found that SBG0326 of Salmonella bongori is homologous to lacI of Escherichia coli. Salmonella bongori is the only other species of the genus Salmonella and it lacks the virulence genes of Salmonella pathogenicity island 2. Overall, our results demonstrate that LacI is an antivirulence factor of Salmonella enterica and suggest that absence of lacI has facilitated the acquisition of virulence genes of Salmonella pathogenicity island 2 in Salmonella enterica making it a successful systemic pathogen.

  6. Expression, purification, crystallization and structure determination of the N terminal domain of Fhb, a factor H binding protein from Streptococcus suis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chunmao [State Key Laboratory of Pathogen and Biosecurity, Beijng Institute of Microbiology and Infectious Disease, No. 20 Dongda Street, Fengtai District, Beijing 100071 (China); Yu, You [Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084, Beijing (China); Yang, Maojun, E-mail: maojunyang@tsinghua.edu.cn [Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084, Beijing (China); Jiang, Yongqiang, E-mail: jiangyq@bmi.ac.cn [State Key Laboratory of Pathogen and Biosecurity, Beijng Institute of Microbiology and Infectious Disease, No. 20 Dongda Street, Fengtai District, Beijing 100071 (China)

    2015-10-23

    Fhb is a surface virulence protein from Streptococcus suis, which could aid bacterial evasion of host innate immune defense by recruiting complement regulator factor H to inactivate C3b deposited on bacterial surface in blood. Here we successfully expressed and purified the N terminal domain of Fhb (N-Fhb) and obtained crystals of the N-Fhb by sitting-drop vapor diffusion method with a resolution of 1.50 Å. The crystals belong to space group C2 with unit cell parameters a = 127.1 Å, b = 77.3 Å, c = 131.6 Å, α = 90°, β = 115.9°, γ = 90°. The structure of N-Fhb was determined by SAD method and the core structure of N-Fhb is a β sandwich. We speculated that binding of Fhb to human factor H may be mainly mediated by surface amino acids with negative charges. - Highlights: • We expressed N-Fhb as the soluble protein in Escherichia coli. • Crystals of N-Fhb were grown by sitting drop vapor diffusion method. • Crystals of N-Fhb could diffracted to 1.5 Å. • The core structure of N-Fhb was a β sandwich. • A part of the surface of N-Fhb was rich with negative charges.

  7. Expression, purification, crystallization and structure determination of the N terminal domain of Fhb, a factor H binding protein from Streptococcus suis

    International Nuclear Information System (INIS)

    Zhang, Chunmao; Yu, You; Yang, Maojun; Jiang, Yongqiang

    2015-01-01

    Fhb is a surface virulence protein from Streptococcus suis, which could aid bacterial evasion of host innate immune defense by recruiting complement regulator factor H to inactivate C3b deposited on bacterial surface in blood. Here we successfully expressed and purified the N terminal domain of Fhb (N-Fhb) and obtained crystals of the N-Fhb by sitting-drop vapor diffusion method with a resolution of 1.50 Å. The crystals belong to space group C2 with unit cell parameters a = 127.1 Å, b = 77.3 Å, c = 131.6 Å, α = 90°, β = 115.9°, γ = 90°. The structure of N-Fhb was determined by SAD method and the core structure of N-Fhb is a β sandwich. We speculated that binding of Fhb to human factor H may be mainly mediated by surface amino acids with negative charges. - Highlights: • We expressed N-Fhb as the soluble protein in Escherichia coli. • Crystals of N-Fhb were grown by sitting drop vapor diffusion method. • Crystals of N-Fhb could diffracted to 1.5 Å. • The core structure of N-Fhb was a β sandwich. • A part of the surface of N-Fhb was rich with negative charges.

  8. Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants

    Directory of Open Access Journals (Sweden)

    Maia Amanda M

    2012-07-01

    Full Text Available Abstract Background Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47, MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS, which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD simulations, focusing on the structural changes of the wild-type versus mutant dimers. Results The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Conclusions Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro

  9. Engineering N-terminal domain of tissue inhibitor of metalloproteinase (TIMP)-3 to be a better inhibitor against tumour necrosis factor-alpha-converting enzyme.

    Science.gov (United States)

    Lee, Meng-Huee; Verma, Vandana; Maskos, Klaus; Nath, Deepa; Knäuper, Vera; Dodds, Philippa; Amour, Augustin; Murphy, Gillian

    2002-01-01

    We previously reported that full-length tissue inhibitor of metalloproteinase-3 (TIMP-3) and its N-terminal domain form (N-TIMP-3) displayed equal binding affinity for tissue necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE). Based on the computer graphic of TACE docked with a TIMP-3 model, we created a number of N-TIMP-3 mutants that showed significant improvement in TACE inhibition. Our strategy was to select those N-TIMP-3 residues that were believed to be in actual contact with the active-site pockets of TACE and mutate them to amino acids of a better-fitting nature. The activities of these mutants were examined by measuring their binding affinities (K(app)(i)) and association rates (k(on)) against TACE. Nearly all mutants at position Thr-2 exhibited slightly impaired affinity as well as association rate constants. On the other hand, some Ser-4 mutants displayed a remarkable increase in their binding tightness with TACE. In fact, the binding affinities of several mutants were less than 60 pM, beyond the sensitivity limits of fluorimetric assays. Further studies on cell-based processing of pro-TNF-alpha demonstrated that wild-type N-TIMP-3 and one of its tight-binding mutants, Ser-4Met, were capable of inhibiting the proteolytic shedding of TNF-alpha. Furthermore, the Ser-4Met mutant was also significantly more active (P<0.05) than the wild-type N-TIMP-3 in its cellular inhibition. Comparison of N-TIMP-3 and full-length TIMP-3 revealed that, despite their identical TACE-interaction kinetics, the latter was nearly 10 times more efficient in the inhibition of TNF-alpha shedding, with concomitant implications for the importance of the TIMP-3 C-terminal domain in vivo. PMID:11988096

  10. Breast tissue composition and its dependence on demographic risk factors for breast cancer: non-invasive assessment by time domain diffuse optical spectroscopy.

    Directory of Open Access Journals (Sweden)

    Paola Taroni

    Full Text Available Breast tissue composition is recognized as a strong and independent risk factor for breast cancer. It is a heritable feature, but is also significantly affected by several other elements (e.g., age, menopause. Nowadays it is quantified by mammographic density, thus requiring the use of ionizing radiation. Optical techniques are absolutely non-invasive and have already proved effective in the investigation of biological tissues, as they are sensitive to tissue composition and structure.Time domain diffuse optical spectroscopy was performed at 7 wavelengths (635-1060 nm on 200 subjects to derive their breast tissue composition (in terms of water, lipid and collagen content, blood parameters (total hemoglobin content and oxygen saturation level, and information on the microscopic structure (scattering amplitude and power. The dependence of all optically-derived parameters on age, menopausal status, body mass index, and use of oral contraceptives, and the correlation with mammographic density were investigated.Younger age, premenopausal status, lower body mass index values, and use of oral contraceptives all correspond to significantly higher water, collagen and total hemoglobin content, and lower lipid content (always p < 0.05 and often p < 10-4, while oxygen saturation level and scattering parameters show significant dependence only on some conditions. Even when age-adjusted groups of subjects are compared, several optically derived parameters (and in particular always collagen and total hemoglobin content remain significantly different.Time domain diffuse optical spectroscopy can probe non-invasively breast tissue composition and physiologic blood parameters, and provide information on tissue structure. The measurement is suitable for in vivo studies and monitoring of changes in breast tissue (e.g., with age, lifestyle, chemotherapy, etc. and to gain insight into related processes, like the origin of cancer risk associated with breast density.

  11. Structural and dynamic studies of the dimerization and DNA-binding domains of the transcription factors v-Myc and Max

    International Nuclear Information System (INIS)

    Fieber, W.

    2001-05-01

    In the present work, solution structural and dynamic properties of the dimerization and DNA binding domains of the transcription factors v-Myc and Max were characterized by NMR and CD spectroscopy. It could be demonstrated that v-Myc in the absence of its authentic binding partner Max does not homodimerize, but exists in a monomeric and prestructured form. Two separated α-helical regions in the leucine zipper region and in the basic-H1 region, respectively, could be identified, while the latter appeared to be less stable. Both helices lack stabilizing tertiary side chain interactions and represent exceptional examples for loosely coupled, structured segments in a native protein. The structure of v-Myc is dynamic and can be described as a distribution of conformational substates. Motion within the substates comprise fast (picosecond to nanosecond) local backbone fluctuations like helical fraying, whereas motion between the substates comprise the relative orientation of the two helices and occur at larger time scales (microsecond to millisecond). The preformation of the specific protein and DNA binding sites, leucine zipper and the basic region, presumably allows rapid and accurate recognition of the respective binding partners. v-Myc-Max and Max-Max protein preparations were shown to form stable dimers. Thermodynamic analysis of the dissociation reactions of v-Myc-Max revealed a significant higher stability of the heterodimer than of the Max-Max homodimer over the whole temperature range. It could be demonstrated that the restricted conformational space of the v-Myc bHLHZip domain reduces the entropy penalty associated with dimerization and contributes to the preference of Max to form heterodimers with v-Myc rather than homodimers. (author)

  12. p38α phosphorylates serine 258 within the cytoplasmic domain of tissue factor and prevents its incorporation into cell-derived microparticles.

    Science.gov (United States)

    Ettelaie, Camille; Elkeeb, Azza M; Maraveyas, Anthony; Collier, Mary Elizabeth W

    2013-03-01

    We previously showed that the phosphorylation of Ser253 within the cytoplasmic domain of human tissue factor (TF) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of Ser258 terminates this process. However, the identity of the kinase responsible for the phosphorylation of Ser258 and mode of action of this enzyme remain unknown. In this study, p38α was identified as the proline-directed kinase capable of phosphorylating Ser258 specifically, and without any detectable activity towards Ser253. Furthermore, using synthetic peptides, it was shown that the Km for the reaction decreased by approximately 10 fold on substitution of Ser253 with phospho-Ser253. Either inhibition of p38 using SB202190 or knockdown of p38α expression in coronary artery endothelial cells overexpressing wild-type TF, resulted in decreased phosphorylation of Ser258, following activation of cells with PAR2-agonist peptide (PAR2-AP). In agreement with our previous data, inhibition of phosphorylation of this residue maintained the release of TF. Activation of PAR2 in cells transfected to overexpress TF, resulted in two separate peaks of p38 activity at approximately 40 and 120 min post-activation. Furthermore, overexpression of Ala253-substituted TF enhanced the second p38 activation peak. However, the second peak was absent in cells devoid of TF or in cells overexpressing the Asp253-substituted TF. Our data clearly identifies p38α as a kinase capable of phosphorylating Ser258 within the cytoplasmic domain of TF. Moreover, it appears that the presence of TF within the cells regulates the late activation of p38 and consequently the termination of TF release into microparticles. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor

    International Nuclear Information System (INIS)

    Mills, Philippe; Lafreniere, Jean-Francois; Benabdallah, Basma Fattouma; El Fahime, El Mostafa; Tremblay, Jacques-P.

    2007-01-01

    Duchenne muscular dystrophy (DMD) is an inherited disease that leads to progressive muscle wasting. Myogenic precursor cell transplantation is an approach that can introduce the normal dystrophin gene in the muscle fibers of the patients. Unfortunately, these myogenic precursor cells do not migrate well in the muscle and thus many injections have to be done to enable a good graft success. Recent reports have shown that there is extensive splicing of the IGF-1 gene in muscles. The MGF isoform contains a C-terminal 24 amino acids peptide in the E domain (MGF-Ct24E) that has intrinsic properties. It can promote the proliferation while delaying the differentiation of C 2 C 12 cells. Here, we demonstrated that this synthetic peptide is a motogenic factor for human precursor myogenic cells in vitro and in vivo. Indeed, MGF-Ct24E peptide can modulate members of the fibrinolytic and metalloproteinase systems, which are implicated in the migration of myogenic cells. MGF-Ct24E peptide enhances the expression of u-PA, u-PAR and MMP-7 while reducing PAI-1 activity. Moreover, it has no effect on the gelatinases MMP-2 and -9. Those combined effects can favour cell migration. Finally, we present some results suggesting that the MGF-Ct24E peptide induces these cell responses through a mechanism that does not involve the IGF-1 receptor. Thus, this MGF-Ct24E peptide has a new pro-migratory activity on human myogenic precursor cells that may be helpful in the treatment of DMD. Those results reinforce the possibility that the IGF-1Ec isoform may produce an E domain peptide that can act as a cytokine

  14. Characterization of the factors having an influence on the evolution of the EPR signal of irradiated alanine

    International Nuclear Information System (INIS)

    Feaugas-Le-Berre, Valerie

    1999-01-01

    EPR/alanine dosimetry has been used by the LNHB (Laboratoire National Henri Becquerel) since many years for applied metrology. This technic is based on the measurement of the EPR signal of the free radicals induced in alanine by irradiation. The aim of this work is to characterize the factors having an influence on the evolution of the amplitude of the EPR signal of irradiated alanine to limit the uncertainties on the determination of the absorbed dose. The first step of this work has been the choice of the dosimeter. A bibliographic study completed by experiments on the response of alanine isomers to the dose and on its stability with time has lead us to choose L-α-alanine powder as dosimeter. The influence of the recording parameter of the spectrometer on the characteristics of the EPR spectrum has then been studied. This has enabled us to optimize the recording conditions of EPR spectra. As the angular anisotropy of the EPR signal limits the measurements reproducibility, an experimental protocol has been defined to solve this problem. The repeatability of the measurements has been enhanced by modifying the spectrometer and using an internal standard constituted of single crystals of CuSO 4 .5H 2 O. As the amplitude of the EPR signal is sensitive to the measurement temperature, a method of normalization of the results to 20 C has been determined. We have studied the influence of an irradiation parameter and of environmental parameters. We have shown that the EPR signal amplitude increases with irradiation temperature. The EPR signal amplitude and its evolution vary strongly with storage conditions (temperature and moisture) of the dosimeter before and after irradiation. The presence of moisture in alanine powder leads to a loss of signal amplitude. The dosimeters exposition to light also entails a loss of amplitude. Oxygen does not influence the EPR spectrum of alanine. We have noticed that the EPR signal amplitude of samples stored in absence of moisture

  15. Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

    Science.gov (United States)

    Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

    2018-04-01

    Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Quantifying the Forcing Factors Responsible for the Tectono-Geomorphological Evolution of Neogene Rift Basins, Baja California

    Science.gov (United States)

    El-Sobky, H. F.; Dorobek, S. L.

    2005-12-01

    The Gulf of California and its surrounding land areas provide a classic example of recently rifted continental lithosphere, where back-arc stretching of a continental volcanic arc has culminated in the ongoing seafloor spreading that characterizes the present-day axis of the gulf. The recent tectonic history of eastern Baja California, which includes most of the land area eastward of the main drainage divide that extends north-south along the length of the peninsula, has been dominated by oblique rifting that began at about 5 Ma. Thus, extensional tectonics, bedrock lithology, long-term climatic changes, and evolving surface processes have controlled the tectono-geomorphological evolution of the eastern part of the peninsula since 5 Ma. No previous studies, however, examined the effect of these combined factors on the current tectono-geomorphological characteristics of eastern Baja California. We assume that although long-term climate may have changed along the peninsula over the last several million years, precipitation amounts are likely to have changed in a similar way along the entire length of the peninsula, regardless of the long-term climatic trend. This suggests that climatic variation can be largely ruled out as an explanation for the geomorphologic variability between basins. In an attempt to quantify the factors that affected the geomorphologic development along the eastern side of Baja California, thirty-four drainage basins were extracted from a 15-m-resolution absolute digital elevation model (DEM). The stacked-vector method was applied to utilize the different terrain attributes (e.g., hillshaded relief, aspect, slope, etc.) for supervised classification of bedrock lithologies using object-oriented techniques. Stream-length gradient indices were then measured for the main stream in each of the basins. Bedrock lithologies and alluvium were plotted along the stream profiles to identify any relationship between lithology, structure, and stream gradient

  17. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    remote access via IP-based devices such as smartphones. The Trusted Domain platform fits existing legacy technologies by managing their interoperability and access controls, and it seeks to avoid the security issues of relying on third-party servers outside the home. It is a distributed system...... of wireless standards, limited resources of embedded systems, etc. Taking these challenges into account, we present a Trusted Domain home automation platform, which dynamically and securely connects heterogeneous networks of Short-Range Wireless devices via simple non-expert user. interactions, and allows......In the digital age of home automation and with the proliferation of mobile Internet access, the intelligent home and its devices should be accessible at any time from anywhere. There are many challenges such as security, privacy, ease of configuration, incompatible legacy devices, a wealth...

  18. Domain: Labour market

    NARCIS (Netherlands)

    Oude Mulders, J.; Wadensjö, E.; Hasselhorn, H.M.; Apt, W.

    This domain chapter is dedicated to summarize research on the effects of labour market contextual factors on labour market participation of older workers (aged 50+) and identify research gaps. While employment participation and the timing of (early) retirement is often modelled as an individual

  19. The evolution of refractive status in Chinese infants during the first year of life and its affected factors

    Directory of Open Access Journals (Sweden)

    Shu-Juan Yu

    2017-08-01

    Full Text Available AIM: To study the evolution of the refractive status and examine the affected factors in infants during the first year of life in a large sample size in China. METHODS: A total of 1258 babies (2516 eyes aged 32wk gestational age to 1y participated in the study, including 766 premature and 492 full-term infants. First, each baby received an orthoptic examination, slit-lamp checking and fundus imaging. Patients with diseases which might affect refractive status were excluded from the cohort. The cycloplegia retinoscopy was performed. Their neonatal histories were reviewed. Each measurement contained the refractive status and calculation of the spherical equivalent (SE. RESULTS: Refractive state showed an average hyperopia of +0.94±1.63 D at early ages, followed by a trend toward more hyperopia. The refractive state reached the top (+2.43±1.46 D at the age of one to two months. Then gliding till one year old when the refractive state reached +0.59±1.41 D. The prevalence of astigmatism was 42.17% in the study, being 2.82% myopic astigmatism and 39.35% hyperopic astigmatism. The 94.1% of hyperopic astigmatism was with-the-rule astigmatism and 71.83% of myopic astigmatism was with-the-rule astigmatism. Refractive state between boys and girls was different. The mean SE of boys was +1.97±1.57 D, while that of girls was +1.79±1.46 D, and the difference was significant. CONCLUSION: Before one year old, the change of refractive status is associated with checking age and sex. At the age of one to two months, the degree of hyperopia reaches the top. Boys have more hyperopic degree than girls, and with-the-rule astigmatism is predominant. Excluding premature infants with advanced retinopathy of prematurity, premature and full-term children have same refraction status.

  20. Vegetation type and the presence of ash as factors in the evolution of soil water repellency after a forest fire

    Directory of Open Access Journals (Sweden)

    P. Jiménez-Pinilla

    2013-05-01

    Full Text Available After wildfires, burning may induce the occurrence of soil water repellency. Soil water repellency may vary in space and time in function of vegetation, the presence of ash and soil moisture. This study analyzes the evolution of fire-induced soil water repellency in function of these factors, and proposes measures to promote the restoration of fire-affected soils. Burnt and unburnt (control soil plots under pine and shrub from a recently burned area (Gorga, Alicante, SE Spain were established. Three treatments were applied: in some of the plots, the original ash layer was kept on the ground; in a second group, the ash layer was removed for simulating the effects of erosion; finally, in a third group, percolating irrigation was conducted to simulate a possible good input of water into the soil profile after burning, that could occur if the first rains were with high quantity but low intensity. During the dry season, soil moisture content was significantly lower in burned plots due to fire-induced water repellency and reduced vegetation cover. During the wet season, soil moisture decreased in the control unburnt plots due to direct evaporation of water intercepted by vegetation and consumption by roots. Fire increased soil water repellency only in plots under pine. Water repellency decreased during the wet season, disappearing in January and reappearing after declining rainfalls. This baseline recovery of soil water repellency was lower where ash removal was simulated. In unburned plots, seasonal fluctuations were less important. In general, ash removal promotes a rapid reduction of water repellency, since it can induce washing of hydrophobic compounds. Irrigation performed immediately after the fire also contributed to decreased water repellency.

  1. A separable domain of the p150 subunit of human chromatin assembly factor-1 promotes protein and chromosome associations with nucleoli.

    Science.gov (United States)

    Smith, Corey L; Matheson, Timothy D; Trombly, Daniel J; Sun, Xiaoming; Campeau, Eric; Han, Xuemei; Yates, John R; Kaufman, Paul D

    2014-09-15

    Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Of note, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces α-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus. © 2014 Smith et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  2. Increased activity of the Vesicular Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor TI-VAMP/VAMP7 by Tyrosine Phosphorylation in the Longin Domain*

    Science.gov (United States)

    Burgo, Andrea; Casano, Alessandra M.; Kuster, Aurelia; Arold, Stefan T.; Wang, Guan; Nola, Sébastien; Verraes, Agathe; Dingli, Florent; Loew, Damarys; Galli, Thierry

    2013-01-01

    Vesicular (v)- and target (t)-SNAREs play essential roles in intracellular membrane fusion through the formation of cytoplasmic α-helical bundles. Several v-SNAREs have a Longin N-terminal extension that, by promoting a closed conformation, plays an autoinhibitory function and decreases SNARE complex formation and membrane fusion efficiency. The molecular mechanism leading to Longin v-SNARE activation is largely unknown. Here we find that exocytosis mediated by the Longin v-SNARE TI-VAMP/VAMP7 is activated by tonic treatment with insulin and insulin-like growth factor-1 but not by depolarization and intracellular calcium rise. In search of a potential downstream mechanism, we found that TI-VAMP is phosphorylated in vitro by c-Src kinase on tyrosine 45 of the Longin domain. Accordingly, a mutation of tyrosine 45 into glutamate, but not phenylalanine, activates both t-SNARE binding and exocytosis. Activation of TI-VAMP-mediated exocytosis thus relies on tyrosine phosphorylation. PMID:23471971

  3. Characterization of an entomopathogenic fungi target integument protein, Bombyx mori single domain von Willebrand factor type C, in the silkworm, Bombyx mori.

    Science.gov (United States)

    Han, F; Lu, A; Yuan, Y; Huang, W; Beerntsen, B T; Huang, J; Ling, E

    2017-06-01

    The insect cuticle works as the first line of defence to protect insects from pathogenic infections and water evaporation. However, the old cuticle must be shed in order to enter the next developmental stage. During each ecdysis, moulting fluids are produced and secreted into the area among the old and new cuticles. In a previous study, the protein Bombyx mori single domain von Willebrand factor type C (BmSVWC; BGIBMGA011399) was identified in the moulting fluids of Bo. mori and demonstrated to regulate ecdysis. In this study we show that in Bo. mori larvae, BmSVWC primarily locates to the integument (epidermal cells and cuticle), wing discs and head. During the moulting stage, BmSVWC is released into the moulting fluids, and is then produced again by epidermal cells after ecdysis. Fungal infection was shown to decrease the amount of BmSVWC in the cuticle, which indicates that BmSVWC is a target protein of entomopathogenic fungi. Thus, BmSVWC is mainly involved in maintaining the integrity of the integument structure, which serves to protect insects from physical damage and pathogenic infection. © 2017 The Royal Entomological Society.

  4. The kunitz protease inhibitor domain of protease nexin-2 inhibits factor XIa and murine carotid artery and middle cerebral artery thrombosis

    Science.gov (United States)

    Wu, Wenman; Li, Hongbo; Navaneetham, Duraiswamy; Reichenbach, Zachary W.; Tuma, Ronald F.

    2012-01-01

    Coagulation factor XI (FXI) plays an important part in both venous and arterial thrombosis, rendering FXIa a potential target for the development of antithrombotic therapy. The kunitz protease inhibitor (KPI) domain of protease nexin-2 (PN2) is a potent, highly specific inhibitor of FXIa, suggesting its possible role in the inhibition of FXI-dependent thrombosis in vivo. Therefore, we examined the effect of PN2KPI on thrombosis in the murine carotid artery and the middle cerebral artery. Intravenous administration of PN2KPI prolonged the clotting time of both human and murine plasma, and PN2KPI inhibited FXIa activity in both human and murine plasma in vitro. The intravenous administration of PN2KPI into WT mice dramatically decreased the progress of FeCl3-induced thrombus formation in the carotid artery. After a similar initial rate of thrombus formation with and without PN2KPI treatment, the propagation of thrombus formation after 10 minutes and the amount of thrombus formed were significantly decreased in mice treated with PN2KPI injection compared with untreated mice. In the middle cerebral artery occlusion model, the volume and fraction of ischemic brain tissue were significantly decreased in PN2KPI-treated compared with untreated mice. Thus, inhibition of FXIa by PN2KPI is a promising approach to antithrombotic therapy. PMID:22674803

  5. Crystallization and preliminary X-ray analysis of the mRNA-binding domain of elongation factor SelB from Escherichia coli in complex with RNA

    International Nuclear Information System (INIS)

    Soler, Nicolas; Fourmy, Dominique; Yoshizawa, Satoko

    2007-01-01

    The mRNA-binding domain of E. coli selenocysteine-specific elongation factor SelB (residues 478–614; SelB-WH3/4) was overproduced in E. coli and its cognate mRNA ligand, 23 nucleotides of the SECIS RNA hairpin, was prepared by in vitro transcription. The purified SelB-WH3/4–SECIS RNA complex crystallized in space group C2 and diffracted to 2.3 Å. In bacteria, selenocysteine (the 21st amino acid) is incorporated into proteins via machinery that includes SelB, a specific translational elongation factor. SelB binds to an mRNA hairpin called the selenocysteine-insertion sequence (SECIS) and delivers selenocysteyl-tRNA Sec to the ribosomal A site. The minimum C-terminal fragment (residues 478–614) of Escherichia coli SelB (SelB-WH3/4) required for SECIS binding has been overexpressed and purified. This protein was crystallized in complex with 23 nucleotides of the SECIS hairpin at 294 K using the hanging-drop vapour-diffusion method. A data set was collected to 2.3 Å resolution from a single crystal at 100 K using ESRF beamline BM-30. The crystal belongs to space group C2, with unit-cell parameters a = 103.50, b = 56.51, c = 48.41 Å. The asymmetric unit contains one WH3/4-domain–RNA complex. The Matthews coefficient was calculated to be 3.37 Å 3 Da −1 and the solvent content was estimated to be 67.4%

  6. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial.

    Science.gov (United States)

    Hansen, T F; Christensen, R dP; Andersen, R F; Sørensen, F B; Johnsson, A; Jakobsen, A

    2013-09-03

    This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC). A total of 230 patients from a randomised phase III study were included. The primary microRNA-126 (pri-miRNA-126) A24G single-nucleotide polymorphism and the mature miRNA-126 were analysed by PCR using genomic DNA (full blood) and formalin-fixed paraffin-embedded tissue sections, respectively. The epidermal growth factor-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry. High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95% confidence interval=0.29-0.84, P=0.009). Although not significant, a relationship between EGFL7 expression and response rates is suggested, with EGFL7 expression at the invasive front being lower in responding patients than in the non-responders (P=0.063). The results validate the previous findings on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics.

  7. Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.

    Science.gov (United States)

    Alzan, Heba F; Knowles, Donald P; Suarez, Carlos E

    2016-11-01

    Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i) identify and map genes encoding for these transcription factors among three parasites' genomes; (ii) identify a previously unreported HMG gene in B. microti; (iii) define a repertoire of eight conserved Myb genes; and (iv) identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

  8. Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.

    Directory of Open Access Journals (Sweden)

    Heba F Alzan

    2016-11-01

    Full Text Available Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i identify and map genes encoding for these transcription factors among three parasites' genomes; (ii identify a previously unreported HMG gene in B. microti; (iii define a repertoire of eight conserved Myb genes; and (iv identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

  9. Basic Fibroblast Growth Factor Fused with Tandem Collagen-Binding Domains from Clostridium histolyticum Collagenase ColG Increases Bone Formation

    Directory of Open Access Journals (Sweden)

    Hiroyuki Sekiguchi

    2018-01-01

    Full Text Available Basic fibroblast growth factor 2 (bFGF accelerates bone formation during fracture healing. Because the efficacy of bFGF decreases rapidly following its diffusion from fracture sites, however, repeated dosing is required to ensure a sustained therapeutic effect. We previously developed a fusion protein comprising bFGF, a polycystic kidney disease domain (PKD; s2b, and collagen-binding domain (CBD; s3 sourced from the Clostridium histolyticum class II collagenase, ColH, and reported that the combination of this fusion protein with a collagen-like peptide, poly(Pro-Hyp-Gly10, induced mesenchymal cell proliferation and callus formation at fracture sites. In addition, C. histolyticum produces class I collagenase (ColG with tandem CBDs (s3a and s3b at the C-terminus. We therefore hypothesized that a bFGF fusion protein containing ColG-derived tandem CBDs (s3a and s3b would show enhanced collagen-binding activity, leading to improved bone formation. Here, we examined the binding affinity of four collagen anchors derived from the two clostridial collagenases to H-Gly-Pro-Arg-Gly-(Pro-Hyp-Gly12-NH2, a collagenous peptide, by surface plasmon resonance and found that tandem CBDs (s3a-s3b have the highest affinity for the collagenous peptide. We also constructed four fusion proteins consisting of bFGF and s3 (bFGF-s3, s2b-s3b (bFGF-s2b-s3, s3b (bFGF-s3b, and s3a-s3b (bFGF-s3a-s3b and compared their biological activities to those of a previous fusion construct (bFGF-s2b-s3 using a cell proliferation assay in vitro and a mouse femoral fracture model in vivo. Among these CB-bFGFs, bFGF-s3a-s3b showed the highest capacity to induce mesenchymal cell proliferation and callus formation in the mice fracture model. The poly(Pro-Hyp-Gly10/bFGF-s3a-s3b construct may therefore have the potential to promote bone formation in clinical settings.

  10. Cryo-EM structure of the archaeal 50S ribosomal subunit in complex with initiation factor 6 and implications for ribosome evolution

    DEFF Research Database (Denmark)

    Greber, Basil J; Boehringer, Daniel; Godinic-Mikulcic, Vlatka

    2012-01-01

    additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter...... between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes......, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea....

  11. A single amino acid change within the R2 domain of the VvMYB5b transcription factor modulates affinity for protein partners and target promoters selectivity

    Directory of Open Access Journals (Sweden)

    Granier Thierry

    2011-08-01

    Full Text Available Abstract Background Flavonoid pathway is spatially and temporally controlled during plant development and the transcriptional regulation of the structural genes is mostly orchestrated by a ternary protein complex that involves three classes of transcription factors (R2-R3-MYB, bHLH and WDR. In grapevine (Vitis vinifera L., several MYB transcription factors have been identified but the interactions with their putative bHLH partners to regulate specific branches of the flavonoid pathway are still poorly understood. Results In this work, we describe the effects of a single amino acid substitution (R69L located in the R2 domain of VvMYB5b and predicted to affect the formation of a salt bridge within the protein. The activity of the mutated protein (name VvMYB5bL, the native protein being referred as VvMYB5bR was assessed in different in vivo systems: yeast, grape cell suspensions, and tobacco. In the first two systems, VvMYB5bL exhibited a modified trans-activation capability. Moreover, using yeast two-hybrid assay, we demonstrated that modification of VvMYB5b transcriptional properties impaired its ability to correctly interact with VvMYC1, a grape bHLH protein. These results were further substantiated by overexpression of VvMYB5bR and VvMYB5bL genes in tobacco. Flowers from 35S::VvMYB5bL transgenic plants showed a distinct phenotype in comparison with 35S::VvMYB5bR and the control plants. Finally, significant differences in transcript abundance of flavonoid metabolism genes were observed along with variations in pigments accumulation. Conclusions Taken together, our findings indicate that VvMYB5bL is still able to bind DNA but the structural consequences linked to the mutation affect the capacity of the protein to activate the transcription of some flavonoid genes by modifying the interaction with its co-partner(s. In addition, this study underlines the importance of an internal salt bridge for protein conformation and thus for the establishment

  12. Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease

    NARCIS (Netherlands)

    Tjernberg, Pernilla; Vos, Hans L.; Spaargaren-van Riel, Caroline C.; Luken, Brenda M.; Voorberg, Jan; Bertina, Rogier M.; Eikenboom, Jeroen C. J.

    2006-01-01

    Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 von Willebrand disease (VWD). Our objective

  13. Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

    2015-01-01

    factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases. Methods: A total of 126 patients were included. Analyses were performed...

  14. Evolution of Replication Machines

    Science.gov (United States)

    Yao, Nina Y.; O'Donnell, Mike E.

    2016-01-01

    The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337

  15. Extraordinary molecular evolution in the PRDM9 fertility gene.

    Directory of Open Access Journals (Sweden)

    James H Thomas

    2009-12-01

    Full Text Available Recent work indicates that allelic incompatibility in the mouse PRDM9 (Meisetz gene can cause hybrid male sterility, contributing to genetic isolation and potentially speciation. The only phenotype of mouse PRDM9 knockouts is a meiosis I block that causes sterility in both sexes. The PRDM9 gene encodes a protein with histone H3(K4 trimethyltransferase activity, a KRAB domain, and a DNA-binding domain consisting of multiple tandem C2H2 zinc finger (ZF domains. We have analyzed human coding polymorphism and interspecies evolutionary changes in the PRDM9 gene. The ZF domains of PRDM9 are evolving very rapidly, with compelling evidence of positive selection in primates. Positively selected amino acids are predominantly those known to make nucleotide specific contacts in C2H2 zinc fingers. These results suggest that PRDM9 is subject to recurrent selection to change DNA-binding specificity. The human PRDM9 protein is highly polymorphic in its ZF domains and nearly all polymorphisms affect the same nucleotide contact residues that are subject to positive selection. ZF domain nucleotide sequences are strongly homogenized within species, indicating that interfinger recombination contributes to their evolution. PRDM9 has previously been assumed to be a transcription factor required to induce meiosis specific genes, a role that is inconsistent with its molecular evolution. We suggest instead that PRDM9 is involved in some aspect of centromere segregation conflict and that rapidly evolving centromeric DNA drives changes in PRDM9 DNA-binding domains.

  16. The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF is separated from its N-terminal

    Directory of Open Access Journals (Sweden)

    YONG ZHANG

    2009-01-01

    Full Text Available Apoptosis-inducing factor (AIF is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFΔ1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFΔ1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFΔ1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFΔ1-480. Therefore, AIFΔ 1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFΔ 1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFΔ 1-480. Human Jurkat cells transfected with the immuno-AIFΔl-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFΔl-480 gene as a novel approach to treating HER2-overexpressing cancers.

  17. Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice.

    Science.gov (United States)

    Cai, Wang-Yu; Lin, Ling-Yun; Hao, Han; Zhang, Sai-Man; Ma, Fei; Hong, Xin-Xin; Zhang, Hui; Liu, Qing-Feng; Ye, Guo-Dong; Sun, Guang-Bin; Liu, Yun-Jia; Li, Sheng-Nan; Xie, Yuan-Yuan; Cai, Jian-Chun; Li, Bo-An

    2017-04-01

    Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221). © 2016 by the American Association for the Study of Liver Diseases.

  18. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  19. Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

    2017-05-01

    Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic

  20. A conserved motif in the linker domain of STAT1 transcription factor is required for both recognition and release from high-affinity DNA-binding sites.

    Science.gov (United States)

    Hüntelmann, Bettina; Staab, Julia; Herrmann-Lingen, Christoph; Meyer, Thomas

    2014-01-01

    Binding to specific palindromic sequences termed gamma-activated sites (GAS) is a hallmark of gene activation by members of the STAT (signal transducer and activator of transcription) family of cytokine-inducible transcription factors. However, the precise molecular mechanisms involved in the signal-dependent finding of target genes by STAT dimers have not yet been very well studied. In this study, we have characterized a sequence motif in the STAT1 linker domain which is highly conserved among the seven human STAT proteins and includes surface-exposed residues in close proximity to the bound DNA. Using site-directed mutagenesis, we have demonstrated that a lysine residue in position 567 of the full-length molecule is required for GAS recognition. The substitution of alanine for this residue completely abolished both binding to high-affinity GAS elements and transcriptional activation of endogenous target genes in cells stimulated with interferon-γ (IFNγ), while the time course of transient nuclear accumulation and tyrosine phosphorylation were virtually unchanged. In contrast, two glutamic acid residues (E559 and E563) on each monomer are important for the dissociation of dimeric STAT1 from DNA and, when mutated to alanine, result in elevated levels of tyrosine-phosphorylated STAT1 as well as prolonged IFNγ-stimulated nuclear accumulation. In conclusion, our data indicate that the kinetics of signal-dependent GAS binding is determined by an array of glutamic acid residues located at the interior surface of the STAT1 dimer. These negatively charged residues appear to align the long axis of the STAT1 dimer in a position perpendicular to the DNA, thereby facilitating the interaction between lysine 567 and the phosphodiester backbone of a bound GAS element, which is a prerequisite for transient gene induction.

  1. Alanine Zipper-Like Coiled-Coil Domains Are Necessary for Homotypic Dimerization of Plant GAGA-Factors in the Nucleus and Nucleolus

    Science.gov (United States)

    Bloss, Ulrich; Hecker, Andreas; Elgass, Kirstin; Hummel, Sabine; Hahn, Achim; Caesar, Katharina; Schleifenbaum, Frank; Harter, Klaus; Berendzen, Kenneth W.

    2011-01-01

    GAGA-motif binding proteins control transcriptional activation or repression of homeotic genes. Interestingly, there are no sequence similarities between animal and plant proteins. Plant BBR/BPC-proteins can be classified into two distinct groups: Previous studies have elaborated on group I members only and so little is known about group II proteins. Here, we focused on the initial characterization of AtBPC6, a group II protein from Arabidopsis thaliana. Comparison of orthologous BBR/BPC sequences disclosed two conserved signatures besides the DNA binding domain. A first peptide signature is essential and sufficient to target AtBPC6-GFP to the nucleus and nucleolus. A second domain is predicted to form a zipper-like coiled-coil structure. This novel type of domain is similar to Leucine zippers, but contains invariant alanine residues with a heptad spacing of 7 amino acids. By yeast-2-hybrid and BiFC-assays we could show that this Alanine zipper domain is essential for homotypic dimerization of group II proteins in vivo. Interhelical salt bridges and charge-stabilized hydrogen bonds between acidic and basic residues of the two monomers are predicted to form an interaction domain, which does not follow the classical knobs-into-holes zipper model. FRET-FLIM analysis of GFP/RFP-hybrid fusion proteins validates the formation of parallel dimers in planta. Sequence comparison uncovered that this type of domain is not restricted to BBR/BPC proteins, but is found in all kingdoms. PMID:21347358

  2. [Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia].

    Science.gov (United States)

    Ma, Yan; Chen, Bo-Bin; Wang, Xiao-Qin; Xu, Xiao-Ping; Lin, Guo-Wei

    2015-12-01

    To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort. All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models. A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model

  3. Insights into Hox protein function from a large scale combinatorial analysis of protein domains.

    Directory of Open Access Journals (Sweden)

    Samir Merabet

    2011-10-01

    Full Text Available Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA, we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences.

  4. .Gov Domains API

    Data.gov (United States)

    General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

  5. The C-terminal SH2 domain of p85 accounts for the high affinity and specificity of the binding of phosphatidylinositol 3-kinase to phosphorylated platelet-derived growth factor beta receptor.

    Science.gov (United States)

    Klippel, A; Escobedo, J A; Fantl, W J; Williams, L T

    1992-01-01

    Upon stimulation by its ligand, the platelet-derived growth factor (PDGF) receptor associates with the 85-kDa subunit of phosphatidylinositol (PI) 3-kinase. The 85-kDa protein (p85) contains two Src homology 2 (SH2) domains and one SH3 domain. To define the part of p85 that interacts with the PDGF receptor, a series of truncated p85 mutants was analyzed for association with immobilized PDGF receptor in vitro. We found that a fragment of p85 that contains a single Src homology domain, the C-terminal SH2 domain (SH2-C), was sufficient for directing the high-affinity interaction with the receptor. Half-maximal binding of SH2-C to the receptor was observed at an SH2-C concentration of 0.06 nM. SH2-C, like full-length p85, was able to distinguish between wild-type PDGF receptor and a mutant receptor lacking the PI 3-kinase binding site. An excess of SH2-C blocked binding of full-length p85 and PI 3-kinase to the receptor but did not interfere with the binding of two other SH2-containing proteins, phospholipase C-gamma and GTPase-activating protein. These results demonstrate that a region of p85 containing a single SH2 domain accounts both for the high affinity and specificity of binding of PI 3-kinase to the PDGF receptor. Images PMID:1312663

  6. Changes in pH and NADPH regulate the DNA binding activity of neuronal PAS domain protein 2, a mammalian circadian transcription factor.

    Science.gov (United States)

    Yoshii, Katsuhiro; Tajima, Fumihisa; Ishijima, Sumio; Sagami, Ikuko

    2015-01-20

    Neuronal PAS domain protein 2 (NPAS2) is a core clock transcription factor that forms a heterodimer with BMAL1 to bind the E-box in the promoter of clock genes and is regulated by various environmental stimuli such as heme, carbon monoxide, and NAD(P)H. In this study, we investigated the effects of pH and NADPH on the DNA binding activity of NPAS2. In an electrophoretic mobility shift (EMS) assay, the pH of the reaction mixture affected the DNA binding activity of the NPAS2/BMAL1 heterodimer but not that of the BMAL1/BMAL1 homodimer. A change in pH from 7.0 to 7.5 resulted in a 1.7-fold increase in activity in the absence of NADPH, and NADPH additively enhanced the activity up to 2.7-fold at pH 7.5. The experiments using truncated mutants revealed that N-terminal amino acids 1-61 of NPAS2 were sufficient to sense the change in both pH and NADPH. We further analyzed the kinetics of formation and DNA binding of the NPAS2/BMAL1 heterodimer at various pH values. In the absence of NADPH, a change in pH from 6.5 to 8.0 decreased the KD(app) value of the E-box from 125 to 22 nM, with an 8-fold increase in the maximal level of DNA binding for the NPAS2/BMAL1 heterodimer. The addition of NADPH resulted in a further decrease in KD(app) to 9 nM at pH 8.0. Furthermore, NPAS2-dependent transcriptional activity in a luciferase assay using NIH3T3 cells also increased with the pH of the culture medium. These results suggest that NPAS2 has a role as a pH and metabolite sensor in regulating circadian rhythms.

  7. HTLV-1 bZIP Factor Impairs Anti-viral Immunity by Inducing Co-inhibitory Molecule, T Cell Immunoglobulin and ITIM Domain (TIGIT.

    Directory of Open Access Journals (Sweden)

    Keiko Yasuma

    2016-01-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 infects CD4+ T cells and induces proliferation of infected cells in vivo, which leads to the onset of adult T-cell leukemia (ATL in some infected individuals. The HTLV-1 bZIP factor (HBZ gene, which is encoded in the minus strand of HTLV-1, plays critical roles in pathogenesis. In this study, RNA-seq and ChIP-seq analyses using HBZ transduced T cells revealed that HBZ upregulates the expression and promoter acetylation levels of a co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT, in addition to those of regulatory T cells related genes, Foxp3 and Ccr4. TIGIT was expressed on CD4+ T cells from HBZ-transgenic (HBZ-Tg mice, and on ATL cells and HTLV-1 infected CD4+ T cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP in vivo. Expression of Blimp1 and IL-10 was upregulated in TIGIT+CD4+ cells of HBZ-Tg mice compared with TIGIT-CD4+ T cells, suggesting the correlation between TIGIT expression and IL-10 production. When CD4+ T cells from HBZ-Tg mice were stimulated with TIGIT's ligand, CD155, their production of the inhibitory cytokine IL-10 was enhanced. Furthermore, dendritic cells from HBZ-Tg mice produced high levels of IL-10 after stimulation. These data suggest that HBZ alters immune system to suppressive state via TIGIT and IL-10. Importantly, TIGIT suppressed T-cell responses to another HTLV-1 virus protein, Tax, in vitro. Blocking of TIGIT and PD-1 slightly increased anti-Tax T-cell activity in some HAM/TSP patients. These results suggest that HBZ-induced TIGIT on HTLV-1 infected cells impairs T-cell responses to viral antigens. This study shows that HBZ-induced TIGIT plays a pivotal role in attenuating host immune responses and shaping a microenvironment favorable to HTLV-1.

  8. RRM domain of Arabidopsis splicing factor SF1 is important for pre-mRNA splicing of a specific set of genes

    KAUST Repository

    Lee, Keh Chien; Jang, Yun Hee; Kim, SoonKap; Park, Hyo-Young; Thu, May Phyo; Lee, Jeong Hwan; Kim, Jeong-Kook

    2017-01-01

    , but not the abscisic acid sensitivity response during seed germination. The alternative splicing of FLOWERING LOCUS M (FLM) pre-mRNA is involved in flowering time control. We found that the RRM domain of AtSF1 protein alters the production of alternatively spliced FLM

  9. Computational design of binding proteins to EGFR domain II.

    Directory of Open Access Journals (Sweden)

    Yoon Sup Choi

    Full Text Available We developed a process to produce novel interactions between two previously unrelated proteins. This process selects protein scaffolds and designs protein interfaces that bind to a surface patch of interest on a target protein. Scaffolds with shapes complementary to the target surface patch were screened using an exhaustive computational search of the human proteome and optimized by directed evolution using phage display. This method was applied to successfully design scaffolds that bind to epidermal growth factor receptor (EGFR domain II, the interface of EGFR dimerization, with high reactivity toward the target surface patch of EGFR domain II. One potential application of these tailor-made protein interactions is the development of therapeutic agents against specific protein targets.

  10. A micromagnetic study of domain structure modeling

    International Nuclear Information System (INIS)

    Matsuo, Tetsuji; Mimuro, Naoki; Shimasaki, Masaaki

    2008-01-01

    To develop a mesoscopic model for magnetic-domain behavior, a domain structure model (DSM) was examined and compared with a micromagnetic simulation. The domain structure of this model is given by several domains with uniform magnetization vectors and domain walls. The directions of magnetization vectors and the locations of domain walls are determined so as to minimize the magnetic total energy of the magnetic material. The DSM was modified to improve its representation capability for domain behavior. The domain wall energy is multiplied by a vanishing factor to represent the disappearance of magnetic domain. The sequential quadratic programming procedure is divided into two steps to improve an energy minimization process. A comparison with micromagnetic simulation shows that the modified DSM improves the representation accuracy of the magnetization process

  11. Cooperation of three WRKY-domain transcription factors WRKY18, WRKY40, and WRKY60 in repressing two ABA-responsive genes ABI4 and ABI5 in Arabidopsis

    OpenAIRE

    Liu, Zhi-Qiang; Yan, Lu; Wu, Zhen; Mei, Chao; Lu, Kai; Yu, Yong-Tao; Liang, Shan; Zhang, Xiao-Feng; Wang, Xiao-Fang; Zhang, Da-Peng

    2012-01-01

    Three evolutionarily closely related WRKY-domain transcription factors WRKY18, WRKY40, and WRKY60 in Arabidopsis were previously identified as negative abscisic acid (ABA) signalling regulators, of which WRKY40 regulates ABI4 and ABI5 expression, but it remains unclear whether and how the three transcription factors cooperate to regulate expression of ABI4 and ABI5. In the present experiments, it was shown that WRKY18 and WRKY60, like WRKY40, interact with the W-box in the promoters of ABI4 a...

  12. Epidermal Growth Factor Cytoplasmic Domain Affects ErbB Protein Degradation by the Lysosomal and Ubiquitin-Proteasome Pathway in Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Aleksandra Glogowska

    2012-05-01

    Full Text Available The cytoplasmic domains of EGF-like ligands, including EGF cytoplasmic domain (EGFcyt, have important biological functions. Using specific constructs and peptides of human EGF cytoplasmic domain, we demonstrate that EGFcyt facilitates lysosomal and proteasomal protein degradation, and this coincided with growth inhibition of human thyroid and glioma carcinoma cells. EGFcyt and exon 22–23-encoded peptide (EGF22.23 enhanced procathepsin B (procathB expression and procathB-mediated lysosomal degradation of EGFR/ErbB1 as determined by inhibitors for procathB and the lysosomal ATPase inhibitor BafA1. Presence of mbEGFctF, EGFcyt, EGF22.23, and exon 23-encoded peptides suppressed the expression of the deubiqitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1. This coincided with hyperubiquitination of total cellular proteins and ErbB1/2 and reduced proteasome activity. Upon small interfering RNA-mediated silencing of endogenously expressed UCH-L1, a similar hyperubiquitinylation phenotype, reduced ErbB1/2 content, and attenuated growth was observed. The exon 23-encoded peptide region of EGFcyt was important for these biologic actions. Structural homology modeling of human EGFcyt showed that this molecular region formed an exposed surface loop. Peptides derived from this EGFcyt loop structure may aid in the design of novel peptide therapeutics aimed at inhibiting growth of cancer cells.

  13. Incompleteness in the finite domain

    Czech Academy of Sciences Publication Activity Database

    Pudlák, Pavel

    2017-01-01

    Roč. 23, č. 4 (2017), s. 405-441 ISSN 1079-8986 EU Projects: European Commission(XE) 339691 - FEALORA Institutional support: RVO:67985840 Keywords : finite domain Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.742, year: 2016 https://www.cambridge.org/core/journals/bulletin-of-symbolic-logic/article/incompleteness-in-the-finite-domain/D239B1761A73DCA534A4805A76D81C76

  14. A KH-Domain RNA-Binding Protein Interacts with FIERY2/CTD Phosphatase-Like 1 and Splicing Factors and Is Important for Pre-mRNA Splicing in Arabidopsis

    KAUST Repository

    Chen, Tao

    2013-10-17

    Eukaryotic genomes encode hundreds of RNA-binding proteins, yet the functions of most of these proteins are unknown. In a genetic study of stress signal transduction in Arabidopsis, we identified a K homology (KH)-domain RNA-binding protein, HOS5 (High Osmotic Stress Gene Expression 5), as required for stress gene regulation and stress tolerance. HOS5 was found to interact with FIERY2/RNA polymerase II (RNAP II) carboxyl terminal domain (CTD) phosphatase-like 1 (FRY2/CPL1) both in vitro and in vivo. This interaction is mediated by the first double-stranded RNA-binding domain of FRY2/CPL1 and the KH domains of HOS5. Interestingly, both HOS5 and FRY2/CPL1 also interact with two novel serine-arginine (SR)-rich splicing factors, RS40 and RS41, in nuclear speckles. Importantly, FRY2/CPL1 is required for the recruitment of HOS5. In fry2 mutants, HOS5 failed to be localized in nuclear speckles but was found mainly in the nucleoplasm. hos5 mutants were impaired in mRNA export and accumulated a significant amount of mRNA in the nuclei, particularly under salt stress conditions. Arabidopsis mutants of all these genes exhibit similar stress-sensitive phenotypes. RNA-seq analyses of these mutants detected significant intron retention in many stress-related genes under salt stress but not under normal conditions. Our study not only identified several novel regulators of pre-mRNA processing as important for plant stress response but also suggested that, in addition to RNAP II CTD that is a well-recognized platform for the recruitment of mRNA processing factors, FRY2/CPL1 may also recruit specific factors to regulate the co-transcriptional processing of certain transcripts to deal with environmental challenges. © 2013 Chen et al.

  15. A KH-Domain RNA-Binding Protein Interacts with FIERY2/CTD Phosphatase-Like 1 and Splicing Factors and Is Important for Pre-mRNA Splicing in Arabidopsis

    KAUST Repository

    Chen, Tao; Cui, Peng; Chen, Hao; Ali, Shahjahan; Zhang, ShouDong; Xiong, Liming

    2013-01-01

    Eukaryotic genomes encode hundreds of RNA-binding proteins, yet the functions of most of these proteins are unknown. In a genetic study of stress signal transduction in Arabidopsis, we identified a K homology (KH)-domain RNA-binding protein, HOS5 (High Osmotic Stress Gene Expression 5), as required for stress gene regulation and stress tolerance. HOS5 was found to interact with FIERY2/RNA polymerase II (RNAP II) carboxyl terminal domain (CTD) phosphatase-like 1 (FRY2/CPL1) both in vitro and in vivo. This interaction is mediated by the first double-stranded RNA-binding domain of FRY2/CPL1 and the KH domains of HOS5. Interestingly, both HOS5 and FRY2/CPL1 also interact with two novel serine-arginine (SR)-rich splicing factors, RS40 and RS41, in nuclear speckles. Importantly, FRY2/CPL1 is required for the recruitment of HOS5. In fry2 mutants, HOS5 failed to be localized in nuclear speckles but was found mainly in the nucleoplasm. hos5 mutants were impaired in mRNA export and accumulated a significant amount of mRNA in the nuclei, particularly under salt stress conditions. Arabidopsis mutants of all these genes exhibit similar stress-sensitive phenotypes. RNA-seq analyses of these mutants detected significant intron retention in many stress-related genes under salt stress but not under normal conditions. Our study not only identified several novel regulators of pre-mRNA processing as important for plant stress response but also suggested that, in addition to RNAP II CTD that is a well-recognized platform for the recruitment of mRNA processing factors, FRY2/CPL1 may also recruit specific factors to regulate the co-transcriptional processing of certain transcripts to deal with environmental challenges. © 2013 Chen et al.

  16. Evolution of postmating reproductive isolation: measuring the fitness effects of chromosomal regions containing hybrid male sterility factors.

    Science.gov (United States)

    Johnson, N A; Wu, C I

    1993-08-01

    At least six regions of the X chromosome can cause male sterility when introgressed from Drosophila mauritiana into Drosophila simulans. In this article, we present the results of the other fitness effects caused by two X-linked regions that contain hybrid male sterility factors. In both regions, females that are heterozygous for an introgression with such a sterility factor produce substantially-fewer offspring than females heterozygous for an introgression that lacks the sterility factor. Thus, the hybrid male sterility factors, or other genes nearby, have substantial effects on female productivity. In contrast, hybrid male sterility factors have little or no effect on the relative viabilities of either sex. The evolutionary implications of these findings are discussed.

  17. DNA Binding Drugs Targeting the Regulatory DNA Binding Site of the ETS Domain Family Transcription Factor Associated With Human Breast Cancer

    National Research Council Canada - National Science Library

    Wang, Yong-Dong

    1999-01-01

    .... The key approach is to prevent the binding of two transcription factors, ESX and AP-2, to the consensus DNA binding sites contained within the Her2/neu promoter resulting in inhibition of transcription factor function...

  18. Genetically engineered fusion of MAP-1 and factor H domains 1-5 generates a potent dual upstream inhibitor of both the lectin and alternative complement pathways

    DEFF Research Database (Denmark)

    Nordmaj, Mie Anemone; Munthe-Fog, Lea; Hein, Estrid

    2015-01-01

    Inhibition of the complement cascade has emerged as an option for treatment of a range of diseases. Mannose-binding lectin/ficolin/collectin-associated protein (MAP-1) is a pattern recognition molecule (PRM)-associated inhibitor of the lectin pathway. The central regulator of the alternative......:4 in a solid-phase functional assay, only the first 5 N-terminal domains of complement FH fused to the C-terminal part of full-length MAP-1 chimeric construct were able to combine inhibition of lectin and AP activation with an half maximal inhibitory concentration of ∼ 100 and 20 nM, respectively. No effect...

  19. Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells.

    Science.gov (United States)

    Kawprasertsri, Sornsawan; Pietras, Richard J; Marquez-Garban, Diana C; Boonyaratanakornkit, Viroj

    2016-05-01

    Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BΔSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020-mediated inhibition of cell proliferation. Expression of PR-BΔSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BΔSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Factors controlling the evolution of the Perdido Fold Belt, northwestern Gulf of Mexico, determined from numerical models

    Science.gov (United States)

    Gradmann, Sofie; Beaumont, Christopher; Albertz, Markus

    2009-04-01

    The Perdido Fold Belt (PFB) is a prominent salt-cored deep water structure in the northwestern Gulf of Mexico. It is characterized by symmetric, kink-banded folds of a ˜4.5 km thick prekinematic layer and its vicinity to the extensive Sigsbee Salt Canopy. We use 2-D finite element numerical models to study the evolution of the PFB as a gravity-driven fold belt both in a local context and in the context of the larger-scale passive margin, influenced by adjacent allochthonous salt structures. We show that parameters such as overburden strength, salt geometry, or salt viscosity determine timing, extent, and location of the modeled fold belt. Simplified models of the Gulf of Mexico show that toe-of-slope folding is a viable mechanism to develop diapirs in the deep salt basin and to delay folding of the distal overburden. In this scenario, the PFB likely represents the terminal folding of a much larger, diachronously formed fold belt system.

  1. Gossip Consensus Algorithm Based on Time-Varying Influence Factors and Weakly Connected Graph for Opinion Evolution in Social Networks

    Directory of Open Access Journals (Sweden)

    Lingyun Li

    2013-01-01

    Full Text Available We provide a new gossip algorithm to investigate the problem of opinion consensus with the time-varying influence factors and weakly connected graph among multiple agents. What is more, we discuss not only the effect of the time-varying factors and the randomized topological structure but also the spread of misinformation and communication constrains described by probabilistic quantized communication in the social network. Under the underlying weakly connected graph, we first denote that all opinion states converge to a stochastic consensus almost surely; that is, our algorithm indeed achieves the consensus with probability one. Furthermore, our results show that the mean of all the opinion states converges to the average of the initial states when time-varying influence factors satisfy some conditions. Finally, we give a result about the square mean error between the dynamic opinion states and the benchmark without quantized communication.

  2. Classification and Lineage Tracing of SH2 Domains Throughout Eukaryotes.

    Science.gov (United States)

    Liu, Bernard A

    2017-01-01

    Today there exists a rapidly expanding number of sequenced genomes. Cataloging protein interaction domains such as the Src Homology 2 (SH2) domain across these various genomes can be accomplished with ease due to existing algorithms and predictions models. An evolutionary analysis of SH2 domains provides a step towards understanding how SH2 proteins integrated with existing signaling networks to position phosphotyrosine signaling as a crucial driver of robust cellular communication networks in metazoans. However organizing and tracing SH2 domain across organisms and understanding their evolutionary trajectory remains a challenge. This chapter describes several methodologies towards analyzing the evolutionary trajectory of SH2 domains including a global SH2 domain classification system, which facilitates annotation of new SH2 sequences essential for tracing the lineage of SH2 domains throughout eukaryote evolution. This classification utilizes a combination of sequence homology, protein domain architecture and the boundary positions between introns and exons within the SH2 domain or genes encoding these domains. Discrete SH2 families can then be traced across various genomes to provide insight into its origins. Furthermore, additional methods for examining potential mechanisms for divergence of SH2 domains from structural changes to alterations in the protein domain content and genome duplication will be discussed. Therefore a better understanding of SH2 domain evolution may enhance our insight into the emergence of phosphotyrosine signaling and the expansion of protein interaction domains.

  3. The origin of the supernumerary subunits and assembly factors of complex I: A treasure trove of pathway evolution

    NARCIS (Netherlands)

    Elurbe, D.M.; Huynen, M.A.

    2016-01-01

    We review and document the evolutionary origin of all complex I assembly factors and nine supernumerary subunits from protein families. Based on experimental data and the conservation of critical residues we identify a spectrum of protein function conservation between the complex I representatives

  4. Small Boreal Lake Ecosystem Evolution under the Influence of Natural and Anthropogenic Factors: Results of Multidisciplinary Long-Term Study

    Directory of Open Access Journals (Sweden)

    Liudmila Shirokova

    2016-07-01

    Full Text Available Small aquatic ecosystems of the boreal zone are known to be most sensitive indicators of on-going environmental change as well as local anthropogenic pressure, while being highly vulnerable to external impacts. Compared to rather detailed knowledge of the evolution of large and small lakes in Scandinavia and Canada, and large lakes in Eurasia, highly abundant small boreal lakes of northwest Russia have received very little attention, although they may become important centers of attraction of growing rural population in the near future. Here we present the results of a multidisciplinary, multi-annual study of a small boreal humic lake of NW Russia. A shallow (3 m and a deep (16 m site of this lake were regularly sampled for a range of chemical and biological parameters. Average multi-daily, summer-time values of the epilimnion (upper oxygenated layer of the lake provided indications of possible trends in temperature, nutrients, and bacterio-plankton concentration that revealed the local pollution impact in the shallow zone and overall environmental trend in the deep sampling point of the lake. Organic phosphorus, nitrate, and lead were found to be most efficient tracers of local anthropogenic pollution, especially visible in the surface layer of the shallow site of the lake. Cycling of trace elements between the epilimnion and hypolimnion is tightly linked to dissolved organic matter speciation and size fractionation due to the dominance of organic and organo-ferric colloids. The capacity of lake self-purification depends on the ratio of primary productivity to mineralization of organic matter. This ratio remained >1 both during winter and summer periods, which suggests a high potential of lake recovery from the input of allochthonous dissolved organic matter and local anthropogenic pollution.

  5. Transfer of the amino-terminal nuclear envelope targeting domain of human MX2 converts MX1 into an HIV-1 resistance factor.

    Science.gov (United States)

    Goujon, Caroline; Moncorgé, Olivier; Bauby, Hélène; Doyle, Tomas; Barclay, Wendy S; Malim, Michael H

    2014-08-01

    The myxovirus resistance 2 (MX2) protein of humans has been identified recently as an interferon (IFN)-inducible inhibitor of human immunodeficiency virus type 1 (HIV-1) that acts at a late postentry step of infection to prevent the nuclear accumulation of viral cDNA (C. Goujon et al., Nature 502:559-562, 2013, http://dx.doi.org/10.1038/nature12542; M. Kane et al., Nature 502:563-566, 2013, http://dx.doi.org/10.1038/nature12653; Z. Liu et al., Cell Host Microbe 14:398-410, 2013, http://dx.doi.org/10.1016/j.chom.2013.08.015). In contrast, the closely related human MX1 protein, which suppresses infection by a range of RNA and DNA viruses (such as influenza A virus [FluAV]), is ineffective against HIV-1. Using a panel of engineered chimeric MX1/2 proteins, we demonstrate that the amino-terminal 91-amino-acid domain of MX2 confers full anti-HIV-1 function when transferred to the amino terminus of MX1, and that this fusion protein retains full anti-FluAV activity. Confocal microscopy experiments further show that this MX1/2 fusion, similar to MX2 but not MX1, can localize to the nuclear envelope (NE), linking HIV-1 inhibition with MX accumulation at the NE. MX proteins are dynamin-like GTPases, and while MX1 antiviral function requires GTPase activity, neither MX2 nor MX1/2 chimeras require this attribute to inhibit HIV-1. This key discrepancy between the characteristics of MX1- and MX2-mediated viral resistance, together with previous observations showing that the L4 loop of the stalk domain of MX1 is a critical determinant of viral substrate specificity, presumably reflect fundamental differences in the mechanisms of antiviral suppression. Accordingly, we propose that further comparative studies of MX proteins will help illuminate the molecular basis and subcellular localization requirements for implementing the noted diversity of virus inhibition by MX proteins. Interferon (IFN) elicits an antiviral state in cells through the induction of hundreds of IFN

  6. A Gly1127Ser mutation in an EGF-like domain of the Fibrillin-I gene is a risk factor for ascending aortic aneurysm and dissection

    Energy Technology Data Exchange (ETDEWEB)

    Francke, U.; Berg, M.A.; Tynan, K. [Stanford Univ. Medical Center, CA (United States)] [and others

    1995-06-01

    Ascending aortic disease, ranging from mild aortic root enlargement to aneurysm and/or dissection, has been identified in 10 individuals of a kindred, none of whom had classical Marfan syndrome (MFS). Single-strand conformation analysis of the entire fibrillin-1 (FBN1) cDNA of an affected family member revealed a G-to-A transition at nucleotide 3379, predicting a Gly1127Ser substitution. The glycine in this position is highly conserved in EGF-like domains of FBN1 and other proteins. This mutation was present in 9 of 10 affected family members and in 1 young unaffected member but was not found in other unaffected members, in 168 chromsomes from normal controls, and in 188 chromosomes from other individuals with MFS or related phenotypes. FBN1 intragenic marker haplotypes ruled out the possibility that the other allele played a significant role in modulating the phenotype in this family. Pulse-chase studies revealed normal fibrillin synthesis but reduced fibrillin deposition into the extracellular matrix in cultured fibroblasts from a Gly1127Ser carrier. We postulate that the Gly1127Ser FBN1 mutation is responsible for reduced matrix deposition. We suggest that mutations such as this one may disrupt EFG-like domain folding less drastically than do substitutions of cysteine or of other amino acids important for calcium-binding that cause classical MFS. The Gly 1127Ser mutation, therefore, produces a mild form of autosomal dominantly inherited weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection later in life. 33 refs., 6 figs.

  7. On the structure of order domains

    DEFF Research Database (Denmark)

    Geil, Olav; Pellikaan, Ruud

    2002-01-01

    The notion of an order domain is generalized. The behaviour of an order domain by taking a subalgebra, the extension of scalars, and the tensor product is studied. The relation of an order domain with valuation theory, Gröbner algebras, and graded structures is given. The theory of Gröbner bases...... for order domains is developed and used to show that the factor ring theorem and its converse, the presentation theorem, hold. The dimension of an order domain is related to the rank of its value semigroup....

  8. The architectural design of networks of protein domain architectures.

    Science.gov (United States)

    Hsu, Chia-Hsin; Chen, Chien-Kuo; Hwang, Ming-Jing

    2013-08-23

    Protein domain architectures (PDAs), in which single domains are linked to form multiple-domain proteins, are a major molecular form used by evolution for the diversification of protein functions. However, the design principles of PDAs remain largely uninvestigated. In this study, we constructed networks to connect domain architectures that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. Our results shed light on nature's blueprint for protein architecture and provide a framework for understanding architectural design from a network perspective.

  9. Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a

    OpenAIRE

    Klose, Jana; Wendt, Norbert; Kubald, Sybille; Krause, Eberhard; Fechner, Klaus; Beyermann, Michael; Bienert, Michael; Rudolph, Rainer; Rothemund, Sven

    2004-01-01

    The oxidative folding, particularly the arrangement of disulfide bonds of recombinant extracellular N-terminal domains of the corticotropin-releasing factor receptor type 2a bearing five cysteines (C2 to C6), was investigated. Depending on the position of a His-tag, two types of disulfide patterns were found. In the case of an N-terminal His-tag, the disulfide bonds C2–C3 and C4–C6 were found, leaving C5 free, whereas the C-terminal position of the His-tag led to the disulfide pattern C2–C5 a...

  10. The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of α2δ subunits is key to trafficking voltage-gated Ca2+ channels

    Science.gov (United States)

    Cantí, C.; Nieto-Rostro, M.; Foucault, I.; Heblich, F.; Wratten, J.; Richards, M. W.; Hendrich, J.; Douglas, L.; Page, K. M.; Davies, A.; Dolphin, A. C.

    2005-01-01

    All auxiliary α2δ subunits of voltage-gated Ca2+ (CaV) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in α2δ-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the α2δ-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant α2δ-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT α2δ-2, the MIDAS mutant α2δ-2 subunit did not enhance and, in some cases, further diminished CaV1.2, -2.1, and -2.2 currents coexpressed with β1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant α2δ-2 reduced surface expression and strongly increased the perinuclear retention of CaVα1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108–15 cells. Despite the presence of endogenous α2δ subunits, heterologous expression of α2δ-2 in differentiated NG108–15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that α2δ subunits normally interact with the CaVα1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the α2δ subunit is required to promote trafficking of the α1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains. PMID:16061813

  11. Structure of Stenotrophomonas maltophilia FeoA complexed with zinc: a unique prokaryotic SH3-domain protein that possibly acts as a bacterial ferrous iron-transport activating factor

    International Nuclear Information System (INIS)

    Su, Yi-Che; Chin, Ko-Hsin; Hung, Hui-Chih; Shen, Gwan-Han; Wang, Andrew H.-J.; Chou, Shan-Ho

    2010-01-01

    The crystal structure of FeoA from Stenotrophomonas maltophilia has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach and revealed a unique dimer cross-linked by two zinc ions and six chloride ions. Iron is vital to the majority of prokaryotes, with ferrous iron believed to be the preferred form for iron uptake owing to its much better solubility. The major route for bacterial ferrous iron uptake is found to be via an Feo (ferrous iron-transport) system comprising the three proteins FeoA, FeoB and FeoC. Although the structure and function of FeoB have received much attention recently, the roles played by FeoA and FeoC have been little investigated to date. Here, the tertiary structure of FeoA from Stenotrophomonas maltophilia (Sm), a vital opportunistic pathogen in immunodepressed hosts, is reported. The crystal structure of SmFeoA has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach. Although SmFeoA bears low sequence identity to eukaryotic proteins, its structure is found to adopt a eukaryotic SH3-domain-like fold. It also bears weak similarity to the C-terminal SH3 domain of bacterial DtxR (diphtheria toxin regulator), with some unique characteristics. Intriguingly, SmFeoA is found to adopt a unique dimer cross-linked by two zinc ions and six anions (chloride ions). Since FeoB has been found to contain a G-protein-like domain with low GTPase activity, FeoA may interact with FeoB through the SH3–G-protein domain interaction to act as a ferrous iron-transport activating factor

  12. Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients.

    Directory of Open Access Journals (Sweden)

    Paolo Pandolfi

    Full Text Available Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD. We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes in a group of COPD patients.Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant'Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines.229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage. Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis. Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01-16.54, having two or more comorbidities (HR = 4.71; 95% CI 2.52-8.83, belonging to moderate (HR = 3.50; 95% CI 1.01-12.18 or very severe COPD stage (HR = 8.23; 95% CI 2.35-28.85.Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients.

  13. Managing Software Process Evolution

    DEFF Research Database (Denmark)

    This book focuses on the design, development, management, governance and application of evolving software processes that are aligned with changing business objectives, such as expansion to new domains or shifting to global production. In the context of an evolving business world, it examines...... the complete software process lifecycle, from the initial definition of a product to its systematic improvement. In doing so, it addresses difficult problems, such as how to implement processes in highly regulated domains or where to find a suitable notation system for documenting processes, and provides...... essential insights and tips to help readers manage process evolutions. And last but not least, it provides a wealth of examples and cases on how to deal with software evolution in practice. Reflecting these topics, the book is divided into three parts. Part 1 focuses on software business transformation...

  14. Senescence-associated barley NAC (NAM, ATAF1,2, CUC) transcription factor interacts with radical-induced cell death 1 through a disordered regulatory domain

    DEFF Research Database (Denmark)

    Kjaersgaard, Trine; Jensen, Michael K; Christiansen, Michael W

    2011-01-01

    as a transcriptional activator suggesting that an involvement of HvNAC013 and HvNAC005 in senescence will be different. HvNAC013 interacted with barley radical-induced cell death 1 (RCD1) via the very C-terminal part of its TRD, outside of the region containing the LP motif. No significant secondary structure...... (NAM, ATAF1,2, CUC) TF family are up-regulated during senescence in barley (Hordeum vulgare). Both HvNAC005 and HvNAC013 bound the conserved NAC DNA target sequence. Computational and biophysical analyses showed that both proteins are intrinsically disordered in their large C-terminal domains, which...... was induced in the HvNAC013 TRD upon interaction with RCD1. RCD1 also interacted with regions dominated by intrinsic disorder in TFs of the MYB and basic helix-loop-helix families. We propose that RCD1 is a regulatory protein capable of interacting with many different TFs by exploiting their intrinsic...

  15. Software evolution and maintenance

    CERN Document Server

    Tripathy, Priyadarshi

    2014-01-01

    Software Evolution and Maintenance: A Practitioner's Approach is an accessible textbook for students and professionals, which collates the advances in software development and provides the most current models and techniques in maintenance.Explains two maintenance standards: IEEE/EIA 1219 and ISO/IEC14764Discusses several commercial reverse and domain engineering toolkitsSlides for instructors are available onlineInformation is based on the IEEE SWEBOK (Software Engineering Body of Knowledge)

  16. Gender, politics, and regionalism: factors in the evolution of registered psychiatric nursing in Manitoba, 1920-1960.

    Science.gov (United States)

    Hicks, Beverly

    2011-01-01

    In Canada, psychiatric nursing care is provided by two kinds of nurses. East of Manitoba, it is provided by registered nurses who may or may not have specialized psychiatric nursing education. In the four western provinces, a distinct professional group, registered psychiatric nurses, also provide care. Saskatchewan was the first province to achieve distinct legislation, in 1948, followed by British Columbia in 1951, Alberta in 1955, and Manitoba in 1960. Several factors coalesced to sway Manitoba to adopt the distinct profession model. First, there was little interest by the general nursing body in mental hospital nursing. Second, the other three western provinces had formed a Canadian Council of Psychiatric Nursing that encouraged mental hospital attendants and nurses in Manitoba. Third, a group of male attendants took on leadership roles supported by the mental hospital superintendents. Finally, Manitoba was culturally and geographically more aligned with western than eastern Canada.

  17. Crystallization and preliminary crystal structure analysis of the ligand-binding domain of PqsR (MvfR), the Pseudomonas quinolone signal (PQS) responsive quorum-sensing transcription factor of Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Xu, Ningna; Yu, Shen; Moniot, Sébastien; Weyand, Michael; Blankenfeldt, Wulf

    2012-01-01

    The ligand-binding domain of the transcription factor PqsR from P. aeruginosa has been crystallized and initial phases have been obtained using SAD data from seleno-l-methionine-labelled crystals. The opportunistic bacterial pathogen Pseudomonas aeruginosa employs three transcriptional regulators, LasR, RhlR and PqsR, to control the transcription of a large subset of its genes in a cell-density-dependent process known as quorum sensing. Here, the recombinant production, crystallization and structure solution of the ligand-binding domain of PqsR (MvfR), the LysR-type transcription factor that responds to the Pseudomonas quinolone signal (PQS), a quinolone-based quorum-sensing signal that is unique to P. aeruginosa and possibly a small number of other bacteria, is reported. PqsR regulates the expression of many virulence genes and may therefore be an interesting drug target. The ligand-binding domain (residues 91–319) was produced as a fusion with SUMO, and hexagonal-shaped crystals of purified PqsR-91–319 were obtained using the vapour-diffusion method. Crystallization in the presence of a PQS precursor allowed data collection to 3.25 Å resolution on a synchrotron beamline, and initial phases have been obtained using single-wavelength anomalous diffraction data from seleno-l-methionine-labelled crystals, revealing the space group to be P6 5 22, with unit-cell parameters a = b = 116–120, c = 115–117 Å

  18. cDNA for the human β2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor

    International Nuclear Information System (INIS)

    Kobilka, B.K.; Dixon, R.A.F.; Frielle, T.

    1987-01-01

    The authors have isolated and sequenced a cDNA encoding the human β 2 -adrenergic receptor. The deduced amino acid sequence (413 residues) is that of a protein containing seven clusters of hydrophobic amino acids suggestive of membrane-spanning domains. While the protein is 87% identical overall with the previously cloned hamster β 2 -adrenergic receptor, the most highly conserved regions are the putative transmembrane helices (95% identical) and cytoplasmic loops (93% identical), suggesting that these regions of the molecule harbor important functional domains. Several of the transmembrane helices also share lesser degrees of identity with comparable regions of select members of the opsin family of visual pigments. They have localized the gene for the β 2 -adrenergic receptor to q31-q32 on chromosome 5. This is the same position recently determined for the gene encoding the receptor for platelet-derived growth factor and is adjacent to that for the FMS protooncogene, which encodes the receptor for the macrophage colony-stimulating factor

  19. Scaling properties of domain wall networks

    International Nuclear Information System (INIS)

    Leite, A. M. M.; Martins, C. J. A. P.

    2011-01-01

    We revisit the cosmological evolution of domain wall networks, taking advantage of recent improvements in computing power. We carry out high-resolution field theory simulations in two, three and four spatial dimensions to study the effects of dimensionality and damping on the evolution of the network. Our results are consistent with the expected scale-invariant evolution of the network, which suggests that previous hints of deviations from this behavior may have been due to the limited dynamical range of those simulations. We also use the results of very large (1024 3 ) simulations in three cosmological epochs to provide a calibration for the velocity-dependent one-scale model for domain walls: we numerically determine the two free model parameters to have the values c w =0.5±0.2 and k w =1.1±0.3.

  20. Processing of cell-surface signalling anti-sigma factors prior to signal recognition is aconserved autoproteolytic mechanism that produces two functional domains.

    NARCIS (Netherlands)

    Bastiaansen, K.C.J.T.; Otero-Asman, J.R.; Luirink, J.; Bitter, W.; Llamas, M.A.

    2015-01-01

    Cell-surface signalling (CSS) enables Gram-negative bacteria to transduce an environmental signal into a cytosolic response. This regulatory cascade involves an outer membrane receptor that transmits the signal to an anti-sigma factor in the cytoplasmic membrane, allowing the activation of an

  1. Solution structure of domain 1.1 of the sigma(A) factor from Bacillus subtilis is preformed for binding to the RNA polymerase core

    Czech Academy of Sciences Publication Activity Database

    Zachrdla, M.; Padrta, P.; Rabatinová, Alžběta; Šanderová, Hana; Barvík, I.; Krásný, Libor; Žídek, L.

    2017-01-01

    Roč. 292, č. 28 (2017), s. 11610-11617 ISSN 0021-9258 R&D Projects: GA ČR GA13-16842S; GA MŠk(CZ) LQ1601 Institutional support: RVO:61388971 Keywords : Bacillus * molecular modeling * nuclear magnetic resonance (NMR) Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.125, year: 2016

  2. In Silico Analysis for Transcription Factors With Zn(II2C6 Binuclear Cluster DNA-Binding Domains in Candida albicans

    Directory of Open Access Journals (Sweden)

    Sergi Maicas

    2005-01-01

    presence of the CysX2CysX6CysX5-16CysX2CysX6-8Cys motif and a putative nuclear localization signal. Using this approach, 70 putative Zn(II2C6 transcription factors have been found in the genome of C. albicans.

  3. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    International Nuclear Information System (INIS)

    Tsukamoto, Yuta; Kagiwada, Satoshi; Shimazu, Sayuri; Takegawa, Kaoru; Noguchi, Tetsuko; Miyamoto, Masaaki

    2015-01-01

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed

  4. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Yuta [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Kagiwada, Satoshi [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Shimazu, Sayuri [Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Takegawa, Kaoru [Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Noguchi, Tetsuko [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan)

    2015-03-20

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed.

  5. Factors of impact on the evolution of electricity markets from renewable energy sources: a comparison between Romania and Germany

    Directory of Open Access Journals (Sweden)

    Clodnițchi Roxana

    2015-06-01

    Full Text Available When talking about the future of Europe we also think about alternative energy sources. It is up to national governments to decide how to encourage investments in this field in order to contribute to the 20-20-20 EU-objective. Until the network delivery cost for electricity produced from renewable sources will be comparable to the cost for energy from traditional sources ("grid parity", the development of businesses and markets for electricity from renewable sources is going to be driven by support schemes. The state of the grids and the facility of grid-access constitute another two key factors influencing the development of this sector. Last but not least, the question of policy consistency is raised within the business community. Over the past years some support schemes have proved to be more effective than others, and grid conditions have also evolved. Policies supporting the development of renewables also changed at EU-level and at national levels. Based on statistics, scientific literature and the feedback of the business community, this study aims to analyse the development of renewable energy sectors in the European Union by comparing Germany’s and Romania’s experience. Also this study describes the current and expected future market situation in these countries relying on data gained from questionnaires and interviews with specialists in the renewable field.

  6. The Eucalyptus grandis R2R3-MYB transcription factor family: evidence for woody growth-related evolution and function.

    Science.gov (United States)

    Soler, Marçal; Camargo, Eduardo Leal Oliveira; Carocha, Victor; Cassan-Wang, Hua; San Clemente, Hélène; Savelli, Bruno; Hefer, Charles A; Paiva, Jorge A Pinto; Myburg, Alexander A; Grima-Pettenati, Jacqueline

    2015-06-01

    The R2R3-MYB family, one of the largest transcription factor families in higher plants, controls a wide variety of plant-specific processes including, notably, phenylpropanoid metabolism and secondary cell wall formation. We performed a genome-wide analysis of this superfamily in Eucalyptus, one of the most planted hardwood trees world-wide. A total of 141 predicted R2R3-MYB sequences identified in the Eucalyptus grandis genome sequence were subjected to comparative phylogenetic analyses with Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera. We analysed features such as gene structure, conserved motifs and genome location. Transcript abundance patterns were assessed by RNAseq and validated by high-throughput quantitative PCR. We found some R2R3-MYB subgroups with expanded membership in E. grandis, V. vinifera and P. trichocarpa, and others preferentially found in woody species, suggesting diversification of specific functions in woody plants. By contrast, subgroups containing key genes regulating lignin biosynthesis and secondary cell wall formation are more conserved across all of the species analysed. In Eucalyptus, R2R3-MYB tandem gene duplications seem to disproportionately affect woody-preferential and woody-expanded subgroups. Interestingly, some of the genes belonging to woody-preferential subgroups show higher expression in the cambial region, suggesting a putative role in the regulation of secondary growth. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  7. The role of anthropogenic and natural factors in shaping the geochemical evolution of groundwater in the Subei Lake basin, Ordos energy base, Northwestern China.

    Science.gov (United States)

    Liu, Fei; Song, Xianfang; Yang, Lihu; Han, Dongmei; Zhang, Yinghua; Ma, Ying; Bu, Hongmei

    2015-12-15

    Groundwater resources are increasingly exploited for industrial and agricultural purposes in many arid regions globally, it is urgent to gain the impact of the enhanced anthropogenic pressure on the groundwater chemistry. The aim of this study was to acquire a comprehensive understanding of the evolution of groundwater chemistry and to identify the impact of natural and anthropogenic factors on the groundwater chemistry in the Subei Lake basin, Northwestern China. A total of 153 groundwater samples were collected and major ions were measured during the three campaigns (August and December 2013, May 2014). At present, the major hydrochemical facies in unconfined groundwater are Ca-Mg-HCO3, Ca-Na-HCO3, Na-Ca-HCO3, Na-HCO3, Ca-Mg-SO4 and Na-SO4-Cl types, while the main hydrochemical facies in confined groundwater are Ca-Mg-HCO3, Ca-Na-HCO3, Na-Ca-HCO3, Ca-HCO3 and Na-HCO3 types. Relatively greater seasonal variation can be observed in the chemical constituents of confined groundwater than that of unconfined groundwater. Rock weathering predominates the evolution of groundwater chemistry in conjunction with the cation exchange, and the dissolution/precipitation of gypsum, halite, feldspar, calcite and dolomite are responsible for the chemical constituents of groundwater. Anthropogenic activities can be classified as: (1) groundwater overexploitation; (2) excessive application of fertilizers in agricultural areas. Due to intensive groundwater pumping, the accelerated groundwater mineralization resulted in the local changes in hydrochemical facies of unconfined groundwater, while the strong mixture, especially a large influx of downward leakage from the unconfined aquifer into the confined aquifer, played a vital role in the fundamental variation of hydrochemical facies in confined aquifer. The nitrate contamination is mainly controlled by the local hydrogeological settings coupled with the traditional flood irrigation. The deeper insight into geochemical evolution of

  8. Anesthesiologists’ and surgeons’ perceptions about routine pre-operative testing in low-risk patients: application of the Theoretical Domains Framework (TDF to identify factors that influence physicians’ decisions to order pre-operative tests

    Directory of Open Access Journals (Sweden)

    Patey Andrea M

    2012-06-01

    Full Text Available Abstract Background Routine pre-operative tests for anesthesia management are often ordered by both anesthesiologists and surgeons for healthy patients undergoing low-risk surgery. The Theoretical Domains Framework (TDF was developed to investigate determinants of behaviour and identify potential behaviour change interventions. In this study, the TDF is used to explore anaesthesiologists’ and surgeons’ perceptions of ordering routine tests for healthy patients undergoing low-risk surgery. Methods Sixteen clinicians (eleven anesthesiologists and five surgeons throughout Ontario were recruited. An interview guide based on the TDF was developed to identify beliefs about pre-operative testing practices. Content analysis of physicians’ statements into the relevant theoretical domains was performed. Specific beliefs were identified by grouping similar utterances of the interview participants. Relevant domains were identified by noting the frequencies of the beliefs reported, presence of conflicting beliefs, and perceived influence on the performance of the behaviour under investigation. Results Seven of the twelve domains were identified as likely relevant to changing clinicians’ behaviour about pre-operative test ordering for anesthesia management. Key beliefs were identified within these domains including: conflicting comments about who was responsible for the test-ordering (Social/professional role and identity; inability to cancel tests ordered by fellow physicians (Beliefs about capabilities and social influences; and the problem with tests being completed before the anesthesiologists see the patient (Beliefs about capabilities and Environmental context and resources. Often, tests were ordered by an anesthesiologist based on who may be the attending anesthesiologist on the day of surgery while surg