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Sample records for related jmjc domain

  1. Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins

    PubMed Central

    Hahn, Phillip; Böse, Jens; Edler, Stefanie; Lengeling, Andreas

    2008-01-01

    provide novel insights into the evolution of Jmjd6 and other related members of the superfamily of JmjC domain containing proteins. Finally, we discuss possibilities of the involvement of Jmjd6 and 1110005A03Rik in an antagonistic biochemical pathway. PMID:18564434

  2. Structure of the JmjC domain-containing protein NO66 complexed with ribosomal protein Rpl8

    SciTech Connect

    Wang, Chengliang; Zhang, Qiongdi; Hang, Tianrong; Tao, Yue; Ma, Xukai; Wu, Minhao; Zhang, Xuan Zang, Jianye

    2015-08-28

    The structure of the complex of NO66 and Rpl8 was solved in the native state and NO66 recognizes the consensus motif NHXH . Tetramerization is required for efficient substrate binding and catalysis by NO66. The JmjC domain-containing proteins belong to a large family of oxygenases possessing distinct substrate specificities which are involved in the regulation of different biological processes, such as gene transcription, RNA processing and translation. Nucleolar protein 66 (NO66) is a JmjC domain-containing protein which has been reported to be a histone demethylase and a ribosome protein 8 (Rpl8) hydroxylase. The present biochemical study confirmed the hydroxylase activity of NO66 and showed that oligomerization is required for NO66 to efficiently catalyze the hydroxylation of Rpl8. The structures of NO66{sup 176–C} complexed with Rpl8{sup 204–224} in a tetrameric form and of the mutant protein M2 in a dimeric form were solved. Based on the results of structural and biochemical analyses, the consensus sequence motif NHXH recognized by NO66 was confirmed. Several potential substrates of NO66 were found by a BLAST search according to the consensus sequence motif. When binding to substrate, the relative positions of each subunit in the NO66 tetramer shift. Oligomerization may facilitate the motion of each subunit in the NO66 tetramer and affect the catalytic activity.

  3. Genome-Wide Analysis of Soybean JmjC Domain-Containing Proteins Suggests Evolutionary Conservation Following Whole-Genome Duplication

    PubMed Central

    Han, Yapeng; Li, Xiangyong; Cheng, Lin; Liu, Yanchun; Wang, Hui; Ke, Danxia; Yuan, Hongyu; Zhang, Liangsheng; Wang, Lei

    2016-01-01

    Histone modifications, such as methylation and demethylation, play an important role in regulating chromatin structure and gene expression. The JmjC domain-containing proteins, an important family of histone lysine demethylases (KDMs), play a key role in maintaining homeostasis of histone methylation in vivo. In this study, we performed a comprehensive analysis of the jumonji C (JmjC) gene family in the soybean genome and identified 48 JmjC genes (GmJMJs) distributed unevenly across 18 chromosomes. Phylogenetic analysis showed that these JmjC domain-containing genes can be divided into eight groups. GmJMJs within the same phylogenetic group share similar exon/intron organization and domain composition. In addition, 16 duplicated gene pairs were formed by a Glycine-specific whole-genome duplication (WGD) event approximately 13 million years ago (Mya). By investigating the expression profiles of these gene pairs in various tissues, we showed that the expression pattern is conserved in the polyploidy-derived JmjC duplicates, demonstrating that the majority of GmJMJs were preferentially retained after the most recent WGD event and suggesting important roles for demethylase duplications in soybean evolution. These results shed light on the evolutionary history of this family in soybean and provide insights into the JmjCs which will be helpful to reveal their functions in controlling soybean development. PMID:27994610

  4. MoJMJ1, Encoding a Histone Demethylase Containing JmjC Domain, Is Required for Pathogenic Development of the Rice Blast Fungus, Magnaporthe oryzae.

    PubMed

    Huh, Aram; Dubey, Akanksha; Kim, Seongbeom; Jeon, Junhyun; Lee, Yong-Hwan

    2017-04-01

    Histone methylation plays important roles in regulating chromatin dynamics and transcription in eukaryotes. Implication of histone modifications in fungal pathogenesis is, however, beginning to emerge. Here, we report identification and functional analysis of a putative JmjC-domain-containing histone demethylase in Magnaporthe oryzae. Through bioinformatics analysis, we identified seven genes, which encode putative histone demethylases containing JmjC domain. Deletion of one gene, MoJMJ1, belonging to JARID group, resulted in defects in vegetative growth, asexual reproduction, appressorium formation as well as invasive growth in the fungus. Western blot analysis showed that global H3K4me3 level increased in the deletion mutant, compared to wild-type strain, indicating histone demethylase activity of MoJMJ1. Introduction of MoJMJ1 gene into ΔMojmj1 restored defects in pre-penetration developments including appressorium formation, indicating the importance of histone demethylation through MoJMJ1 during infection-specific morphogenesis. However, defects in penetration and invasive growth were not complemented. We discuss such incomplete complementation in detail here. Our work on MoJMJ1 provides insights into H3K4me3-mediated regulation of infection-specific development in the plant pathogenic fungus.

  5. MoJMJ1, Encoding a Histone Demethylase Containing JmjC Domain, Is Required for Pathogenic Development of the Rice Blast Fungus, Magnaporthe oryzae

    PubMed Central

    Huh, Aram; Dubey, Akanksha; Kim, Seongbeom; Jeon, Junhyun; Lee, Yong-Hwan

    2017-01-01

    Histone methylation plays important roles in regulating chromatin dynamics and transcription in eukaryotes. Implication of histone modifications in fungal pathogenesis is, however, beginning to emerge. Here, we report identification and functional analysis of a putative JmjC-domain-containing histone demethylase in Magnaporthe oryzae. Through bioinformatics analysis, we identified seven genes, which encode putative histone demethylases containing JmjC domain. Deletion of one gene, MoJMJ1, belonging to JARID group, resulted in defects in vegetative growth, asexual reproduction, appressorium formation as well as invasive growth in the fungus. Western blot analysis showed that global H3K4me3 level increased in the deletion mutant, compared to wild-type strain, indicating histone demethylase activity of MoJMJ1. Introduction of MoJMJ1 gene into ΔMojmj1 restored defects in pre-penetration developments including appressorium formation, indicating the importance of histone demethylation through MoJMJ1 during infection-specific morphogenesis. However, defects in penetration and invasive growth were not complemented. We discuss such incomplete complementation in detail here. Our work on MoJMJ1 provides insights into H3K4me3-mediated regulation of infection-specific development in the plant pathogenic fungus. PMID:28381966

  6. Knockdown of a JmjC domain-containing gene JMJ524 confers altered gibberellin responses by transcriptional regulation of GRAS protein lacking the DELLA domain genes in tomato.

    PubMed

    Li, Jinhua; Yu, Chuying; Wu, Hua; Luo, Zhidan; Ouyang, Bo; Cui, Long; Zhang, Junhong; Ye, Zhibiao

    2015-03-01

    Plants integrate responses to independent hormonal and environmental signals to survive adversity. In particular, the phytohormone gibberellin (GA) regulates a variety of developmental processes and stress responses. In this study, the Jumonji-C (JmjC) domain-containing gene JMJ524 was characterized in tomato. JMJ524 responded to circadian rhythms and was upregulated by GA treatment. Knockdown of JMJ524 by RNAi caused a GA-insensitive dwarf phenotype with shrunken leaves and shortened internodes. However, in these transgenic plants, higher levels of endogenous GAs were detected. A genome-wide gene expression analysis by RNA-seq indicated that the expression levels of two DELLA-like genes, SlGLD1 ('GRAS protein Lacking the DELLA domain') and SlGLD2, were increased in JMJ524-RNAi transgenic plants. Nevertheless, only the overexpression of SlGLD1 in tomato resulted in a GA-insensitive dwarf phenotype, suggesting that SlGLD1 acts as a repressor of GA signalling. This study proposes that JMJ524 is required for stem elongation by altering GA responses, at least partially by regulating SlGLD1. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  7. Jmjd6, a JmjC Dioxygenase with Many Interaction Partners and Pleiotropic Functions

    PubMed Central

    Kwok, Janice; O’Shea, Marie; Hume, David A.; Lengeling, Andreas

    2017-01-01

    Lysyl hydroxylation and arginyl demethylation are post-translational events that are important for many cellular processes. The jumonji domain containing protein 6 (JMJD6) has been reported to catalyze both lysyl hydroxylation and arginyl demethylation on diverse protein substrates. It also interacts directly with RNA. This review summarizes knowledge of JMJD6 functions that have emerged in the last 15 years and considers how a single Jumonji C (JmjC) domain-containing enzyme can target so many different substrates. New links and synergies between the three main proposed functions of Jmjd6 in histone demethylation, promoter proximal pause release of polymerase II and RNA splicing are discussed. The physiological context of the described molecular functions is considered and recently described novel roles for JMJD6 in cancer and immune biology are reviewed. The increased knowledge of JMJD6 functions has wider implications for our general understanding of the JmjC protein family of which JMJD6 is a member. PMID:28360925

  8. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases

    PubMed Central

    Walport, Louise J.; Hopkinson, Richard J.; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J.

    2016-01-01

    While the oxygen-dependent reversal of lysine Nɛ-methylation is well established, the existence of bona fide Nω-methylarginine demethylases (RDMs) is controversial. Lysine demethylation, as catalysed by two families of lysine demethylases (the flavin-dependent KDM1 enzymes and the 2-oxoglutarate- and oxygen-dependent JmjC KDMs, respectively), proceeds via oxidation of the N-methyl group, resulting in the release of formaldehyde. Here we report detailed biochemical studies clearly demonstrating that, in purified form, a subset of JmjC KDMs can also act as RDMs, both on histone and non-histone fragments, resulting in formaldehyde release. RDM catalysis is studied using peptides of wild-type sequences known to be arginine-methylated and sequences in which the KDM's methylated target lysine is substituted for a methylated arginine. Notably, the preferred sequence requirements for KDM and RDM activity vary even with the same JmjC enzymes. The demonstration of RDM activity by isolated JmjC enzymes will stimulate efforts to detect biologically relevant RDM activity. PMID:27337104

  9. The Garrison Domain: Civil Military Relations in the Cyberspace Domain

    DTIC Science & Technology

    2015-04-01

    through the creation of the Advanced Research Projects Agency Network ( ARPANET ), and was not codified as a domain until the early part of the 21st...therefore viewed as less important . The powers of the legislative and judicial branches of government become weak in relation to the executive branch

  10. The Activity of JmjC Histone Lysine Demethylase KDM4A is Highly Sensitive to Oxygen Concentrations.

    PubMed

    Hancock, Rebecca L; Masson, Norma; Dunne, Kate; Flashman, Emily; Kawamura, Akane

    2017-04-21

    The JmjC histone lysine demethylases (KDMs) are epigenetic regulators involved in the removal of methyl groups from post-translationally modified lysyl residues within histone tails, modulating gene transcription. These enzymes require molecular oxygen for catalytic activity and, as 2-oxoglutarate (2OG)-dependent oxygenases, are related to the cellular oxygen sensing HIF hydroxylases PHD2 and FIH. Recent studies have indicated that the activity of some KDMs, including the pseudogene-encoded KDM4E, may be sensitive to changing oxygen concentrations. Here, we report detailed analysis of the effect of oxygen availability on the activity of the KDM4 subfamily member KDM4A, importantly demonstrating a high level of O2 sensitivity both with isolated protein and in cells. Kinetic analysis of the recombinant enzyme revealed a high KM(app)(O2) of 173 ± 23 μM, indicating that the activity of the enzyme is able to respond sensitively to a reduction in oxygen concentration. Furthermore, immunofluorescence experiments in U2OS cells conditionally overexpressing KDM4A showed that the cellular activity of KDM4A against its primary substrate, H3K9me3, displayed a graded response to depleting oxygen concentrations in line with the data obtained using isolated protein. These results suggest that KDM4A possesses the potential to act as an oxygen sensor in the context of chromatin modifications, with possible implications for epigenetic regulation in hypoxic disease states. Importantly, this correlation between the oxygen sensitivity of the catalytic activity of KDM4A in biochemical and cellular assays demonstrates the utility of biochemical studies in understanding the factors contributing to the diverse biological functions and varied activity of the 2OG oxygenases.

  11. On thick domain walls in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    Planar scalar field configurations in general relativity differ considerably from those in flat space. It is shown that static domain walls of finite thickness in curved space-time do not possess a reflection symmetry. At infinity, the space-time tends to the Taub vacuum on one side of the wall and to the Minkowski vacuum (Rindler space-time) on the other. Massive test particles are always accelerated towards the Minkowski side, i.e., domain walls are attractive on the Taub side, but repulsive on the Minkowski side (Taub-vacuum cleaner). It is also proved that the pressure in all directions is always negative. Finally, a brief comment is made concerning the possibility of infinite, i.e., bigger than horizon size, domain walls in our universe. All of the results are independent of the form of the potential V(phi) greater than or equal to 0 of the scalar field phi.

  12. Relating hippocampus to relational memory processing across domains and delays.

    PubMed

    Monti, Jim M; Cooke, Gillian E; Watson, Patrick D; Voss, Michelle W; Kramer, Arthur F; Cohen, Neal J

    2015-02-01

    The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study-test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains.

  13. Relating Hippocampus to Relational Memory Processing across Domains and Delays

    PubMed Central

    Monti, Jim M.; Cooke, Gillian E.; Watson, Patrick D.; Voss, Michelle W.; Kramer, Arthur F.; Cohen, Neal J.

    2015-01-01

    The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study–test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains. PMID:25203273

  14. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    ERIC Educational Resources Information Center

    Ruiz, Francisco J.; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among…

  15. Between- and Within-Domain Relations of Students' Academic Emotions

    ERIC Educational Resources Information Center

    Goetz, Thomas; Frenzel, Anne C.; Pekrun, Reinhard; Hall, Nathan C.; Ludtke, Oliver

    2007-01-01

    The authors investigated between- and within-domain relations of academic emotions, including students' enjoyment, pride, anxiety, anger, and boredom experienced in mathematics, physics, German, and English classes (N = 542; Grades 8 and 11). Corroborating assumptions of domain specificity, the between-domains relations of these emotions were weak…

  16. Between-domain relations of students' academic emotions and their judgments of school domain similarity

    PubMed Central

    Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

    2014-01-01

    With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

  17. The Definition, Dimensions, and Domain of Public Relations.

    ERIC Educational Resources Information Center

    Hutton, James G.

    1999-01-01

    Discusses how the field of public relations has left itself vulnerable to other fields that are making inroads into public relations' traditional domain, and to critics who are filling in their own definitions of public relations. Proposes a definition and a three-dimensional framework to compare competing philosophies of public relations and to…

  18. Domain fusion analysis by applying relational algebra to protein sequence and domain databases

    PubMed Central

    Truong, Kevin; Ikura, Mitsuhiko

    2003-01-01

    Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

  19. Domain fusion analysis by applying relational algebra to protein sequence and domain databases.

    PubMed

    Truong, Kevin; Ikura, Mitsuhiko

    2003-05-06

    Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.

  20. de Gennes Narrowing Describes the Relative Motion of Protein Domains

    NASA Astrophysics Data System (ADS)

    Hong, Liang; Smolin, Nikolai; Smith, Jeremy C.

    2014-04-01

    The relative motion of structural domains is essential for the biological function of many proteins. Here, by analyzing neutron scattering data and performing molecular dynamics simulations, we find that interdomain motion in several proteins obeys the principle of de Gennes narrowing, in which the wave vector dependence of the interdomain diffusion coefficient is inversely proportional to the interdomain structure factor. Thus, the rate of interdomain motion is inversely proportional to the probability distribution of the spatial configurations of domains.

  1. Approximation method to compute domain related integrals in structural studies

    NASA Astrophysics Data System (ADS)

    Oanta, E.; Panait, C.; Raicu, A.; Barhalescu, M.; Axinte, T.

    2015-11-01

    Various engineering calculi use integral calculus in theoretical models, i.e. analytical and numerical models. For usual problems, integrals have mathematical exact solutions. If the domain of integration is complicated, there may be used several methods to calculate the integral. The first idea is to divide the domain in smaller sub-domains for which there are direct calculus relations, i.e. in strength of materials the bending moment may be computed in some discrete points using the graphical integration of the shear force diagram, which usually has a simple shape. Another example is in mathematics, where the surface of a subgraph may be approximated by a set of rectangles or trapezoids used to calculate the definite integral. The goal of the work is to introduce our studies about the calculus of the integrals in the transverse section domains, computer aided solutions and a generalizing method. The aim of our research is to create general computer based methods to execute the calculi in structural studies. Thus, we define a Boolean algebra which operates with ‘simple’ shape domains. This algebraic standpoint uses addition and subtraction, conditioned by the sign of every ‘simple’ shape (-1 for the shapes to be subtracted). By ‘simple’ shape or ‘basic’ shape we define either shapes for which there are direct calculus relations, or domains for which their frontiers are approximated by known functions and the according calculus is carried out using an algorithm. The ‘basic’ shapes are linked to the calculus of the most significant stresses in the section, refined aspect which needs special attention. Starting from this idea, in the libraries of ‘basic’ shapes, there were included rectangles, ellipses and domains whose frontiers are approximated by spline functions. The domain triangularization methods suggested that another ‘basic’ shape to be considered is the triangle. The subsequent phase was to deduce the exact relations for the

  2. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    PubMed Central

    Ruiz, Francisco J; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning. PMID:21547072

  3. Cross-domain analogies as relating derived relations among two separate relational networks.

    PubMed

    Ruiz, Francisco J; Luciano, Carmen

    2011-05-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning.

  4. Some proposed relations among the domains of behavior analysis

    PubMed Central

    Moore, J.; Cooper, John O.

    2003-01-01

    The present article examines the nature of and relations among the domains of behavior analysis. It first proposes a set of annotated, descriptive criteria to aid in distinguishing the experimental analysis of behavior, applied behavior analysis, and service delivery. It then argues that the experimental analysis of behavior lies at one end of a continuum of behavior-analytic activity, with applied behavior analysis in the middle, service delivery at the other end, and the theoretical-philosophical-conceptual position known as “radical behaviorism” informing the three domains on the continuum. Finally, it argues that clarifying the distinctions among the domains of behavior analysis will help the behavior-analytic community to focus its efforts in training programs and overall support of behavior analysis. PMID:22478395

  5. Kernel-Based Learning for Domain-Specific Relation Extraction

    NASA Astrophysics Data System (ADS)

    Basili, Roberto; Giannone, Cristina; Del Vescovo, Chiara; Moschitti, Alessandro; Naggar, Paolo

    In a specific process of business intelligence, i.e. investigation on organized crime, empirical language processing technologies can play a crucial role. The analysis of transcriptions on investigative activities, such as police interrogatories, for the recognition and storage of complex relations among people and locations is a very difficult and time consuming task, ultimately based on pools of experts. We discuss here an inductive relation extraction platform that opens the way to much cheaper and consistent workflows. The presented empirical investigation shows that accurate results, comparable to the expert teams, can be achieved, and parametrization allows to fine tune the system behavior for fitting domain-specific requirements.

  6. A Time Domain Waveform for Testing General Relativity

    NASA Astrophysics Data System (ADS)

    Huwyler, Cédric; Porter, Edward K.; Jetzer, Philippe

    2015-05-01

    Gravitational-wave parameter estimation is only as good as the theory the waveform generation models are based upon. It is therefore crucial to test General Relativity (GR) once data becomes available. Many previous works, such as studies connected with the ppE framework by Yunes and Pretorius, rely on the stationary phase approximation (SPA) to model deviations from GR in the frequency domain. As Fast Fourier Transform algorithms have become considerably faster and in order to circumvent possible problems with the SPA, we test GR with corrected time domain waveforms instead of SPA waveforms. Since a considerable amount of work has been done already in the field using SPA waveforms, we establish a connection between leading-order-corrected waveforms in time and frequency domain, concentrating on phase-only corrected terms. In a Markov Chain Monte Carlo study, whose results are preliminary and will only be available later, we will assess the ability of the eLISA detector to measure deviations from GR for signals coming from supermassive black hole inspirals using these corrected waveforms.

  7. Domain Importance and Involvement: Relations between Domain Self-Concepts and General Self-Esteem in Preadolescence.

    ERIC Educational Resources Information Center

    Forte, Ellen E.; Vispoel, Walter P.

    This study examined the role that domain importance plays in mediating the relations between domain-specific (such as verbal ability, physical appearance, opposite sex relations, and honesty) and general self-perceptions. Focusing on two previous studies by Hoge and McCarthy (1984) and Marsh (1986), the current study was designed to address the…

  8. Delineating relative homogeneous G+C domains in DNA sequences.

    PubMed

    Li, W

    2001-10-03

    The concept of homogeneity of G+C content is always relative and subjective. This point is emphasized and quantified in this paper using a simple example of one sequence segmented into two subsequences. Whether the sequence is homogeneous or not can be answered by whether the two-subsequence model describes the DNA sequence better than the one-sequence model. There are at least three equivalent ways of looking at the 1-to-2 segmentation: Jensen-Shannon divergence measure, log likelihood ratio test, and model selection using Bayesian information criterion. Once a criterion is chosen, a DNA sequence can be recursively segmented into multiple domains. We use one subjective criterion called segmentation strength based on the Bayesian information criterion. Whether or not a sequence is homogeneous and how many domains it has depend on this criterion. We compare six different genome sequences (yeast S. cerevisiae chromosome III and IV, bacterium M. pneumoniae, human major histocompatibility complex sequence, longest contigs in human chromosome 21 and 22) by recursive segmentations at different strength criteria. Results by recursive segmentation confirm that yeast chromosome IV is more homogeneous than yeast chromosome III, human chromosome 21 is more homogeneous than human chromosome 22, and bacterial genomes may not be homogeneous due to short segments with distinct base compositions. The recursive segmentation also provides a quantitative criterion for identifying isochores in human sequences. Some features of our recursive segmentation, such as the possibility of delineating domain borders accurately, are superior to those of the moving-window approach commonly used in such analyses.

  9. A relational metric, its application to domain analysis, and an example analysis and model of a remote sensing domain

    NASA Technical Reports Server (NTRS)

    Mcgreevy, Michael W.

    1995-01-01

    An objective and quantitative method has been developed for deriving models of complex and specialized spheres of activity (domains) from domain-generated verbal data. The method was developed for analysis of interview transcripts, incident reports, and other text documents whose original source is people who are knowledgeable about, and participate in, the domain in question. To test the method, it is applied here to a report describing a remote sensing project within the scope of the Earth Observing System (EOS). The method has the potential to improve the designs of domain-related computer systems and software by quickly providing developers with explicit and objective models of the domain in a form which is useful for design. Results of the analysis include a network model of the domain, and an object-oriented relational analysis report which describes the nodes and relationships in the network model. Other products include a database of relationships in the domain, and an interactive concordance. The analysis method utilizes a newly developed relational metric, a proximity-weighted frequency of co-occurrence. The metric is applied to relations between the most frequently occurring terms (words or multiword entities) in the domain text, and the terms found within the contexts of these terms. Contextual scope is selectable. Because of the discriminating power of the metric, data reduction from the association matrix to the network is simple. In addition to their value for design. the models produced by the method are also useful for understanding the domains themselves. They can, for example, be interpreted as models of presence in the domain.

  10. Examining the Relation between Domain-Related Communication and Collaborative Inquiry Learning

    ERIC Educational Resources Information Center

    Anjewierden, Anjo; Gijlers, Hannie; Kolloffel, Bas; Saab, Nadira; de Hoog, Robert

    2011-01-01

    Research suggests that providing others with elaborated explanations is more beneficial for learning than receiving explanations (e.g., Webb, 1989). Applied to chat communication in a collaborative inquiry learning environment, we would expect that in a dyad learners with more domain-related contributions than their partners would learn more. In…

  11. Examining the Relation between Domain-Related Communication and Collaborative Inquiry Learning

    ERIC Educational Resources Information Center

    Anjewierden, Anjo; Gijlers, Hannie; Kolloffel, Bas; Saab, Nadira; de Hoog, Robert

    2011-01-01

    Research suggests that providing others with elaborated explanations is more beneficial for learning than receiving explanations (e.g., Webb, 1989). Applied to chat communication in a collaborative inquiry learning environment, we would expect that in a dyad learners with more domain-related contributions than their partners would learn more. In…

  12. The Jumonji C domain-containing protein JMJ30 regulates period length in the Arabidopsis circadian clock.

    PubMed

    Lu, Sheen X; Knowles, Stephen M; Webb, Candace J; Celaya, R Brandon; Cha, Chuah; Siu, Jonathan P; Tobin, Elaine M

    2011-02-01

    Histone methylation plays an essential role in regulating chromatin structure and gene expression. Jumonji C (JmjC) domain-containing proteins are generally known as histone demethylases. Circadian clocks regulate a large number of biological processes, and recent studies suggest that chromatin remodeling has evolved as an important mechanism for regulating both plant and mammalian circadian systems. Here, we analyzed a subgroup of JmjC domain-containing proteins and identified Arabidopsis (Arabidopsis thaliana) JMJ30 as a novel clock component involved in controlling the circadian period. Analysis of loss- and gain-of-function mutants of JMJ30 indicates that this evening-expressed gene is a genetic regulator of period length in the Arabidopsis circadian clock. Furthermore, two key components of the central oscillator of plants, transcription factors CIRCADIAN CLOCK ASSOCIATED1 and LATE ELONGATED HYPOCOTYL, bind directly to the JMJ30 promoter to repress its expression, suggesting that JMJ30 regulates the pace of the circadian clock in close association with the central oscillator. JMJ30 represents, to our knowledge, the first JmjC domain-containing protein involved in circadian function, and we envision that this provides a possible molecular connection between chromatin remodeling and the circadian clock.

  13. Protein Domain Analysis of Genomic Sequence Data Reveals Regulation of LRR Related Domains in Plant Transpiration in Ficus

    PubMed Central

    Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H.; Du, Fang K.

    2014-01-01

    Predicting protein domains is essential for understanding a protein’s function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion. PMID:25269070

  14. A Structure for the Affective Domain in Relation to Science Education.

    ERIC Educational Resources Information Center

    Klopfer, Leopold E.

    A classification scheme for the affective domain in relation to science education is presented in this article to clarify student's affective behaviors and their representative phenomena. Discussion is made in connection with the content-objectives grid in the cognitive domain. An analogous grid for the affective domain is delineated by a…

  15. Accelerating Imitation Learning in Relational Domains via Transfer by Initialization

    DTIC Science & Technology

    2013-08-28

    Warcraft , regulation of traffic lights, logistics, and a variety of planning domains. A supervised learning method for imitation learning was recently...strategy (RTS) game engine written in C based off the Warcraft series of games. Like all RTS games, it allows multiple agents to be controlled

  16. Extending Black Domain Name List by Using Co-occurrence Relation between DNS Queries

    NASA Astrophysics Data System (ADS)

    Sato, Kazumichi; Ishibashi, Keisuke; Toyono, Tsuyoshi; Hasegawa, Haruhisa; Yoshino, Hideaki

    Botnet threats, such as server attacks or sending of spam e-mail, have been increasing. Therefore, infected hosts must be found and their malicious activities mitigated. An effective method for finding infected hosts is to use a blacklist of domain names. When a bot receives attack commands from a Command and Control (C&C) server, it attempts to resolve domain names of C&C servers. We can thus detect infected hosts by finding these that send queries on black domain names. However, we cannot find all infected hosts because of the inaccuracy of blacklists. There are many black domain names, and the lifetimes of these domain names are short; therefore a blacklist cannot cover all black domain names. We thus present a method for finding unknown black domain names by using DNS query data and an existing blacklist of known black domain names. To achieve this, we focus on DNS queries sent by infected hosts. One bot sends several queries on black domain names due to C&C server redundancy. We use the co-occurrence relation of two different domain names to find unknown black domain names and extend the blacklist. If a domain name frequently co-occurs with a known black name, we assume that the domain name is also black. A cross-validation evaluation of the proposed method showed that 91.2% of domain names that are on the validation list scored in the top 1%.

  17. Conserved gene regulatory function of the carboxy-terminal domain of dictyostelid C-module-binding factor.

    PubMed

    Schmith, Anika; Groth, Marco; Ratka, Josephine; Gatz, Sara; Spaller, Thomas; Siol, Oliver; Glöckner, Gernot; Winckler, Thomas

    2013-03-01

    C-module-binding factor A (CbfA) is a jumonji-type transcription regulator that is important for maintaining the expression and mobility of the retrotransposable element TRE5-A in the social amoeba Dictyostelium discoideum. CbfA-deficient cells have lost TRE5-A retrotransposition, are impaired in the ability to feed on bacteria, and do not enter multicellular development because of a block in cell aggregation. In this study, we performed Illumina RNA-seq of growing CbfA mutant cells to obtain a list of CbfA-regulated genes. We demonstrate that the carboxy-terminal domain of CbfA alone is sufficient to mediate most CbfA-dependent gene expression. The carboxy-terminal domain of CbfA from the distantly related social amoeba Polysphondylium pallidum restored the expression of CbfA-dependent genes in the D. discoideum CbfA mutant, indicating a deep conservation in the gene regulatory function of this domain in the dictyostelid clade. The CbfA-like protein CbfB displays ∼25% sequence identity with CbfA in the amino-terminal region, which contains a JmjC domain and two zinc finger regions and is thought to mediate chromatin-remodeling activity. In contrast to CbfA proteins, where the carboxy-terminal domains are strictly conserved in all dictyostelids, CbfB proteins have completely unrelated carboxy-terminal domains. Outside the dictyostelid clade, CbfA-like proteins with the CbfA-archetypical JmjC/zinc finger arrangement and individual carboxy-terminal domains are prominent in filamentous fungi but are not found in yeasts, plants, and metazoans. Our data suggest that two functional regions of the CbfA-like proteins evolved at different rates to allow the occurrence of species-specific adaptation processes during genome evolution.

  18. Conserved Gene Regulatory Function of the Carboxy-Terminal Domain of Dictyostelid C-Module-Binding Factor

    PubMed Central

    Schmith, Anika; Groth, Marco; Ratka, Josephine; Gatz, Sara; Spaller, Thomas; Siol, Oliver; Glöckner, Gernot

    2013-01-01

    C-module-binding factor A (CbfA) is a jumonji-type transcription regulator that is important for maintaining the expression and mobility of the retrotransposable element TRE5-A in the social amoeba Dictyostelium discoideum. CbfA-deficient cells have lost TRE5-A retrotransposition, are impaired in the ability to feed on bacteria, and do not enter multicellular development because of a block in cell aggregation. In this study, we performed Illumina RNA-seq of growing CbfA mutant cells to obtain a list of CbfA-regulated genes. We demonstrate that the carboxy-terminal domain of CbfA alone is sufficient to mediate most CbfA-dependent gene expression. The carboxy-terminal domain of CbfA from the distantly related social amoeba Polysphondylium pallidum restored the expression of CbfA-dependent genes in the D. discoideum CbfA mutant, indicating a deep conservation in the gene regulatory function of this domain in the dictyostelid clade. The CbfA-like protein CbfB displays ∼25% sequence identity with CbfA in the amino-terminal region, which contains a JmjC domain and two zinc finger regions and is thought to mediate chromatin-remodeling activity. In contrast to CbfA proteins, where the carboxy-terminal domains are strictly conserved in all dictyostelids, CbfB proteins have completely unrelated carboxy-terminal domains. Outside the dictyostelid clade, CbfA-like proteins with the CbfA-archetypical JmjC/zinc finger arrangement and individual carboxy-terminal domains are prominent in filamentous fungi but are not found in yeasts, plants, and metazoans. Our data suggest that two functional regions of the CbfA-like proteins evolved at different rates to allow the occurrence of species-specific adaptation processes during genome evolution. PMID:23355006

  19. Relation of neurocardiovascular instability to cognitive, emotional and functional domains.

    PubMed

    Bendini, C; Angelini, A; Salsi, F; Finelli, M E; Martini, E; Neviani, F; Mussi, C; Neri, M

    2007-01-01

    There is bulk of evidence suggesting that blood pressure dysregulation, as low blood pressure (LBP) or hypotension, orthostatic hypotension (OH) and high blood pressure (HPB) or hypertension are associated with alterations in cognitive and emotional domains. Some studies suggest that LBP, neurocardiovascular instability, like the OH, and atherosclerosis resulting from long standing HBP, reduces cerebral blood flow, increasing the risk of cognitive impairment, morbidity and mortality. This study aims to evaluate whether patients with cognitive impairment and cardiovascular disease would show any differences in some anamnestic indicators and/or psychometric measures of cognitive performance and affective symptoms. We recruited 36 patients over 65 years of age admitted to both psycho- and cardio-geriatric ambulatories of our hospital during the last year. The population (mean age of 80.5 years, 72.2% females, 27.8% males) was divided in 2 groups, with OH (25%), and without OH (75%). The first group was subdivided in subgroups: patients with HBP, normal BP and LBP, respectively. Cognitive and depressive domains were assessed with the mini mental state examination (MMSE) and the Italian "scala di valutazione del benessere emotivo nell' anziano" (SVEBA). Information about the present status, comorbidities (cumulative illness rating scale=CIRS), functional ability (activities of daily living=ADL, instrumental ADL=IADL) and drugs were collected during clinical examination. BP was measured 4 times, at the beginning of examination, then with the patient in clinostatic and orthostatic position (1st and 3rd minute). Data were analyzed by MANCOVA, considering age and gender as covariates, MMSE, SVEBA, CIRS, ADL, IADL and drugs as dependent variables, and presence/absence of OH as factor. Covariates were not significant sources of variance, as well as overall factor. Due to the heuristic aim of the study, we considered of interest the results of subsequent ANOVAs showing

  20. Relational Reasoning in STEM Domains: A Foundation for Academic Development

    ERIC Educational Resources Information Center

    Alexander, Patricia A.

    2017-01-01

    What is relational reasoning? Why is it critical to consider the role of relational reasoning in students learning and development in science, technology, engineering, and mathematics (STEM)? Moreover, how do the particular contributions populating this special issue address the pressing societal needs and offer guidance to researchers and…

  1. Relational Reasoning in STEM Domains: A Foundation for Academic Development

    ERIC Educational Resources Information Center

    Alexander, Patricia A.

    2017-01-01

    What is relational reasoning? Why is it critical to consider the role of relational reasoning in students learning and development in science, technology, engineering, and mathematics (STEM)? Moreover, how do the particular contributions populating this special issue address the pressing societal needs and offer guidance to researchers and…

  2. Domain-specific reports of visual imagery vividness are not related to perceptual expertise.

    PubMed

    Sunday, Mackenzie; McGugin, Rankin W; Gauthier, Isabel

    2016-04-08

    Just as people vary in their perceptual expertise with a given domain, they also vary in their abilities to imagine objects. Visual imagery and perception share common mechanisms. However, it is unclear whether domain-specific expertise is relevant to visual imagery. Although the vividness of visual imagery is typically measured as a domain-general construct, a component of this vividness may be domain-specific. For example, individuals who have gained perceptual expertise with a specific domain might experience clearer mental images within this domain. Here we investigated whether perceptual expertise for cars relates to visual imagery vividness in the same domain, by assessing the correlations between a widely used domain-general measure of visual imagery vividness (the Vividness of Visual Imagery Questionnaire; Marks in British Journal of Psychology, 64, 17-24, 1973), a new measure of visual imagery vividness specific to cars, and behavioral tests of car expertise. We found that domain-specific imagery relates most strongly to general imagery vividness and less strongly to self-reported expertise, while it does not relate to perceptual or semantic expertise.

  3. International note: between-domain relations of Chinese high school students' academic achievements.

    PubMed

    Yangyang, Liu

    2012-08-01

    The present study examined the between-domain relations of Chinese high school students' academic achievements. In a sample of 1870 Chinese 10th grade students, the results indicated that Chinese high school students' academic achievements were correlated across nine subjects. In line with the previous Western findings, the findings suggested that academic achievement was largely domain-general in nature.

  4. Alcohol-Induced Behaviors Require a Subset of Drosophila JmjC-Domain Histone Demethylases in the Nervous System.

    PubMed

    Pinzón, Jorge H; Reed, Addison R; Shalaby, Nevine A; Buszczak, Michael; Rodan, Aylin R; Rothenfluh, Adrian

    2017-09-21

    Long-lasting transcriptional changes underlie a number of adaptations that contribute to alcohol use disorders (AUD). Chromatin remodeling, including histone methylation, can confer distinct, long-lasting transcriptional changes, and histone methylases are known to play a role in the development of addiction. Conversely, little is known about the relevance of Jumonji (JmjC) domain-containing demethylases in AUDs. We systematically surveyed the alcohol-induced phenotypes of null mutations in all 13 Drosophila JmjC genes. We used a collection of JmjC mutants, the majority of which we generated by homologous recombination, and assayed them in the Booze-o-mat to determine their naïve sensitivity to sedation and their tolerance (change in sensitivity upon repeat exposure). Mutants with reproducible phenotypes had their phenotypes rescued with tagged genomic transgenes, and/or phenocopied by nervous system-specific knock down using RNA interference (RNAi). Four of the 13 JmjC genes (KDM3, lid, NO66 and HSPBAP1) showed reproducible ethanol-sensitivity phenotypes. Some of the phenotypes were observed across doses, e.g. the enhanced ethanol-sensitivity of KDM3(KO) and NO66(KO) , but others were dose-dependent, such as the reduced ethanol sensitivity of HSPBAP1(KO) , or the enhanced ethanol tolerance of NO66(KO) . These phenotypes were rescued by their respective genomic transgenes in KDM3(KO) and NO66(KO) mutants. While we were unable to rescue lid(k) mutants, knock down of lid in the nervous system recapitulated the lid(k) phenotype, as was observed for KDM3(KO) and NO66(KO) RNAi-mediated knock down. Our study reveals that the Drosophila JmjC-domain histone demethylases Lid, KDM3, NO66, and HSPBAP1 are required for normal ethanol-induced sedation and tolerance. Three of three tested of those four JmjC genes are required in the nervous system for normal alcohol-induced behavioral responses, suggesting that this gene family is an intriguing avenue for future research. This

  5. Defining Novel Health-Related Quality of Life Domains in Lung Transplantation: A Qualitative Analysis

    PubMed Central

    Singer, Jonathan Paul; Chen, Joan; Katz, Patricia P; Blanc, Paul David; Kagawa-Singer, Marjorie; Stewart, Anita L.

    2014-01-01

    Purpose Health-related quality of life (HRQL) domains vary across disease conditions and are determined by standards, values, and priorities internal to patients. Although the clinical goals of lung transplantation are to improve patient survival and HRQL, what defines HRQL in lung transplantation is unknown. Employing a qualitative approach, we aimed to identify HRQL domains important in lung transplantation. Methods We conducted semi-structured interviews in purposefully sampled lung transplant recipients (n=8) representing a spectrum of ages, gender, indications for transplantation, and time since transplantation as well as health-care practitioners representing a spectrum of practitioner types (n=9). Grounded Theory was used to identify HRQL domains important in lung transplantation, building on but going beyond domains already defined in the SF-36, the most commonly used instrument in this population. Results In addition to confirming the relevance of the eight SF-36 domains, we identified 11 novel HRQL domains. Palliation of respiratory symptoms was identified as important. After transplant surgery, new HRQL domains emerged including: distressing symptoms spanning multiple organ systems; worry about infection and acute rejection; treatment burden; and depression. Further, patients identified challenges to intimacy, changes in social relationships, and problems with cognitive functioning. Saliently, worry about limited life expectancy was pervasive and impaired life planning. Conclusions We found that HRQL in lung transplantation is defined by both generic and transplant-specific domains. Delineating and refining these domains can inform efforts to improve clinical outcomes and HRQL measurement in lung transplantation. PMID:25471287

  6. ArchSchema: a tool for interactive graphing of related Pfam domain architectures.

    PubMed

    Tamuri, Asif U; Laskowski, Roman A

    2010-05-01

    ArchSchema is a Java Web Start application that generates a dynamic 2D network of related Pfam domain architectures. Each node corresponds to a different architecture (shown as a sequence of coloured boxes) and indicates whether any 3D structural information is available in the PDB. Satellite nodes can show either the UniProt codes or the PDB codes of proteins having the given architecture. Search options allow search by UniProt code or Pfam domain identifier, and results can be filtered by domain, organism, or by selecting only proteins in the PDB. ArchSchema can be freely accessed at http://www.ebi.ac.uk/Tools/archschema.

  7. VASCULAR-RELATED NAC-DOMAIN6 and VASCULAR-RELATED NAC-DOMAIN7 effectively induce transdifferentiation into xylem vessel elements under control of an induction system.

    PubMed

    Yamaguchi, Masatoshi; Goué, Nadia; Igarashi, Hisako; Ohtani, Misato; Nakano, Yoshimi; Mortimer, Jennifer C; Nishikubo, Nobuyuki; Kubo, Minoru; Katayama, Yoshihiro; Kakegawa, Koichi; Dupree, Paul; Demura, Taku

    2010-07-01

    We previously showed that the VASCULAR-RELATED NAC-DOMAIN6 (VND6) and VND7 genes, which encode NAM/ATAF/CUC domain protein transcription factors, act as key regulators of xylem vessel differentiation. Here, we report a glucocorticoid-mediated posttranslational induction system of VND6 and VND7. In this system, VND6 or VND7 is expressed as a fused protein with the activation domain of the herpes virus VP16 protein and hormone-binding domain of the animal glucocorticoid receptor, and the protein's activity is induced by treatment with dexamethasone (DEX), a glucocorticoid derivative. Upon DEX treatment, transgenic Arabidopsis (Arabidopsis thaliana) plants carrying the chimeric gene exhibited transdifferentiation of various types of cells into xylem vessel elements, and the plants died. Many genes involved in xylem vessel differentiation, such as secondary wall biosynthesis and programmed cell death, were up-regulated in these plants after DEX treatment. Chemical analysis showed that xylan, a major hemicellulose component of the dicot secondary cell wall, was increased in the transgenic plants after DEX treatment. This induction system worked in poplar (Populus tremula x tremuloides) trees and in suspension cultures of cells from Arabidopsis and tobacco (Nicotiana tabacum); more than 90% of the tobacco BY-2 cells expressing VND7-VP16-GR transdifferentiated into xylem vessel elements after DEX treatment. These data demonstrate that the induction systems controlling VND6 and VND7 activities can be used as powerful tools for understanding xylem cell differentiation.

  8. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases*

    PubMed Central

    Horton, John R.; Engstrom, Amanda; Zoeller, Elizabeth L.; Liu, Xu; Shanks, John R.; Zhang, Xing; Johns, Margaret A.; Vertino, Paula M.; Fu, Haian; Cheng, Xiaodong

    2016-01-01

    The KDM5/JARID1 family of Fe(II)- and α-ketoglutarate-dependent demethylases remove methyl groups from tri- and dimethylated lysine 4 of histone H3. Accumulating evidence from primary tumors and model systems supports a role for KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) as oncogenic drivers. The KDM5 family is unique among the Jumonji domain-containing histone demethylases in that there is an atypical insertion of a DNA-binding ARID domain and a histone-binding PHD domain into the Jumonji domain, which separates the catalytic domain into two fragments (JmjN and JmjC). Here we demonstrate that internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. We present a crystal structure of the linked JmjN-JmjC domain from KDM5A, which reveals that the linked domain fully reconstitutes the cofactor (metal ion and α-ketoglutarate) binding characteristics of other structurally characterized Jumonji domain demethylases. Docking studies with GSK-J1, a selective inhibitor of the KDM6/KDM5 subfamilies, identify critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. Further, we found that GSK-J1 inhibited the demethylase activity of KDM5C with 8.5-fold increased potency compared with that of KDM5B at 1 mm α-ketoglutarate. In contrast, JIB-04 (a pan-inhibitor of the Jumonji demethylase superfamily) had the opposite effect and was ∼8-fold more potent against KDM5B than against KDM5C. Interestingly, the relative selectivity of JIB-04 toward KDM5B over KDM5C in vitro translates to a ∼10–50-fold greater growth-inhibitory activity against breast cancer cell lines. These data define the minimal requirements for enzymatic activity of the KDM5 family to be the linked JmjN-JmjC domain coupled with the immediate C-terminal helical zinc-binding domain and provide structural characterization of the linked JmjN-JmjC domain for the KDM5 family, which should prove useful in

  9. Structural genomics reveals EVE as a new ASCH/PUA-related domain

    PubMed Central

    Bertonati, Claudia; Punta, Marco; Fischer, Markus; Yachdav, Guy; Forouhar, Farhad; Zhou, Weihong; Kuzin, Alexander P.; Seetharaman, Jayaraman; Abashidze, Mariam; Ramelot, Theresa A.; Kennedy, Michael A.; Cort, John R.; Belachew, Adam; Hunt, John F.; Tong, Liang; Montelione, Gaetano T.; Rost, Burkhard

    2014-01-01

    Summary We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE. Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links. PMID:19191354

  10. Structural genomics reveals EVE as a new ASCH/PUA-related domain.

    PubMed

    Bertonati, Claudia; Punta, Marco; Fischer, Markus; Yachdav, Guy; Forouhar, Farhad; Zhou, Weihong; Kuzin, Alexander P; Seetharaman, Jayaraman; Abashidze, Mariam; Ramelot, Theresa A; Kennedy, Michael A; Cort, John R; Belachew, Adam; Hunt, John F; Tong, Liang; Montelione, Gaetano T; Rost, Burkhard

    2009-05-15

    We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE. Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links.

  11. Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution

    PubMed Central

    Van Damme, Els J. M.; Nakamura-Tsuruta, Sachiko; Smith, David F.; Ongenaert, Maté; Winter, Harry C.; Rougé, Pierre; Goldstein, Irwin J.; Mo, Hanqing; Kominami, Junko; Culerrier, Raphaël; Barre, Annick; Hirabayashi, Jun; Peumans, Willy J.

    2007-01-01

    A re-investigation of the occurrence and taxonomic distribution of proteins built up of protomers consisting of two tandem arrayed domains equivalent to the GNA [Galanthus nivalis (snowdrop) agglutinin] revealed that these are widespread among monotyledonous plants. Phylogenetic analysis of the available sequences indicated that these proteins do not represent a monophylogenetic group but most probably result from multiple independent domain duplication/in tandem insertion events. To corroborate the relationship between inter-domain sequence divergence and the widening of specificity range, a detailed comparative analysis was made of the sequences and specificity of a set of two-domain GNA-related lectins. Glycan microarray analyses, frontal affinity chromatography and surface plasmon resonance measurements demonstrated that the two-domain GNA-related lectins acquired a marked diversity in carbohydrate-binding specificity that strikingly contrasts the canonical exclusive specificity of their single domain counterparts towards mannose. Moreover, it appears that most two-domain GNA-related lectins interact with both high mannose and complex N-glycans and that this dual specificity relies on the simultaneous presence of at least two different independently acting binding sites. The combined phylogenetic, specificity and structural data strongly suggest that plants used domain duplication followed by divergent evolution as a mechanism to generate multispecific lectins from a single mannose-binding domain. Taking into account that the shift in specificity of some binding sites from high mannose to complex type N-glycans implies that the two-domain GNA-related lectins are primarily directed against typical animal glycans, it is tempting to speculate that plants developed two-domain GNA-related lectins for defence purposes. PMID:17288538

  12. A cross-cultural comparison of the coexistence and domain superiority of individuating and relating autonomy.

    PubMed

    Yeh, Kuang-Hui; Bedford, Olwen; Yang, Yung-Jui

    2009-06-01

    The consensus definition of autonomy in the psychological literature emphasizes self-governance through free volition, not separation or independence from others. Since the concept of self may differ cross-culturally, several researchers have tried to incorporate types of self into the notion of autonomy; however, only the dual model of autonomy has been able to do this while retaining an emphasis on volition. The dual model describes two distinct forms of autonomy-individuating and relating-each with superior function in a specific domain of individual functioning. Individuating autonomy represents a volitional capacity to act against social constraints and offers a route to achieve an independent self-identity by expressing individualistic attributes and distinctions. Relating autonomy represents a volitional capacity to act by emphasizing the harmony of self-in-relation-to-others, the quality of interpersonal relationships, and self-transcendence. These two forms of autonomy have been shown to coexist at the individual level in a Taiwanese sample. This study takes the next step, with a cross-cultural test of the coexistence and domain superiority hypotheses of individuating and relating autonomy. Participants included 306 college students from Taiwan and 183 college students from the United States. Structural equation modelling by multigroup analyses confirmed the cross-cultural equivalence of the two-factor individuating autonomy and relating autonomy measurement model. Across both samples the two forms of autonomy were shown to be mutually inclusive and not exclusive or independent. The domain-superior function of each form of autonomy was also confirmed cross-culturally; each form of autonomy has a dominant, but not necessarily exclusive, domain of functioning. Specifically, individuating autonomy was more associated with intrapersonal than interpersonal domain dependent variables, while relating autonomy was more associated with interpersonal than

  13. The neurofibromin recruitment factor Spred1 binds to the GAP related domain without affecting Ras inactivation

    PubMed Central

    Dunzendorfer-Matt, Theresia; Mercado, Ellen L.; Maly, Karl; McCormick, Frank; Scheffzek, Klaus

    2016-01-01

    Neurofibromatosis type 1 (NF1) and Legius syndrome are related diseases with partially overlapping symptoms caused by alterations of the tumor suppressor genes NF1 (encoding the protein neurofibromin) and SPRED1 (encoding sprouty-related, EVH1 domain-containing protein 1, Spred1), respectively. Both proteins are negative regulators of Ras/MAPK signaling with neurofibromin functioning as a Ras-specific GTPase activating protein (GAP) and Spred1 acting on hitherto undefined components of the pathway. Importantly, neurofibromin has been identified as a key protein in the development of cancer, as it is genetically altered in a large number of sporadic human malignancies unrelated to NF1. Spred1 has previously been demonstrated to interact with neurofibromin via its N-terminal Ena/VASP Homology 1 (EVH1) domain and to mediate membrane translocation of its target dependent on its C-terminal Sprouty domain. However, the region of neurofibromin required for the interaction with Spred1 has remained unclear. Here we show that the EVH1 domain of Spred1 binds to the noncatalytic (GAPex) portion of the GAP-related domain (GRD) of neurofibromin. Binding is compatible with simultaneous binding of Ras and does not interfere with GAP activity. Our study points to a potential targeting function of the GAPex subdomain of neurofibromin that is present in all known canonical RasGAPs. PMID:27313208

  14. Bidirectional Transfer between Metaphorical Related Domains in Implicit Learning of Form-Meaning Connections

    PubMed Central

    Yang, Zhiliang; Dienes, Zoltan

    2013-01-01

    People can implicitly learn a connection between linguistic forms and meanings, for example between specific determiners (e.g. this, that…) and the type of nouns to which they apply. Li et al (2013) recently found that transfer of form-meaning connections from a concrete domain (height) to an abstract domain (power) was achieved in a metaphor-consistent way without awareness, showing that unconscious knowledge can be abstract and flexibly deployed. The current study aims to determine whether people transfer knowledge of form-meaning connections not only from a concrete domain to an abstract one, but also vice versa, consistent with metaphor representation being bi-directional. With a similar paradigm as used by Li et al, participants learnt form- meaning connections of different domains (concrete vs. abstract) and then were tested on two kinds of generalizations (same and different domain generalization). As predicted, transfer of form-meaning connections occurred bidirectionally when structural knowledge was unconscious. Moreover, the present study also revealed that more transfer occurred between metaphorically related domains when judgment knowledge was conscious (intuition) rather than unconscious (guess). Conscious and unconscious judgment knowledge may have different functional properties. PMID:23844159

  15. How do individual differences in children's domain specific and domain general abilities relate to brain activity within the intraparietal sulcus during arithmetic? An fMRI study.

    PubMed

    Matejko, Anna A; Ansari, Daniel

    2017-08-01

    Previous research has demonstrated that children recruit the intraparietal sulcus (IPS) during arithmetic, which has largely been attributed to domain-specific processes such as quantity manipulations. However, the IPS has also been found to be important for domain-general abilities, such as visuo-spatial working memory (VSWM). Based on the current literature it is unclear whether individual differences in domain-specific skills, domain-general skills, or a combination of the two, are related to the recruitment of the IPS during arithmetic. This study examines how individual differences in both domain general and domain specific competencies relate to brain activity in the IPS during arithmetic, and whether the relationships are related to how brain activity is measured. In a sample of 44 school-aged children, we found that VSWM was only weakly related to a neural index of arithmetic complexity (neural problem size effect), whereas symbolic number processing skills (symbolic comparison and ordering) were related to overall arithmetic activity (both small and large problems). By simultaneously examining multiple domain-general and domain specific measures, we were also able to determine that symbolic skills were a stronger predictor of brain activity within the IPS than domain general skills such as VSWM and domain specific skills such as non-symbolic number processing. Together, these findings highlight that neural problem size effect may reflect different cognitive processes than brain activity across both small and large arithmetic problems, and that symbolic number processing skills are a critical predictor of variability in IPS activity during arithmetic. Hum Brain Mapp 38:3941-3956, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Uniqueness in shape identification of a time-varying domain and related parabolic equations on non-cylindrical domains

    NASA Astrophysics Data System (ADS)

    Kawakami, Hajime; Tsuchiya, Masaaki

    2010-12-01

    The paper deals with an inverse problem determining the shape of a time-varying Lipschitz domain by boundary measurements of the temperature; such a domain is treated as a non-cylindrical domain in the time-space. Here we focus on the uniqueness of the shape identification. As a general treatment to show the uniqueness, a comparability condition on a pair of domains is introduced; the condition holds automatically in the time-independent case. Based on the condition, we provide several classes of domains in which the uniqueness of the shape identification holds under an appropriate initial shape condition or initial temperature condition. Each of such classes is characterized by a certain geometric condition on its each single element; in particular, it is verified that the class of polyhedral domains and any class of domains with C1 smoothness and with a common initial shape fulfil the uniqueness property. The inverse problem is studied via a parabolic equation with a mixed boundary condition. Then the unique continuation property of weak solutions and the uniqueness of weak solutions to an induced parabolic equation with the homogeneous Dirichlet boundary condition on a non-cylindrical non-Lipschitz domain play key roles. This work was partially supported by JSPS Grant-in-Aid for Scientific Research 21540160.

  17. Constructing Domain-Specific Knowledge in Kindergarten: Relations among Knowledge, Intelligence, and Strategic Performance

    ERIC Educational Resources Information Center

    Alexander, Joyce M.; Johnson, Kathy E.; Leibham, Mary E.; DeBauge, Christiane

    2005-01-01

    Thirty kindergarten children from two classrooms participated in a 3-week curricular unit on dinosaurs designed to teach taxonomic relations and distinguishing features aligned with 15 dinosaur species. Both domain-specific learning and strategic performance on a Twenty Questions game were assessed twice throughout the curriculum, as well as…

  18. Constructing Domain-Specific Knowledge in Kindergarten: Relations among Knowledge, Intelligence, and Strategic Performance

    ERIC Educational Resources Information Center

    Alexander, Joyce M.; Johnson, Kathy E.; Leibham, Mary E.; DeBauge, Christiane

    2005-01-01

    Thirty kindergarten children from two classrooms participated in a 3-week curricular unit on dinosaurs designed to teach taxonomic relations and distinguishing features aligned with 15 dinosaur species. Both domain-specific learning and strategic performance on a Twenty Questions game were assessed twice throughout the curriculum, as well as…

  19. The Dynamics of Effective Performance Evaluation Systems in Education: Conceptual, Human Relations, and Technical Domains.

    ERIC Educational Resources Information Center

    Stronge, James H.

    1991-01-01

    A triad of conceptual, human relations, and technical domains is proposed as a basis for effective performance evaluation systems in education. Systems incorporating the relevant issues in this triad address a fundamental rule of performance evaluation: if it is worth doing, it is worth doing well. (SLD)

  20. International Note: Between-Domain Relations of Chinese High School Students' Academic Achievements

    ERIC Educational Resources Information Center

    Yangyang, Liu

    2012-01-01

    The present study examined the between-domain relations of Chinese high school students' academic achievements. In a sample of 1870 Chinese 10th grade students, the results indicated that Chinese high school students' academic achievements were correlated across nine subjects. In line with the previous Western findings, the findings suggested that…

  1. Domain-based identification and analysis of glutamate receptor ion channels and their relatives in prokaryotes.

    PubMed

    Ger, Mao-Feng; Rendon, Gloria; Tilson, Jeffrey L; Jakobsson, Eric

    2010-10-06

    Voltage-gated and ligand-gated ion channels are used in eukaryotic organisms for the purpose of electrochemical signaling. There are prokaryotic homologues to major eukaryotic channels of these sorts, including voltage-gated sodium, potassium, and calcium channels, Ach-receptor and glutamate-receptor channels. The prokaryotic homologues have been less well characterized functionally than their eukaryotic counterparts. In this study we identify likely prokaryotic functional counterparts of eukaryotic glutamate receptor channels by comprehensive analysis of the prokaryotic sequences in the context of known functional domains present in the eukaryotic members of this family. In particular, we searched the nonredundant protein database for all proteins containing the following motif: the two sections of the extracellular glutamate binding domain flanking two transmembrane helices. We discovered 100 prokaryotic sequences containing this motif, with a wide variety of functional annotations. Two groups within this family have the same topology as eukaryotic glutamate receptor channels. Group 1 has a potassium-like selectivity filter. Group 2 is most closely related to eukaryotic glutamate receptor channels. We present analysis of the functional domain architecture for the group of 100, a putative phylogenetic tree, comparison of the protein phylogeny with the corresponding species phylogeny, consideration of the distribution of these proteins among classes of prokaryotes, and orthologous relationships between prokaryotic and human glutamate receptor channels. We introduce a construct called the Evolutionary Domain Network, which represents a putative pathway of domain rearrangements underlying the domain composition of present channels. We believe that scientists interested in ion channels in general, and ligand-gated ion channels in particular, will be interested in this work. The work should also be of interest to bioinformatics researchers who are interested in the use

  2. Severity of personality disorders and domains of general personality dysfunction related to attachment.

    PubMed

    Hengartner, Michael P; von Wyl, Agnes; Tanis, Thachell; Halmi, Winter; Galynker, Igor; Cohen, Lisa J

    2015-08-01

    This is the first study to link attachment to both severity of total DSM-IV personality disorder (PD) traits and domains of general personality dysfunction, using a sample of 72 inpatients from New York City. We assessed a measure of global PD severity and the core domains of personality functioning using the severity indices of personality problems (SIPP-118). Attachment was measured with the experience in close relationships-revised (ECR-R) and the relationship style questionnaire (RSQ). Global PD severity correlated most strongly with attachment anxiety (r = 0.65). Regression of the SIPP-118 domains on attachment produced models that accounted for a substantial proportion of variance in those scales (R(2) ranging from 28.2 to 54.2%). SIPP-118 relational capacities were the strongest predictor of ECR-R avoidance (β = -0.88) and anxiety (β = -0.58), as well as RSQ secure (β = 0.53) and fearful (β = -0.65). In conclusion, insecure attachment strongly related to the severity of global PD traits and specifically to relational capacities, which are a higher-order domain of general personality dysfunction. These findings provide further evidence that interpersonal problems are at the core of PDs and that attachment could constitute an important mediator of the social dysfunction in persons with personality pathology.

  3. Domain-specific physical activity and health-related quality of life in university students.

    PubMed

    Pedišić, Zeljko; Rakovac, Marija; Titze, Sylvia; Jurakić, Danijel; Oja, Pekka

    2014-01-01

    Information on the relationship between domain-specific physical activity (PA) and health-related quality of life (HRQoL) in the general population and specific groups is still scarce. The aim of this study was to determine the relationship between PA in work, transport, domestic and leisure-time domains and HRQoL among university students. PA and HRQoL were assessed in a random stratified sample of 1750 university students using the International Physical Activity Questionnaire - long form and 12-item Short Form Health Survey, respectively. The Spearman's rank correlations, adjusted for age, community size, personal monthly budget, body mass index, smoking habits and alcohol intake ranged from -0.11 to 0.18 in female students and -0.29 to 0.19 in male students. Leisure-time, domestic, transport-related PA and total PA were positively related to HRQoL. Inverse correlations with HRQoL were only found for work-related PA in male students. Multiple linear regression analysis showed that only leisure-time PA was related to the Physical Summary Component score (β = 0.08 for females and β = 0.10 for males, P < 0.05). Domain-specific PA levels were not significantly related to the Mental Component Summary score. To get a more comprehensive insight in the relationship between PA and HRQoL, future studies should not only analyse total PA levels but also domain-specific PA levels. The evidence on the positive relationship of leisure-time, transport and domestic PA with HRQoL can potentially be used to support evidence-based promotion of PA in a university setting, and as a hypothesis for future longitudinal studies on such potential causal relationships.

  4. Are maladaptive schema domains and perfectionism related to body image concerns in eating disorder patients?

    PubMed

    Boone, Liesbet; Braet, Caroline; Vandereycken, Walter; Claes, Laurence

    2013-01-01

    Both maladaptive schemas (MS) and perfectionism have been associated with eating pathology. However, previous research has not examined these variables simultaneously and has not studied possible mediating relationships between MS and multidimensional perfectionism for body image concerns in eating disorder (ED) patients. Eighty-eight female ED patients completed the Young Schema Questionnaire, the Frost Multidimensional Perfectionism Scale, and the Body Attitude Test. Body image concerns were found to be positively related to Personal Standards (PS) and Evaluative Concerns (EC) perfectionism and all five schema domains. PS Perfectionism was positively associated with Disconnection, Other-directedness, and Overvigilance. EC Perfectionism was positively related to Disconnection, Impaired Autonomy, Other-directedness, and Overvigilance. Moreover, EC perfectionism was found to be a significant mediator in the relationship between the schema domains Impaired Autonomy and Overvigilance and body image concerns. These findings denote the importance to address both core beliefs and perfectionism in ED treatment.

  5. The effect of domain-general inhibition-related training on language switching: An ERP study.

    PubMed

    Liu, Huanhuan; Liang, Lijuan; Dunlap, Susan; Fan, Ning; Chen, Baoguo

    2016-01-01

    Previous studies have demonstrated that inhibitory control ability could be improved by training, and the Inhibitory Control (IC) Model implies that enhanced domain-general inhibition may elicit certain changes in language switch costs. In the present study, we aimed to examine the effects of domain-general inhibition training on performance in a language switching task, including which phase of domain-general inhibitory control benefits from training during an overt picture naming task in L1 and L2, using the event-related brain potentials (ERPs). Results showed that the language switch costs of bilinguals with high inhibitory control (high-IC) were symmetrical in both pretest and posttest, and those of bilinguals with low inhibitory control (low-IC) were asymmetrical in the pretest, but symmetrical in the posttest. Moreover, the high-IC group showed a larger LPC (late positive component) for L2 switch trials than for L1 trials in both pretest and posttest. In contrast, the low-IC group only exhibited a similar pattern of LPC in the posttest, but not in the pretest. These results indicate that inhibition training could increase the efficiency of language switching, and inhibitory control may play a key role during the lexical selection response phase. Overall, the present study is the first one to provide electrophysiological evidence for individual differences in the domain-general inhibition impact on language switching performance in low-proficient bilinguals.

  6. Ring-like oligomers of Synaptotagmins and related C2 domain proteins

    PubMed Central

    Zanetti, Maria N; Bello, Oscar D; Wang, Jing; Coleman, Jeff; Cai, Yiying; Sindelar, Charles V; Rothman, James E; Krishnakumar, Shyam S

    2016-01-01

    We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca2+ involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca2+ influx. DOI: http://dx.doi.org/10.7554/eLife.17262.001 PMID:27434670

  7. Recognizing Mantle Domains Related to an Extensional Cycle: the Record from Western Europe

    NASA Astrophysics Data System (ADS)

    Picazo, S.; Muntener, O.; Manatschal, G.

    2015-12-01

    Most of the studies on rifted margins have shown that the classical predictions of models assuming a "homogeneous" mantle lithosphere without some inheritance are unable to capture the observed large variety of magmatic budgets as a function of extension. More recently, new ideas and concepts have been developed to understand the evolution of the mantle lithosphere in hyper-extended magma-poor rifted margins that are mainly based on observations from the present-day Iberia-Newfoundland and ancient Alpine Tethys rifted margins and the Pyrenean systems. In contrast to the classical assumption assuming a simple, isotropic mantle lithosphere, these new models integrate observations from exposed and drilled mantle rocks and propose that the mantle lithosphere evolved and was modified during an extensional cycle from post-orogenic collapse through several periods of rifting to embryonic oceanic (ultra-) slow seafloor spreading. But it is, at present, unclear how far these ideas can be generalized and if they can explain the nature of mantle rocks observed across Western Europe and, in a more general way, at Atlantic type rifted margins. We review the available mantle data from Western Europe, i.e. ophiolite massifs, xenoliths and dredged samples, revisit the available terminology concerning mantle massifs and xenoliths and compile the available data to identify different mantle domains. We define chemical and petrological characteristics of mantle domains based on clinopyroxene and spinel compositions and compile them on present-day and paleo-geographic maps of Western Europe. Finally we link the observed distribution of mantle domains to the post-Variscan extensional cycle and link domains to processes related to the late post-Variscan extension, the rift evolution and refertilization associated to hyper-extension and the development of embryonic oceanic domains.

  8. Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

    PubMed

    Chládek, J; Brázdil, M; Halámek, J; Plešinger, F; Jurák, P

    2013-01-01

    We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas.

  9. A mathematically related singularity and the maximum size of protein domains.

    PubMed

    Szilágyi, András

    2008-06-01

    In a paper titled "A topologically related singularity suggests a maximum preferred size for protein domains" (Zbilut et al., Proteins 2007;66:621-629), Zbilut et al. claim to have found a singularity in certain geometrical properties of protein structures, and suggest that this singularity may limit the maximum size of protein domains. They find further support for the singularity in their analysis of G-factors calculated by the PROCHECK program. Here, we show that the claimed singularity is a mathematical artifact with no physical meaning, and we reanalyze the G-factors to show that Zbilut et al.'s results are due to a single outlier in the data. Thus, the existence of an actual singularity in the topological properties of proteins is not supported by the findings of Zbilut et al.

  10. The H+ related defects in near-stoichiometric lithium niobate crystals investigated by domain reversal

    NASA Astrophysics Data System (ADS)

    Yan, Wenbo; Kong, Yongfa; Shi, Lihong; Xie, Xiang; Li, Xiaochun; Xu, Jingjun; Lou, Cibo; Liu, Hongde; Zhang, Wanlin; Zhang, Guangyin

    2004-07-01

    Domain reversal and heat treatment were carried out on near-stoichiometric lithium niobate crystals and H+ related defect structure of this crystal was studied through infrared absorption spectra. It is found that the position and halfwidth of some deconvoluted peaks of absorption band change apparently during domain reversal and heat treatment. According to these experimental results, a more suitable model about the location of Li-vacancy in LiNbO3 is introduced. In this model, the four Li vacancies, charge-compensating an anti-site Nb5+ ion (Nb4+Li), occupy two types of lattice positions: three of them at the nearest Li-sites Nb4+Li and the other one at a nearer Li-site above the same oxygen plane with Nb4+Li.

  11. Parametric forcing of waves with a nonmonotonic dispersion relation: Domain structures in ferrofluids

    SciTech Connect

    Raitt, D.; Riecke, H.

    1997-05-01

    Surface waves on ferrofluids exposed to a dc magnetic field exhibit a nonmonotonic dispersion relation. The effect of a parametric driving on such waves is studied within suitable coupled Ginzburg-Landau equations. Due to the nonmonotonicity the neutral curve for the excitation of standing waves can have up to three minima. The stability of the waves with respect to long-wave perturbations is determined via a phase-diffusion equation. It shows that the band of stable wave numbers can split up into two or three subbands. The resulting competition between the wave numbers corresponding to the respective subbands leads quite naturally to patterns consisting of multiple domains of standing waves which differ in their wave number. The coarsening dynamics of such domain structures is addressed. {copyright} {ital 1997} {ital The American Physical Society}

  12. StAR-related lipid transfer domain protein 5 binds primary bile acids[S

    PubMed Central

    Létourneau, Danny; Lorin, Aurélien; Lefebvre, Andrée; Frappier, Vincent; Gaudreault, Francis; Najmanovich, Rafael; Lavigne, Pierre; LeHoux, Jean-Guy

    2012-01-01

    Steroidogenic acute regulatory-related lipid transfer (START) domain proteins are involved in the nonvesicular intracellular transport of lipids and sterols. The STARD1 (STARD1 and STARD3) and STARD4 subfamilies (STARD4–6) have an internal cavity large enough to accommodate sterols. To provide a deeper understanding on the structural biology of this domain, the binding of sterols to STARD5, a member of the STARD4 subfamily, was monitored. The SAR by NMR [1H-15N heteronuclear single-quantum coherence (HSQC)] approach, complemented by circular dichroism (CD) and isothermal titration calorimetry (ITC), was used. Titration of STARD5 with cholic (CA) and chenodeoxycholic acid (CDCA), ligands of the farnesoid X receptor (FXR), leads to drastic perturbation of the 1H-15N HSQC spectra and the identification of the residues in contact with those ligands. The most perturbed residues in presence of ligands are lining the internal cavity of the protein. Ka values of 1.8·10−4 M−1 and 6.3·104 M−1 were measured for CA and CDCA, respectively. This is the first report of a START domain protein in complex with a sterol ligand. Our original findings indicate that STARD5 may be involved in the transport of bile acids rather than cholesterol. PMID:23018617

  13. Switching VO₂ Single Crystals and Related Phenomena: Sliding Domains and Crack Formation.

    PubMed

    Fisher, Bertina; Patlagan, Larisa

    2017-05-19

    VO₂ is the prototype material for insulator-metal transition (IMT). Its transition at TIMT = 340 K is fast and consists of a large resistance jump (up to approximately five orders of magnitude), a large change in its optical properties in the visible range, and symmetry change from monoclinic to tetragonal (expansion by 1% along the tetragonal c-axis and 0.5% contraction in the perpendicular direction). It is a candidate for potential applications such as smart windows, fast optoelectronic switches, and field-effect transistors. The change in optical properties at the IMT allows distinguishing between the insulating and the metallic phases in the mixed state. Static or dynamic domain patterns in the mixed-state of self-heated single crystals during electric-field induced switching are in strong contrast with the percolative nature of the mixed state in switching VO₂ films. The most impressive effect-so far unique to VO₂-is the sliding of narrow semiconducting domains within a metallic background in the positive sense of the electric current. Here we show images from videos obtained using optical microscopy for sliding domains along VO₂ needles and confirm a relation suggested in the past for their velocity. We also show images for the disturbing damage induced by the structural changes in switching VO₂ crystals obtained for only a few current-voltage cycles.

  14. Examining Complexity across Domains: Relating Subjective and Objective Measures of Affective Environmental Scenes, Paintings and Music

    PubMed Central

    Marin, Manuela M.; Leder, Helmut

    2013-01-01

    Subjective complexity has been found to be related to hedonic measures of preference, pleasantness and beauty, but there is no consensus about the nature of this relationship in the visual and musical domains. Moreover, the affective content of stimuli has been largely neglected so far in the study of complexity but is crucial in many everyday contexts and in aesthetic experiences. We thus propose a cross-domain approach that acknowledges the multidimensional nature of complexity and that uses a wide range of objective complexity measures combined with subjective ratings. In four experiments, we employed pictures of affective environmental scenes, representational paintings, and Romantic solo and chamber music excerpts. Stimuli were pre-selected to vary in emotional content (pleasantness and arousal) and complexity (low versus high number of elements). For each set of stimuli, in a between-subjects design, ratings of familiarity, complexity, pleasantness and arousal were obtained for a presentation time of 25 s from 152 participants. In line with Berlyne’s collative-motivation model, statistical analyses controlling for familiarity revealed a positive relationship between subjective complexity and arousal, and the highest correlations were observed for musical stimuli. Evidence for a mediating role of arousal in the complexity-pleasantness relationship was demonstrated in all experiments, but was only significant for females with regard to music. The direction and strength of the linear relationship between complexity and pleasantness depended on the stimulus type and gender. For environmental scenes, the root mean square contrast measures and measures of compressed file size correlated best with subjective complexity, whereas only edge detection based on phase congruency yielded equivalent results for representational paintings. Measures of compressed file size and event density also showed positive correlations with complexity and arousal in music, which is

  15. Examining complexity across domains: relating subjective and objective measures of affective environmental scenes, paintings and music.

    PubMed

    Marin, Manuela M; Leder, Helmut

    2013-01-01

    Subjective complexity has been found to be related to hedonic measures of preference, pleasantness and beauty, but there is no consensus about the nature of this relationship in the visual and musical domains. Moreover, the affective content of stimuli has been largely neglected so far in the study of complexity but is crucial in many everyday contexts and in aesthetic experiences. We thus propose a cross-domain approach that acknowledges the multidimensional nature of complexity and that uses a wide range of objective complexity measures combined with subjective ratings. In four experiments, we employed pictures of affective environmental scenes, representational paintings, and Romantic solo and chamber music excerpts. Stimuli were pre-selected to vary in emotional content (pleasantness and arousal) and complexity (low versus high number of elements). For each set of stimuli, in a between-subjects design, ratings of familiarity, complexity, pleasantness and arousal were obtained for a presentation time of 25 s from 152 participants. In line with Berlyne's collative-motivation model, statistical analyses controlling for familiarity revealed a positive relationship between subjective complexity and arousal, and the highest correlations were observed for musical stimuli. Evidence for a mediating role of arousal in the complexity-pleasantness relationship was demonstrated in all experiments, but was only significant for females with regard to music. The direction and strength of the linear relationship between complexity and pleasantness depended on the stimulus type and gender. For environmental scenes, the root mean square contrast measures and measures of compressed file size correlated best with subjective complexity, whereas only edge detection based on phase congruency yielded equivalent results for representational paintings. Measures of compressed file size and event density also showed positive correlations with complexity and arousal in music, which is

  16. On the relation between traditional iterative methods and modern multilevel/domain decomposition methods

    SciTech Connect

    Griebel, M.

    1994-12-31

    In recent years, it has turned out that many modern iterative algorithms (multigrid schemes, multilevel preconditioners, domain decomposition methods etc.) for solving problems resulting from the discretization of PDEs can be interpreted as additive (Jacobi-like) or multiplicative (Gauss-Seidel-like) subspace correction methods. The key to their analysis is the study of certain metric properties of the underlying splitting of the discretization space V into a sum of subspaces V{sub j}, j = 1{hor_ellipsis}, J resp. of the variational problem on V into auxiliary problems on these subspaces. Here, the author proposes a modified approach to the abstract convergence theory of these additive and multiplicative Schwarz iterative methods, that makes the relation to traditional iteration methods more explicit. To this end he introduces the enlarged Hilbert space V = V{sub 0} x {hor_ellipsis} x V{sub j} which is nothing else but the usual construction of the Cartesian product of the Hilbert spaces V{sub j} and use it now in the discretization process. This results in an enlarged, semidefinite linear system to be solved instead of the usual definite system. Then, modern multilevel methods as well as domain decomposition methods simplify to just traditional (block-) iteration methods. Now, the convergence analysis can be carried out directly for these traditional iterations on the enlarged system, making convergence proofs of multilevel and domain decomposition methods more clear, or, at least, more classical. The terms that enter the convergence proofs are exactly the ones of the classical iterative methods. It remains to estimate them properly. The convergence proof itself follow basically line by line the old proofs of the respective traditional iterative methods. Additionally, new multilevel/domain decomposition methods are constructed straightforwardly by now applying just other old and well known traditional iterative methods to the enlarged system.

  17. Determine the Dispersion Relation of an A6 Magnetron Using Conformal Finite Difference Time Domain Method

    NASA Astrophysics Data System (ADS)

    Lin, M. C.; Nieter, C.; Stoltz, P. H.; Smithe, D. N.

    2009-05-01

    This work introduces a conformal finite difference time domain (CFDTD) method to accurately determine the dispersion relation of an A6 relativistic magnetron. The accuracy is measured by comparing with accurate SUPERFISH calculations based on finite element method. The results show that an accuracy of 99.4% can be achieved by using only 10,000 mesh points with Dey-Mittra algorithm. By comparison, a mesh number of 360,000 is needed to preserve 99% accuracy using conventional FDTD method. This suggests one can efficiently and accurately study the hot tests of microwave tubes using CFDTD particle-in-cell method instead of conventional FDTD one.

  18. The NIMH Research Domain Criteria initiative and error-related brain activity.

    PubMed

    Hanna, Gregory L; Gehring, William J

    2016-03-01

    Research on the neural response to errors has an important role in the Research Domain Criteria (RDoC) project, since it is likely to link psychopathology to the dysfunction of neural systems underlying basic behavioral functions, with the error-related negativity (ERN) appearing as a unit of measurement in three RDoC domains. A recent report builds on previous research by examining the ERN as a measure of the sustained threat construct and providing evidence that the ERN may reflect sensitivity more specifically to endogenous threat. Data from 515 adolescent females indicate that the ERN was enlarged primarily in older adolescents with self-reported checking behaviors, although it was blunted in adolescents with depressive symptoms regardless of age. Potential future studies for replicating and extending the research on the ERN and obsessive-compulsive (OC) behaviors are discussed, including studies that more fully characterize OC symptom dimensions, studies that integrate other measures of error-related brain activity and use computational modeling, studies that combine longitudinal, family, and molecular genetic measures, and interventional studies that specifically modulate error-related brain activity in individuals with OC behaviors.

  19. Development of quantitative diagnostic observables for age-related macular degeneration using Spectral Domain OCT

    NASA Astrophysics Data System (ADS)

    Bower, Bradley A.; Chiu, Stephanie J.; Davies, Emily; Davis, Anjul M.; Zawadzki, Robert J.; Fuller, Alfred R.; Wiley, David F.; Izatt, Joseph A.; Toth, Cynthia A.

    2007-02-01

    We report on the development of quantitative, reproducible diagnostic observables for age-related macular degeneration (AMD) based on high speed spectral domain optical coherence tomography (SDOCT). 3D SDOCT volumetric data sets (512 x 1000 x 100 voxels) were collected (5.7 seconds acquisition time) in over 50 patients with age-related macular degeneration and geographic atrophy using a state-of-the-art SDOCT scanner. Commercial and custom software utilities were used for manual and semi-automated segmentation of photoreceptor layer thickness, total drusen volume, and geographic atrophy cross-sectional area. In a preliminary test of reproducibility in segmentation of total drusen volume and geographic atrophy surface area, inter-observer error was less than 5%. Extracted volume and surface area of AMD-related drusen and geographic atrophy, respectively, may serve as useful observables for tracking disease state that were not accessible without the rapid 3D volumetric imaging capability unique to retinal SDOCT.

  20. The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the diaphanous-related formin inhibitory domain.

    PubMed

    Wallar, Bradley J; Stropich, Brittany N; Schoenherr, Jessica A; Holman, Holly A; Kitchen, Susan M; Alberts, Arthur S

    2006-02-17

    Mammalian diaphanous-related (mDia) formins act as Rho GTPase effectors during cytoskeletal remodeling. Rho binding to mDia amino-terminal GTPase-binding domains (GBDs) causes the adjacent Dia-inhibitory domain (DID) to release the carboxyl-terminal Dia-autoregulatory (DAD) domain that flanks the formin homology-2 (FH2) domain. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments. DAD, initially discovered as a region of homology shared between a phylogenetically divergent set of formin proteins, is comprised of a core motif, MDXLLXL, and an adjacent region is comprised of numerous basic residues, typically RRKR in the mDia family. Here, we show that these specific amino acids within the basic region of DAD contribute to the binding of DID and therefore the maintenance of the mDia autoregulatory mechanism. In addition, expression of full-length versions of mDia2 containing amino acid substitutions in either the DAD core or basic regions causes profound changes in the F-actin architecture, including the formation of filopodia-like structures that rapidly elongate from the cell edge. These studies further refine our understanding of the molecular contribution of DAD to mDia control and the role of mDia2 in the assembly of membrane protrusions.

  1. Cysteine-rich domains related to Frizzled receptors and Hedgehog-interacting proteins

    PubMed Central

    Pei, Jimin; Grishin, Nick V

    2012-01-01

    Frizzled and Smoothened are homologous seven-transmembrane proteins functioning in the Wnt and Hedgehog signaling pathways, respectively. They harbor an extracellular cysteine-rich domain (FZ-CRD), a mobile evolutionary unit that has been found in a number of other metazoan proteins and Frizzled-like proteins in Dictyostelium. Domains distantly related to FZ-CRDs, in Hedgehog-interacting proteins (HHIPs), folate receptors and riboflavin-binding proteins (FRBPs), and Niemann-Pick Type C1 proteins (NPC1s), referred to as HFN-CRDs, exhibit similar structures and disulfide connectivity patterns compared with FZ-CRDs. We used computational analyses to expand the homologous set of FZ-CRDs and HFN-CRDs, providing a better understanding of their evolution and classification. First, FZ-CRD-containing proteins with various domain compositions were identified in several major eukaryotic lineages including plants and Chromalveolata, revealing a wider phylogenetic distribution of FZ-CRDs than previously recognized. Second, two new and distinct groups of highly divergent FZ-CRDs were found by sensitive similarity searches. One of them is present in the calcium channel component Mid1 in fungi and the uncharacterized FAM155 proteins in metazoans. Members of the other new FZ-CRD group occur in the metazoan-specific RECK (reversion-inducing-cysteine-rich protein with Kazal motifs) proteins that are putative tumor suppressors acting as inhibitors of matrix metalloproteases. Finally, sequence and three-dimensional structural comparisons helped us uncover a divergent HFN-CRD in glypicans, which are important morphogen-binding heparan sulfate proteoglycans. Such a finding reinforces the evolutionary ties between the Wnt and Hedgehog signaling pathways and underscores the importance of gene duplications in creating essential signaling components in metazoan evolution. PMID:22693159

  2. Spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss.

    PubMed

    Shalchi, Zaid; Mahroo, Omar A; Shunmugam, Manoharan; Mohamed, Moin; Sullivan, Paul M; Williamson, Tom H

    2015-03-01

    To investigate spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss. Four symptomatic patients were reviewed 4 years to 9 years after vitrectomy with silicone oil tamponade for macula-on retinal detachment. Three lost vision with oil in situ, with one at the time of oil removal. Eleven control eyes with good vision were included. Patients underwent assessment of best-corrected visual acuity, contrast sensitivity, Farnsworth-Munsell 100 Hue testing, static perimetry, and spectral domain optical coherence tomography imaging of the macula and disk. Long-term best-corrected visual acuity was significantly reduced in affected eyes (range, 0.44-1.02), as was contrast sensitivity (0.75-1.35) and color discrimination (Farnsworth-Munsell-100 Hue score, 151-390). Static perimetry showed a central scotoma in all affected eyes. Optical coherence tomography revealed microcystic macular changes in the inner nuclear layer of all affected eyes associated with severe loss of the papillofoveal retinal nerve fiber layer. In one patient, serial optical coherence tomography images showed development of microcystic macular changes 18 months after oil removal. Control eyes lacked these features, except two asymptomatic eyes that showed microcystic changes on optical coherence tomography with a corresponding paracentral scotoma. We have demonstrated microcystic macular changes in the inner nuclear layer of affected eyes, as well as focal severe loss of the papillofoveal projection. These changes share significant morphologic features reported in multiple sclerosis-associated optic neuritis and Leber hereditary optic neuropathy.

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

    PubMed Central

    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

  4. Spire contains actin binding domains and is related to ascidian posterior end mark-5.

    PubMed

    Wellington, A; Emmons, S; James, B; Calley, J; Grover, M; Tolias, P; Manseau, L

    1999-12-01

    Spire is a maternal effect locus that affects both the dorsal-ventral and anterior-posterior axes of the Drosophila egg and embryo. It is required for localization of determinants within the developing oocyte to the posterior pole and to the dorsal anterior corner. During mid-oogenesis, spire mutants display premature microtubule-dependent cytoplasmic streaming, a phenotype that can be mimicked by pharmacological disruption of the actin cytoskeleton with cytochalasin D. Spire has been cloned by transposon tagging and is related to posterior end mark-5, a gene from sea squirts that encodes a posteriorly localized mRNA. Spire mRNA is not, however, localized to the posterior pole. SPIRE also contains two domains with similarity to the actin monomer-binding WH2 domain, and we demonstrate that SPIRE binds to actin in the interaction trap system and in vitro. In addition, SPIRE interacts with the rho family GTPases RHOA, RAC1 and CDC42 in the interaction trap system. Thus, our evidence supports the model that SPIRE links rho family signaling to the actin cytoskeleton.

  5. Characterization of genes encoding proteins containing HD-related output domain in Xanthomonas campestris pv. campestris.

    PubMed

    Lee, Hsien-Ming; Liao, Chao-Tsai; Chiang, Ying-Chuan; Chang, Yu-Yin; Yeh, Yu-Tzu; Du, Shin-Chiao; Hsiao, Yi-Min

    2016-04-01

    The Gram-negative plant pathogen Xanthomonas campestris pv. campestris (Xcc) is the causative agent of black rot in crucifers. The production of Xcc virulence factors is regulated by Clp and RpfF. HD-related output domain (HDOD) is a protein domain of unknown biochemical function. The genome of Xcc encodes three proteins (GsmR, HdpA, and HdpB) with an HDOD. The GsmR has been reported to play a role in the general stress response and cell motility and its expression is positively regulated by Clp. Here, the function and transcription of hdpA and hdpB were characterized. Mutation of hdpA resulted in enhanced bacterial attachment. In addition, the expression of hdpA was positively regulated by RpfF but not by Clp, subject to catabolite repression and affected by several stress conditions. However, mutational analysis and reporter assay showed that hdpB had no effect on the production of a range of virulence factors and its expression was independent of Clp and RpfF. The results shown here not only extend the previous work on RpfF regulation to show that it influences the expression of hdpA in Xcc, but also expand knowledge of the function of the HDOD containing proteins in bacteria.

  6. Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway

    PubMed Central

    2010-01-01

    Background Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. Results Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1 phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. Conclusions Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition. PMID:20226085

  7. Between-Domain Relations of Academic Emotions: Does Having the Same Instructor Make a Difference?

    ERIC Educational Resources Information Center

    Goetz, Thomas; Frenzel, Anne C.; Ludtke, Oliver; Hall, Nathan C.

    2011-01-01

    Previous research indicates that academic emotions are largely organized along domain-specific lines. In the present study (N = 1,687; Grades 8/11), the authors explored the domain specificity of academic emotions in terms of the moderating influence of having the same versus a different course instructor across domains. The authors evaluated…

  8. Dual-band Fourier domain optical coherence tomography with depth-related compensations

    PubMed Central

    Zhang, Miao; Ma, Lixin; Yu, Ping

    2013-01-01

    Dual-band Fourier domain optical coherence tomography (FD-OCT) provides depth-resolved spectroscopic imaging that enhances tissue contrast and reduces image speckle. However, previous dual-band FD-OCT systems could not correctly give the tissue spectroscopic contrast due to depth-related discrepancy in the imaging method and attenuation in biological tissue samples. We designed a new dual-band full-range FD-OCT imaging system and developed an algorithm to compensate depth-related fall-off and light attenuation. In our imaging system, the images from two wavelength bands were intrinsically overlapped and their intensities were balanced. The processing time of dual-band OCT image reconstruction and depth-related compensations were minimized by using multiple threads that execute in parallel. Using the newly developed system, we studied tissue phantoms and human cancer xenografts and muscle tissues dissected from severely compromised immune deficient mice. Improved spectroscopic contrast and sensitivity were achieved, benefiting from the depth-related compensations. PMID:24466485

  9. Domain General Mediators of the Relation between Kindergarten Number Sense and First-Grade Mathematics Achievement

    PubMed Central

    Hassinger-Das, Brenna; Jordan, Nancy C.; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

    2013-01-01

    Domain general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that attention problems and executive functioning both were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance while executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID:24237789

  10. Topography of Somatostatin Gene Expression Relative to Molecular Progenitor Domains during Ontogeny of the Mouse Hypothalamus

    PubMed Central

    Morales-Delgado, Nicanor; Merchan, Paloma; Bardet, Sylvia M.; Ferrán, José L.; Puelles, Luis; Díaz, Carmen

    2010-01-01

    The hypothalamus comprises alar, basal, and floor plate developmental compartments. Recent molecular data support a rostrocaudal subdivision into rostral (terminal) and caudal (peduncular) halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst) mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp), Distal-less 5 (Dlx5), Sonic Hedgehog (Shh), and Nk2 homeobox 1 (Nkx2.1). At embryonic day 10.5 (E10.5), Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh-, and Otp-positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the alar plate and one in the basal plate. In the alar plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralward into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical, and entopeduncular nuclei. Our data provide a topologic map of molecularly defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization. PMID:21441981

  11. Crystalline lipid domains: characterization by X-ray diffraction and their relation to biology.

    PubMed

    Ziblat, Roy; Leiserowitz, Leslie; Addadi, Lia

    2011-04-11

    Biological membranes comprise thousands of different lipids, differing in their alkyl chains, headgroups, and degree of saturation. It is estimated that 5% of the genes in the human genome are responsible for regulating the lipid composition of cell membranes. Conceivably, the functional explanation for this diversity is found, at least in part, in the propensity of lipids to segregate into distinct domains, which are important for cell function. X-ray diffraction has been used increasingly to characterize the packing and phase behavior of lipids in membranes. Crystalline domains have been studied in synthetic membranes using wide- and small-angle X-ray scattering, and grazing incidence X-ray diffraction. Herein we summarize recent results obtained using the various X-ray methods, discuss the correlation between crystalline domains and liquid ordered domains studied with other techniques, and the relevance of crystalline domains to functional lipid domains in biological membranes.

  12. Polyomavirus middle-T antigen associates with the kinase domain of Src-related tyrosine kinases.

    PubMed Central

    Dunant, N M; Senften, M; Ballmer-Hofer, K

    1996-01-01

    Middle-T antigen of mouse polyomavirus, an oncogenic DNA virus, associates with and activates the cellular tyrosine kinases c-Src, c-Yes, and Fyn. This interaction is essential for polyomavirus-mediated transformation of cells in culture and tumor formation in animals. To determine the domain of c-Src directing association with middle-T, mutant c-Src proteins lacking the amino-terminal unique domain and the myristylation signal, the SH2 domain, the SH3 domain, or all three of these domains were coexpressed with middle-T in NIH 3T3 cells. All mutants were found to associate with middle-T, demonstrating that the kinase domain of c-Src, including the carboxy-terminal regulatory tail, is sufficient for association with middle-T. Moreover, we found that Hck, another member of the Src kinase family, does not bind middle-T, while chimeric kinases consisting of the amino-terminal domains of c-Src fused to the kinase domain of Hck or the amino-terminal domains of Hck fused to the kinase domain of c-Src associated with middle-T. Hck mutated at its carboxy-terminal regulatory residue, tyrosine 501, was also found to associate with middle-T. These results suggest that in Hck, the postulated intramolecular interaction between the carboxy-terminal regulatory tyrosine and the SH2 domain prevents association with middle-T. This intramolecular interaction apparently also limits the ability of c-Src to associate with middle-T, since removal of the SH2 or SH3 domain increases the efficiency with which middle-T binds c-Src. PMID:8627648

  13. Hetero-oligomerization of C2 domains of phospholipase C-related but catalytically inactive protein and synaptotagmin-1.

    PubMed

    Wang, DaGuang; Takeuchi, Hiroshi; Gao, Jing; Zhang, Zhao; Hirata, Masato

    2015-01-01

    The C2 domain is a protein module often found in molecules that regulate exocytosis. C2 domains mediate interactions between the parental molecule and Ca(2+), phospholipids, and proteins. Although various molecules have been shown to interact with several C2 domains, no interactions between the C2 domains from different molecules have yet been reported. In the present study, we identified direct interactions between the C2 domain of PRIP (phospholipase C-related but catalytically inactive protein) and the C2 domains of other molecules. Among the C2 domains examined, those of synaptotagmin-1 (Syt1-C2A and Syt1-C2B) and phospholipase C δ-1 bound to the C2 domain of PRIP. We investigated the interactions between the C2 domain of PRIP (PRIP-C2) with Syt1-C2A and Syt1-C2B, and the mode of binding of each was Ca(2+)-dependent and -independent, respectively. We further demonstrated that the Ca(2+) dependence of the interaction between PRIP-C2 and Syt1-C2A was attributed to Ca(2+) binding with Syt1-C2A, but not PRIP-C2, using a series of mutants prepared from both C2 domains. We previously reported that the interaction between PRIP-C2 and the membrane fusion machinery suggested a critical role for PRIP in exocytosis; therefore, the results of the present study further support the importance of PRIP-C2 in the inhibitory function of PRIP in regulating exocytosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Children's Comprehension of Object Relative Sentences: It's Extant Language Knowledge That Matters, Not Domain-General Working Memory.

    PubMed

    Rusli, Yazmin Ahmad; Montgomery, James W

    2017-09-15

    The aim of this study was to determine whether extant language (lexical) knowledge or domain-general working memory is the better predictor of comprehension of object relative sentences for children with typical development. We hypothesized that extant language knowledge, not domain-general working memory, is the better predictor. Fifty-three children (ages 9-11 years) completed a word-level verbal working-memory task, indexing extant language (lexical) knowledge; an analog nonverbal working-memory task, representing domain-general working memory; and a hybrid sentence comprehension task incorporating elements of both agent selection and cross-modal picture-priming paradigms. Images of the agent and patient were displayed at the syntactic gap in the object relative sentences, and the children were asked to select the agent of the sentence. Results of general linear modeling revealed that extant language knowledge accounted for a unique 21.3% of variance in the children's object relative sentence comprehension over and above age (8.3%). Domain-general working memory accounted for a nonsignificant 1.6% of variance. We interpret the results to suggest that extant language knowledge and not domain-general working memory is a critically important contributor to children's object relative sentence comprehension. Results support a connectionist view of the association between working memory and object relative sentence comprehension. https://doi.org/10.23641/asha.5404573.

  15. A method for finding candidate conformations for molecular replacement using relative rotation between domains of a known structure.

    PubMed

    Jeong, Jay I; Lattman, Eaton E; Chirikjian, Gregory S

    2006-04-01

    This paper presents a methodology to obtain candidate conformations of multidomain proteins for use in molecular replacement. For each separate domain, the orientational relationship between the template and the target structure is obtained using standard molecular replacement. The orientational relationships of the domains are then used to calculate the relative rotation between the domains in the target conformation by using pose-estimation techniques from the field of robotics and computer vision. With the angle of relative rotation between the domains as a cost function, iterative normal-mode analysis is used to drive the template structure to a candidate conformation that matches the X-ray crystallographic data obtained for the target conformation. The selection of the correct intra-protein domain orientations from among the many spurious maxima in the rotation function (including orientations obtained from domains in symmetry mates rather than within the same copy of the protein) presents a challenge. This problem is resolved by checking R factors of each domain, measuring the absolute value of relative rotation between domains, and evaluating the cost value after each candidate conformation is driven to convergence with iterative NMA. As a validation, the proposed method is applied to three test proteins: ribose-binding protein, lactoferrin and calcium ATPase. In each test case, the orientation and translation of the final candidate conformation in the unit cell are generated correctly from the suggested procedure. The results show that the proposed method can yield viable candidate conformations for use in molecular replacement and can reveal the structural details and pose of the target conformation in the crystallographic unit cell.

  16. Polyphase tectono-magmatic and fluid history related to mantle exhumation in an ultra-distal rift domain: example of the fossil Platta domain, SE Switzerland

    NASA Astrophysics Data System (ADS)

    Epin, Marie-Eva; Manatschal, Gianreto; Amann, Méderic; Lescanne, Marc

    2017-04-01

    Despite the fact that many studies have investigated mantle exhumation at magma-poor rifted margins, there are still numerous questions concerning the 3D architecture, magmatic, fluid and thermal evolution of these ultra-distal domains that remain unexplained. Indeed, it has been observed in seismic data from ultra-distal magma-poor rifted margins that top basement is heavily structured and complex, however, the processes controlling the morpho-tectonic and magmatic evolution of these domains remain unknown. The aim of this study is to describe the 3D top basement morphology of an exhumed mantle domain, exposed over 200 km2 in the fossil Platta domain in SE Switzerland, and to define the timing and processes controlling its evolution. The examined Platta nappe corresponds to a remnant of the former ultra-distal Adriatic margin of the Alpine Tethys. The rift-structures are relatively well preserved due to the weak Alpine tectonic and metamorphic overprint during the emplacement in the Alpine nappe stack. Detailed mapping of parts of the Platta nappe enabled us to document the top basement architecture of an exhumed mantle domain and to investigate its link to later, rift/oceanic structures, magmatic additions and fluids. Our observations show a polyphase and/or complex: 1) deformation history associated with mantle exhumation along low-angle exhumation faults overprinted by later high-angle normal faults, 2) top basement morphology capped by magmato-sedimentary rocks, 3) tectono-magmatic evolution that includes gabbros, emplaced at deeper levels and subsequently exhumed and overlain by younger extrusive magmatic additions, and 4) fluid history including serpentinization, calcification, hydrothermal vent, rodingitization and spilitization affecting exhumed mantle and associated magmatic rocks. The overall observations provide important information on the temporal and spatial evolution of the tectonic, magmatic and fluid systems controlling the formation of ultra

  17. Response Biases and Their Relation to Sex Differences in Multiple Domains of Self-Concept.

    ERIC Educational Resources Information Center

    Vispoel, Walter P.; Forte Fast, Ellen E.

    2000-01-01

    Examined the influence of two forms of socially desirable responding on scores within 17 domains of self-concept from 3 measures completed by 390 college students. Found significant sex differences in 12 domains. Discusses the role of impression management in creating some apparent sex differences. (SLD)

  18. Response Biases and Their Relation to Sex Differences in Multiple Domains of Self-Concept.

    ERIC Educational Resources Information Center

    Vispoel, Walter P.; Forte Fast, Ellen E.

    2000-01-01

    Examined the influence of two forms of socially desirable responding on scores within 17 domains of self-concept from 3 measures completed by 390 college students. Found significant sex differences in 12 domains. Discusses the role of impression management in creating some apparent sex differences. (SLD)

  19. Medical Resident Ability to Self-Assess in Relation to Their Competence within the Assessed Domain

    ERIC Educational Resources Information Center

    Whicker, Shari Ann

    2012-01-01

    The purpose of the study was to examine the relationship between resident communication skills competence and their ability to self-assess within that domain. Six research questions guided the study. The first research question sought to explore the varied levels with which residents demonstrated competence within the domain of communication…

  20. Medical Resident Ability to Self-Assess in Relation to Their Competence within the Assessed Domain

    ERIC Educational Resources Information Center

    Whicker, Shari Ann

    2012-01-01

    The purpose of the study was to examine the relationship between resident communication skills competence and their ability to self-assess within that domain. Six research questions guided the study. The first research question sought to explore the varied levels with which residents demonstrated competence within the domain of communication…

  1. Issues Related to the Construction of a Purpose-Built Domain-Specific Word Corpus

    ERIC Educational Resources Information Center

    Thomas, Lisa; Pfister, H. Peter; Peterson, Peter

    2004-01-01

    There is growing interest in the use of semantic collections in order to identify and analyse domain knowledge. This paper describes some technical issues to consider when contemplating research which incorporates small-to-medium domain-specific word sets. The purpose of the corpus construction described was to provide an external word collection…

  2. Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.

    PubMed

    Leettola, Catherine N; Knight, Mary Jane; Cascio, Duilio; Hoffman, Sigrid; Bowie, James U

    2014-07-07

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function.

  3. Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3

    PubMed Central

    2014-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. Results The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. Conclusions ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function. PMID:24998259

  4. Immunocytochemical distribution of WARP (von Willebrand A domain-related protein) in the inner ear.

    PubMed

    Duong, Trac; Lopez, Ivan A; Ishiyama, Akira; Ishiyama, Gail

    2011-01-07

    The basic components of the epithelial, perineural, and perivascular basement membranes in the inner ear have been well-documented in several animal models and in the human inner ear. The von Willebrand A domain-related protein (WARP) is an extracellular matrix molecule with restricted expression in cartilage, and a subset of basement membranes in peripheral nerves, muscle, and central nervous system vasculature. It has been suggested that WARP has an important role in maintaining the blood-brain barrier. To date no studies on WARP distribution have been performed in the inner ear, which is equipped with an intricate vasculature network. In the present study, we determined the distribution of WARP by immunocytochemistry in the human inner ear using auditory and vestibular endorgans microdissected from human temporal bones obtained at autopsy. All subjects (n=5, aged 55-87years old) had documented normal auditory and vestibular function. We also determined the WARP immunolocalization in the mouse inner ear. WARP immunoreactivity localized to the vasculature throughout the stroma of the cristae ampullaris, the maculae utricle, and saccule in the human and mouse. In the human and mouse inner ear, WARP immunoreactivity delineated blood vessels located in the stria vascularis, spiral ligament, sub-basilar region, stromal tissue, and the spiral and vestibular ganglia. The distinct localization of WARP in the inner ear vasculature suggests an important role in maintaining its integrity. In addition, WARP allows delineation of microvessels in the inner ear allowing the study of vascular pathology in the development of otological diseases.

  5. Ambivalence about health-related behaviours: an exploration in the domain of food choice.

    PubMed

    Sparks, P; Conner, M; James, R; Shepherd, R; Povey, R

    2001-02-01

    Interest in attitudes and ambivalence has highlighted problems with the adequacy of conceptualizing attitudes as unitary, unidimensional, evaluations. In this paper, we report an application of the Theory of Planned Behaviour (Ajzen, 1991) in the domain of dietary choice which investigates the hypothesis that ambivalence will attenuate observed attitude-intention relationships (since the evaluations influencing the expression of attitudes are more likely to differ from the evaluations influencing the expression of intentions for people who are more ambivalent. Participants completed a postal questionnaire which contained, inter alia, measures assessing the components of the Theory of Planned Behaviour and a measure of ambivalence. Participants (N = 296) were recruited via advertisements placed in local newspapers, asking for volunteers to assist in a research project. Participants were randomly assigned to complete a questionnaire about either their chocolate consumption or their meat consumption. Participants were paid 4. The findings show considerable support for the hypothesis: there was a tendency for attitude-intention relationships to be attenuated among participants with higher levels of ambivalence, compared to participants with lower levels of ambivalence. The research supports the widespread view that ambivalence is an important issue, both for those involved in basic attitude research and for those who seek to use attitude theories in applied research. In particular, the findings indicate that ambivalence may often have implications for the predictive ability of attitude-intention-behaviour models, especially when applied to health-related behaviours that are characterized by motivational conflicts.

  6. Event-related brain responses to emotional words, pictures, and faces - a cross-domain comparison.

    PubMed

    Bayer, Mareike; Schacht, Annekathrin

    2014-01-01

    Emotion effects in event-related brain potentials (ERPs) have previously been reported for a range of visual stimuli, including emotional words, pictures, and facial expressions. Still, little is known about the actual comparability of emotion effects across these stimulus classes. The present study aimed to fill this gap by investigating emotion effects in response to words, pictures, and facial expressions using a blocked within-subject design. Furthermore, ratings of stimulus arousal and valence were collected from an independent sample of participants. Modulations of early posterior negativity (EPN) and late positive complex (LPC) were visible for all stimulus domains, but showed clear differences, particularly in valence processing. While emotion effects were limited to positive stimuli for words, they were predominant for negative stimuli in pictures and facial expressions. These findings corroborate the notion of a positivity offset for words and a negativity bias for pictures and facial expressions, which was assumed to be caused by generally lower arousal levels of written language. Interestingly, however, these assumed differences were not confirmed by arousal ratings. Instead, words were rated as overall more positive than pictures and facial expressions. Taken together, the present results point toward systematic differences in the processing of written words and pictorial stimuli of emotional content, not only in terms of a valence bias evident in ERPs, but also concerning their emotional evaluation captured by ratings of stimulus valence and arousal.

  7. Plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.

    PubMed

    Al-Khattaf, Fatimah S; Tremp, Annie Z; Dessens, Johannes T

    2015-02-01

    The invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. The pellicle is characterised by a double-layered 'inner membrane complex' (IMC) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (SPN). The SPN consists of intermediate filaments, whose major constituents include a family of proteins called alveolins. Here, we re-appraise the alveolins in the genus Plasmodium with respect to their repertoire, structure and interrelatedness. Amongst 13 family members identified, we distinguish two domain types that, albeit distinct at the primary structure level, are structurally related and contain tandem repeats with a consensus 12-amino acid periodicity. Analysis in Plasmodium berghei of the most divergent alveolin, PbIMC1d, reveals a zoite-specific expression in ookinetes and a subcellular localisation in the pellicle, consistent with its predicted role as a SPN component. Knockout of PbIMC1d gives rise to a wild-type phenotype with respect to ookinete morphogenesis, tensile strength, gliding motility and infectivity, presenting the first example of apparent functional redundancy amongst alveolin family members.

  8. Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

    SciTech Connect

    Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K. . E-mail: George.Devries@med.va.gov

    2006-09-29

    Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells.

  9. The NHR domains of Neuralized and related proteins: Beyond Notch signalling.

    PubMed

    Liu, Sili; Boulianne, Gabrielle L

    2017-01-01

    Neuralized Homology Repeats (NHRs) were first identified in Neuralized, an E3-ubiquitin ligase that plays a key role in the Notch signalling pathway. Since their original discovery, NHR domains have been shown to regulate protein-protein interactions in a broad range of developmental processes and in a wide variety of species from flies to humans. The NHR family of proteins can be categorized into three groups: (1) those that contain a RING finger, (2) those that contain a SOCS box and, (3) those that only have NHR domains. Here we review the structure and function of NHR domains in various cellular and developmental processes.

  10. Age-Related Differences in Locus of Control Orientation in Three Behavior Domains

    ERIC Educational Resources Information Center

    Bradley, Robert H.; Webb, Roger

    1976-01-01

    Age correlated differences in locus of control orientation were examined for 306 persons aged 13 to 90 in three areas of activity: intellectual, social and physical. The Locus of Control Inventory for Three Achievement Domains was administered. (MS)

  11. Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

    SciTech Connect

    Zhou, Dongwen; Chung, Suhman; Miller, Maria; Le Grice, Stuart F.J.; Wlodawer, Alexander

    2012-06-19

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site {alpha}-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with {beta}-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

  12. Myocardin-Related Transcription Factor A Activation by Competition with WH2 Domain Proteins for Actin Binding

    PubMed Central

    Weissbach, Julia; Schikora, Franziska; Weber, Anja; Kessels, Michael

    2016-01-01

    The myocardin-related transcription factors (MRTFs) are coactivators of serum response factor (SRF)-mediated gene expression. Activation of MRTF-A occurs in response to alterations in actin dynamics and critically requires the dissociation of repressive G-actin–MRTF-A complexes. However, the mechanism leading to the release of MRTF-A remains unclear. Here we show that WH2 domains compete directly with MRTF-A for actin binding. Actin nucleation-promoting factors, such as N-WASP and WAVE2, as well as isolated WH2 domains, including those of Spire2 and Cobl, activate MRTF-A independently of changes in actin dynamics. Simultaneous inhibition of Arp2-Arp3 or mutation of the CA region only partially reduces MRTF-A activation by N-WASP and WAVE2. Recombinant WH2 domains and the RPEL domain of MRTF-A bind mutually exclusively to cellular and purified G-actin in vitro. The competition by different WH2 domains correlates with MRTF-SRF activation. Following serum stimulation, nonpolymerizable actin dissociates from MRTF-A, and de novo formation of the G-actin–RPEL complex is impaired by a transferable factor. Our work demonstrates that WH2 domains activate MRTF-A and contribute to target gene regulation by a competitive mechanism, independently of their role in actin filament formation. PMID:26976641

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

    PubMed Central

    Ravagnani, Adriana; Finan, Christopher L; Young, Michael

    2005-01-01

    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. PMID:15774001

  14. Molecular evolution and domain structure of plasminogen-related growth factors (HGF/SF and HGF1/MSP).

    PubMed Central

    Donate, L. E.; Gherardi, E.; Srinivasan, N.; Sowdhamini, R.; Aparicio, S.; Blundell, T. L.

    1994-01-01

    Plasminogen-related growth factors, a new family of polypeptide growth factors with the basic domain organization and mechanism of activation of the blood proteinase plasminogen, include hepatocyte growth factor/scatter factor (HGF/SF), a potent effector of the growth, movement, and differentiation of epithelia and endothelia, and hepatocyte growth factor-like/macrophage stimulating protein (HGF1/MSP), an effector of macrophage chemotaxis and phagocytosis. Phylogeny of the serine proteinase domains and analysis of intron-exon boundaries and kringle sequences indicate that HGF/SF, HGF1/MSP, plasminogen, and apolipoprotein (a) have evolved from a common ancestral gene that consisted of an N-terminal domain corresponding to plasminogen activation peptide (PAP), 3 copies of the kringle domain, and a serine proteinase domain. Models of the N domains of HGF/SF, HGF1/MSP, and plasminogen, characterized by the presence of 4 conserved Cys residues forming a loop in a loop, have been modeled based on disulfide-bond constraints. There is a distinct pattern of charged and hydrophobic residues in the helix-strand-helix motif proposed for the PAP domain of HGF/SF; these may be important for receptor interaction. Three-dimensional structures of the 4 kringle and the serine proteinase domains of HGF/SF were constructed by comparative modeling using the suite of programs COMPOSER and were energy minimized. Docking of a lysine analogue indicates a putative lysine-binding pocket within kringle 2 (and possibly another in kringle 4). The models suggest a mechanism for the formation of a noncovalent HGF/SF homodimer that may be responsible for the activation of the Met receptor. These data provide evidence for the divergent evolution and structural similarity of plasminogen, HGF/SF, and HGF1/MSP, and highlight a new strategy for growth factor evolution, namely the adaptation of a proteolytic enzyme to a role in receptor activation. PMID:7756992

  15. Steroidogenic acute regulatory-related lipid transfer domain protein 5 localization and regulation in renal tubules

    PubMed Central

    Chen, Yu-Chyu; Meier, Renate K.; Zheng, Shirong; Khundmiri, Syed J.; Tseng, Michael T.; Lederer, Eleanor D.; Epstein, Paul N.; Clark, Barbara J.

    2009-01-01

    STARD5 is a cytosolic sterol transport protein that is predominantly expressed in liver and kidney. This study provides the first report on STARD5 protein expression and distribution in mouse kidney. Immunohistochemical analysis of C57BL/6J mouse kidney sections revealed that STARD5 is expressed in tubular cells within the renal cortex and medullar regions with no detectable staining within the glomeruli. Within the epithelial cells of proximal renal tubules, STARD5 is present in the cytoplasm with high staining intensity along the apical brush-border membrane. Transmission electronmicroscopy of a renal proximal tubule revealed STARD5 is abundant at the basal domain of the microvilli and localizes mainly in the rough endoplasmic reticulum (ER) with undetectable staining in the Golgi apparatus and mitochondria. Confocal microscopy of STARD5 distribution in HK-2 human proximal tubule cells showed a diffuse punctuate pattern that is distinct from the early endosome marker EEA1 but similar to the ER membrane marker GRP78. Treatment of HK-2 cells with inducers of ER stress increased STARD5 mRNA expression and resulted in redistribution of STARD5 protein to the perinuclear and cell periphery regions. Since recent reports show elevated ER stress response gene expression and increased lipid levels in kidneys from diabetic rodent models, we tested STARD5 and cholesterol levels in kidneys from the OVE26 type I diabetic mouse model. Stard5 mRNA and protein levels are increased 2.8- and 1.5-fold, respectively, in OVE26 diabetic kidneys relative to FVB control kidneys. Renal free cholesterol levels are 44% elevated in the OVE26 mice. Together, our data support STARD5 functioning in kidney, specifically within proximal tubule cells, and suggest a role in ER-associated cholesterol transport. PMID:19474188

  16. Mutational analysis of the NF1 GAP-related domain in neuroectodermal tumors

    SciTech Connect

    Vinanzi, C.; Basso, G.; Perilongo, G.

    1994-09-01

    To try to contribute to the more precise characterization of the function of the NF1 gene in tumorigenesis we have analyzed the most conserved region of its coding sequence, the GAP-related domain (NF1 GRD), which is attributed with tumor suppressor function. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region, in situations such as tumors of neuroepithelial tissues. In these situations, the activity of the NF1 gene product, neurofibromis, a GTPase activating protein, seems to be crucial in regulating the mechanisms of signal transduction mediated by p21 ras. We have studied the NF1 GRD region by PCR amplification of each exon (exons 21-27a) followed by subsequent PAGE and SSCP analysis of the amplification products in 60 primary sporadic neuroectodermal tumors. Our sample included: 14 neuroblastoma, 11 glioblastoma, 8 medulloblastoma, 7 ependimoma, 6 peripheral PNET, 1 ganglioneuroma, 1 glioma, 1 Ewing sarcoma, 1 meningioma and 1 schwannoma. We have not identified structural alterations of the NF1 GRD region in the tumors analysed, with one possible exception now in the process of being characterized. We can conclude that the loss of the NF1 gene tumor suppressor function that might lead or contribute to the development of malignancies in tissues of neuroectodermal origin is not due to structural abnormalities of the region of the gene interacting with p21 ras, either as a negative regulator or as a downstream effector of it. These data, together with the observation that the oncogene ras 21 is not typically mutated in neuroectodermal tumors, and that GTP-ras has been found normally regulated in neurofibromis-deficient melanoma and neuroblastoma cell lines, seem to support the hypothesis that the antioncogene activity of the NF1 gene could be totally independent from its interaction with ras.

  17. Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein.

    PubMed

    Yan, Zhang; Jin, Su; Wei, Zhang; Huilian, Hou; Zhanhai, Yin; Yue, Teng; Juan, Li; Jing, Li; Libo, Yao; Xu, Li

    2014-09-01

    Prostate cancer frequently metastasizes to the skeleton but the underlying mechanism remains largely undefined. Discoidin domain receptor 2 (DDR2) is a member of receptor tyrosine kinase (RTK) family and is activated by collagen binding. This study aimed to investigate the function and detailed mechanism of DDR2 in prostate cancer bone dissemination. Herein we found that DDR2 was strongly expressed in bone-metastatic prostate cancer cells and tissues compared to that in normal controls. Enhanced expression of constitutively activated DDR2 led to elevation in motility and invasiveness of prostate cancer cells, whereas knockdown of DDR2 through specific shRNA caused a dramatic repression. Knockdown of DDR2 in prostate cancer cells resulted in significant decrease in the proliferation, differentiation and function of osteoblast. Over-expression of DDR2 in prostate cancer cells resulted in notable acceleration of osteoclast differentiation and bone resorption, whereas knockdown of DDR2 exhibited the opposite effects. An intrabone injection bone metastasis animal model demonstrated that DDR2 promoted osteolytic metastasis in vivo. Molecular evidence demonstrated that DDR2 regulated the expression, secretion, and promoter activity of parathyroid hormone-related protein (PTHrP), via modulating Runx2 phosphorylation and transactivity. DDR2 was responsive to TGF-β and involved in TGF-β-mediated osteoclast activation and bone resorption. In addition, DDR2 facilitated prostate cancer cells adhere to type I collagen. This study reveals for the first time that DDR2 plays an essential role in prostate cancer bone metastasis. The mechanism disclosure may provide therapeutic targets for the treatment of prostate cancer.

  18. Immunocytochemical distribution of WARP (von Willebrand A domain-related protein) in the inner ear

    PubMed Central

    Duong, Trac; Lopez, Ivan A.; Ishiyama, Akira; Ishiyama, Gail

    2010-01-01

    The basic components of the epithelial, perineural and perivascular basement membranes in the inner ear have been well-documented in several animal models and in the human inner ear. The von Willebrand A domain-related protein (WARP) is an extracellular matrix molecule with restricted expression in cartilage, and a subset of basement membranes in peripheral nerves, muscle and central nervous system vasculature. It has been suggested that WARP have an important role in maintaining the blood-brain barrier. To date no studies on WARP distribution have been performed in the inner that is equipped with an intricate vasculature network. In the present study we determined the distribution of WARP by immunocytochemistry in the human inner ear using auditory and vestibular endorgans microdissected from human temporal bones obtained at autopsy. All subjects (n=5, ages 55-87 years old) had documented normal auditory and vestibular function. We also determined the WARP immunolocalization in the mouse inner ear. WARP-immunoreactivity localized to the vasculature throughout the stroma of the cristae ampullaris, the maculae utricle and saccule in the human and mouse. In the human and mouse inner ear, WARP-immunoreactivity delineated blood vessels located in the stria vascularis, spiral ligament, sub-basilar region, stromal tissue, and the spiral and vestibular ganglia. The distinct localization of WARP in the inner ear vasculature suggests an important role in maintaining its integrity. In addition, WARP allows delineation of microvessels in the inner ear allowing the study of vascular pathology in the development of otological diseases. PMID:20971096

  19. Comparative Analysis of Barophily-Related Amino Acid Content in Protein Domains of Pyrococcus abyssi and Pyrococcus furiosus

    PubMed Central

    Yafremava, Liudmila S.; Di Giulio, Massimo; Caetano-Anollés, Gustavo

    2013-01-01

    Amino acid substitution patterns between the nonbarophilic Pyrococcus furiosus and its barophilic relative P. abyssi confirm that hydrostatic pressure asymmetry indices reflect the extent to which amino acids are preferred by barophilic archaeal organisms. Substitution patterns in entire protein sequences, shared protein domains defined at fold superfamily level, domains in homologous sequence pairs, and domains of very ancient and very recent origin now provide further clues about the environment that led to the genetic code and diversified life. The pyrococcal proteomes are very similar and share a very early ancestor. Relative amino acid abundance analyses showed that biases in the use of amino acids are due to their shared fold superfamilies. Within these repertoires, only two of the five amino acids that are preferentially barophilic, aspartic acid and arginine, displayed this preference significantly and consistently across structure and in domains appearing in the ancestor. The more primordial asparagine, lysine and threonine displayed a consistent preference for nonbarophily across structure and in the ancestor. Since barophilic preferences are already evident in ancient domains that are at least ~3 billion year old, we conclude that barophily is a very ancient trait that unfolded concurrently with genetic idiosyncrasies in convergence towards a universal code. PMID:24187517

  20. How Working Memory Relates to Children's Reading Comprehension: The Importance of Domain-Specificity in Storage and Processing

    ERIC Educational Resources Information Center

    Nouwens, Suzan; Groen, Margriet A.; Verhoeven, Ludo

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the current study, we investigated the contribution of…

  1. How Working Memory Relates to Children's Reading Comprehension: The Importance of Domain-Specificity in Storage and Processing

    ERIC Educational Resources Information Center

    Nouwens, Suzan; Groen, Margriet A.; Verhoeven, Ludo

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the current study, we investigated the contribution of…

  2. Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

    PubMed

    Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

    2013-01-01

    In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

  3. BC-box protein domain-related mechanism for VHL protein degradation

    PubMed Central

    Pozzebon, Maria Elena; Varadaraj, Archana; Mattoscio, Domenico; Jaffray, Ellis G.; Miccolo, Claudia; Galimberti, Viviana; Tommasino, Massimo; Hay, Ronald T.; Chiocca, Susanna

    2013-01-01

    The tumor suppressor VHL (von Hippel–Lindau) protein is a substrate receptor for Ubiquitin Cullin Ring Ligase complexes (CRLs), containing a BC-box domain that associates to the adaptor Elongin B/C. VHL targets hypoxia-inducible factor 1α to proteasome-dependent degradation. Gam1 is an adenoviral protein, which also possesses a BC-box domain that interacts with the host Elongin B/C, thereby acting as a viral substrate receptor. Gam1 associates with both Cullin2 and Cullin5 to form CRL complexes targeting the host protein SUMO enzyme SAE1 for proteasomal degradation. We show that Gam1 protein expression induces VHL protein degradation leading to hypoxia-inducible factor 1α stabilization and induction of its downstream targets. We also characterize the CRL-dependent mechanism that drives VHL protein degradation via proteasome. Interestingly, expression of Suppressor of Cytokine Signaling (SOCS) domain-containing viral proteins and cellular BC-box proteins leads to VHL protein degradation, in a SOCS domain-containing manner. Our work underscores the exquisite ability of viral domains to uncover new regulatory mechanisms by hijacking key cellular proteins. PMID:24145437

  4. Putative chitin synthases from Branchiostoma floridae show extracellular matrix-related domains and mosaic structures.

    PubMed

    Guerriero, Gea

    2012-08-01

    The transition from unicellular to multicellular life forms requires the development of a specialized structural component, the extracellular matrix (ECM). In Metazoans, there are two main supportive systems, which are based on chitin and collagen/hyaluronan, respectively. Chitin is the major constituent of fungal cell walls and arthropod exoskeleton. However, presence of chitin/chitooligosaccharides has been reported in lower chordates and during specific stages of vertebrate development. In this study, the occurrence of chitin synthases (CHSs) was investigated with a bioinformatics approach in the cephalochordate Branchiostoma floridae, in which the presence of chitin was initially reported in the skeletal rods of the pharyngeal gill basket. Twelve genes coding for proteins containing conserved amino acid residues of processive glycosyltransferases from GT2 family were found and 10 of them display mosaic structures with novel domains never reported previously in a chitin synthase. In particular, the presence of a discoidin (DS) and a sterile alpha motif (SAM) domain was found in nine identified proteins. Sequence analyses and homology modelling suggest that these domains might interact with the extracellular matrix and mediate protein-protein interaction. The multi-domain putative chitin synthases from B. floridae constitute an emblematic example of the explosion of domain innovation and shuffling which predate Metazoans.

  5. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: role of Jumonji C-domain containing protein 6 in RHA demethylation.

    PubMed

    Lawrence, Paul; Conderino, Joseph S; Rieder, Elizabeth

    2014-03-01

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication.

  6. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: Role of Jumonji C-domain containing protein 6 in RHA demethylation

    SciTech Connect

    Lawrence, Paul; Conderino, Joseph S.; Rieder, Elizabeth

    2014-03-15

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication. - Highlights: • We examined the role of JMJD6 in FMDV-induced RHA demethylation process. • Using an arginine demethylation assay showed that JMJD6 is involved in RHA demethylation. • A demethylases inhibitor reduced cytoplasmic accumulation of RHA and FMDV titers.

  7. Dielectric permittivity of room temperature ionic liquids: a relation to the polar and nonpolar domain structures.

    PubMed

    Mizoshiri, Makoto; Nagao, Takena; Mizoguchi, Yuri; Yao, Makoto

    2010-04-28

    We measured microwave transmission and reflection spectra for typical room temperature ionic liquids, [C(4)min][TFSA], [C(4)min][PF(6)], [C(6)min][PF(6)], and [C(8)min][PF(6)], at frequencies between 40 MHz and 40 GHz in the temperature range up to 100 degrees C. The transmission spectra were analyzed using complex dielectric functions, and the static permittivity epsilon(S) was determined as a function of temperature. Applying the effective medium approximation to epsilon(S), we have estimated that the static permittivity of the polar domain is around 20, and that of the nonpolar domain around 2.5.

  8. The new health-related top-level domains are coming: will cureforcancer.health go to the highest bidder?

    PubMed

    Eysenbach, Gunther

    2014-03-05

    In 2012, the Internet Corporation for Assigned Names and Numbers (ICANN) opened a new round of applications for generic top-level domain (gTLD) names, receiving 1930 applications, of which at least 18 were related to health (eg, ".doctor", ".health", ".med"). The entry of new, commercial players applying to create health-related names reopens the debate on the role of international organizations, governments, non-governmental organizations, and other stakeholders regarding the safeguards and policies needed to protect consumers.

  9. PDZ domain protein GIPC interacts with the cytoplasmic tail of melanosomal membrane protein gp75 (tyrosinase-related protein-1).

    PubMed

    Liu, T F; Kandala, G; Setaluri, V

    2001-09-21

    Tyrosinase and tyrosinase-related proteins (TRPs) are a family of melanosomal membrane proteins involved in mammalian pigmentation. Whereas the melanogenic functions of TRPs are localized in their amino-terminal domains that reside within the lumen of melanosomes, the sorting and targeting of these proteins to melanosomes is mediated by signals in their cytoplasmic domains. To identify proteins that interact with the cytoplasmic tail of gp75 (TRP-1), the most abundant melanosomal membrane protein, we performed yeast two-hybrid screening of a melanocyte cDNA library. Here, we show that the cytoplasmic domain of gp75 interacts with a PDZ domain-containing protein. The gp75-interacting protein is identical to GIPC, an RGS (regulator of G protein signaling)/GAIP-interacting protein, and to SEMCAP-1, a transmembrane semaphorin-binding protein. Carboxyl-terminal amino acid residues, Ser-Val-Val, of gp75 are necessary and sufficient for interaction of gp75 with the single PDZ domain in GIPC. Although endogenous and transfected GIPCs bind efficiently to transiently expressed gp75, only a small amount of GIPC is found associated with gp75 at steady state. Using a strategy to selectively synchronize the biosynthesis of endogenous gp75, we demonstrate that only newly synthesized gp75 associates with GIPC, primarily in the juxtanuclear Golgi region. Our data suggest that GIPC/SEMCAP-1 plays a role in biosynthetic sorting of proteins, specifically gp75, to melanosomes.

  10. Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3).

    PubMed

    Qi, Shiqian; O'Hayre, Morgan; Gutkind, J Silvio; Hurley, James H

    2014-02-21

    After protracted stimulation, the β2-adrenergic receptor and many other G-protein-coupled receptors are ubiquitinated and down-regulated. Arrestin-related domain-containing protein-3 (ARRDC3) has been proposed to recruit the ubiquitin ligase Nedd4 to the β2-adrenergic receptor. ARRDC3 contains two PPXY motifs that could potentially interact with any of the four WW domains of Nedd4. Here we dissect the interaction determinants. ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 μM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. Structures of the uncomplexed and PPXY1-bound WW3 domain were determined at 1.1 and 1.7 Å resolution. The structures revealed conformational changes upon binding and the hydrogen bonding network in exquisite detail. Tight packing of ARRDC3 Val-352', part of a 310 helix at the C terminus of PPXY1, is important for high affinity binding to WW3. Although no single WW domain is strictly essential for the binding of Nedd4 and ARRDC3 expressed in HEK293 cells, high affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations, with Kd values as low as 300 nM.

  11. Intracellular coiled-coil domain engaged in subunit interaction and assembly of melastatin-related transient receptor potential channel 2

    PubMed Central

    Mei, Zhu-Zhong; Xia, Rong; Beech, David J; Jiang, Lin-Hua

    2006-01-01

    TRPM2 channels, activated by adenosine diphosphoribose (ADPR) and related molecules, are assembled as oligomers and most likely tetramers. However, the molecular determinants driving the subunit interaction and assembly of the TRPM2 channels are not well defined. Here we examined, using site-directed mutagenesis in conjunction with co-immunoprecipitation and patch clamp recording, the role of a coiled-coil domain in the intracellular C-terminus of TRPM2 subunit in the subunit interaction and the channel assembly. Deletion of the coiled-coil domain resulted in severe disruption of the subunit interaction and substantial loss of the ADPR-evoked channel currents. Individual or combined mutations to glutamine of the hydrophobic residues at positions a and d of the abcdef heptad repeat, key residues for protein-protein interaction, significantly reduced the subunit interaction and the channel currents; the mutational effects on the subunit interaction and the channel currents were clearly correlated. Furthermore, deletion of the coiled-coil domain in a pore mutant subunit abolished its dominant negative phenotypic functional suppression. These results provide strong evidence that the coiled-coil domain is critically engaged in the TRPM2 subunit interaction and such interaction is required for assembly of functional TRPM2 channel. The coiled-coil domain, which is highly conserved within the TRPM subfamily, may serve as a general structural element governing the assembly of TRPM channels. PMID:17060318

  12. The Separate, Relative, and Joint Effects of Employee Job Performance Domains on Supervisors' Willingness to Mentor

    ERIC Educational Resources Information Center

    Lapierre, Laurent M.; Bonaccio, Silvia; Allen, Tammy D.

    2009-01-01

    The purpose of our study was to further elucidate how employees should behave at work to increase their chances of being mentored by their immediate supervisor. To that end, we experimentally tested how three domains of employee performance [task performance (TP), organizational citizenship behavior (OCB) targeting the supervisor, and…

  13. Grammatical Language Impairment and the Specificity of Cognitive Domains: Relations between Auditory and Language Abilities

    ERIC Educational Resources Information Center

    van der Lely, Heather K. J.; Rosen, Stuart; Adlard, Alan

    2004-01-01

    Grammatical-specific language impairment (G-SLI) in children, arguably, provides evidence for the existence of a specialised grammatical sub-system in the brain, necessary for normal language development. Some researchers challenge this, claiming that domain-general, low-level auditory deficits, particular to rapid processing, cause phonological…

  14. Domain-Specific Self-Concept in Relation to Traditional and Cyber Peer Aggression

    ERIC Educational Resources Information Center

    Toledano, Shanee; Werch, Brittany L.; Wiens, Brenda A.

    2015-01-01

    Individuals who aggress against others have been described both as having overall low self-concept and as having high, inflated self-concept. The conceptualization of self-concept as domain specific provides an alternate means to resolving this controversy. In this study, 223 middle school students completed self-report measures assessing…

  15. Preschool Children's Conceptions of Trangressions: Effects of Varying Moral and Conventional Domain-Related Attributes.

    ERIC Educational Resources Information Center

    Smetana, Judith G.

    1985-01-01

    Preschool children reasoned and made judgments about stories that varied in dimensions previously found to be associated with judgments in two social-cognitive domains, moral and conventional, to examine types of information that produce differentiated judgments in young children. (Author/DST)

  16. Modulation of neurotransmitter receptors and synaptic differentiation by proteins containing complement-related domains.

    PubMed

    Nakayama, Minoru; Hama, Chihiro

    2011-02-01

    Neurotransmitter receptors play central roles in basic neurotransmission and synaptic plasticity. Recent studies have revealed that some transmembrane and extracellular proteins bind to neurotransmitter receptors, forming protein complexes that are required for proper synaptic localization or gating of core receptor molecules. Consequently, the components of these complexes contribute to long-term potentiation, a process that is critical for learning and memory. Here, we review factors that regulate neurotransmitter receptors, with a focus on proteins containing CUB (complement C1r/C1s, Uegf, Bmp1) or CCP (complement control protein) domains, which are frequently found in complement system proteins. Proteins that contain these domains are structurally distinct from TARPs (transmembrane AMPA receptor regulatory proteins), and may constitute new protein families that modulate either the localization or function of neurotransmitter receptors. In addition, other CCP domain-containing proteins participate in dendritic patterning and/or synaptic differentiation, although current evidence has not identified any direct activities on neurotransmitter receptors. Some of these proteins are involved in pathologic conditions such as epileptic seizure and mental retardation. Together, these lines of information have shown that CUB and CCP domain-containing proteins contribute to a wide variety of neuronal events that ultimately establish neural circuits.

  17. Moral/Non-Moral Domain Shift in Young Adolescents in Relation to Delinquent Behaviour

    ERIC Educational Resources Information Center

    Leenders, Ineke; Brugman, Daniel

    2005-01-01

    Because moral transgressions are considered more serious than non-moral (i.e. conventional or personal) transgressions, it is less threatening to self-esteem to interpret one's own delinquent act as a non-moral transgression rather than a moral transgression. This 'domain shift' could be a way of reducing cognitive dissonance. It was expected that…

  18. Boundary shape identification problems in two-dimensional domains related to thermal testing of materials

    NASA Technical Reports Server (NTRS)

    Banks, H. T.; Kojima, Fumio

    1988-01-01

    The identification of the geometrical structure of the system boundary for a two-dimensional diffusion system is reported. The domain identification problem treated here is converted into an optimization problem based on a fit-to-data criterion and theoretical convergence results for approximate identification techniques are discussed. Results of numerical experiments to demonstrate the efficacy of the theoretical ideas are reported.

  19. Domain-Specific Self-Concept in Relation to Traditional and Cyber Peer Aggression

    ERIC Educational Resources Information Center

    Toledano, Shanee; Werch, Brittany L.; Wiens, Brenda A.

    2015-01-01

    Individuals who aggress against others have been described both as having overall low self-concept and as having high, inflated self-concept. The conceptualization of self-concept as domain specific provides an alternate means to resolving this controversy. In this study, 223 middle school students completed self-report measures assessing…

  20. The Relative Influence of Different Domains of Social Connectedness on Self-Directed Violence in Adolescence

    ERIC Educational Resources Information Center

    Kaminski, Jennifer W.; Puddy, Richard W.; Hall, Diane M.; Cashman, Sandra Y.; Crosby, Alexander E.; Ortega, LaVonne A. G.

    2010-01-01

    Previous research has linked greater social connectedness with a lowered risk of self-directed violence among adolescents. However, few studies have analyzed the comparative strength of different domains of connectedness (e.g., family, peers and school) to determine where limited resources might best be focused. Data to address that gap were taken…

  1. VASCULAR-RELATED NAC-DOMAIN6 and VASCULAR-RELATED NAC-DOMAIN7 Effectively Induce Transdifferentiation into Xylem Vessel Elements under Control of an Induction System1[W

    PubMed Central

    Yamaguchi, Masatoshi; Goué, Nadia; Igarashi, Hisako; Ohtani, Misato; Nakano, Yoshimi; Mortimer, Jennifer C.; Nishikubo, Nobuyuki; Kubo, Minoru; Katayama, Yoshihiro; Kakegawa, Koichi; Dupree, Paul; Demura, Taku

    2010-01-01

    We previously showed that the VASCULAR-RELATED NAC-DOMAIN6 (VND6) and VND7 genes, which encode NAM/ATAF/CUC domain protein transcription factors, act as key regulators of xylem vessel differentiation. Here, we report a glucocorticoid-mediated posttranslational induction system of VND6 and VND7. In this system, VND6 or VND7 is expressed as a fused protein with the activation domain of the herpes virus VP16 protein and hormone-binding domain of the animal glucocorticoid receptor, and the protein's activity is induced by treatment with dexamethasone (DEX), a glucocorticoid derivative. Upon DEX treatment, transgenic Arabidopsis (Arabidopsis thaliana) plants carrying the chimeric gene exhibited transdifferentiation of various types of cells into xylem vessel elements, and the plants died. Many genes involved in xylem vessel differentiation, such as secondary wall biosynthesis and programmed cell death, were up-regulated in these plants after DEX treatment. Chemical analysis showed that xylan, a major hemicellulose component of the dicot secondary cell wall, was increased in the transgenic plants after DEX treatment. This induction system worked in poplar (Populus tremula × tremuloides) trees and in suspension cultures of cells from Arabidopsis and tobacco (Nicotiana tabacum); more than 90% of the tobacco BY-2 cells expressing VND7-VP16-GR transdifferentiated into xylem vessel elements after DEX treatment. These data demonstrate that the induction systems controlling VND6 and VND7 activities can be used as powerful tools for understanding xylem cell differentiation. PMID:20488898

  2. Telomere Capping Proteins are Structurally Related to RPA with an additional Telomere-Specific Domain

    SciTech Connect

    Gelinas, A.; Paschini, M; Reyes, F; Heroux, A; Batey, R; Lundblad, V; Wuttke, D

    2009-01-01

    Telomeres must be capped to preserve chromosomal stability. The conserved Stn1 and Ten1 proteins are required for proper capping of the telomere, although the mechanistic details of how they contribute to telomere maintenance are unclear. Here, we report the crystal structures of the C-terminal domain of the Saccharomyces cerevisiae Stn1 and the Schizosaccharomyces pombe Ten1 proteins. These structures reveal striking similarities to corresponding subunits in the replication protein A complex, further supporting an evolutionary link between telomere maintenance proteins and DNA repair complexes. Our structural and in vivo data of Stn1 identify a new domain that has evolved to support a telomere-specific role in chromosome maintenance. These findings endorse a model of an evolutionarily conserved mechanism of DNA maintenance that has developed as a result of increased chromosomal structural complexity.

  3. Structural priming across cognitive domains: from simple arithmetic to relative-clause attachment.

    PubMed

    Scheepers, Christoph; Sturt, Patrick; Martin, Catherine J; Myachykov, Andriy; Teevan, Kay; Viskupova, Izabela

    2011-10-01

    In the two experiments reported here, we uncovered evidence for shared structural representations between arithmetic and language. Specifically, we primed subjects using mathematical equations either with or without parenthetical groupings, such as 80 - (9 + 1) × 5 or 80 - 9 + 1 × 5, and then presented a target sentence fragment, such as "The tourist guide mentioned the bells of the church that . . .," which subjects had to complete. When the mathematical equations were solved correctly, their structure influenced the noun phrase--for example, either "the bells of the church" or "the church," respectively--that subjects chose to attach their sentence completion to. These experiments provide the first demonstration of cross-domain structural priming from mathematics to language. They highlight the importance of global structural representations at a very high level of abstraction and have potentially far-reaching implications regarding the domain generality of structural representations.

  4. Mapping domain structures in silks from insects and spiders related to protein assembly.

    PubMed

    Bini, Elisabetta; Knight, David P; Kaplan, David L

    2004-01-02

    The exceptional solubility in vivo (20-30%, w/v) of the silk proteins of insects and spiders is dictated by both the need to produce solid fibres with a high packing fraction and the high mesogen concentration required for lyotropic liquid crystalline spinning. A further design requirement for silk proteins is a strong predominance of hydrophobic amino acid residues to provide for the hydrophobic interactions, water exclusion, and beta-crystallite formation required to produce strong insoluble threads. Thus, the domain structure of silk proteins needs to enable nanoscale phase separation to achieve high solubility of hydrophobic proteins in aqueous solutions. Additionally, silk proteins need to avoid premature precipitation as beta-sheets during storage and processing. Here we use mapping of domain types, sizes and distributions in silks to identify consistent design features that have evolved to meet these requirements. We show that silk proteins consist of conspicuously hydrophilic terminal domains flanking a very long central portion constructed from hydrophobic blocks separated by hydrophilic ones, discussing the domain structure in detail. The general rules of construction for silk proteins based on our observations should give a useful guide to the way in which Nature has solved the problem of processing hydrophobic proteins in water and how this can be copied industrially. Following these rules may also help in obtaining adequate expression, soluble products and controllable conformational switches in the production of genetically engineered or chemically synthesized silk analogues. Thus these insights have implications for structural biology and relevance to fundamental and applied questions in material science and engineering.

  5. Structural Analyses of the Ankyrin Repeat Domain of TRPV6 and Related TRPV Ion Channels

    SciTech Connect

    Phelps, C.B.; Huang, R.J.; Lishko, P.V.; Wang, R.R.; Gaudet, R.

    2008-06-03

    Transient receptor potential (TRP) proteins are cation channels composed of a transmembrane domain flanked by large N- and C-terminal cytoplasmic domains. All members of the vanilloid family of TRP channels (TRPV) possess an N-terminal ankyrin repeat domain (ARD). The ARD of mammalian TRPV6, an important regulator of calcium uptake and homeostasis, is essential for channel assembly and regulation. The 1.7 A crystal structure of the TRPV6-ARD reveals conserved structural elements unique to the ARDs of TRPV proteins. First, a large twist between the fourth and fifth repeats is induced by residues conserved in all TRPV ARDs. Second, the third finger loop is the most variable region in sequence, length and conformation. In TRPV6, a number of putative regulatory phosphorylation sites map to the base of this third finger. Size exclusion chromatography and crystal packing indicate that the TRPV6-ARD does not assemble as a tetramer and is monomeric in solution. Adenosine triphosphate-agarose and calmodulin-agarose pull-down assays show that the TRPV6-ARD does not interact with either ligand, indicating a different functional role for the TRPV6-ARD than in the paralogous thermosensitive TRPV1 channel. Similar biochemical findings are also presented for the highly homologous mammalian TRPV5-ARD. The implications of the structural and biochemical data on the role of the ankyrin repeats in different TRPV channels are discussed.

  6. Persistent Complex Bereavement Disorder Symptom Domains Relate Differentially to PTSD and Depression: A Study of War-Exposed Bosnian Adolescents.

    PubMed

    Claycomb, Meredith A; Charak, Ruby; Kaplow, Julie; Layne, Christopher M; Pynoos, Robert; Elhai, Jon D

    2016-10-01

    Persistent Complex Bereavement Disorder (PCBD) is a newly proposed diagnosis placed in the Appendix of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as an invitation for further research. To date, no studies have examined the dimensionality of PCBD or explored whether different PCBD criteria domains relate in similar, versus differential, ways to other psychological conditions common to war-exposed bereaved youth, including symptoms of Posttraumatic Stress Disorder (PTSD) and depression. We evaluated the dimensionality of proposed PCBD B and C symptom domains, and their respective relations with measures of PTSD and depression, in 1142 bereaved Bosnian adolescents exposed to the 1992-1995 Bosnian civil war. Instruments included the UCLA PTSD Reaction Index, the Depression Self-Rating Scale, and the UCLA Grief Screening Scale (a prototype measure of PCBD symptoms). We investigated potential differences in grief, PTSD, and depression scores as a function of cause of death. We then examined hypothesized differential relations between PCBD B and C symptom domain subscales and selected external correlates, specifically measures of depression and the four-factor emotional numbing model of PTSD. Results of both analyses provide preliminary evidence of a multidimensional structure for PCBD in this population, in that the PCBD Criterion C subscale score covaried more strongly with each of the four PTSD factors and with depression than did PCBD Criterion B. We conclude by discussing theoretical, methodological, clinical, and policy-related implications linked to the ongoing study of essential features of PCBD.

  7. Multivariate trajectories across multiple domains of health-related quality of life in children with new-onset epilepsy.

    PubMed

    Sajobi, Tolulope T; Wang, Meng; Ferro, Mark A; Brobbey, Anita; Goodwin, Shane; Speechley, Kathy N; Wiebe, Samuel

    2017-10-01

    The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified

  8. [Interspecific polymorphism of the glucosyltransferase domain of the sucrose synthase gene in the genus Malus and related species of Rosaceae].

    PubMed

    Boris, K V; Kochieva, E Z; Kudryavtsev, A M

    2014-12-01

    The sequences that encode the main functional glucosyltransferase domain of sucrose synthase genes have been identified for the first time in 14 species of the genus Malus and related species of the family Rosaceae, and their polymorphism was investigated. Single nucleotide substitutions leading to amino acid substitutions in the protein sequence, including the conservative transmembrane motif sequence common to all sucrose synthase genes of higher plants, were detected in the studied sequences.

  9. A novel Krueppel related factor consisting of only a KRAB domain is expressed in the murine trigeminal ganglion

    SciTech Connect

    Nikulina, Karina; Bodeker, MacDara; Warren, John; Matthews, Philip; Margolis, Todd P. . E-mail: todd.margolis@ucsf.edu

    2006-09-29

    The largest family of zinc-finger (ZnF) transcription factors is that containing the Krueppel-associated box, or KRAB domain. The amino-terminal KRAB domain of these proteins functions as a transcriptional repressor with the downstream ZnF motifs providing DNA-binding specificity. Here we report the identification and characterization of a novel murine Krueppel-related factor (KLF), MIF1, which contains a KRAB domain but lacks a ZnF motif. Western blot analysis identified MIF1-like proteins in the murine trigeminal ganglion (TG) and immunostaining localized these proteins primarily to the cytoplasm of TG neuronal cell bodies. In situ hybridization for Mif1 transcripts confirms the selective expression of Mif1 in TG neurons. Consistent with the non-nuclear localization of MIF1 we could detect no transcriptional repressor activity of the MIF1 protein. However MIF1 appears to be capable of interacting with the co-repressor TIF1{beta} and exhibits transcription repressor activity when fused to yeast GAL4 binding domain protein. Genomic analysis of Mif1 sequence suggests that the Mif1 transcript may result from splicing of a longer KRAB-ZnF containing transcript.

  10. An exact solution for a thick domain wall in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    An exact solution of the Einstein equations for a static, planar domain wall with finite thickness is presented. At infinity, density and pressure vanish and the space-time tends to the Minkowski vacuum on one side of the wall and to the Taub vacuum on the other side. A surprising feature of this solution is that the density and pressure distribution are symmetric about the central plane of the wall whereas the space-time metric and therefore also the gravitational field experienced by a test particle is asymmetric.

  11. Cognitive Composites Domain Scores Related to Neuroimaging Biomarkers within Probable-Amnestic Mild Cognitive Impairment-Storage Subtype.

    PubMed

    Espinosa, Ana; Alegret, Montserrat; Pesini, Pedro; Valero, Sergi; Lafuente, Asunción; Buendía, Mar; San José, Itziar; Ibarria, Marta; Tejero, Miguel A; Giménez, Joan; Ruiz, Susana; Hernández, Isabel; Pujadas, Francesc; Martínez-Lage, Pablo; Munuera, Josep; Arbizu, Javier; Tárraga, Lluis; Hendrix, Suzanne B; Ruiz, Agustín; Becker, James T; Landau, Susan M; Sotolongo-Grau, Oscar; Sarasa, Manuel; Boada, Mercè

    2017-01-01

    The probable-amnestic (Pr-a) mild cognitive impairment (MCI)-storage subtype is a phenotype with 8.5 times more risk of conversion to dementia, mainly Alzheimer's disease (AD), than the possible non-amnestic (Pss-na) MCI. The aim of this study was to find the optimized cognitive composites (CCs) domain scores most related to neuroimaging biomarkers within Pr-aMCI-storage subtype patients. The Fundació ACE (ACE) study with 20 Pr-aMCI-storage subtype subjects (MCI) were analyzed. All subjects underwent a neuropsychological assessment, a structural MRI, FDG-PET, and PIB-PET. The adjusted hippocampal volume (aHV) on MRI, the standard uptake value ratio (SUVR) on FDG-PET and PIB-PET SUVR measures were analyzed. The construction of the CCs domain scores, and the aHV on MRI and FDG-PET SUVR measures, were replicated in the parental AB255 study database (n = 133 MCI). Partial correlations adjusted by age, gender, and education were calculated with the associated p-value among every CC domain score and the neuroimaging biomarkers. The results were replicated in the "MCI due to AD" with memory storage impairments from ADNI. Delayed Recall CC domain score was significantly correlated with PIB-PET SUVR (β= -0.61, p = 0.003) in the ACE study and also with aHV on MRI (β= 0.27, p = 0.01) and FDG-PET SUVR (β= 0.27, p = 0.01) in the AB255 study. After a median survival time of 20.6 months, 85% from the ACE MCI converted to AD. The replication of our results in the ADNI dataset also confirmed our findings. Delayed Recall is the CC domain score best correlated with neuroimaging biomarkers associated with prodromal AD diagnosis.

  12. Cognitive Composites Domain Scores Related to Neuroimaging Biomarkers within Probable-Amnestic Mild Cognitive Impairment-Storage Subtype

    PubMed Central

    Espinosa, Ana; Alegret, Montserrat; Pesini, Pedro; Valero, Sergi; Lafuente, Asunción; Buendía, Mar; San José, Itziar; Ibarria, Marta; Tejero, Miguel A.; Giménez, Joan; Ruiz, Susana; Hernández, Isabel; Pujadas, Francesc; Martínez-Lage, Pablo; Munuera, Josep; Arbizu, Javier; Tárraga, Lluis; Hendrix, Suzanne B.; Ruiz, Agustín; Becker, James T.; Landau, Susan M.; Sotolongo-Grau, Oscar; Sarasa, Manuel; Boada, Mercè

    2017-01-01

    The probable-amnestic (Pr-a) mild cognitive impairment (MCI)-storage subtype is a phenotype with 8.5 times more risk of conversion to dementia, mainly Alzheimer’s disease (AD), than the possible non-amnestic (Pss-na) MCI. The aim of this study was to find the optimized cognitive composites (CCs) domain scores most related to neuroimaging biomarkers within Pr-aMCI-storage subtype patients. The Fundació ACE (ACE) study with 20 Pr-aMCI-storage subtype subjects (MCI) were analyzed. All subjects underwent a neuropsychological assessment, a structural MRI, FDG-PET, and PIB-PET. The adjusted hippocampal volume (aHV) on MRI, the standard uptake value ratio (SUVR) on FDG-PET and PIB-PET SUVR measures were analyzed. The construction of the CCs domain scores, and the aHV on MRI and FDG-PET SUVR measures, were replicated in the parental AB255 study database (n = 133 MCI). Partial correlations adjusted by age, gender, and education were calculated with the associated p-value among every CC domain score and the neuroimaging biomarkers. The results were replicated in the “MCI due to AD” with memory storage impairments from ADNI. Delayed Recall CC domain score was significantly correlated with PIB-PET SUVR (β= –0.61, p = 0.003) in the ACE study and also with aHV on MRI (β= 0.27, p = 0.01) and FDG-PET SUVR (β= 0.27, p = 0.01) in the AB255 study. After a median survival time of 20.6 months, 85% from the ACE MCI converted to AD. The replication of our results in the ADNI dataset also confirmed our findings. Delayed Recall is the CC domain score best correlated with neuroimaging biomarkers associated with prodromal AD diagnosis. PMID:28269787

  13. Identification of Scoliosis Research Society-22r Health-Related Quality of Life questionnaire domains using factor analysis methodology.

    PubMed

    Lai, Sue-Min; Asher, Marc A; Burton, Douglas C; Carlson, Brandon B

    2010-05-20

    Cross-sectional mail questionnaire. Examination of the underlying construct validity of the Scoliosis Research Society-22r (SRS-22r) Health-Related Quality of Life (HRQoL) Questionnaire using factor analysis. The original SRS-24 HRQoL questionnaire has undergone a series of modifications in an effort to further improve its psychometric properties and validate its use in patients from 10 years of age until well into adulthood. The SRS-22r questionnaire is the result of this effort. To date, the underlying construct validity of the original English version has not been analyzed by factor analysis. A questionnaire including all questions on the SRS-24, -23, -22, and -22r questionnaires (49 total questions) was mailed to a consecutive series of 235 patients who had received primary posterior or anterior instrumentation and arthrodesis. Domain structure of the SRS-22r questions was analyzed using iterated principal factor analysis with orthogonal rotation. One hundred twenty-one (51%) of the patients, age 23.34 +/- 4.52 years (range, 14.16-34.57 years), returned the questionnaire at 8.63 +/- 4.00 years (range, 2.32-15.94 years) following surgery. Factor analysis using all 22 questions resulted in 3 factors with many shared items because of significant collinearity of the satisfaction/dissatisfaction with management questions with the others. After 18 iterations, factor analysis using the 20 nonmanagement questions revealed 4 factors that explained 98% of the variance. These factors parallel the assigned domains of the SRS-22r questionnaire. Three questions (2 self-image and 1 function) were identified that had high loading in 2 factors. However, internal consistency was best when 2 of the questions (1 self-image and 1 function) were retained in their assigned SRS-22r domains and the third decreased self-image internal consistency by only 0.01%. The internal consistencies (Cronbach alpha) of the assigned SRS-22r nonmanagement domains were excellent or very good: function

  14. The New Health-Related Top-Level Domains Are Coming: Will Cureforcancer.health Go to the Highest Bidder?

    PubMed Central

    2014-01-01

    In 2012, the Internet Corporation for Assigned Names and Numbers (ICANN) opened a new round of applications for generic top-level domain (gTLD) names, receiving 1930 applications, of which at least 18 were related to health (eg, “.doctor”, “.health”, “.med”). The entry of new, commercial players applying to create health-related names reopens the debate on the role of international organizations, governments, non-governmental organizations, and other stakeholders regarding the safeguards and policies needed to protect consumers. PMID:24598704

  15. Trait physical disgust is related to moral judgments outside of the purity domain.

    PubMed

    Chapman, Hanah A; Anderson, Adam K

    2014-04-01

    Although there is an emerging consensus that disgust plays a role in human morality, it remains unclear whether this role is limited to transgressions that contain elements of physical disgust (e.g., gory murders, sexual crimes), or whether disgust is also involved in "pure" forms of morality. To address this issue, we examined the relationship between individual differences in the tendency to experience disgust toward physical stimuli (i.e., trait physical disgust) and reactions to pure moral transgressions. Across two studies, individuals higher in trait physical disgust judged moral transgressions to be more wrong than did their low-disgust counterparts, and were also more likely to moralize violations of social convention. Controlling for gender, trait anxiety, trait anger, and social conservatism did not eliminate trait disgust effects. These results suggest that disgust's role in morality is not limited to issues of purity or bodily norms, and that disgust may play a role in setting the boundaries of the moral domain.

  16. Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

    PubMed

    Lee, G L; Pang, G S Y; Akhileswaran, R; Ow, M Y L; Fan, G K T; Wong, C C F; Wee, H L; Cheung, Y B

    2016-03-01

    Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

  17. Extraction of gene-disease relations from Medline using domain dictionaries and machine learning.

    PubMed

    Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

    2006-01-01

    We describe a system that extracts disease-gene relations from Medline. We constructed a dictionary for disease and gene names from six public databases and extracted relation candidates by dictionary matching. Since dictionary matching produces a large number of false positives, we developed a method of machine learning-based named entity recognition (NER) to filter out false recognitions of disease/gene names. We found that the performance of relation extraction is heavily dependent upon the performance of NER filtering and that the filtering improves the precision of relation extraction by 26.7% at the cost of a small reduction in recall.

  18. Team deliberate practice in medicine and related domains: a consideration of the issues.

    PubMed

    Harris, Kevin R; Eccles, David W; Shatzer, John H

    2017-03-01

    A better understanding of the factors influencing medical team performance and accounting for expert medical team performance should benefit medical practice. Therefore, the aim here is to highlight key issues with using deliberate practice to improve medical team performance, especially given the success of deliberate practice for developing individual expert performance in medicine and other domains. Highlighting these issues will inform the development of training for medical teams. The authors first describe team coordination and its critical role in medical teams. Presented next are the cognitive mechanisms that allow expert performers to accurately interpret the current situation via the creation of an accurate mental "model" of the current situation, known as a situation model. Following this, the authors propose that effective team performance depends at least in part on team members having similar models of the situation, known as a shared situation model. The authors then propose guiding principles for implementing team deliberate practice in medicine and describe how team deliberate practice can be used in an attempt to reduce barriers inherent in medical teams to the development of shared situation models. The paper concludes with considerations of limitations, and future research directions, concerning the implementation of team deliberate practice within medicine.

  19. The relative influence of different domains of social connectedness on self-directed violence in adolescence.

    PubMed

    Kaminski, Jennifer W; Puddy, Richard W; Hall, Diane M; Cashman, Sandra Y; Crosby, Alexander E; Ortega, Lavonne A G

    2010-05-01

    Previous research has linked greater social connectedness with a lowered risk of self-directed violence among adolescents. However, few studies have analyzed the comparative strength of different domains of connectedness (e.g., family, peers and school) to determine where limited resources might best be focused. Data to address that gap were taken from the Centers for Disease Control and Prevention's Student Health and Safety Survey, administered to 4,131 7th-12th graders (51.5% female; 43.8% Hispanic; 22.6% African American or Black). Logistic regressions (controlling for age, gender, race/ethnicity, family structure, academic performance, and depressive symptoms) suggest that family connectedness was a stronger predictor than connectedness to peers, school, or adults at school for non-suicidal self-harm, suicidal ideation, suicide plans, and non-fatal suicidal behavior. In some analyses, peer connectedness was unexpectedly a risk factor. Results have implications for prevention of suicide in adolescence, especially in the context of the current trend towards school-based prevention programs.

  20. Expression and purification of human MHC class I-related chain molecule B-α1 domain.

    PubMed

    Wang, Shufen; Xiang, Zemin; Wang, Ya; Xu, Huanhuan; Zhang, Dengyang; Wang, Xuanjun; Sheng, Jun

    2016-07-01

    Major histocompatibility complex (MHC) class I-related chain A/B (MICA/B) is a type of stress-induced molecule that plays an important role in tumor surveillance. MICA/B shares a similar structure with MHC class I molecules, but MICA/B contains a closed cleft, not an open one, in its N-terminal alpha1 domain. The alpha 1 domain was believed to have no roles in antigen presentation, because the closed cleft provides limited space for binding with known molecules, and the cleft of MICA/B have been reported no known functions. To study the possible function of the cleft located in human MICA/B's alpha 1 domain, we attempted to express the human MICB-α1 (hMICB-α1) domain allele protein, which is approximately 20.5 kDa, by utilizing an Escherichia coli (E. coli) secretory pathway. Protein expression was accomplished through the phosphate-limited inducible promoter. After purification using ammonium sulfate precipitation, phenyl hydrophobic Sepharose, SP Sepharose and HisTrap affinity Sepharose, recombinant human MICB-α1 (rhMICB-α1) was obtained with 94.3% purity. The binding capacity of rhMICB-α1 with natural killer group 2, member D (NKG2D) was evaluated in vitro. The results demonstrated that rhMICB-α1 can be prepared through the E. coli secretory pathway. Purified rhMICB-α1 protein was able to functionally bind with NKG2D. This method can be further used to obtain functionally active rhMICB-α1 protein, which can served as the basis for further studies of the possible function of the MICB cleft. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Spatial and temporal frequency domain laser-ultrasound applied in the direct measurement of dispersion relations of surface acoustic waves

    NASA Astrophysics Data System (ADS)

    Grünsteidl, Clemens; Veres, István A.; Roither, Jürgen; Burgholzer, Peter; Murray, Todd W.; Berer, Thomas

    2013-01-01

    We present a laser-ultrasound measurement technique which combines adjustable spatial and temporal modulation of the excitation laser beam. Our method spreads the intensity of an amplitude modulated continuous wave laser over a micro-scale pattern on the sample surface to excite surface acoustic waves. The excitation pattern consists of parallel, equidistant lines and the waves generated from the individual lines interfere on the sample surface. Measurement is done in the spatial-temporal frequency domain allowing the direct determination of dispersion relations. The technique performs with high signal-to-noise-ratios and low peak power densities on the sample.

  2. Demand-Driven Clustering in Relational Domains for Predicting Adverse Drug Events.

    PubMed

    Davis, Jesse; Costa, Vítor Santos; Peissig, Peggy; Caldwell, Michael; Berg, Elizabeth; Page, David

    2012-01-01

    Learning from electronic medical records (EMR) is challenging due to their relational nature and the uncertain dependence between a patient's past and future health status. Statistical relational learning is a natural fit for analyzing EMRs but is less adept at handling their inherent latent structure, such as connections between related medications or diseases. One way to capture the latent structure is via a relational clustering of objects. We propose a novel approach that, instead of pre-clustering the objects, performs a demand-driven clustering during learning. We evaluate our algorithm on three real-world tasks where the goal is to use EMRs to predict whether a patient will have an adverse reaction to a medication. We find that our approach is more accurate than performing no clustering, pre-clustering, and using expert-constructed medical heterarchies.

  3. Demand-Driven Clustering in Relational Domains for Predicting Adverse Drug Events

    PubMed Central

    Davis, Jesse; Costa, Vítor Santos; Peissig, Peggy; Caldwell, Michael; Berg, Elizabeth; Page, David

    2013-01-01

    Learning from electronic medical records (EMR) is challenging due to their relational nature and the uncertain dependence between a patient's past and future health status. Statistical relational learning is a natural fit for analyzing EMRs but is less adept at handling their inherent latent structure, such as connections between related medications or diseases. One way to capture the latent structure is via a relational clustering of objects. We propose a novel approach that, instead of pre-clustering the objects, performs a demand-driven clustering during learning. We evaluate our algorithm on three real-world tasks where the goal is to use EMRs to predict whether a patient will have an adverse reaction to a medication. We find that our approach is more accurate than performing no clustering, pre-clustering, and using expert-constructed medical heterarchies. PMID:25285329

  4. Using Conjoined Rigid Body/Torsion Angle Simulated Annealing to Determine the Relative Orientation of Covalently Linked Protein Domains from Dipolar Couplings

    NASA Astrophysics Data System (ADS)

    Clore, G. Marius; Bewley, Carole A.

    2002-02-01

    A simple and robust method for determining the relative orientations of covalently linked protein domains using conjoined rigid body/torsion angle dynamics simulated annealing on the basis of residual dipolar couplings is presented. In this approach each domain is treated as a rigid body and the relevant degrees of conformational freedom are restricted to the backbone torsion angles (φ, ψ) of the linker between the domains. By this means translational information afforded by the presence of an intact linker is preserved. We illustrate this approach using the domain-swapped dimer of the HIV-inactivating protein cyanovirin-N as an example.

  5. Working memory and language: skill-specific or domain-general relations to mathematics?

    PubMed

    Purpura, David J; Ganley, Colleen M

    2014-06-01

    Children's early mathematics skills develop in a cumulative fashion; foundational skills form a basis for the acquisition of later skills. However, non-mathematical factors such as working memory and language skills have also been linked to mathematical development at a broad level. Unfortunately, little research has been conducted to evaluate the specific relations of these two non-mathematical factors to individual aspects of early mathematics. Thus, the focus of this study was to determine whether working memory and language were related to only individual aspects of early mathematics or related to many components of early mathematics skills. A total of 199 4- to 6-year-old preschool and kindergarten children were assessed on a battery of early mathematics tasks as well as measures of working memory and language. Results indicated that working memory has a specific relation to only a few-but critically important-early mathematics skills and language has a broad relation to nearly all early mathematics skills. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Academic Self-Concept and Emotion Relations: Domain Specificity and Age Effects

    ERIC Educational Resources Information Center

    Goetz, Thomas; Cronjaeger, Hanna; Frenzel, Anne C.; Ludtke, Oliver; Hall, Nathan C.

    2010-01-01

    The present study investigated the relations between academic self-concepts and the emotions of enjoyment, pride, anxiety, anger, and boredom as experienced in mathematics, physics, German, and English classes (N=1710; grades 8 and 11). In line with our hypotheses derived from appraisal-based emotion theories and self-efficacy research,…

  7. Academic Self-Concept and Emotion Relations: Domain Specificity and Age Effects

    ERIC Educational Resources Information Center

    Goetz, Thomas; Cronjaeger, Hanna; Frenzel, Anne C.; Ludtke, Oliver; Hall, Nathan C.

    2010-01-01

    The present study investigated the relations between academic self-concepts and the emotions of enjoyment, pride, anxiety, anger, and boredom as experienced in mathematics, physics, German, and English classes (N=1710; grades 8 and 11). In line with our hypotheses derived from appraisal-based emotion theories and self-efficacy research,…

  8. Quality of Parental Homework Involvement: Predictors and Reciprocal Relations with Academic Functioning in the Reading Domain

    ERIC Educational Resources Information Center

    Dumont, Hanna; Trautwein, Ulrich; Nagy, Gabriel; Nagengast, Benjamin

    2014-01-01

    This study examined predictors of the quality of parental homework involvement and reciprocal relations between the quality of parental homework involvement and students' reading achievement and academic functioning in a reading-intensive subject (German). Data from 2,830 students in nonacademic tracks and their parents who were surveyed in both…

  9. What Is Learned when Concept Learning Fails?--A Theory of Restricted-Domain Relational Learning

    ERIC Educational Resources Information Center

    Wright, Anthony A.; Lickteig, Mark T.

    2010-01-01

    Two matching-to-sample (MTS) and four same/different (S/D) experiments employed tests to distinguish between item-specific learning and relational learning. One MTS experiment showed item-specific learning when concept learning failed (i.e., no novel-stimulus transfer). Another MTS experiment showed item-specific learning when pigeons'…

  10. Quality of Parental Homework Involvement: Predictors and Reciprocal Relations with Academic Functioning in the Reading Domain

    ERIC Educational Resources Information Center

    Dumont, Hanna; Trautwein, Ulrich; Nagy, Gabriel; Nagengast, Benjamin

    2014-01-01

    This study examined predictors of the quality of parental homework involvement and reciprocal relations between the quality of parental homework involvement and students' reading achievement and academic functioning in a reading-intensive subject (German). Data from 2,830 students in nonacademic tracks and their parents who were surveyed in both…

  11. Structural and functional characterization of the CAP domain of pathogen-related yeast 1 (Pry1) protein

    PubMed Central

    Darwiche, Rabih; Kelleher, Alan; Hudspeth, Elissa M.; Schneiter, Roger; Asojo, Oluwatoyin A.

    2016-01-01

    The production, crystal structure, and functional characterization of the C-terminal cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domain of pathogen-related yeast protein-1 (Pry1) from Saccharomyces cerevisiae is presented. The CAP domain of Pry1 (Pry1CAP) is functional in vivo as its expression restores cholesterol export to yeast mutants lacking endogenous Pry1 and Pry2. Recombinant Pry1CAP forms dimers in solution, is sufficient for in vitro cholesterol binding, and has comparable binding properties as full-length Pry1. Two crystal structures of Pry1CAP are reported, one with Mg2+ coordinated to the conserved CAP tetrad (His208, Glu215, Glu233 and His250) in spacegroup I41 and the other without divalent cations in spacegroup P6122. The latter structure contains four 1,4-dioxane molecules from the crystallization solution, one of which sits in the cholesterol binding site. Both structures reveal that the divalent cation and cholesterol binding sites are connected upon dimerization, providing a structural basis for the observed Mg2+-dependent sterol binding by Pry1. PMID:27344972

  12. Structural and functional characterization of the CAP domain of pathogen-related yeast 1 (Pry1) protein

    NASA Astrophysics Data System (ADS)

    Darwiche, Rabih; Kelleher, Alan; Hudspeth, Elissa M.; Schneiter, Roger; Asojo, Oluwatoyin A.

    2016-06-01

    The production, crystal structure, and functional characterization of the C-terminal cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domain of pathogen-related yeast protein-1 (Pry1) from Saccharomyces cerevisiae is presented. The CAP domain of Pry1 (Pry1CAP) is functional in vivo as its expression restores cholesterol export to yeast mutants lacking endogenous Pry1 and Pry2. Recombinant Pry1CAP forms dimers in solution, is sufficient for in vitro cholesterol binding, and has comparable binding properties as full-length Pry1. Two crystal structures of Pry1CAP are reported, one with Mg2+ coordinated to the conserved CAP tetrad (His208, Glu215, Glu233 and His250) in spacegroup I41 and the other without divalent cations in spacegroup P6122. The latter structure contains four 1,4-dioxane molecules from the crystallization solution, one of which sits in the cholesterol binding site. Both structures reveal that the divalent cation and cholesterol binding sites are connected upon dimerization, providing a structural basis for the observed Mg2+-dependent sterol binding by Pry1.

  13. Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.

    PubMed

    Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

    2017-01-01

    Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

  14. Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

    PubMed Central

    Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

    2017-01-01

    Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome. PMID:28127577

  15. Smoothing individual head-related transfer functions in the frequency and spatial domains.

    PubMed

    Rasumow, Eugen; Blau, Matthias; Hansen, Martin; van de Par, Steven; Doclo, Simon; Mellert, Volker; Püschel, Dirk

    2014-04-01

    When re-synthesizing individual head related transfer functions (HRTFs) with a microphone array, smoothing HRTFs spectrally and/or spatially prior to the computation of appropriate microphone filters may improve the synthesis accuracy. In this study, the limits of the associated HRTF modifications, until which no perceptual degradations occur, are explored. First, complex spectral smoothing of HRTFs into constant relative bandwidths was considered. As a prerequisite to complex smoothing, the HRTF phase spectra were substituted by linear phases, either for the whole frequency range or above a certain cut-off frequency only. The results indicate that a broadband phase linearization of HRTFs can be perceived for certain directions/subjects and that the thresholds can be predicted by a simple model. HRTF phase spectra can be linearized above 1 kHz without being detectable. After substituting the original phase by a linear phase above 5 kHz, HRTFs may be smoothed complexly into constant relative bandwidths of 1/5 octave, without introducing noticeable artifacts. Second, spatially smoother HRTF directivity patterns were obtained by levelling out spatial notches. It turned out that spatial notches do not have to be retained if they are less than 29 dB below the maximum level in the directivity pattern.

  16. Student Agency: an Analysis of Students' Networked Relations Across the Informal and Formal Learning Domains

    NASA Astrophysics Data System (ADS)

    Rappa, Natasha Anne; Tang, Kok-Sing

    2016-05-01

    Agency is a construct facilitating our examination of when and how young people extend their own learning across contexts. However, little is known about the role played by adolescent learners' sense of agency. This paper reports two cases of students' agentively employing and developing science literacy practices—one in Singapore and the other in the USA. The paper illustrates how these two adolescent learners in different ways creatively accessed, navigated and integrated in-school and out-of-school discourses to support and nurture their learning of physics. Data were gleaned from students' work and interviews with students participating in a physics curricular programme in which they made linkages between their chosen out-of-school texts and several physics concepts learnt in school. The students' agentive moves were identified by means of situational mapping, which involved a relational analysis of the students' chosen artefacts and discourses across time and space. This relational analysis enabled us to address questions of student agency—how it can be effected, realised, construed and examined. It highlights possible ways to intervene in these networked relations to facilitate adolescents' agentive moves in their learning endeavours.

  17. Student Agency: an Analysis of Students' Networked Relations Across the Informal and Formal Learning Domains

    NASA Astrophysics Data System (ADS)

    Rappa, Natasha Anne; Tang, Kok-Sing

    2017-06-01

    Agency is a construct facilitating our examination of when and how young people extend their own learning across contexts. However, little is known about the role played by adolescent learners' sense of agency. This paper reports two cases of students' agentively employing and developing science literacy practices—one in Singapore and the other in the USA. The paper illustrates how these two adolescent learners in different ways creatively accessed, navigated and integrated in-school and out-of-school discourses to support and nurture their learning of physics. Data were gleaned from students' work and interviews with students participating in a physics curricular programme in which they made linkages between their chosen out-of-school texts and several physics concepts learnt in school. The students' agentive moves were identified by means of situational mapping, which involved a relational analysis of the students' chosen artefacts and discourses across time and space. This relational analysis enabled us to address questions of student agency—how it can be effected, realised, construed and examined. It highlights possible ways to intervene in these networked relations to facilitate adolescents' agentive moves in their learning endeavours.

  18. Relative increase in Alzheimer's disease of soluble forms of cerebral Abeta amyloid protein precursor containing the Kunitz protease inhibitory domain.

    PubMed

    Moir, R D; Lynch, T; Bush, A I; Whyte, S; Henry, A; Portbury, S; Multhaup, G; Small, D H; Tanzi, R E; Beyreuther, K; Masters, C L

    1998-02-27

    Although a number of studies have examined amyloid precursor protein (APP) mRNA levels in Alzheimer's disease (AD), no clear consensus has emerged as to whether the levels of transcripts for isoforms containing a Kunitz protease inhibitory (KPI)-encoded region are increased or decreased in AD. Here we compare AD and control brain for the relative amounts of APP protein containing KPI to APP protein lacking this domain. APP protein was purified from the soluble subcellular fraction and Triton X-100 membrane pellet extract of one hemisphere of AD (n = 10), normal (n = 7), and neurological control (n = 5) brains. The amount of KPI-containing APP in the purified protein samples was determined using two independent assay methods. The first assay exploited the inhibitory action of KPI-containing APP on trypsin. The second assay employed reflectance analysis of Western blots. The proportion of KPI-containing forms of APP in the soluble subcellular fraction of AD brains is significantly elevated (p < 0.01) compared with controls. Species containing a KPI domain comprise 32-41 and 76-77% of purified soluble APP from control and AD brains, respectively. For purified membrane-associated APP, 72-77 and 65-82% of control and AD samples, respectively, contain a KPI domain. Since KPI-containing species of APP may be more amyloidogenic (Ho, L., Fukuchi, K., and Yonkin, S. G. (1996) J. Biol. Chem. 271, 30929-30934), our findings support an imbalance of isoforms as one possible mechanism for amyloid deposition in sporadic AD.

  19. Assessing the co-occurrence of intimate partner violence domains across the life-course: relating typologies to mental health

    PubMed Central

    Armour, Cherie; Sleath, Emma

    2014-01-01

    Background The inter-generational transmission of violence (ITV) hypothesis and polyvictimisation have been studied extensively. The extant evidence suggests that individuals from violent families are at increased risk of subsequent intimate partner violence (IPV) and that a proportion of individuals experience victimisation across multiple rather than single IPV domains. Both ITV and polyvictimisation are shown to increase the risk of psychiatric morbidity, alcohol use, and anger expression. Objective The current study aimed to 1) ascertain if underlying typologies of victimisation across the life-course and over multiple victimisation domains were present and 2) ascertain if groupings differed on mean scores of posttraumatic stress disorder (PTSD), depression, alcohol use, and anger expression. Method University students (N=318) were queried in relation to victimisation experiences and psychological well-being. Responses across multiple domains of IPV spanning the life-course were used in a latent profile analysis. ANOVA was subsequently used to determine if profiles differed in their mean scores on PTSD, depression, alcohol use, and anger expression. Results Three distinct profiles were identified; one of which comprised individuals who experienced “life-course polyvictimisation,” another showing individuals who experienced “witnessing parental victimisation,” and one which experienced “psychological victimisation only.” Life-course polyvictims scored the highest across most assessed measures. Conclusion Witnessing severe physical aggression and injury in parental relationships as a child has an interesting impact on the ITV into adolescence and adulthood. Life-course polyvictims are shown to experience increased levels of psychiatric morbidity and issues with alcohol misuse and anger expression. PMID:25279106

  20. Offline Versus Online Suicide-Related Help Seeking: Changing Domains, Changing Paradigms.

    PubMed

    Seward, Amy-Lee; Harris, Keith M

    2016-06-01

    Suicidal individuals are among the most reluctant help-seekers, which limits opportunities for treating and preventing unnecessary suffering and self-inflicted deaths. This study aimed to assist outreach, prevention, and treatment efforts by elucidating relationships between suicidality and both online and offline help seeking. An anonymous online survey provided data on 713 participants, aged 18-71 years. Measures included an expanded General Help-Seeking Questionnaire and the Suicidal Affect-Behavior-Cognition Scale. General linear modeling results showed that, as predicted, face-to-face help-seeking willingness decreased as risk level increased. However, for emerging adults help-seeking likelihood increased with informal online sources as risk increased, while other online help-seeking attitudes differed little by risk level. Linear regression modeling determined that, for suicidal individuals, willingness to seek help from online mental health professionals and online professional support sites was strongly related (ps < .001). Help seeking from social networking sites and anonymous online forums was also interrelated, but more complex, demonstrating the importance of age and social support factors (ps < .001). These findings show that the Internet has altered the suicide-related help-seeking paradigm. Online help seeking for suicidality was not more popular than face-to-face help seeking, even for emerging adults. However, treatment and prevention professionals have good reasons to increase their online efforts, because that is where some of the highest risk individuals are going for help with their most severe personal problems. © 2016 Wiley Periodicals, Inc.

  1. Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance.

    PubMed

    Reid, Donna; Moss, Jo; Nelson, Lisa; Groves, Laura; Oliver, Chris

    2017-08-15

    The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

  2. Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance.

    PubMed

    Reid, Donna; Moss, Jo; Nelson, Lisa; Groves, Laura; Oliver, Chris

    2017-01-01

    The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

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

    PubMed

    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.

  4. Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A

    SciTech Connect

    Huang,Y.; Fang, J.; Bedford, M.; Zhang, Y.; Xu, R.

    2006-01-01

    Biological responses to histone methylation critically depend on the faithful readout and transduction of the methyl-lysine signal by 'effector' proteins, yet our understanding of methyl-lysine recognition has so far been limited to the study of histone binding by chromodomain and WD40-repeat proteins. The double tudor domain of JMJD2A, a Jmjc domain-containing histone demethylase, binds methylated histone H3-K4 and H4-K20. We found that the double tudor domain has an interdigitated structure, and the unusual fold is required for its ability to bind methylated histone tails. The cocrystal structure of the JMJD2A double tudor domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is bound in a cage of three aromatic residues, two of which are from the tudor-2 motif, whereas the binding specificity is determined by side-chain interactions involving amino acids from the tudor-1 motif. Our study provides mechanistic insights into recognition of methylated histone tails by tudor domains and reveals the structural intricacy of methyl-lysine recognition by two closely spaced effector domains.

  5. PRIP (Phospholipase C-related but Catalytically Inactive Protein) Inhibits Exocytosis by Direct Interactions with Syntaxin 1 and SNAP-25 through Its C2 Domain*

    PubMed Central

    Zhang, Zhao; Takeuchi, Hiroshi; Gao, Jing; Wang, DaGuang; James, Declan J.; Martin, Thomas F. J.; Hirata, Masato

    2013-01-01

    Membrane fusion for exocytosis is mediated by SNAREs, forming trans-ternary complexes to bridge vesicle and target membranes. There is an array of accessory proteins that directly interact with and regulate SNARE proteins. PRIP (phospholipase C-related but catalytically inactive protein) is likely one of these proteins; PRIP, consisting of multiple functional modules including pleckstrin homology and C2 domains, inhibited exocytosis, probably via the binding to membrane phosphoinositides through the pleckstrin homology domain. However, the roles of the C2 domain have not yet been investigated. In this study, we found that the C2 domain of PRIP directly interacts with syntaxin 1 and SNAP-25 but not with VAMP2. The C2 domain promoted PRIP to co-localize with syntaxin 1 and SNAP-25 in PC12 cells. The binding profile of the C2 domain to SNAP-25 was comparable with that of synaptotagmin I, and PRIP inhibited synaptotagmin I in binding to SNAP-25 and syntaxin 1. It was also shown that the C2 domain was required for PRIP to suppress SDS-resistant ternary SNARE complex formation and inhibit high K+-induced noradrenalin release from PC12 cells. These results suggest that PRIP inhibits regulated exocytosis through the interaction of its C2 domain with syntaxin 1 and SNAP-25, potentially competing with other SNARE-binding, C2 domain-containing accessory proteins such as synaptotagmin I and by directly inhibiting trans-SNARE complex formation. PMID:23341457

  6. Typhoon Strength, Related Precipitation, and Sea Surface Temperatures in the Southeastern Part of the NEESPI domain

    NASA Astrophysics Data System (ADS)

    Groisman, P. Y.; Knight, R. W.; Reynolds, R. W.; Bulygina, O. N.; Zhai, P.; Karl, T. R.

    2006-12-01

    Model simulations using CO2-induced sea surface temperature increases indicate that TC wind speeds and related daily precipitation may increase. We investigated changes in the TC-related rainfall distributions as a function of TC strength at landfall and impact of SST ahead of TCs on the TC strength for several preferred tropical cyclone regions. Our findings were that a warmer climate and (projected with it) SST increases over the tropical North Atlantic and Pacific Oceans will likely be accompanied by more frequent strong landfalling hurricanes over the U.S. and China coasts. The fraction of strong hurricanes that make landfall on these coasts is positively correlated with daily SSTs in the path of the TCs. But, there were no landfalling strong hurricanes at, or above Category 3 in the Saffir-Simpson Hurricane Scale (strong to catastrophic hurricanes) when the SST was below the threshold of 28°C, which is likely a primary reason of their absence at the Russian Far East coast during the past fifty years. However, during the past 20 years there have already been strong landfalling typhoons north of Shanghai (with SST = 28.9°C) and several tropical storms that hit China north of 40°N and/or Russia with SST ahead of the storm tracks well above 28.5°C. With the ongoing warming (including the SST increases in the western part of the Northern Pacific by 0.8°C 100yr-1 during the typhoon season) these situations may become more frequent. Therefore, we focus on the southeastern edge of the NEESPI region (Russian Far East, northern China, Korea, and northern Japan) to assess the relationships that control the TC activity changes with the SST increase and to trace the above mentioned threshold shift northward during the typhoon season.

  7. A study of event related potential frequency domain coherency using multichannel electroencephalogram subspace analysis.

    PubMed

    Razavipour, Fatemeh; Sameni, Reza

    2015-07-15

    Event related potentials (ERP) are time-locked electrical activities of the brain in direct response to a specific sensory, cognitive, or motor stimulus. ERP components, such as the P300 wave, which are involved in the process of decision-making, help scientists diagnose specific cognitive disabilities. In this study, we utilize the angles between multichannel electroencephalogram (EEG) subspaces in different frequency bands, as a similarity factor for studying the spatial coherency between ERP frequency responses. A matched filter is used to enhance the ERP from background EEG. While previous researches have focused on frequencies below 10 Hz, as the major frequency band of ERP, it is shown that by using the proposed method, significant ERP-related information can also be found in the 25-40 Hz band. These frequency bands are selected by calculating the correlation coefficient between P300 response segments and synthetic EEG, and ERP segments without P300 waves, and by rejecting the bands having the most association with background EEG and non-P300 components. The significance of the results is assessed by real EEG acquired in brain computer interface experiments versus synthetic EEG produced by existing methods in the literature, to assure that the results are not systematic side effects of the proposed framework. The overall results show that the equivalent dipoles corresponding to narrow-band events in the brain are spatially coherent within different (not necessarily adjacent) frequency bands. The results of this study can lead into novel perspectives in ERP studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development

    PubMed Central

    Cara, Lukas; Baitemirova, Medina; Follis, Jack; Larios-Sanz, Maia; Ribes-Zamora, Albert

    2016-01-01

    ATM and ATR are cellular kinases with a well-characterized role in the DNA-damage response. Although the complete set of ATM/ATR targets is unknown, they often contain clusters of S/TQ motifs that constitute an SCD domain. In this study, we identified putative ATM/ATR targets that have a conserved SCD domain across vertebrates. Using this approach, we have identified novel putative ATM/ATR targets in pathways known to be under direct control of these kinases. Our analysis has also unveiled significant enrichment of SCD-containing proteins in cellular pathways, such as vesicle trafficking and actin cytoskeleton, where a regulating role for ATM/ATR is either unknown or poorly understood, hinting at a much broader and overarching role for these kinases in the cell. Of particular note is the overrepresentation of conserved SCD-containing proteins involved in pathways related to neural development. This finding suggests that ATM/ATR could be directly involved in controlling this process, which may be linked to the adverse neurological effects observed in patients with mutations in ATM. PMID:26743489

  9. Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties.

    PubMed

    Hein, Nichole D; Stuckey, Jeanne A; Rainier, Shirley R; Fink, John K; Richardson, Rudy J

    2010-07-01

    Neuropathy target esterase (NTE) is a phospholipase/lysophospholipase associated with organophosphorus (OP) compound-induced delayed neurotoxicity (OPIDN). Distal degeneration of motor axons occurs in both OPIDN and the hereditary spastic paraplegias (HSPs). Recently, mutations within the esterase domain of NTE were identified in patients with a novel type of HSP (SPG39) designated NTE-related motor neuron disease (NTE-MND). Two of these mutations, arginine 890 to histidine (R890H) and methionine 1012 to valine (M1012V), were created in human recombinant NTE catalytic domain (NEST) to measure possible changes in catalytic properties. These mutated enzymes had decreased specific activities for hydrolysis of the artificial substrate, phenyl valerate. In addition, the M1012V mutant exhibited a reduced bimolecular rate constant of inhibition (k(i)) for all three inhibitors tested: mipafox, diisopropylphosphorofluoridate, and chlorpyrifos oxon. Finally, while both mutated enzymes inhibited by OP compounds exhibited altered time-dependent loss of their ability to be reactivated by nucleophiles (aging), more pronounced effects were seen with the M1012V mutant. Taken together, the results from specific activity, inhibition, and aging experiments suggest that the mutations found in association with NTE-MND have functional correlates in altered enzymological properties of NTE.

  10. How working memory relates to children's reading comprehension: the importance of domain-specificity in storage and processing.

    PubMed

    Nouwens, Suzan; Groen, Margriet A; Verhoeven, Ludo

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the current study, we investigated the contribution of phonological and semantic storage, and phonological and semantic processing to reading comprehension in 123 Dutch children in fifth grade. We conducted regression and mediation analyses to find out to what extent variation in reading comprehension could be explained by storage and processing capacities in both the phonological and the semantic domain, while controlling for children's decoding and vocabulary. The analyses included tasks that reflect storage only, and working memory tasks that assess processing in addition to storage. Regression analysis including only storage tasks as predictor measures, revealed semantic storage to be a better predictor of reading comprehension than phonological storage. Adding phonological and semantic working memory tasks as additional predictors to the model showed that semantic working memory explained individual variation in reading comprehension over and above all other memory measures. Additional mediation analysis made it clear that semantic storage contributed indirectly to reading comprehension via semantic working memory, indicating that semantic storage tapped by working memory, in addition to processing capacities, explains individual variation in reading comprehension. It can thus be concluded that semantic storage plays a more important role in children's reading comprehension than previously thought.

  11. The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development.

    PubMed

    Cara, Lukas; Baitemirova, Medina; Follis, Jack; Larios-Sanz, Maia; Ribes-Zamora, Albert

    2016-01-08

    ATM and ATR are cellular kinases with a well-characterized role in the DNA-damage response. Although the complete set of ATM/ATR targets is unknown, they often contain clusters of S/TQ motifs that constitute an SCD domain. In this study, we identified putative ATM/ATR targets that have a conserved SCD domain across vertebrates. Using this approach, we have identified novel putative ATM/ATR targets in pathways known to be under direct control of these kinases. Our analysis has also unveiled significant enrichment of SCD-containing proteins in cellular pathways, such as vesicle trafficking and actin cytoskeleton, where a regulating role for ATM/ATR is either unknown or poorly understood, hinting at a much broader and overarching role for these kinases in the cell. Of particular note is the overrepresentation of conserved SCD-containing proteins involved in pathways related to neural development. This finding suggests that ATM/ATR could be directly involved in controlling this process, which may be linked to the adverse neurological effects observed in patients with mutations in ATM.

  12. Evolutionary relationships among group II intron-encoded proteins and identification of a conserved domain that may be related to maturase function.

    PubMed Central

    Mohr, G; Perlman, P S; Lambowitz, A M

    1993-01-01

    Many group II introns encode reverse transcriptase-like proteins that potentially function in intron mobility and RNA splicing. We compared 34 intron-encoded open reading frames and four related open reading frames that are not encoded in introns. Many of these open reading frames have a reverse transcriptase-like domain, followed by an additional conserved domain X, and a Zn(2+)-finger-like region. Some open reading frames have lost conserved sequence blocks or key amino acids characteristic of functional reverse transcriptases, and some lack the Zn(2+)-finger-like region. The open reading frames encoded by the chloroplast tRNA(Lys) genes and the related Epifagus virginiana matK open reading frame lack a Zn(2+)-finger-like region and have only remnants of a reverse transcriptase-like domain, but retain a readily identifiable domain X. Several findings lead us to speculate that domain X may function in binding of the intron RNA during reverse transcription and RNA splicing. Overall, our findings are consistent with the hypothesis that all of the known group II intron open reading frames evolved from an ancestral open reading frame, which contained reverse transcriptase, X, and Zn(2+)-finger-like domains, and that the reverse transcriptase and Zn(2+)-finger-like domains were lost in some cases. The retention of domain X in most proteins may reflect an essential function in RNA splicing, which is independent of the reverse transcriptase activity of these proteins. PMID:8255751

  13. Evolutionary relationships among group II intron-encoded proteins and identification of a conserved domain that may be related to maturase function.

    PubMed

    Mohr, G; Perlman, P S; Lambowitz, A M

    1993-11-11

    Many group II introns encode reverse transcriptase-like proteins that potentially function in intron mobility and RNA splicing. We compared 34 intron-encoded open reading frames and four related open reading frames that are not encoded in introns. Many of these open reading frames have a reverse transcriptase-like domain, followed by an additional conserved domain X, and a Zn(2+)-finger-like region. Some open reading frames have lost conserved sequence blocks or key amino acids characteristic of functional reverse transcriptases, and some lack the Zn(2+)-finger-like region. The open reading frames encoded by the chloroplast tRNA(Lys) genes and the related Epifagus virginiana matK open reading frame lack a Zn(2+)-finger-like region and have only remnants of a reverse transcriptase-like domain, but retain a readily identifiable domain X. Several findings lead us to speculate that domain X may function in binding of the intron RNA during reverse transcription and RNA splicing. Overall, our findings are consistent with the hypothesis that all of the known group II intron open reading frames evolved from an ancestral open reading frame, which contained reverse transcriptase, X, and Zn(2+)-finger-like domains, and that the reverse transcriptase and Zn(2+)-finger-like domains were lost in some cases. The retention of domain X in most proteins may reflect an essential function in RNA splicing, which is independent of the reverse transcriptase activity of these proteins.

  14. Development of the serotonergic cells in murine raphe nuclei and their relations with rhombomeric domains.

    PubMed

    Alonso, Antonia; Merchán, Paloma; Sandoval, Juan E; Sánchez-Arrones, Luisa; Garcia-Cazorla, Angels; Artuch, Rafael; Ferrán, José L; Martínez-de-la-Torre, Margaret; Puelles, Luis

    2013-09-01

    The raphe nuclei represent the origin of central serotonergic projections. The literature distinguishes seven nuclei grouped into rostral and caudal clusters relative to the pons. The boundaries of these nuclei have not been defined precisely enough, particularly with regard to developmental units, notably hindbrain rhombomeres. We hold that a developmental point of view considering rhombomeres may explain observed differences in connectivity and function. There are twelve rhombomeres characterized by particular genetic profiles, and each develops between one and four distinct serotonergic populations. We have studied the distribution of the conventional seven raphe nuclei among these twelve units. To this aim, we correlated 5-HT-immunoreacted neurons with rhombomeric boundary landmarks in sagittal mouse brain sections at different developmental stages. Furthermore, we performed a partial genoarchitectonic analysis of the developing raphe nuclei, mapping all known serotonergic differentiation markers, and compared these results, jointly with others found in the literature, with our map of serotonin-containing populations, in order to examine regional variations in correspondence. Examples of regionally selective gene patterns were identified. As a result, we produced a rhombomeric classification of some 45 serotonergic populations, and suggested a corresponding modified terminology. Only a minor rostral part of the dorsal raphe nucleus lies in the midbrain. Some serotonergic neurons were found in rhombomere 4, contrary to the conventional assumption that it lacks such neurons. We expect that our reclassification of raphe nuclei may be useful for causal analysis of their differential molecular specification, as well as for studies of differential connectivity and function.

  15. Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement.

    PubMed

    Hassinger-Das, Brenna; Jordan, Nancy C; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

    2014-02-01

    Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense.

  16. Adaptive extraction of emotion-related EEG segments using multidimensional directed information in time-frequency domain.

    PubMed

    Petrantonakis, Panagiotis C; Hadjileontiadis, Leontios J

    2010-01-01

    Emotion discrimination from electroencephalogram (EEG) has gained attention the last decade as a user-friendly and effective approach to EEG-based emotion recognition (EEG-ER) systems. Nevertheless, challenging issues regarding the emotion elicitation procedure, especially its effectiveness, raise. In this work, a novel method, which not only evaluates the degree of emotion elicitation but localizes the emotion information in the time-frequency domain, as well, is proposed. The latter, incorporates multidimensional directed information at the time-frequency EEG representation, extracted using empirical mode decomposition, and introduces an asymmetry index for adaptive emotion-related EEG segment selection. Experimental results derived from 16 subjects visually stimulated with pictures from the valence/arousal space drawn from the International Affective Picture System database, justify the effectiveness of the proposed approach and its potential contribution to the enhancement of EEG-ER systems.

  17. Archaeal surface layer proteins contain beta propeller, PKD, and beta helix domains and are related to metazoan cell surface proteins.

    PubMed

    Jing, Hua; Takagi, Junichi; Liu, Jin-huan; Lindgren, Sara; Zhang, Rong-guang; Joachimiak, A; Wang, Jia-huai; Springer, Timothy A

    2002-10-01

    The surface layer of archaeobacteria protects cells from extreme environments and, in Methanosarcina, may regulate cell adhesion. We identify three domain types that account for the complete architecture of numerous Methanosarcina surface layer proteins (SLPs). We solve the crystal structure for two of these domains, which correspond to the two N-terminal domains of an M. mazei SLP. One domain displays a unique, highly symmetrical, seven-bladed beta propeller fold, and the other belongs to the polycystic kidney disease (PKD) superfamily fold. The third domain is predicted to adopt a beta helix fold. These domains have homologs in metazoan cell surface proteins, suggesting remarkable relationships between domains in archaeal SLPs and metazoan cell surface proteins.

  18. Is there an evolutionary relationship between WARP (von Willebrand factor A-domain-related protein) and the FACIT and FACIT-like collagens?

    PubMed

    Fitzgerald, Jamie; Bateman, John F

    2003-09-25

    We suggest that there is an evolutionary relationship between von Willebrand factor A-domain-related protein (WARP), and the fibril-associated collagen with interrupted triple helix (FACIT) and FACIT-like subfamilies of collagens. Data from a comparison of amino acid sequences, domain organisation and chromosomal location are consistent with the hypothesis that WARP and these collagens share a common collagen ancestor. In support of this is the observation that the WARP 3' coding region is GC-rich suggesting that this may represent the remnant of a triple helix protein domain which WARP has 'lost' during evolution.

  19. Structural Studies of the Tandem Tudor Domains of Fragile X Mental Retardation Related Proteins FXR1 and FXR2

    SciTech Connect

    Adams-Cioaba, Melanie A.; Guo, Yahong; Bian, ChuanBing; Amaya, Maria F.; Lam, Robert; Wasney, Gregory A.; Vedadi, Masoud; Xu, Chao; Min, Jinrong

    2011-11-23

    Expansion of the CGG trinucleotide repeat in the 5'-untranslated region of the FMR1, fragile X mental retardation 1, gene results in suppression of protein expression for this gene and is the underlying cause of Fragile X syndrome. In unaffected individuals, the FMRP protein, together with two additional paralogues (Fragile X Mental Retardation Syndrome-related Protein 1 and 2), associates with mRNA to form a ribonucleoprotein complex in the nucleus that is transported to dendrites and spines of neuronal cells. It is thought that the fragile X family of proteins contributes to the regulation of protein synthesis at sites where mRNAs are locally translated in response to stimuli. Here, we report the X-ray crystal structures of the non-canonical nuclear localization signals of the FXR1 and FXR2 autosomal paralogues of FMRP, which were determined at 2.50 and 1.92 {angstrom}, respectively. The nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain architectures, closely resembling that of UHRF1, which is proposed to bind methylated histone H3K9. The FMRP, FXR1 and FXR2 proteins comprise a small family of highly conserved proteins that appear to be important in translational regulation, particularly in neuronal cells. The crystal structures of the N-terminal tandem Tudor domains of FXR1 and FXR2 revealed a conserved architecture with that of FMRP. Biochemical analysis of the tandem Tudor doamins reveals their ability to preferentially recognize trimethylated peptides in a sequence-specific manner.

  20. A meta-analysis of criterion effects for the Implicit Relational Assessment Procedure (IRAP) in the clinical domain.

    PubMed

    Vahey, Nigel A; Nicholson, Emma; Barnes-Holmes, Dermot

    2015-09-01

    The Implicit Relational Assessment Procedure (IRAP) is a technique that is attracting a substantial body of research literature, particularly within the clinical domain. In response, the present paper outlines a meta-analysis of clinically-focused IRAP effects (N = 494) to provide the first estimate of how well such effects validate against their respective criterion variables in general. The meta-analysis incorporated clinically-focused IRAP effects from 15 studies yielding a large effect size, r¯ = .45, with a desirably narrow 95% credibility interval (.23, .67). The funnel plot and subsequent sensitivity analyses indicated that this meta-effect was not subject to publication bias. The present meta-effect is an estimate based upon an IRAP literature that is still evolving rapidly in the clinical domain, and so as per its accompanying credibility interval, all conclusions that follow are necessarily provisional even if bounded. Apart from the fact that the current meta-effect might be subject to inadvertent under- and/or over-estimations of the current literature, the present meta-effect might strengthen with further refinements of the IRAP. The current meta-effect provides the means to calculate what sample size would be required to achieve a statistical power of .80 when testing the criterion validity of clinically-focused IRAP effects using a given parametric statistic. For example, first-order Pearson correlations would hypothetically require an N of 29-37 for such purposes depending upon how conservatively over-estimation of the present meta-effect is controlled for. Overall, the IRAP compares favourably with alternative implicit measures in clinical psychology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Age-Related Differences in Longitudinal Structural Change by Spectral-Domain Optical Coherence Tomography in Early Experimental Glaucoma

    PubMed Central

    Yang, Hongli; He, Lin; Gardiner, Stuart K.; Reynaud, Juan; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Downs, J. Crawford; Fortune, Brad; Burgoyne, Claude F.

    2014-01-01

    Purpose. To characterize age-related differences in the magnitude of spectral-domain optical coherence tomography (SD-OCT) structural change in early experimental glaucoma (EG). Methods. Both eyes from four young (1.4–2.6 years) and four old (18.6–21.9 years) rhesus monkeys were imaged at least three times at baseline, and then every 2 weeks after laser-induced, chronic, unilateral IOP elevation until the onset of EG (confocal scanning laser tomographic surface change confirmed twice). Two to 20 weeks after EG onset, animals were euthanized and optic nerve axon counts for all eyes were performed. Masked operators delineated retinal and ONH landmarks in 40 radial B-scans from each eye and imaging session to quantify change from baseline in five SD-OCT neural and connective tissue parameters. The effects of EG, age, and EG × age interactions on the magnitude, rate (magnitude per postlaser time), and IOP responsiveness (magnitude per cumulative IOP insult) of postlaser parameter change were individually assessed using general estimating equation models. Results. Presac SD-OCT RNFLT and minimum rim width change and postmortem axon loss was not significantly different in old compared with young EG eyes. The rate of change and IOP responsiveness of the parameters anterior lamina cribrosa surface depth relative to Bruch's membrane opening (BMO) and BMO depth relative to peripheral Bruch's membrane were significantly lower (P < 0.05) in the old compared with the young EG eyes. Conclusions. At similar postlaser times, levels of cumulative IOP insult and axonal damage, SD-OCT–detected ONH connective tissue structural change is greater in young compared with old monkey EG eyes. PMID:25190652

  2. Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1*♦

    PubMed Central

    Hirata, Yasuko; Brems, Hilde; Suzuki, Mayu; Kanamori, Mitsuhiro; Okada, Masahiro; Morita, Rimpei; Llano-Rivas, Isabel; Ose, Toyoyuki; Messiaen, Ludwine; Legius, Eric; Yoshimura, Akihiko

    2016-01-01

    Constitutional heterozygous loss-of-function mutations in the SPRED1 gene cause a phenotype known as Legius syndrome, which consists of symptoms of multiple café-au-lait macules, axillary freckling, learning disabilities, and macrocephaly. Legius syndrome resembles a mild neurofibromatosis type 1 (NF1) phenotype. It has been demonstrated that SPRED1 functions as a negative regulator of the Ras-ERK pathway and interacts with neurofibromin, the NF1 gene product. However, the molecular details of this interaction and the effects of the mutations identified in Legius syndrome and NF1 on this interaction have not yet been investigated. In this study, using a yeast two-hybrid system and an immunoprecipitation assay in HEK293 cells, we found that the SPRED1 EVH1 domain interacts with the N-terminal 16 amino acids and the C-terminal 20 amino acids of the GTPase-activating protein (GAP)-related domain (GRD) of neurofibromin, which form two crossing α-helix coils outside the GAP domain. These regions have been shown to be dispensable for GAP activity and are not present in p120GAP. Several mutations in these N- and C-terminal regions of the GRD in NF1 patients and pathogenic missense mutations in the EVH1 domain of SPRED1 in Legius syndrome reduced the binding affinity between the EVH1 domain and the GRD. EVH1 domain mutations with reduced binding to the GRD also disrupted the ERK suppression activity of SPRED1. These data clearly demonstrate that SPRED1 inhibits the Ras-ERK pathway by recruiting neurofibromin to Ras through the EVH1-GRD interaction, and this study also provides molecular basis for the pathogenic mutations of NF1 and Legius syndrome. PMID:26635368

  3. Fusion activity of HIV gp41 fusion domain is related to its secondary structure and depth of membrane insertion in a cholesterol-dependent fashion.

    PubMed

    Lai, Alex L; Moorthy, Anna Eswara; Li, Yinling; Tamm, Lukas K

    2012-04-20

    The human immunodeficiency virus (HIV) gp41 fusion domain plays a critical role in membrane fusion during viral entry. A thorough understanding of the relationship between the structure and the activity of the fusion domain in different lipid environments helps to formulate mechanistic models on how it might function in mediating membrane fusion. The secondary structure of the fusion domain in small liposomes composed of different lipid mixtures was investigated by circular dichroism spectroscopy.  The fusion domain formed an α-helix in membranes containing less than 30 mol% cholesterol and  formed β-sheet secondary structure in membranes containing ≥30 mol% cholesterol. EPR spectra of spin-labeled fusion domains also indicated different conformations in membranes with and without cholesterol. Power saturation EPR data were further used to determine the orientation and depth of α-helical fusion domains in lipid bilayers. Fusion and membrane perturbation activities of the gp41 fusion domain were measured by lipid mixing and contents leakage. The fusion domain fused membranes in both its helical form and its β-sheet form. High cholesterol, which induced β-sheets, promoted fusion; however, acidic lipids, which promoted relatively deep membrane insertion as an α-helix, also induced fusion. The results indicate that the structure of the HIV gp41 fusion domain is plastic and depends critically on the lipid environment. Provided that their membrane insertion is deep, α-helical and β-sheet conformations contribute to membrane fusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The H+ related defects involved in domain reversal for both near-stoichiometric and heavily Mg-doped lithium niobate crystals

    NASA Astrophysics Data System (ADS)

    Yan, W.; Kong, Y.; Shi, L.; Yao, J.; Chen, S.; Sun, L.; Zhao, D.; Xu, J.; Zhang, G.

    2005-02-01

    Domain reversal was performed on both near-stoichiometric and heavily Mg-doped lithium niobate crystals. H+ related defect structures in these two types of crystals were studied through the infrared absorption spectra. It is found that the intensity of some decomposed peaks of absorption band change apparently during domain reversal for near-stoichiometric lithium niobate crystals but not for heavily Mg-doped lithium niobate crystals. According to these experimental results, distinct models about H+ related defect structure in LiNbO3 lattice were supposed for them. Nb4+Li and Mg3-Nb were considered as the centers of H+ related defect complex for near-stoichiometric and heavily Mg-doped lithium niobate crystals respectively. Different behavior of them was used to explain the difference of infrared absorption spectra during domain reversal between two types of crystals.

  5. Limited polymorphism in Plasmodium falciparum ookinete surface antigen, von Willebrand factor A domain-related protein from clinical isolates

    PubMed Central

    Richards, Jack S; MacDonald, Nicholas J; Eisen, Damon P

    2006-01-01

    Background As malaria becomes increasingly drug resistant and more costly to treat, there is increasing urgency to develop effective vaccines. In comparison to other stages of the malaria lifecycle, sexual stage antigens are under less immune selection pressure and hence are likely to have limited antigenic diversity. Methods Clinical isolates from a wide range of geographical regions were collected. Direct sequencing of PCR products was then used to determine the extent of polymorphisms for the novel Plasmodium falciparum sexual stage antigen von Willebrand Factor A domain-related Protein (PfWARP). These isolates were also used to confirm the extent of diversity of sexual stage antigen Pfs28. Results PfWARP was shown to have non-synonymous substitutions at 3 positions and Pfs28 was confirmed to have a single non-synonymous substitution as previously described. Conclusion This study demonstrates the limited antigenic diversity of two prospective P. falciparum sexual stage antigens, PfWARP and Pfs28. This provides further encouragement for the proceeding with vaccine trials based on these antigens. PMID:16820064

  6. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain.

    PubMed

    He, Shuning; Mansour, Marc R; Zimmerman, Mark W; Ki, Dong Hyuk; Layden, Hillary M; Akahane, Koshi; Gjini, Evisa; de Groh, Eric D; Perez-Atayde, Antonio R; Zhu, Shizhen; Epstein, Jonathan A; Look, A Thomas

    2016-04-27

    Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1's role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical "developmental tumor", NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation.

  7. Verticillium infection triggers VASCULAR-RELATED NAC DOMAIN7-dependent de novo xylem formation and enhances drought tolerance in Arabidopsis.

    PubMed

    Reusche, Michael; Thole, Karin; Janz, Dennis; Truskina, Jekaterina; Rindfleisch, Sören; Drübert, Christine; Polle, Andrea; Lipka, Volker; Teichmann, Thomas

    2012-09-01

    The soilborne fungal plant pathogen Verticillium longisporum invades the roots of its Brassicaceae hosts and proliferates in the plant vascular system. Typical aboveground symptoms of Verticillium infection on Brassica napus and Arabidopsis thaliana are stunted growth, vein clearing, and leaf chloroses. Here, we provide evidence that vein clearing is caused by pathogen-induced transdifferentiation of chloroplast-containing bundle sheath cells to functional xylem elements. In addition, our findings suggest that reinitiation of cambial activity and transdifferentiation of xylem parenchyma cells results in xylem hyperplasia within the vasculature of Arabidopsis leaves, hypocotyls, and roots. The observed de novo xylem formation correlates with Verticillium-induced expression of the VASCULAR-RELATED NAC DOMAIN (VND) transcription factor gene VND7. Transgenic Arabidopsis plants expressing the chimeric repressor VND7-SRDX under control of a Verticillium infection-responsive promoter exhibit reduced de novo xylem formation. Interestingly, infected Arabidopsis wild-type plants show higher drought stress tolerance compared with noninfected plants, whereas this effect is attenuated by suppression of VND7 activity. Together, our results suggest that V. longisporum triggers a tissue-specific developmental plant program that compensates for compromised water transport and enhances the water storage capacity of infected Brassicaceae host plants. In conclusion, we provide evidence that this natural plant-fungus pathosystem has conditionally mutualistic features.

  8. Impact of disability on different domains of health-related quality of life in the noninstitutionalized general population

    PubMed Central

    Mar, Javier; Larrañaga, Isabel; Arrospide, Arantzazu; Begiristain, José María

    2010-01-01

    The relationship between disability and health related quality of life (HRQL) is complex because of the role that function plays in the measurement, and certain points need to be dealt with in greater detail when the analysis is applied to the different dimensions of HRQL. The purpose of this study was to assess the impact of disability on different domains of quality of life. Variables were drawn from the 2002 Basque Country Health Survey. Logistic regression models were constructed to measure the adjusted effect of disability on quality of life as determined by the SF-36 questionnaire. The models were adjusted for sociodemographic variables and the presence of comorbidity. The greatest difference between disabled and nondisabled subjects was found in the physical components of the questionnaire. Odds Ratios (ORs) for a suboptimal level of quality of life as determined by functional status were much higher for the physical than for the mental dimensions. Adjustment for different variables showed a decrease in ORs in the physical, mental, and social dimensions. This study establishes a significant relationship between disability and the loss of quality of life in both physical and mental dimensions of SF-36, irrespective of the associated disease. PMID:21935318

  9. Exploring behavioural determinants relating to health professional reporting of medication errors: a qualitative study using the Theoretical Domains Framework.

    PubMed

    Alqubaisi, Mai; Tonna, Antonella; Strath, Alison; Stewart, Derek

    2016-07-01

    Effective and efficient medication reporting processes are essential in promoting patient safety. Few qualitative studies have explored reporting of medication errors by health professionals, and none have made reference to behavioural theories. The objective was to describe and understand the behavioural determinants of health professional reporting of medication errors in the United Arab Emirates (UAE). This was a qualitative study comprising face-to-face, semi-structured interviews within three major medical/surgical hospitals of Abu Dhabi, the UAE. Health professionals were sampled purposively in strata of profession and years of experience. The semi-structured interview schedule focused on behavioural determinants around medication error reporting, facilitators, barriers and experiences. The Theoretical Domains Framework (TDF; a framework of theories of behaviour change) was used as a coding framework. Ethical approval was obtained from a UK university and all participating hospital ethics committees. Data saturation was achieved after interviewing ten nurses, ten pharmacists and nine physicians. Whilst it appeared that patient safety and organisational improvement goals and intentions were behavioural determinants which facilitated reporting, there were key determinants which deterred reporting. These included the beliefs of the consequences of reporting (lack of any feedback following reporting and impacting professional reputation, relationships and career progression), emotions (fear and worry) and issues related to the environmental context (time taken to report). These key behavioural determinants which negatively impact error reporting can facilitate the development of an intervention, centring on organisational safety and reporting culture, to enhance reporting effectiveness and efficiency.

  10. Event-related brain responses to emotional words, pictures, and faces – a cross-domain comparison

    PubMed Central

    Bayer, Mareike; Schacht, Annekathrin

    2014-01-01

    Emotion effects in event-related brain potentials (ERPs) have previously been reported for a range of visual stimuli, including emotional words, pictures, and facial expressions. Still, little is known about the actual comparability of emotion effects across these stimulus classes. The present study aimed to fill this gap by investigating emotion effects in response to words, pictures, and facial expressions using a blocked within-subject design. Furthermore, ratings of stimulus arousal and valence were collected from an independent sample of participants. Modulations of early posterior negativity (EPN) and late positive complex (LPC) were visible for all stimulus domains, but showed clear differences, particularly in valence processing. While emotion effects were limited to positive stimuli for words, they were predominant for negative stimuli in pictures and facial expressions. These findings corroborate the notion of a positivity offset for words and a negativity bias for pictures and facial expressions, which was assumed to be caused by generally lower arousal levels of written language. Interestingly, however, these assumed differences were not confirmed by arousal ratings. Instead, words were rated as overall more positive than pictures and facial expressions. Taken together, the present results point toward systematic differences in the processing of written words and pictorial stimuli of emotional content, not only in terms of a valence bias evident in ERPs, but also concerning their emotional evaluation captured by ratings of stimulus valence and arousal. PMID:25339927

  11. Structure-function relations in the NTPase domain of the antiviral tRNA ribotoxin Escherichia coli PrrC

    SciTech Connect

    Meineke, Birthe; Shuman, Stewart

    2012-06-05

    Breakage of tRNA by Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies a host antiviral response to phage T4 infection. Expression of EcoPrrC is cytocidal in yeast, signifying that PrrC ribotoxicity crosses phylogenetic domain boundaries. EcoPrrC consists of an N-terminal NTPase module that resembles ABC transporters and a C-terminal nuclease module that is sui generis. PrrC homologs are prevalent in many other bacteria. Here we report that Haemophilus influenzae PrrC is toxic in E. coli and yeast. To illuminate structure-activity relations, we conducted a new round of mutational analysis of EcoPrrC guided by primary structure conservation among toxic PrrC homologs. We indentify 17 candidate active site residues in the NTPase module that are essential for toxicity in yeast when EcoPrrC is expressed at high gene dosage. Their functions could be educed by integrating mutational data with the atomic structure of the transition-state complex of a homologous ABC protein.

  12. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain

    PubMed Central

    He, Shuning; Mansour, Marc R; Zimmerman, Mark W; Ki, Dong Hyuk; Layden, Hillary M; Akahane, Koshi; Gjini, Evisa; de Groh, Eric D; Perez-Atayde, Antonio R; Zhu, Shizhen; Epstein, Jonathan A; Look, A Thomas

    2016-01-01

    Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical “developmental tumor”, NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation. DOI: http://dx.doi.org/10.7554/eLife.14713.001 PMID:27130733

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

    PubMed Central

    Gholizadeh, Saber; Djadid, Navid Dinparast; Basseri, Hamid Reza; Zakeri, Sedigheh; Ladoni, Hossein

    2009-01-01

    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. PMID:19549316

  14. Functions of the C-terminal domains of apoptosis-related proteins of the Bcl-2 family.

    PubMed

    Gómez-Fernández, Juan C

    2014-10-01

    Bcl-2 family proteins are involved in cell homeostasis, where they regulate cell death. Some of these proteins are pro-apoptotic and others pro-survival. Moreover, many of them share a similar domain composition with several of the so-called BH domains, although some only have a BH3 domain. A C-terminal domain is present in all the multi-BH domain proteins and in some of the BH3-only ones. This C-terminal domain is hydrophobic or amphipathic, for which reason it was thought when they were discovered that they were membrane anchors. Although this is indeed one of their functions, it has since been observed that they may also serve as regulators of the function of some members of this family, such as Bax. They may also serve to recognize the target membrane of some of these proteins, which only after an apoptotic signal, are incorporated into a membrane. It has been shown that peptides that imitate the sequence of C-terminal domains can form pores and may serve as a model to design cytotoxic molecules.

  15. [Towards the new spectral-domain optical coherence tomography based classification of age-related macular degeneration].

    PubMed

    Gallego-Pinazo, R; Dolz-Marco, R; Díaz-Llopis, M

    2012-08-01

    Age-related macular degeneration (AMD) is major social and health problem in industrialised societies. The contribution of the new diagnostic techniques, mainly spectral-domain optical coherence tomography (SD-OCT), has led to a better understanding of this disease. To review the current clinical classification of AMD, to describe the new tomographic classification of wet AMD, and to review the new topographical findings in dry AMD. There are two classically described forms of AMD: dry and wet; there are also three progressive stages of severity: early, intermediate and advanced. This purely clinical stratification does not take into account any criteria based on SD-OCT. On the other hand, a new SD-OCT based classification has been proposed for choroidal neovascularisations secondary to AMD: types 1 (equivalent to occult), 2 (equivalent to classic), and 3 (equivalent to retinal angiomatous proliferation). Finally, SD-OCT offers exclusive and valuable information on the evaluation of dry AMD as regards subretinal drusenoid deposits, drusenoid pigment epithelium detachments, drusen coalescence, or the appearance of subretinal fluid in absence of choroidal neovascularisation. Dry AMD exhibits a range of tomographical signs that also have their own relative risk of progression to advance stages of the disease. We need an international consensus in order to follow-up and treat in the best way all those patients with AMD, not only with the wet but also with the dry form. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España. All rights reserved.

  16. Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles.

    PubMed

    Hsu, Justin Bo-Kai; Huang, Kai-Yao; Weng, Tzu-Ya; Huang, Chien-Hsun; Lee, Tzong-Yi

    2014-01-01

    Machinery of pre-mRNA splicing is carried out through the interaction of RNA sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g. spliceosome and splicing factors). Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated, partly because SRPs have not yet been exhaustively identified and the experimental identification is labor-intensive. Therefore, we are motivated to design a new method for identifying SRPs with their functional roles in the regulation of RNA splicing. The experimentally verified SRPs were manually curated from research articles. According to the functional annotation of Splicing Related Gene Database, the collected SRPs were further categorized into four functional groups including small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and Novel Spliceosome Protein. The composition of amino acid pairs indicates that there are remarkable differences among four functional groups of SRPs. Then, support vector machines (SVMs) were utilized to learn the predictive models for identifying SRPs as well as their functional roles. The cross-validation evaluation presents that the SVM models trained with significant amino acid pairs and functional domains could provide a better predictive performance. In addition, the independent testing demonstrates that the proposed method could accurately identify SRPs in mammals/plants as well as effectively distinguish between SRPs and RNA-binding proteins. This investigation provides a practical means to identifying potential SRPs and a perspective for exploring the regulation of RNA splicing.

  17. Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles

    NASA Astrophysics Data System (ADS)

    Hsu, Justin Bo-Kai; Huang, Kai-Yao; Weng, Tzu-Ya; Huang, Chien-Hsun; Lee, Tzong-Yi

    2014-01-01

    Machinery of pre-mRNA splicing is carried out through the interaction of RNA sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g. spliceosome and splicing factors). Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated, partly because SRPs have not yet been exhaustively identified and the experimental identification is labor-intensive. Therefore, we are motivated to design a new method for identifying SRPs with their functional roles in the regulation of RNA splicing. The experimentally verified SRPs were manually curated from research articles. According to the functional annotation of Splicing Related Gene Database, the collected SRPs were further categorized into four functional groups including small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and Novel Spliceosome Protein. The composition of amino acid pairs indicates that there are remarkable differences among four functional groups of SRPs. Then, support vector machines (SVMs) were utilized to learn the predictive models for identifying SRPs as well as their functional roles. The cross-validation evaluation presents that the SVM models trained with significant amino acid pairs and functional domains could provide a better predictive performance. In addition, the independent testing demonstrates that the proposed method could accurately identify SRPs in mammals/plants as well as effectively distinguish between SRPs and RNA-binding proteins. This investigation provides a practical means to identifying potential SRPs and a perspective for exploring the regulation of RNA splicing.

  18. Contributions of Domain-Related Phenomena on Dielectric Constant of Lead-Based Ferroelectric Ceramics Under Uniaxial Compressive Pre-Stress

    NASA Astrophysics Data System (ADS)

    Yimnirun, Rattikorn

    The dielectric constant of lead-based ferroelectric ceramics in three different systems, i.e. BT-PZT, PMN-PT and PMN-PZT, was measured under uniaxial compressive pre-stress to investigate the contributions of different domain-phenomena. The dielectric constant was observed at room temperature under the compressive pre-stress up to 15 MPa, 22 MPa and 5 MPa for BT-PZT, PMN-PT and PMN-PZT, respectively, using a homebuilt uniaxial compressometer. Dielectric constant of the BT-PZT ceramics increased significantly with increasing applied stress. Larger changes in the dielectric constant with the applied stress were observed in the PZT-rich compositions. However, for PMN-PT and PMN-PZT ceramic systems, changes in the dielectric constant with the stress were found to depend significantly on the ceramic compositions. The experimental results could be explained by both intrinsic and extrinsic domain-related mechanisms involving domain wall motions, as well as the de-aging phenomenon from the application of the compressive pre-stress. Roles of different types of domains, i.e. micro-domains and nano-domains, were also discussed.

  19. Variants of biculturalism in migrant and host adolescents living in Italy and Spain: Testing the importance of life domains through the Relative Acculturation Extended Model.

    PubMed

    Mancini, Tiziana; Navas, Marisol; López-Rodríguez, Lucia; Bottura, Benedetta

    2017-05-09

    Several variants of biculturalism have recently been proposed (Schwartz, Birman, Benet-Martínez, & Unger, 2016). Nevertheless, few studies have identified different types of bicultural individuals, and no one has addressed the possibility that these types could depend on acculturation domains. By using the Relative Acculturation Extended Model (RAEM), this study aimed to explore if different variants of biculturalism could be individuated, and if some of these variants were sensitive to life domains. Four samples of migrant and host adolescents living in Italy (n = 173 and n = 186) and Spain (n = 139 and n = 156) answered a questionnaire about acculturation perceptions and preferences in central and peripheral life domains. Together with acculturation options consistent with Berry's (1997) model (full-assimilation, full-separation and full-marginalisation), some variants of biculturalism emerged from the latent class analysis: full-high and full-low integration, which were not sensitive to life domains; and "alternate" acculturation options that were sensitive to life domains, with participants switching from their original culture to the host culture according to the peripheral and central domains. Acculturation options varied across the four samples, with Italians switching more from one culture to another, and Spanish adolescents being more full-high or full-low integrated. © 2017 International Union of Psychological Science.

  20. Sprouty-Related Ena/Vasodilator-Stimulated Phosphoprotein Homology 1-Domain-Containing Protein-2 Critically Regulates Influenza A Virus-Induced Pneumonia.

    PubMed

    Ito, Toshihiro; Itakura, Junya; Takahashi, Sakuma; Sato, Miwa; Mino, Megumi; Fushimi, Soichiro; Yamada, Masao; Morishima, Tuneo; Kunkel, Steven L; Matsukawa, Akihiro

    2016-07-01

    Influenza A virus causes acute respiratory infections that induce annual epidemics and occasional pandemics. Although a number of studies indicated that the virus-induced intracellular signaling events are important in combating influenza virus infection, the mechanism how specific molecule plays a critical role among various intracellular signaling events remains unknown. Raf/MEK/extracellular signal-regulated kinase cascade is one of the key signaling pathways during influenza virus infection, and the Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein has recently been identified as a negative regulator of Raf-dependent extracellular signal-regulated kinase activation. Here, we examined the role of Raf/MEK/extracellular signal-regulated kinase cascade through sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein in influenza A viral infection because the expression of sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein was significantly enhanced in human influenza viral-induced pneumonia autopsy samples. Prospective animal trial. Research laboratory. Wild-type and sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 knockout mice inoculated with influenza A. Wild-type or sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 knockout mice were infected by intranasal inoculation of influenza A (A/PR/8). An equal volume of phosphate-buffered saline was inoculated intranasally into mock-infected mice. Influenza A infection of sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 knockout mice led to higher mortality with greater viral load, excessive inflammation, and enhanced cytokine production than wild-type mice. Administration of MEK inhibitor, U0126, improved mortality and reduced both viral load and

  1. Work locus of control and its relationship to stress perception, related affections, attitudes and behaviours from a domain-specific perspective.

    PubMed

    Tong, Jiajin; Wang, Lei

    2012-08-01

    This research aims to examine the value of applying the Work Locus of Control Scale in predicting work-related outcomes. Study 1 surveyed 323 employees from different companies in China and found that the domain-specific scale was more predictive than the general scale in predicting perceived stressors, rather than in predicting organizational affective commitment and altruistic behaviour. Study 2 applied a multi-wave and multi-source design and used commensurate Likert scales to measure work and general locus of control. Participants were 344 employees from one corporation. Work locus of control was found to be more useful in predicting supervisor-rated job performance, conscientious and altruistic behaviours. These findings help understand the theory-based and measurement-based reasons for the advantages of using domain-specific measures. They claim the importance for employing the domain-specific measure to predict work-related perceptions and behaviours. Implications for the theory and practice are discussed.

  2. Social identity, self-evaluation and in-group bias: the relative importance of particular domains of self-esteem to the in-group.

    PubMed

    Hunter, John A; Kypri, Kypros; Stokell, Natalie M; Boyes, Mike; O'Brien, Kerry S; McMenamin, Kathleen E

    2004-03-01

    This investigation sought to assess the link between in-group bias and domain-specific self-esteem. Two experiments were carried out. Experiment 1 revealed that social category members (i.e. Christians), manifested an increase in that domain of self-esteem judged to be relatively more important to the in-group (i.e. physical self-esteem), following the display of in-group bias. A second experiment which sought to examine an alternative explanation for these findings, in terms of enhanced social identity salience, produced identical findings. Domains of self-esteem relatively less important to the in-group (i.e. mathematical self-esteem) were unaffected in each experiment. Consistent with recent revisions to the second corollary of the self-esteem hypothesis, Experiment 2 further revealed that category members with low public collective self-esteem (who believed that Christians were evaluated negatively by Atheists) showed more pronounced in-group bias.

  3. A Combinatorial Code for Gene Expression Generated by Transcription Factor Bach2 and MAZR (MAZ-Related Factor) through the BTB/POZ Domain

    PubMed Central

    Kobayashi, Akira; Yamagiwa, Hironori; Hoshino, Hideto; Muto, Akihiko; Sato, Kazushige; Morita, Masanobu; Hayashi, Norio; Yamamoto, Masayuki; Igarashi, Kazuhiko

    2000-01-01

    Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the BTB/POZ domain, MAZR possesses Zn finger motifs that are closely related to those of the Myc-associated Zn finger (MAZ) protein. MAZR mRNA was coexpressed with Bach2 in B cells among hematopoietic cells and in developing mouse limb buds, suggesting a cooperative role for MAZR and Bach2 in these cells. MAZR forms homo- and hetero-oligomers with Bach2 through the BTB domain, which oligomers bind to guanine-rich sequences. Unlike MAZ, MAZR functioned as a strong activator of the c-myc promoter in transfection assays with B cells. However, it does not possess a typical activation domain, suggesting a role for it as an unusual type of transactivator. The fgf4 gene, which regulates morphogenesis of limb buds, contains both guanine-rich sequences and a Bach2 binding site in its regulatory region. In transfection assays using fibroblast cells, the fgf4 gene was upregulated in the presence of both MAZR and Bach2 in a BTB/POZ domain-dependent manner. The results provide a new perspective on the function of BTB/POZ domain factors and indicate that BTB/POZ domain-mediated oligomers of transcription factors may serve as combinatorial codes for gene expression. PMID:10669750

  4. The Allantoic Core Domain: New Insights Into Development of the Murine Allantois and Its Relation to the Primitive Streak

    PubMed Central

    Downs, Karen M.; Inman, Kimberly E.; Jin, Dexter X.; Enders, Allen C.

    2010-01-01

    The whereabouts and properties of the posterior end of the primitive streak have not been identified in any species. In the mouse, the streak’s posterior terminus is assumed to be confined to the embryonic compartment, and to give rise to the allantois, which links the embryo to its mother during pregnancy. In this study, we have refined our understanding of the biology of the murine posterior primitive streak and its relation to the allantois. Through a combination of immunostaining and morphology, we demonstrate that the primitive streak spans the posterior extraembryonic and embryonic regions at the onset of the neural plate stage (~7.0 days postcoitum, dpc). Several hours later, the allantoic bud emerges from the extraembryonic component of the primitive streak (XPS). Then, possibly in collaboration with overlying allantois-associated extraembryonic visceral endoderm, the XPS establishes a germinal center within the allantois, named here the Allantoic Core Domain (ACD). Microsurgical removal of the ACD beyond headfold (HF) stages resulted in the formation of allantoic regenerates that lacked the ACD and failed to elongate; nevertheless, vasculogenesis and vascular patterning proceeded. In situ and transplantation fate mapping demonstrated that, from HF stages onward, the ACD’s progenitor pool contributed to the allantois exclusive of the proximal flanks. By contrast, the posterior intraembryonic primitive streak (IPS) provided the flanks. Grafting the ACD into TC/TC hosts, whose allantoises are significantly foreshortened, restored allantoic elongation. These results revealed that the ACD is essential for allantoic elongation, but the cues required for vascularization lie outside of it. On the basis of these and previous findings, we conclude that the posterior primitive streak of the mouse conceptus is far more complex than was previously believed. Our results provide new directives for addressing the origin and development of the umbilical cord, and

  5. An Investigation of Broad and Narrow Personality Traits in Relation to General and Domain-Specific Life Satisfaction of College Students

    ERIC Educational Resources Information Center

    Lounsbury, John W.; Saudargas, Richard A.; Gibson, Lucy W.; Leong, Frederick T.

    2005-01-01

    Based on a sample of 532 undergraduates at a Southeastern U.S. university, Big Five and narrow personality traits were examined in relation to a measure of satisfaction with specific domains of college experience (College Satisfaction) and a measure of General Life Satisfaction. Four of the Big Five traits--Agreeableness, Conscientiousness,…

  6. Models of the Joint Structure of Domain-Related and Global Distress: Implications for the Reconciliation of Quality of Life and Mental Health Perspectives

    ERIC Educational Resources Information Center

    Magee, William; St-Arnaud, Sebastien

    2012-01-01

    Research on subjective wellbeing includes studies of both domain-related and global distress. The mental health literature, though, focuses almost exclusively on global distress. This seems to be partly due to a common belief that psychological distress, and the moods that comprise distress, necessarily lack referential content. However, if that…

  7. Binding domains of Bacillus anthracis phage endolysins recognize cell culture age-related features on the bacterial surface.

    PubMed

    Paskaleva, Elena E; Mundra, Ruchir V; Mehta, Krunal K; Pangule, Ravindra C; Wu, Xia; Glatfelter, Willing S; Chen, Zijing; Dordick, Jonathan S; Kane, Ravi S

    2015-01-01

    Bacteriolytic enzymes often possess a C-terminal binding domain that recognizes specific motifs on the bacterial surface and a catalytic domain that cleaves covalent linkages within the cell wall peptidoglycan. PlyPH, one such lytic enzyme of bacteriophage origin, has been reported to be highly effective against Bacillus anthracis, and can kill up to 99.99% of the viable bacteria. The bactericidal activity of this enzyme, however, appears to be strongly dependent on the age of the bacterial culture. Although highly bactericidal against cells in the early exponential phase, the enzyme is substantially less effective against stationary phase cells, thus limiting its application in real-world settings. We hypothesized that the binding domain of PlyPH may differ in affinity to cells in different Bacillus growth stages and may be primarily responsible for the age-restricted activity. We therefore employed an in silico approach to identify phage lysins differing in their specificity for the bacterial cell wall. Specifically we focused our attention on Plyβ, an enzyme with improved cell wall-binding ability and age-independent bactericidal activity. Although PlyPH and Plyβ have dissimilar binding domains, their catalytic domains are highly homologous. We characterized the biocatalytic mechanism of Plyβ by identifying the specific bonds cleaved within the cell wall peptidoglycan. Our results provide an example of the diversity of phage endolysins and the opportunity for these biocatalysts to be used for broad-based protection from bacterial pathogens.

  8. ‘It’s a can of worms’: understanding primary care practitioners’ behaviours in relation to HPV using the theoretical domains framework

    PubMed Central

    2012-01-01

    Background The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theory-based intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about

  9. Children's verbal working memory: relative importance of storage, general processing speed, and domain-general controlled attention.

    PubMed

    Magimairaj, Beula M; Montgomery, James W

    2012-07-01

    This study evaluated multiple constraints of verbal working memory in typically developing 7- to 11-year-olds. Multiple measures of verbal working memory and the predictors-short-term memory storage, general speed, and domain-general controlled attention were used. General linear modeling (GLM) showed that storage and the efficiency of controlled attention (i.e., speed of updating information during attention switching) contributed to significant variance in children's verbal working memory. In a secondary analysis verbal storage and domain-general attention (focus switching accuracy and speed of updating on switch) emerged as significant predictors. Results suggest domain-general attention and verbal storage mechanisms to be independent constraints of verbal working memory. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Multi-domain feature extraction for small event-related potentials through nonnegative multi-way array decomposition from low dense array EEG.

    PubMed

    Cong, Fengyu; Phan, Anh-Huy; Astikainen, Piia; Zhao, Qibin; Wu, Qiang; Hietanen, Jari K; Ristaniemi, Tapani; Cichocki, Andrzej

    2013-04-01

    Non-negative Canonical Polyadic decomposition (NCPD) and non-negative Tucker decomposition (NTD) were compared for extracting the multi-domain feature of visual mismatch negativity (vMMN), a small event-related potential (ERP), for the cognitive research. Since signal-to-noise ratio in vMMN is low, NTD outperformed NCPD. Moreover, we proposed an approach to select the multi-domain feature of an ERP among all extracted features and discussed determination of numbers of extracted components in NCPD and NTD regarding the ERP context.

  11. Method of assessing the state of a rolling bearing based on the relative compensation distance of multiple-domain features and locally linear embedding

    NASA Astrophysics Data System (ADS)

    Kang, Shouqiang; Ma, Danyang; Wang, Yujing; Lan, Chaofeng; Chen, Qingguo; Mikulovich, V. I.

    2017-03-01

    To effectively assess different fault locations and different degrees of performance degradation of a rolling bearing with a unified assessment index, a novel state assessment method based on the relative compensation distance of multiple-domain features and locally linear embedding is proposed. First, for a single-sample signal, time-domain and frequency-domain indexes can be calculated for the original vibration signal and each sensitive intrinsic mode function obtained by improved ensemble empirical mode decomposition, and the singular values of the sensitive intrinsic mode function matrix can be extracted by singular value decomposition to construct a high-dimensional hybrid-domain feature vector. Second, a feature matrix can be constructed by arranging each feature vector of multiple samples, the dimensions of each row vector of the feature matrix can be reduced by the locally linear embedding algorithm, and the compensation distance of each fault state of the rolling bearing can be calculated using the support vector machine. Finally, the relative distance between different fault locations and different degrees of performance degradation and the normal-state optimal classification surface can be compensated, and on the basis of the proposed relative compensation distance, the assessment model can be constructed and an assessment curve drawn. Experimental results show that the proposed method can effectively assess different fault locations and different degrees of performance degradation of the rolling bearing under certain conditions.

  12. How Students' Epistemological Beliefs in the Domain of Physics and Their Conceptual Change Are Related?

    ERIC Educational Resources Information Center

    Kaymak, Ercan; Ogan-Bekiroglu, Feral

    2013-01-01

    The purposes of this study were to determine high school students' epistemological beliefs in the domain of physics and to explore and explain the possible relationship between their beliefs and their conceptual change in physics by taking the students' learning strategies into account. A multi-case study design was used for the research…

  13. The Relation between Preschool Children's False-Belief Understanding and Domain-General Experimentation Skills

    ERIC Educational Resources Information Center

    Piekny, Jeanette; Grube, Dietmar; Maehler, Claudia

    2013-01-01

    The focus of the present study is on the developmental antecedents of domain-general experimentation skills. We hypothesized that false-belief understanding would predict the ability to distinguish a conclusive from an inconclusive experiment. We conducted a longitudinal study with two assessment points (t1 and t2) to investigate this hypothesis.…

  14. The Relative Contribution of Health Status and Quality of Life Domains in Subjective Health in Old Age

    ERIC Educational Resources Information Center

    Prieto-Flores, Maria-Eugenia; Moreno-Jimenez, Antonio; Fernandez-Mayoralas, Gloria; Rojo-Perez, Fermina; Forjaz, Maria Joao

    2012-01-01

    To analyze the influence of different health status dimensions and quality of life (QoL) domains on older adults' subjective health, and to assess the role that residential satisfaction plays in these relationships. A QoL survey was conducted on a representative sample of the community-dwelling older adult population in Madrid province (Spain).…

  15. Sensing the Coherence of Biology in Contrast to Psychology: Young Children's Use of Causal Relations to Distinguish Two Foundational Domains

    ERIC Educational Resources Information Center

    Erickson, Jane E.; Keil, Frank C.; Lockhart, Kristi L.

    2010-01-01

    To what extent do children understand that biological processes fall into 1 coherent domain unified by distinct causal principles? In Experiments 1 and 2 (N = 125) kindergartners are given triads of biological and psychological processes and asked to identify which 2 members of the triad belong together. Results show that 5-year-olds correctly…

  16. Sensing the Coherence of Biology in Contrast to Psychology: Young Children's Use of Causal Relations to Distinguish Two Foundational Domains

    ERIC Educational Resources Information Center

    Erickson, Jane E.; Keil, Frank C.; Lockhart, Kristi L.

    2010-01-01

    To what extent do children understand that biological processes fall into 1 coherent domain unified by distinct causal principles? In Experiments 1 and 2 (N = 125) kindergartners are given triads of biological and psychological processes and asked to identify which 2 members of the triad belong together. Results show that 5-year-olds correctly…

  17. The Relative Contribution of Health Status and Quality of Life Domains in Subjective Health in Old Age

    ERIC Educational Resources Information Center

    Prieto-Flores, Maria-Eugenia; Moreno-Jimenez, Antonio; Fernandez-Mayoralas, Gloria; Rojo-Perez, Fermina; Forjaz, Maria Joao

    2012-01-01

    To analyze the influence of different health status dimensions and quality of life (QoL) domains on older adults' subjective health, and to assess the role that residential satisfaction plays in these relationships. A QoL survey was conducted on a representative sample of the community-dwelling older adult population in Madrid province (Spain).…

  18. Mapping of alkali-sensing sites of the insulin receptor-related receptor. The role of L2 and fibronectin domains.

    PubMed

    Deyev, Igor E; Chachina, Natalia A; Shayahmetova, Dinara M; Serova, Oxana V; Petrenko, Alexander G

    2015-04-01

    Insulin receptor-related receptor (IRR) is a member of the insulin receptor (IR) family that works as an extracellular alkali sensor with positive cooperativity. The pH sensing property of IRR is defined by its extracellular region and involves multiple domains. We have previously demonstrated the primary role of L1C domains and identified potentially important amino acid residues within these domains. In this study, we addressed the roles of L2 and FnIII domains. Within the L2 domain, five amino acid residues (M406, V407, D408, P436 and V437) were identified as IRR-specific by performing a species conservation analysis of the IR family. Single-point mutations of these five residues to alanine produced either little or no negative effect on IRR pH-sensing activity. However, the triple mutation of M406, V407 and D408 (MVD) showed a strong negative effect, with a 4 fold decrease in IRR activity as estimated by in vitro autophosphorylation assay of solubilized receptors. The analysis of this mutant in intact cells revealed the absence of positive cooperativity. Unexpectedly, the double mutation of vicinal P436 and V437 (PV) exhibited a significant positive effect in the in vitro assay and partial positive cooperativity in the whole-cell assay. The role of FnIII domains was addressed by analyzing chimeras of IRR and IR. When the IRR FnIII domains were swapped with those of IR in different combinations, the activity was significantly reduced and positive cooperativity eliminated. However, two mutants with the targeted C-terminal part of IRR alpha subunit that lies within FnIII-2 domain and have been shown to be important for insulin binding by IR, appeared to be as active as wild-type IRR. On the basis of available data, we propose that IRR activation involves two separate centers of pH-dependent rearrangements that act synergistically to induce a major conformational change in the IRR molecule, resulting in internal kinase domains rapprochement and autophosphorylation

  19. The β5-Loop and Lid Domain Contribute to the Substrate Specificity of Pancreatic Lipase-related Protein 2 (PNLIPRP2)*

    PubMed Central

    Xiao, Xunjun; Lowe, Mark E.

    2015-01-01

    Pancreatic triglyceride lipase (PNLIP) is essential for dietary fat digestion in children and adults, whereas a homolog, pancreatic lipase-related protein 2 (PNLIPRP2), is critical in newborns. The two lipases are structurally similar, yet they have different substrate specificities. PNLIP only cleaves neutral fats. PNLIPRP2 cleaves neutral and polar fats. To test the hypothesis that the differences in activity between PNLIP and PNLIPRP2 are governed by surface loops around the active site, we created multiple chimeras of both lipases by exchanging the surface loops singly or in combination. The chimeras were expressed, purified, and tested for activity against various substrates. The structural determinants of PNLIPRP2 galactolipase activity were contained in the N-terminal domain. Of the surface loops tested, the lid domain and the β5-loop influenced activity against triglycerides and galactolipids. Any chimera on PNLIP with the PNLIPRP2 lid domain or β5-loop had decreased triglyceride lipase activity similar to that of PNLIPRP2. The corresponding chimeras of PNLIPRP2 did not increase activity against neutral lipids. Galactolipase activity was abolished by the PNLIP β5-loop and decreased by the PNLIP lid domain. The source of the β9-loop had minimal effect on activity. We conclude that the lid domain and β5-loop contribute to substrate specificity but do not completely account for the differing activities of PNLIP and PNLIPRP2. Other regions in the N-terminal domain must contribute to the galactolipase activity of PNLIPRP2 through direct interactions with the substrate or by altering the conformation of the residues surrounding the hydrophilic cavity in PNLIPRP2. PMID:26494624

  20. The β5-Loop and Lid Domain Contribute to the Substrate Specificity of Pancreatic Lipase-related Protein 2 (PNLIPRP2).

    PubMed

    Xiao, Xunjun; Lowe, Mark E

    2015-11-27

    Pancreatic triglyceride lipase (PNLIP) is essential for dietary fat digestion in children and adults, whereas a homolog, pancreatic lipase-related protein 2 (PNLIPRP2), is critical in newborns. The two lipases are structurally similar, yet they have different substrate specificities. PNLIP only cleaves neutral fats. PNLIPRP2 cleaves neutral and polar fats. To test the hypothesis that the differences in activity between PNLIP and PNLIPRP2 are governed by surface loops around the active site, we created multiple chimeras of both lipases by exchanging the surface loops singly or in combination. The chimeras were expressed, purified, and tested for activity against various substrates. The structural determinants of PNLIPRP2 galactolipase activity were contained in the N-terminal domain. Of the surface loops tested, the lid domain and the β5-loop influenced activity against triglycerides and galactolipids. Any chimera on PNLIP with the PNLIPRP2 lid domain or β5-loop had decreased triglyceride lipase activity similar to that of PNLIPRP2. The corresponding chimeras of PNLIPRP2 did not increase activity against neutral lipids. Galactolipase activity was abolished by the PNLIP β5-loop and decreased by the PNLIP lid domain. The source of the β9-loop had minimal effect on activity. We conclude that the lid domain and β5-loop contribute to substrate specificity but do not completely account for the differing activities of PNLIP and PNLIPRP2. Other regions in the N-terminal domain must contribute to the galactolipase activity of PNLIPRP2 through direct interactions with the substrate or by altering the conformation of the residues surrounding the hydrophilic cavity in PNLIPRP2.

  1. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer

    PubMed Central

    Monk, Brian C.; Tomasiak, Thomas M.; Keniya, Mikhail V.; Huschmann, Franziska U.; Tyndall, Joel D. A.; O’Connell, Joseph D.; Cannon, Richard D.; McDonald, Jeffrey G.; Rodriguez, Andrew; Finer-Moore, Janet S.; Stroud, Robert M.

    2014-01-01

    Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14α-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance. PMID:24613931

  2. Effects of gender-related domain violations and sexual orientation on perceptions of male and female targets: an analogue study.

    PubMed

    Blashill, Aaron J; Powlishta, Kimberly K

    2012-10-01

    The current study examined factors that influenced heterosexual male and female raters' evaluations of male and female targets who were gay or heterosexual, and who displayed varying gender roles (i.e., typical vs. atypical) in multiple domains (i.e., activities, traits, and appearance). Participants were 305 undergraduate students from a private, midwestern Jesuit institution who read vignettes describing one of 24 target types and then rated the target on possession of positive and negative characteristics, psychological adjustment, and on measures reflecting the participants' anticipated behavior toward or comfort with the target. Results showed that gender atypical appearance and activity attributes (but not traits) were viewed more negatively than their gender typical counterparts. It was also found that male participants in particular viewed gay male targets as less desirable than lesbian and heterosexual male targets. These findings suggest a nuanced approach for understanding sexual prejudice, which incorporates a complex relationship among sex, gender, sexual orientation, and domain of gendered attributes.

  3. Cetacean distribution and abundance in relation to oceanographic domains on the eastern Bering Sea shelf: 1999-2004

    NASA Astrophysics Data System (ADS)

    Friday, Nancy A.; Waite, Janice M.; Zerbini, Alexandre N.; Moore, Sue E.

    2012-06-01

    Visual line transect surveys for cetaceans were conducted on the eastern Bering Sea shelf in association with pollock stock assessment surveys aboard the NOAA ship Miller Freeman in June and July of 1999, 2000, 2002, and 2004. Transect survey effort ranged from 1188 km in 1999 to 3761 km in 2002. Fin whales (Balaenoptera physalus) were the most common large whale in all years except 2004 when humpback whales (Megaptera novaeangliae) were more abundant. Dall's porpoise (Phocoenoides dalli) were the most common small cetacean in all years. Abundance estimates were calculated by year for each oceanographic domain: coastal, middle, and outer/slope. The middle and outer/slope domains were divided into two strata ("north" and "south") because of variable survey effort. The distribution and abundance of baleen whales changed between the earlier (colder) and later (warmer) survey years. Fin whales consistently occupied the outer shelf and secondarily the middle shelf, and their abundance was an order of magnitude greater in cold compared to warm years. Humpback whales "lived on the margin" of the northern Alaska Peninsula, eastern Aleutian Islands and Bristol Bay; their preferred habitat is possibly associated with areas of high prey availability due to nutrient upwelling and aggregation mechanisms. Minke whales (Balaenoptera acutorostrata) occur shoreward of fin whales in the outer and middle shelf and in coastal habitats along the Alaska Peninsula. The highest abundance for this species was observed in a cold (1999) year. No clear relationship emerged for odontocetes with regard to warm and cold years. Dall's porpoise occupied both outer and middle domains and harbor porpoise (Phocoena phocoena) were more common in middle and coastal domains. This study provided a unique, broad-scale assessment of cetacean distribution and abundance on the eastern Bering Sea shelf and a baseline for future comparisons.

  4. Relating surface roughness and magnetic domain structure to giant magneto-impedance of Co-rich melt-extracted microwires

    DOE PAGES

    Jiang, S. D.; Eggers, T.; Thiabgoh, O.; ...

    2017-04-11

    Understanding the relationship between the surface conditions and giant magneto-impedance (GMI) in Co-rich melt-extracted microwires is key to optimizing their magnetic responses for magnetic sensor applications. The surface magnetic domain structure (SMDS) parameters of ~45 μm diameter Co69.25Fe4.25Si13B13.5-xZrx (x = 0, 1, 2, 3) microwires, including the magnetic domain period (d) and surface roughness (Rq) as extracted from the magnetic force microscopy (MFM) images, have been correlated with GMI in the range 1–1000 MHz. It was found that substitution of B with 1 at. % Zr increased d of the base alloy from 729 to 740 nm while retaining Rqmore » from ~1 nm to ~3 nm. A tremendous impact on the GMI ratio was found, increasing the ratio from ~360% to ~490% at an operating frequency of 40 MHz. Further substitution with Zr decreased the high frequency GMI ratio, which can be understood by the significant increase in surface roughness evident by force microscopy. Lastly, this study demonstrates the application of the domain period and surface roughness found by force microscopy to the interpretation of the GMI in Co-rich microwires.« less

  5. Relating surface roughness and magnetic domain structure to giant magneto-impedance of Co-rich melt-extracted microwires

    PubMed Central

    Jiang, S. D.; Eggers, T.; Thiabgoh, O.; Xing, D. W.; Fei, W. D.; Shen, H. X.; Liu, J. S.; Zhang, J. R.; Fang, W. B.; Sun, J. F.; Srikanth, H.; Phan, M. H.

    2017-01-01

    Understanding the relationship between the surface conditions and giant magneto-impedance (GMI) in Co-rich melt-extracted microwires is key to optimizing their magnetic responses for magnetic sensor applications. The surface magnetic domain structure (SMDS) parameters of ~45 μm diameter Co69.25Fe4.25Si13B13.5-xZrx (x = 0, 1, 2, 3) microwires, including the magnetic domain period (d) and surface roughness (Rq) as extracted from the magnetic force microscopy (MFM) images, have been correlated with GMI in the range 1–1000 MHz. It was found that substitution of B with 1 at. % Zr increased d of the base alloy from 729 to 740 nm while retaining Rq from ~1 nm to ~3 nm. A tremendous impact on the GMI ratio was found, increasing the ratio from ~360% to ~490% at an operating frequency of 40 MHz. Further substitution with Zr decreased the high frequency GMI ratio, which can be understood by the significant increase in surface roughness evident by force microscopy. This study demonstrates the application of the domain period and surface roughness found by force microscopy to the interpretation of the GMI in Co-rich microwires. PMID:28397832

  6. Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus

    SciTech Connect

    Asojo, Oluwatoyin A.; Loukas, Alex; Inan, Mehmet; Barent, Rick; Huang, Jicai; Plantz, Brad; Swanson, Amber; Gouthro, Mark; Meagher, Michael M.; Hotez, Peter J.

    2005-04-01

    In order to clarify the structural basis of the pathogenesis-related-1 domain, Na-ASP-1, the first multi-domain ASP from the human hookworm parasite N. americanus, has been crystallized. 2.2 Å resolution data have been collected from a crystal belonging to the monoclinic space group P2{sub 1}. Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P2{sub 1} with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit.

  7. Phage phi29 DNA replication organizer membrane protein p16.7 contains a coiled coil and a dimeric, homeodomain-related, functional domain.

    PubMed

    Muñoz-Espín, Daniel; Mateu, Mauricio G; Villar, Laurentino; Marina, Anabel; Salas, Margarita; Meijer, Wilfried J J

    2004-11-26

    The Bacillus subtilis phage varphi29-encoded membrane protein p16.7 is one of the few proteins known to be involved in prokaryotic membrane-associated DNA replication. Protein p16.7 contains an N-terminal transmembrane domain responsible for membrane localization. A soluble variant lacking the N-terminal membrane anchor, p16.7A, forms dimers in solution, binds to DNA, and has affinity for the varphi29 terminal protein. Here we show that the soluble N-terminal half of p16.7A can form a dimeric coiled coil. However, a second domain, located in the C-terminal half of the protein, has been characterized as being the main domain responsible for p16.7 dimerization. This 70-residue C-terminal domain, named p16.7C, also constitutes the functional part of the protein as it binds to DNA and terminal protein. Sequence alignments, secondary structure predictions, and spectroscopic analyses suggest that p16.7C is evolutionarily related to DNA binding homeodomains, present in many eukaryotic transcriptional regulator proteins. Based on the results, a structural model of p16.7 is presented.

  8. Mapping of structural and transcription-related matrix attachment sites in the alpha-globin gene domain of avian erythroblasts and erythrocytes.

    PubMed Central

    Farache, G; Razin, S V; Rzeszowska-Wolny, J; Moreau, J; Targa, F R; Scherrer, K

    1990-01-01

    The positions of preferential DNA interaction with the nuclear matrix were mapped within the domain of the chicken alpha-globin genes in transcriptionally active erythroblast nuclei and inactive nuclei of mature erythrocytes. In the latter, only two major distinct attachment sites were observed, close to the A + T-rich sequences previously found at the boundaries of the domain. Sequencing of these structural matrix attachment points revealed several known DNA motifs; some of them were present on both sides of the domain. In actively transcribing erythroblast nuclei of adult animals, a large fraction of the transcribed area was represented in nuclear matrix DNA, including upstream and downstream elements. In particular, adult alpha A- and alpha D-globin genes were found in matrix DNA, while the transcribed but translationally unexpressed embryonic pi gene was underrepresented. The data are discussed in terms of the existence of stable or structural and expression-related matrix attachment sites; correlations to the origin of replication and the units of transcription of the domain are shown. Images PMID:2398893

  9. Social anxiety disorder and quality of life: How fears of negative and positive evaluation relate to specific domains of life satisfaction.

    PubMed

    Dryman, M Taylor; Gardner, Shani; Weeks, Justin W; Heimberg, Richard G

    2016-03-01

    Individuals with social anxiety disorder (SAD) experience functional impairment in social, educational, and occupational arenas, contributing to poor quality of life. Previous research using the Quality of Life Inventory (QOLI) has identified four distinct domains of quality of life among individuals with SAD: Achievement, Personal Growth, Social Functioning, and Surroundings. The present study was designed to investigate how fear of negative evaluation (FNE) and fear of positive evaluation (FPE) relate to the four QOLI domains among individuals with SAD. We also examined the relationships of FNE and FPE to Satisfaction and Importance ratings on the QOLI. Individuals with SAD (N=129) completed a battery of questionnaires prior to initiating treatment. FNE and FPE showed distinct relationships with the four QOLI domains, even after controlling for demographic characteristics and comorbid depression. Both FNE and FPE were associated with ratings of Satisfaction with the QOLI domains, but neither was associated with ratings of Importance. Our findings highlight the differential impacts of FNE and FPE on SAD. Treatment implications are discussed.

  10. Exact First-Passage Exponents of 1D Domain Growth: Relation to a Reaction-Diffusion Model

    NASA Astrophysics Data System (ADS)

    Derrida, Bernard; Hakim, Vincent; Pasquier, Vincent

    1995-07-01

    In the zero temperature Glauber dynamics of the ferromagnetic Ising or q-state Potts model, the size of domains is known to grow like t1/2. Recent simulations have shown that the fraction r\\(q,t\\) of spins, which have never flipped up to time t, decays like the power law r\\(q,t\\)~t-θ\\(q\\) with a nontrivial dependence of the exponent θ\\(q\\) on q and on space dimension. By mapping the problem on an exactly soluble one-species coagulation model ( A+A-->A), we obtain the exact expression of θ\\(q\\) in dimension one.

  11. Light-induced conformational changes of LOV1 (light oxygen voltage-sensing domain 1) and LOV2 relative to the kinase domain and regulation of kinase activity in Chlamydomonas phototropin.

    PubMed

    Okajima, Koji; Aihara, Yusuke; Takayama, Yuki; Nakajima, Mihoko; Kashojiya, Sachiko; Hikima, Takaaki; Oroguchi, Tomotaka; Kobayashi, Amane; Sekiguchi, Yuki; Yamamoto, Masaki; Suzuki, Tomomi; Nagatani, Akira; Nakasako, Masayoshi; Tokutomi, Satoru

    2014-01-03

    Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that undergoes a cyclic photoreaction upon BL excitation via a signaling state in which the inhibition of the kinase activity by LOV2 is negated. To understand the molecular mechanism underlying the BL-dependent activation of the kinase, the photochemistry, kinase activity, and molecular structure were studied with the phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C. reinhardtii phot showed cyclic photoreaction characteristics with the activation of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the photosensitivity of the kinase activation, which was well explained by the fact that the signaling state lasted for a shorter period of time compared with that of the phot. Small angle x-ray scattering revealed monomeric forms of the proteins in solution and detected BL-dependent conformational changes, suggesting an extension of the global molecular shapes of both samples. Constructed molecular model of full-length phot based on the small angle x-ray scattering data proved the arrangement of LOV1, LOV2, and KD for the first time that showed a tandem arrangement both in the dark and under BL irradiation. The models suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation. This finding demonstrates that LOV1 may interact with LOV2 and modify the photosensitivity of the kinase activation through alteration of the duration of the signaling state in LOV2.

  12. Enhancing the soluble expression of an amylase in Escherichia coli by the mutations related to its domain interactions.

    PubMed

    Wang, Peili; Qin, Weitong; Xu, Jiangtao; Yan, Yaru; Tian, Jian; Wu, Ningfeng; Yao, Bin

    2016-04-01

    The sequence and structure of the target protein exert a marked effect on its soluble expression in Escherichia coli. The effects of the mutation of an amylase isolated from Bacillus licheniformis (BLA) on its soluble expression in E. coli were investigated. A random mutation library of BLA was constructed to screen for mutations that resulted in enhanced soluble expression in E. coli. Two interesting mutations (A390I and D401V) were identified, which are located at the interaction surface between the A and C domains of BLA. The A390I mutation enhanced soluble BLA expression by 2.0-fold compared to wild type, while D401V decreased soluble expression 160-fold. Structural analysis revealed that A390 and D401 residues could affect the interaction between the A and C domains of BLA. Therefore, soluble expression of the target protein in E. coli could be affected by introduction of a mutation in the protein sequence.

  13. Novel interactions of ankyrins-G at the costameres: The muscle-specific Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C

    SciTech Connect

    Maiweilidan, Yimingjiang; Klauza, Izabela; Kordeli, Ekaterini

    2011-04-01

    Ankyrins, the adapters of the spectrin skeleton, are involved in local accumulation and stabilization of integral proteins to the appropriate membrane domains. In striated muscle, tissue-dependent alternative splicing generates unique Ank3 gene products (ankyrins-G); they share the Obscurin/Titin-Binding-related Domain (OTBD), a muscle-specific insert of the C-terminal domain which is highly conserved among ankyrin genes, and binds obscurin and titin to Ank1 gene products. We previously proposed that OTBD sequences constitute a novel domain of protein-protein interactions which confers ankyrins with specific cellular functions in muscle. Here we searched for muscle proteins binding to ankyrin-G OTBD by yeast two hybrid assay, and we found plectin and filamin C, two organizing elements of the cytoskeleton with essential roles in myogenesis, muscle cell cytoarchitecture, and muscle disease. The three proteins coimmunoprecipitate from skeletal muscle extracts and colocalize at costameres in adult muscle fibers. During in vitro myogenesis, muscle ankyrins-G are first expressed in postmitotic myocytes undergoing fusion to myotubes. In western blots of subcellular fractions from C2C12 cells, the majority of muscle ankyrins-G appear associated with membrane compartments. Occasional but not extensive co-localization at nascent costameres suggested that ankyrin-G interactions with plectin and filamin C are not involved in costamere assembly; they would rather reinforce stability and/or modulate molecular interactions in sarcolemma microdomains by establishing novel links between muscle-specific ankyrins-G and the two costameric dystrophin-associated glycoprotein and integrin-based protein complexes. These results report the first protein-protein interactions involving the ankyrin-G OTBD domain and support the hypothesis that OTBD sequences confer ankyrins with a gain of function in vertebrates, bringing further consolidation and resilience of the linkage between sarcomeres

  14. A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division.

    PubMed

    Chang, Chuang-Rung; Manlandro, Cara Marie; Arnoult, Damien; Stadler, Julia; Posey, Ammon E; Hill, R Blake; Blackstone, Craig

    2010-10-15

    Mitochondria dynamically fuse and divide within cells, and the proper balance of fusion and fission is necessary for normal mitochondrial function, morphology, and distribution. Drp1 is a dynamin-related GTPase required for mitochondrial fission in mammalian cells. It harbors four distinct domains: GTP-binding, middle, insert B, and GTPase effector. A lethal mutation (A395D) within the Drp1 middle domain was reported in a neonate with microcephaly, abnormal brain development, optic atrophy, and lactic acidemia (Waterham, H. R., Koster, J., van Roermund, C. W., Mooyer, P. A., Wanders, R. J., and Leonard, J. V. (2007) N. Engl. J. Med. 356, 1736-1741). Mitochondria within patient-derived fibroblasts were markedly elongated, but the molecular mechanisms underlying these findings were not demonstrated. Because the middle domain is particularly important for the self-assembly of some dynamin superfamily proteins, we tested the hypothesis that this A395D mutation, and two other middle domain mutations (G350D, G363D) were important for Drp1 tetramerization, higher order assembly, and function. Although tetramerization appeared largely intact, each of these mutations compromised higher order assembly and assembly-dependent stimulation of Drp1 GTPase activity. Moreover, mutant Drp1 proteins exhibited impaired localization to mitochondria, indicating that this higher order assembly is important for mitochondrial recruitment, retention, or both. Overexpression of these middle domain mutants markedly inhibited mitochondrial division in cells. Thus, the Drp1 A395D lethal defect likely resulted in impaired higher order assembly of Drp1 at mitochondria, leading to decreased fission, elongated mitochondria, and altered cellular distribution of mitochondria.

  15. Proteins Related to the Type I Secretion System Are Associated with Secondary SecA_DEAD Domain Proteins in Some Species of Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi

    PubMed Central

    Kamneva, Olga K.; Poudel, Saroj; Ward, Naomi L.

    2015-01-01

    A number of bacteria belonging to the PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) super-phylum contain unusual ribosome-bearing intracellular membranes. The evolutionary origins and functions of these membranes are unknown. Some proteins putatively associated with the presence of intracellular membranes in PVC bacteria contain signal peptides. Signal peptides mark proteins for translocation across the cytoplasmic membrane in prokaryotes, and the membrane of the endoplasmic reticulum in eukaryotes, by highly conserved Sec machinery. This suggests that proteins might be targeted to intracellular membranes in PVC bacteria via the Sec pathway. Here, we show that canonical signal peptides are significantly over-represented in proteins preferentially present in PVC bacteria possessing intracellular membranes, indicating involvement of Sec translocase in their cellular targeting. We also characterized Sec proteins using comparative genomics approaches, focusing on the PVC super-phylum. While we were unable to detect unique changes in Sec proteins conserved among membrane-bearing PVC species, we identified (1) SecA ATPase domain re-arrangements in some Planctomycetes, and (2) secondary SecA_DEAD domain proteins in the genomes of some Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi. This is the first report of potentially duplicated SecA in Gram-negative bacteria. The phylogenetic distribution of secondary SecA_DEAD domain proteins suggests that the presence of these proteins is not related to the occurrence of PVC endomembranes. Further genomic analysis showed that secondary SecA_DEAD domain proteins are located within genomic neighborhoods that also encode three proteins possessing domains specific for the Type I secretion system. PMID:26030905

  16. Proteins Related to the Type I Secretion System Are Associated with Secondary SecA_DEAD Domain Proteins in Some Species of Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi.

    PubMed

    Kamneva, Olga K; Poudel, Saroj; Ward, Naomi L

    2015-01-01

    A number of bacteria belonging to the PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) super-phylum contain unusual ribosome-bearing intracellular membranes. The evolutionary origins and functions of these membranes are unknown. Some proteins putatively associated with the presence of intracellular membranes in PVC bacteria contain signal peptides. Signal peptides mark proteins for translocation across the cytoplasmic membrane in prokaryotes, and the membrane of the endoplasmic reticulum in eukaryotes, by highly conserved Sec machinery. This suggests that proteins might be targeted to intracellular membranes in PVC bacteria via the Sec pathway. Here, we show that canonical signal peptides are significantly over-represented in proteins preferentially present in PVC bacteria possessing intracellular membranes, indicating involvement of Sec translocase in their cellular targeting. We also characterized Sec proteins using comparative genomics approaches, focusing on the PVC super-phylum. While we were unable to detect unique changes in Sec proteins conserved among membrane-bearing PVC species, we identified (1) SecA ATPase domain re-arrangements in some Planctomycetes, and (2) secondary SecA_DEAD domain proteins in the genomes of some Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi. This is the first report of potentially duplicated SecA in Gram-negative bacteria. The phylogenetic distribution of secondary SecA_DEAD domain proteins suggests that the presence of these proteins is not related to the occurrence of PVC endomembranes. Further genomic analysis showed that secondary SecA_DEAD domain proteins are located within genomic neighborhoods that also encode three proteins possessing domains specific for the Type I secretion system.

  17. The ARM Domain of ARMADILLO-REPEAT KINESIN 1 is Not Required for Microtubule Catastrophe But Can Negatively Regulate NIMA-RELATED KINASE 6 in Arabidopsis thaliana.

    PubMed

    Eng, Ryan C; Halat, Laryssa S; Livingston, Samuel J; Sakai, Tatsuya; Motose, Hiroyasu; Wasteneys, Geoffrey O

    2017-08-01

    Microtubules are dynamic filaments, the assembly and disassembly of which are under precise control of various associated proteins, including motor proteins and regulatory enzymes. In Arabidopsis thaliana, two such proteins are the ARMADILLO-REPEAT KINESIN 1 (ARK1), which promotes microtubule disassembly, and the NIMA-RELATED KINASE 6 (NEK6), which has a role in organizing microtubule arrays. Previous yeast two-hybrid and in vitro pull-down assays determined that NEK6 can interact with ARK1 through the latter protein's Armadillo-repeat (ARM) cargo domain. To explore the function of the ARM domain, we generated fluorescent reporter fusion proteins to ARK1 lacking the ARM domain (ARK1ΔARM-GFP) and to the ARM domain alone (ARM-GFP). Both of these constructs strongly associated with the growing plus ends of microtubules, but only ARK1ΔARM-GFP was capable of inducing microtubule catastrophe and rescuing the ark1-1 root hair phenotype. These results indicate that neither the ARM domain nor NEK6's putative interaction with it is required for ARK1 to induce microtubule catastrophe. In further exploration of the ARK1-NEK6 relationship, we demonstrated that, despite evidence that NEK6 can phosphorylate ARK1 in vitro, the in vivo distribution and function of ARK1 were not affected by the loss of NEK6, and vice versa. Moreover, NEK6 and ARK1 were found to have overlapping but non-identical distribution on microtubules, and hormone treatments known to affect NEK6 activity did not stimulate interaction. These findings suggest that ARK1 and NEK6 function independently in microtubule dynamics and cell morphogenesis. Despite the results of this functional analysis, we found that overexpression of the ARM domain led to complete loss of NEK6 transcription, suggesting that the ARM domain might have a regulatory role in NEK6 expression. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions

  18. Using Common Spatial Distributions of Atoms to Relate Functionally Divergent Influenza Virus N10 and N11 Protein Structures to Functionally Characterized Neuraminidase Structures, Toxin Cell Entry Domains, and Non-Influenza Virus Cell Entry Domains

    PubMed Central

    Weininger, Arthur; Weininger, Susan

    2015-01-01

    The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell

  19. Using common spatial distributions of atoms to relate functionally divergent influenza virus N10 and N11 protein structures to functionally characterized neuraminidase structures, toxin cell entry domains, and non-influenza virus cell entry domains.

    PubMed

    Weininger, Arthur; Weininger, Susan

    2015-01-01

    The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell

  20. Disparate evolution of prion protein domains and the distinct origin of Doppel- and prion-related loci revealed by fish-to-mammal comparisons.

    PubMed

    Rivera-Milla, Eric; Oidtmann, Birgit; Panagiotidis, Cynthia H; Baier, Michael; Sklaviadis, Theodoros; Hoffmann, Rudolf; Zhou, Yi; Solis, Gonzalo P; Stuermer, Claudia A O; Málaga-Trillo, Edward

    2006-02-01

    Prions result from the misfolding and selective accumulation of the host-encoded prion protein (PrP) in the brain. Despite intensive research on mammalian models, basic questions about the biological role of PrP and the evolutionary origin of prion disease remain unanswered. Following our previous identification of novel fish PrP homologues, here we generated new fish PrP sequences and performed genomic analysis to demonstrate the existence of two homologous PrP loci in bony fish, which display extensive molecular variation and are highly expressed in adult and developing fish brains. The fish PrP genomic regions contain PrP-related loci directly downstream of each PrP locus, suggesting an independent origin of prion-related proteins in fish and mammals. Our structural prediction analysis uncovers a conserved molecular "bauplan" for all vertebrate PrPs. The C- and N-terminal protein domains have evolved independently from one another, the former having retained its basic globular structure despite high sequence divergence and the latter having undergone differential expansion-degeneration cycles in its repetitive domains. Our evolutionary analysis redefines fundamental concepts on the functional significance of PrP domains and opens up new possibilities for the experimental analysis of prion misfolding and neurodegeneration in a non-mammalian model like the zebrafish.

  1. Association between P3 event-related potential amplitude and externalizing disorders: a time-domain and time-frequency investigation of 29-year-old adults.

    PubMed

    Yoon, Henry H; Malone, Stephen M; Burwell, Scott J; Bernat, Edward M; Iacono, William G

    2013-07-01

    This study determined whether time-domain P3 amplitude and time-frequency principal component (TF-PC) reductions are present in adulthood (age 29) when participants have largely passed through the age of heaviest substance misuse. Participants were assessed from age 17 through 29 for lifetime externalizing (EXT) disorders. EEG comparisons from three topographic regions were examined for P3 amplitude and TF-PCs at delta and theta frequency ranges. Significant P3 amplitude reductions were found in those with EXT for both regional and site-Pz analyses, with stronger effects observed the greater the EXT comorbidity. Reductions were also observed in all eight TF-PCs extracted, with a delta component yielding frontal effects not apparent in the time domain. Overall, results suggest that these brain measures continue, at age 29, to provide effective indices of EXT that potentially tap a neural substrate related to behavioral disinhibition.

  2. The pepper GNA-related lectin and PAN domain protein gene, CaGLP1, is required for plant cell death and defense signaling during bacterial infection.

    PubMed

    Kim, Nak Hyun; Lee, Dong Hyuk; Choi, Du Seok; Hwang, Byung Kook

    2015-12-01

    Carbohydrate-binding proteins, commonly referred to as lectins or agglutinins, function in defense responses to microbial pathogens. Pepper (Capsicum annuum) GNA-related lectin and PAN-domain protein gene CaGLP1 was isolated and functionally characterized from pepper leaves infected with Xanthomonas campestris pv. vesicatoria (Xcv). CaGLP1 contained an amine-terminus prokaryotic membrane lipoprotein lipid attachment site, a Galanthus nivalis agglutinin (GNA)-related lectin domain responsible for the recognition of high-mannose N-glycans, and a carboxyl-terminus PAN/apple domain. RNA gel blot and immunoblot analyses determined that CaGLP1 was strongly induced in pepper by compatible and incompatible Xcv infection. CaGLP1 protein localized primarily to the plasma membrane and exhibited mannose-binding specificity. CaGLP1-silenced pepper plants were more susceptible to compatible or incompatible Xcv infection compared with that of non-silenced control plants. CaGLP1 silencing in pepper leaves did not accumulate H2O2 and induce cell death during incompatible Xcv infection. Defense-related CaDEF1 (defensin) gene expression was significantly reduced in CaGLP1-silenced pepper plants. CaGLP1-overexpression in Arabidopsis thaliana enhanced resistance to Pseudomonas syringae pv. tomato. Defense-related AtPDF1.2 expression was elevated in CaGLP1-overexpression lines. Together, these results suggest that CaGLP1 is required for plant cell death and defense responses through the reactive oxygen species burst and downstream defense-related gene expression in response to bacterial pathogen challenge. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Identification of Eye-Specific Domains and Their Relation to Callosal Connections in Primary Visual Cortex of Long Evans Rats

    PubMed Central

    Laing, R.J.; Turecek, J.; Takahata, T.; Olavarria, J.F.

    2015-01-01

    Ocular dominance columns (ODCs) exist in many primates and carnivores, but it is believed that they do not exist in rodents. Using a combination of transneuronal tracing, in situ hybridization for Zif268 and electrophysiological recordings, we show that inputs from both eyes are largely segregated in the binocular region of V1 in Long Evans rats. We also show that, interposed between this binocular region and the lateral border of V1, there lies a strip of cortex that is strongly dominated by the contralateral eye. Finally, we show that callosal connections colocalize primarily with ipsilateral eye domains in the binocular region and with contralateral eye input in the lateral cortical strip, mirroring the relationship between patchy callosal connections and specific sets of ODCs described previously in the cat. Our results suggest that development of cortical modular architecture is more conserved among rodents, carnivores, and primates than previously thought. PMID:24969475

  4. Sensing the coherence of biology in contrast to psychology: young children's use of causal relations to distinguish two foundational domains.

    PubMed

    Erickson, Jane E; Keil, Frank C; Lockhart, Kristi L

    2010-01-01

    To what extent do children understand that biological processes fall into 1 coherent domain unified by distinct causal principles? In Experiments 1 and 2 (N = 125) kindergartners are given triads of biological and psychological processes and asked to identify which 2 members of the triad belong together. Results show that 5-year-olds correctly cluster biological processes and separate them from psychological ones. Experiments 3 and 4 (N = 64) examine whether or not children make this distinction because they understand that biological and psychological processes operate according to fundamentally different causal mechanisms. The results suggest that 5-year-olds do possess this understanding, and furthermore, they have intuitions about the nature of these different mechanisms.

  5. Domains of health-related quality of life important and relevant to multiethnic English-speaking Asian systemic lupus erythematosus patients: a focus group study.

    PubMed

    Ow, Yen Ling Mandy; Thumboo, Julian; Cella, David; Cheung, Yin Bun; Yong Fong, Kok; Wee, Hwee Lin

    2011-06-01

    To identify health-related quality of life (HRQOL) domains of importance to multiethnic Asian systemic lupus erythematosus (SLE) patients, to identify content gaps in existing SLE-specific HRQOL measures, and to determine whether the Patient-Reported Outcomes Measurement Information System (PROMIS) item banks could serve as a core set of questions for HRQOL assessment among SLE patients. English-speaking patients with physician-diagnosed SLE from a specialist clinic in a tertiary care hospital in Singapore and a patient support group were recruited. Thematic analysis was performed to distill themes from transcripts through open coding by 2 independent coders and axial coding for refinement of categories. Items from 3 existing SLE-specific measures and PROMIS Version 1.0 Item Banks were compared with identified subthemes. Twenty-seven female and 2 male participants (21 Chinese, 4 Malay, 3 Indian, 1 other) ages 23-62 years participated in 6 focus groups and 2 individual interviews, respectively. Twenty-one domains and 92 subthemes were identified. Domains of family, relationships, stigma and discrimination, and freedom were unaddressed by existing SLE-specific measures. Forty subthemes from 14 domains were addressed by the PROMIS Version 1.0 Item Banks (Physical Function, Pain, Fatigue, Sleep Disturbance, Sleep-Related Impairment, Anger, Anxiety, and Depression banks). Family and stigma and discrimination (identified as content gaps) may be accentuated in the Asian sociocultural context. PROMIS item banks have tremendous potential to serve as a core set of items for HRQOL assessment in SLE patients. Additional items may be written to fill the gaps in existing PROMIS item banks. Copyright © 2011 by the American College of Rheumatology.

  6. Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain-containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites*

    PubMed Central

    Hill, Ross J.; Ringel, Alessa; Knuepfer, Ellen; Moon, Robert W.; Blackman, Michael J.; van Ooij, Christiaan

    2016-01-01

    StAR-related lipid transfer (START) domains are phospholipid- or sterol-binding modules that are present in many proteins. START domain-containing proteins (START proteins) play important functions in eukaryotic cells, including the redistribution of phospholipids to subcellular compartments and delivering sterols to the mitochondrion for steroid synthesis. How the activity of the START domain is regulated remains unknown for most of these proteins. The Plasmodium falciparum START protein PFA0210c (PF3D7_0104200) is a broad-spectrum phospholipid transfer protein that is conserved in all sequenced Plasmodium species and is most closely related to the mammalian START proteins STARD2 and STARD7. PFA0210c is unusual in that it contains a signal sequence and a PEXEL export motif that together mediate transfer of the protein from the parasite to the host erythrocyte. The protein also contains a C-terminal extension, which is very uncommon among mammalian START proteins. Whereas the biochemical properties of PFA0210c have been characterized, the function of the protein remains unknown. Here, we provide evidence that the unusual C-terminal extension negatively regulates phospholipid transfer activity. Furthermore, we use the genetically tractable Plasmodium knowlesi model and recently developed genetic technology in P. falciparum to show that the protein is essential for growth of the parasite during the clinically relevant asexual blood stage life cycle. Finally, we show that the regulation of phospholipid transfer by PFA0210c is required in vivo, and we identify a potential second regulatory domain. These findings provide insight into a novel mechanism of regulation of phospholipid transfer in vivo and may have important implications for the interaction of the malaria parasite with its host cell. PMID:27694132

  7. Emotional Modulation of Conflict Processing in the Affective Domain: Evidence from Event-related Potentials and Event-related Spectral Perturbation Analysis

    PubMed Central

    Ma, Jianling; Liu, Chang; Chen, Xu

    2016-01-01

    Previous studies have revealed the impact of emotion on conflict processing. The present study was conducted to investigate whether cognitive control in the affective domain is also affected by emotion. Emotional face-word and body-word Stroop tasks were explored and contrasted, and both behavioural and electrophysiological measures were recorded. Behavioural results showed that both tasks replicated previous robust interference effects. At the physiological level, the two tasks showed dissociable neural activity in the early attention and perception stages. It was also found that the face-word task evoked more pronounced N1 and P2 amplitudes than the body-word task. However, the two tasks evoked comparable N450 amplitudes. At later processing stages, positive slow potentials were modulated by target emotion and congruency. In addition, time-frequency analyses also revealed that the face-word task induced enhanced theta activity compared to the body-word task at both early and later stages of processing. The present findings provide support for the dual competition framework and suggest the dynamic modulation of emotion on cognitive control in the affective domain. PMID:27511609

  8. Chemical and biochemical issues related to X-ray crystallography of the ligand-binding domain of estrogen receptor alpha.

    PubMed

    Goldstein, S W; Bordner, J; Hoth, L R; Geoghegan, K F

    2001-01-01

    Careful attention to technical issues preceded successful crystallography of the ligand-binding domain of estrogen receptor alpha (ERalpha) complexed with CP-336156, a nonsteroidal estrogen agonist/antagonist. An affinity column based on immobilized estradiol was prepared according to the scheme of Greene et al. (Greene, G. L., Nolan, C., Engler, J. P., and Jensen, E. V. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 5115-5119). It was shown by X-ray crystallography that the major and less polar isomer of the affinity column precursor was 17alpha-((S)-2',3'-epoxyprop-1'-yl)estra-1,3,5(10)-triene-3,17beta-diol. This diastereomer was coupled to Thiopropyl Sepharose, with coupling monitored by observing loss of the phenolic absorption band of estradiol from the reaction supernatant, and gave an affinity matrix containing about 9 micromol of estradiol per milliliter of wet gel. Recombinant ERalpha ligand binding domain was selectively removed from E. coli cell lysate by binding to the column and was partly S-carboxymethylated by treatment with iodoacetic acid while bound to the column as described by previous workers. After being eluted from the column as a complex with drug, the receptor fragment was shown by mass spectrometry to be a mixture of differently modified forms. It was further S-carboxymethylated in solution, after which anion-exchange chromatography was used to isolate protein in which two of the four cysteine residues were S-carboxymethylated. This material, which afforded diffraction-quality crystals, was subjected to digestion with trypsin and peptide mapping analysis by HPLC coupled with mass spectrometry. For this experiment, the two previously unmodified cysteines were alkylated with 4-vinylpyridine to allow definitive identification. It was shown that Cys-417 and Cys-530 were S-carboxymethylated in the crystallized protein, while Cys-381 and Cys-447 remained unmodified. Close attention to such technical issues may be important in structural studies of

  9. Direct Association of Sprouty-related Protein with an EVH1 Domain (SPRED) 1 or SPRED2 with DYRK1A Modifies Substrate/Kinase Interactions*

    PubMed Central

    Li, Dan; Jackson, Rebecca A.; Yusoff, Permeen; Guy, Graeme R.

    2010-01-01

    The mammalian SPRED (Sprouty-related protein with an EVH1 domain) proteins include a family of three members, SPRED1–3. Currently, little is known about their biochemistry. The best described, SPRED1, has been shown to inhibit the Ras/ERK pathway downstream of Ras. All three SPREDs have a cysteine-rich domain (CRD) that has high homology to the CRD of the Sprouty family of proteins, several of which are also Ras/ERK inhibitors. In the belief that binding partners would clarify SPRED function, we assayed for their associated proteins. Here, we describe the direct and endogenous interaction of SPRED1 and SPRED2 with the novel kinase, DYRK1A. DYRK1A has become the subject of recent research focus as it plays a central role in Caenorhabditis elegans oocyte maturation and egg activation, and there is strong evidence that it could be involved in Down syndrome in humans. Both SPRED1 and SPRED2 inhibit the ability of DYRK1A to phosphorylate its substrates, Tau and STAT3. This inhibition occurs via an interaction of the CRD of the SPREDs with the kinase domain of DYRK1A. DYRK1A substrates must bind to the kinase to enable phosphorylation, and SPRED proteins compete for the same binding site to modify this process. Our accumulated evidence indicates that the SPRED proteins are likely physiological modifiers of DYRK1A. PMID:20736167

  10. A Xanthomonas citri subsp citri hypothetical protein related to virulence contains a non-functional HD domain and is implicated in flagellar motility.

    PubMed

    Vieira, F C F; Gonçalves, A M; Mendoza, E F R; Ferreira, R M; Costa, M L M; Balbuena, T S; Sebinelli, H G; Ciancaglini, P; Pizauro Junior, J M; Ferro, J A

    2017-08-31

    Citrus canker, caused by the Gram-negative bacterium Xanthomonas citri subsp citri (Xac), severely affects most economically important citrus varieties worldwide. A previous study showed that disruption of the ORF XAC1201 from the Xac 306 strain by transposon Tn5 decreased bacterium virulence in the Rangpur lime host (Citrus limonia L. Osbeck). However, little is known regarding the possible function of the hypothetical protein XAC1201 and how it affects the virulence of Xac 306. Here, we confirmed that disruption of ORF XAC1201 reduces Xac 306 virulence in two different hosts, delaying the onset of typical symptoms. In silico analysis suggested that XAC1201 interacts with the flagellar proteins FliM and FliL, known to be an important factor for virulence. In fact, motility assays revealed that the XAC1201 mutant has a significant difference in motility compared to the wild-type Xac 306. Also, a 3-D structure model revealed modified cofactor binding sites and suggested that XAC1201 has a non-functional HD domain. This hypothesis was confirmed by enzymatic assays performed in purified, XAC1201 recombinant protein expressed in Escherichia coli, which revealed no significant activities previously associated with HD domains for the tested substrates. Thus, the role of the XAC1201 protein in Xac 306 virulence seems to be related to flagellar motility, although a non-classic role for the HD domain cannot be dismissed.

  11. Vascular-related NAC-DOMAIN7 is involved in the differentiation of all types of xylem vessels in Arabidopsis roots and shoots.

    PubMed

    Yamaguchi, Masatoshi; Kubo, Minoru; Fukuda, Hiroo; Demura, Taku

    2008-08-01

    The Arabidopsis thaliana NAC domain transcription factor, vascular-related NAC-DOMAIN7 (VND7), plays a pivotal role in regulating the differentiation of root protoxylem vessels. In order to understand the mechanisms underscoring the function of VND7 in vessel differentiation in more detail, we conducted extensive molecular analyses in yeast (Saccharomyces cerevisiae), Arabidopsis, and Nicotiana tabacum L. cv. Bright Yellow 2 (tobacco BY-2) cells. The transcriptional activation activity of VND7 was confirmed in yeast and Arabidopsis, and the C-terminal region was shown to be required for VND7 transcriptional activation. Expression of the C-terminus-truncated VND7 protein under the control of the native VND7 promoter resulted in inhibition of the normal development of metaxylem vessels in roots and vessels in aerial organs, as well as protoxylem vessels in roots. The expression pattern of VND7 overlapped that of VND2 to VND5 in most of the differentiating vessels. Furthermore, a yeast two-hybrid assay revealed the ability of VND7 to form homodimers and heterodimers with other VND proteins via their N-termini, which include the NAC domain. The heterologous expression of VND7 in tobacco BY-2 cells demonstrated that the stability of VND7 could be regulated by proteasome-mediated degradation. Together these data suggest that VND7 regulates the differentiation of all types of vessels in roots and shoots, possibly in cooperation with VND2 to VND5 and other regulatory proteins.

  12. PASS2 database for the structure-based sequence alignment of distantly related SCOP domain superfamilies: update to version 5 and added features

    PubMed Central

    Gandhimathi, Arumugam; Ghosh, Pritha; Hariharaputran, Sridhar; Mathew, Oommen K.; Sowdhamini, R.

    2016-01-01

    Structure-based sequence alignment is an essential step in assessing and analysing the relationship of distantly related proteins. PASS2 is a database that records such alignments for protein domain superfamilies and has been constantly updated periodically. This update of the PASS2 version, named as PASS2.5, directly corresponds to the SCOPe 2.04 release. All SCOPe structural domains that share less than 40% sequence identity, as defined by the ASTRAL compendium of protein structures, are included. The current version includes 1977 superfamilies and has been assembled utilizing the structure-based sequence alignment protocol. Such an alignment is obtained initially through MATT, followed by a refinement through the COMPARER program. The JOY program has been used for structural annotations of such alignments. In this update, we have automated the protocol and focused on inclusion of new features such as mapping of GO terms, absolutely conserved residues among the domains in a superfamily and inclusion of PDBs, that are absent in SCOPe 2.04, using the HMM profiles from the alignments of the superfamily members and are provided as a separate list. We have also implemented a more user-friendly manner of data presentation and options for downloading more features. PASS2.5 version is available at http://caps.ncbs.res.in/pass2/. PMID:26553811

  13. Comparative Analysis of Genome and Epigenome in Closely Related Medaka Species Identifies Conserved Sequence Preferences for DNA Hypomethylated Domains.

    PubMed

    Uno, Ayako; Nakamura, Ryohei; Tsukahara, Tatsuya; Qu, Wei; Sugano, Sumio; Suzuki, Yutaka; Morishita, Shinichi; Takeda, Hiroyuki

    2016-08-01

    The genomes of vertebrates are globally methylated, but a small portion of genomic regions are known to be hypomethylated. Although hypomethylated domains (HMDs) have been implicated in transcriptional regulation in various ways, how a HMD is determined in a particular genomic region remains elusive. To search for DNA motifs essential for the formation of HMDs, we performed the genome-wide comparative analysis of genome and DNA methylation patterns of the two medaka inbred lines, Hd-rRII1 and HNI-II, which are derived from northern and southern subpopulations of Japan and exhibit high levels of genetic variations (SNP, ∼ 3%). We successfully mapped > 70% of HMDs in both genomes and found that the majority of those mapped HMDs are conserved between the two lines (common HMDs). Unexpectedly, the average genetic variations are similar in the common HMD and other genome regions. However, we identified short well-conserved motifs that are specifically enriched in HMDs, suggesting that they may play roles in the establishment of HMDs in the medaka genome.

  14. Relationship of work-family conflict with burnout and marital satisfaction: cross-domain or source attribution relations?

    PubMed Central

    Bagherzadeh, Razieh; Taghizadeh, Ziba; Mohammadi, Eesa; Kazemnejad, Anoshirvan; Pourreza, Abolghasem; Ebadi, Abbas

    2016-01-01

    Background: The present study was conducted to examine the relationship between two dimensions of work-family conflict (WFC) with marital satisfaction and burnout in a society in which few studies have been done about the consequences of WFC. Methods: A cross-sectional study was conducted in 2015. Surveys were distributed to 420 employed married women with various jobs living in Bushehr province, Iran. Data were collected using a questionnaire for demographic characteristic, the Netmeyer’s WFC questionnaire, Maslach Burnout Inventory: General Survey (MBI-GS), and Enrich maritalsatisfaction questionnaire. The data were analyzed using descriptive and inferential statistics. Results: There was a negatively significant association between work interference with family(WIF) and overall burnout as well as emotional exhaustion (P < .01). Family interference with work (FIW) was significantly associated with depersonalization (P < .01). The overall marital satisfaction and its subscales were significantly associated with WIF (P < .01) and FIW (P < .01 for overall marital satisfaction and P < .05 for its subscales). Conclusion: In terms of practical implication, to avoid creating disadvantages of WIF and FIW,facilitation in two domains of improving work and family conditions can be a useful means to prevent WFC and its consequences. PMID:27123434

  15. Vibrio type III effector VPA1380 is related to the cysteine protease domain of large bacterial toxins.

    PubMed

    Calder, Thomas; Kinch, Lisa N; Fernandez, Jessie; Salomon, Dor; Grishin, Nick V; Orth, Kim

    2014-01-01

    Vibrio parahaemolyticus is a Gram-negative halophilic bacterium and one of the leading causes of food-borne gastroenteritis. Its genome harbors two Type III Secretion Systems (T3SS1 and T3SS2), but only T3SS2 is required for enterotoxicity seen in animal models. Effector proteins secreted from T3SS2 have been previously shown to promote colonization of the intestinal epithelium, invasion of host cells, and destruction of the epithelial monolayer. In this study, we identify VPA1380, a T3SS2 effector protein that is toxic when expressed in yeast. Bioinformatic analyses revealed that VPA1380 is highly similar to the inositol hexakisphosphate (IP6)-inducible cysteine protease domains of several large bacterial toxins. Mutations in conserved catalytic residues and residues in the putative IP6-binding pocket abolished toxicity in yeast. Furthermore, VPA1380 was not toxic in IP6 deficient yeast cells. Therefore, our findings suggest that VPA1380 is a cysteine protease that requires IP6 as an activator.

  16. Catalytic domain of plasmid pAD1 relaxase TraX defines a group of relaxases related to restriction endonucleases.

    PubMed

    Francia, María Victoria; Clewell, Don B; de la Cruz, Fernando; Moncalián, Gabriel

    2013-08-13

    Plasmid pAD1 is a 60-kb conjugative element commonly found in clinical isolates of Enterococcus faecalis. The relaxase TraX and the primary origin of transfer oriT2 are located close to each other and have been shown to be essential for conjugation. The oriT2 site contains a large inverted repeat (where the nic site is located) adjacent to a series of short direct repeats. TraX does not show any of the typical relaxase sequence motifs but is the prototype of a unique family of relaxases (MOBC). The present study focuses on the genetic, biochemical, and structural analysis of TraX, whose 3D structure could be predicted by protein threading. The structure consists of two domains: (i) an N-terminal domain sharing the topology of the DNA binding domain of the MarR family of transcriptional regulators and (ii) a C-terminal catalytic domain related to the PD-(D/E)XK family of restriction endonucleases. Alignment of MOBC relaxase amino acid sequences pointed to several conserved polar amino acid residues (E28, D152, E170, E172, K176, R180, Y181, and Y203) that were mutated to alanine. Functional analysis of these mutants (in vivo DNA transfer and cleavage assays) revealed the importance of these residues for relaxase activity and suggests Y181 as a potential catalytic residue similarly to His-hydrophobe-His relaxases. We also show that TraX binds specifically to dsDNA containing the oriT2 direct repeat sequences, confirming their role in transfer specificity. The results provide insights into the catalytic mechanism of MOBC relaxases, which differs radically from that of His-hydrophobe-His relaxases.

  17. Catalytic domain of plasmid pAD1 relaxase TraX defines a group of relaxases related to restriction endonucleases

    PubMed Central

    Francia, María Victoria; Clewell, Don B.; de la Cruz, Fernando; Moncalián, Gabriel

    2013-01-01

    Plasmid pAD1 is a 60-kb conjugative element commonly found in clinical isolates of Enterococcus faecalis. The relaxase TraX and the primary origin of transfer oriT2 are located close to each other and have been shown to be essential for conjugation. The oriT2 site contains a large inverted repeat (where the nic site is located) adjacent to a series of short direct repeats. TraX does not show any of the typical relaxase sequence motifs but is the prototype of a unique family of relaxases (MOBC). The present study focuses on the genetic, biochemical, and structural analysis of TraX, whose 3D structure could be predicted by protein threading. The structure consists of two domains: (i) an N-terminal domain sharing the topology of the DNA binding domain of the MarR family of transcriptional regulators and (ii) a C-terminal catalytic domain related to the PD-(D/E)XK family of restriction endonucleases. Alignment of MOBC relaxase amino acid sequences pointed to several conserved polar amino acid residues (E28, D152, E170, E172, K176, R180, Y181, and Y203) that were mutated to alanine. Functional analysis of these mutants (in vivo DNA transfer and cleavage assays) revealed the importance of these residues for relaxase activity and suggests Y181 as a potential catalytic residue similarly to His-hydrophobe-His relaxases. We also show that TraX binds specifically to dsDNA containing the oriT2 direct repeat sequences, confirming their role in transfer specificity. The results provide insights into the catalytic mechanism of MOBC relaxases, which differs radically from that of His-hydrophobe-His relaxases. PMID:23904483

  18. Xerostomia After Treatment for Oral and Oropharyngeal Cancer Using the University of Washington Saliva Domain and a Xerostomia-Related Quality-of-Life Scale

    SciTech Connect

    Rogers, Simon N.; Johnson, Ian A.; Lowe, Derek

    2010-05-01

    Purpose: The first aim of this study was to identify which clinical factors are associated with xerostomia in patients after treatment for oral and oropharyngeal squamous cell carcinoma, using the Xerostomia-Related Quality-of-Life Scale (XeQoLS) and the University of Washington Quality-of-Life Questionnaire Version 4 dry mouth item (UW-QOL v4). The second aim was to compare these two questionnaires and postulate a cutoff in the UW-QOL below which patients are doing sufficient badly to warrant further evaluation and support. Methods and Materials: In all, 371 patients alive and disease free treated between 1992 and 2005 were sent the survey, of whom 250 (67%) responded. Various clinical factors correlated with xerostomia, particularly adjuvant radiotherapy and Pstage. Results: In logistic regression analyses to predict three or more problems on the XeQoLS, only adjuvant radiotherapy (p < 0.001) was significant at the 5% level. There were significant (p < 0.001) correlations between the XeQoLS scores (total average and domain) with all the UW-QOL domain scores, the strongest with swallowing (-0.69), taste (-0.64), chewing (-0.64), mood (-0.60), and saliva (-0.59) domains. Patients scoring <70 (i.e., 0 or 30) on the UW-QOL could be used as a screening cutoff because it formed 1 in 5 of all patients (49/242) but accounted for half (299/566) of the significant problems generated by the XeQoLS. This also identified 13/21 patients with 10 or more problems. Conclusion: The UW-QOL saliva domain seems to be a suitable means of screening for dry mouth in head-and-neck clinics and could be used to trigger interventions.

  19. Arabidopsis VASCULAR-RELATED NAC-DOMAIN6 directly regulates the genes that govern programmed cell death and secondary wall formation during xylem differentiation.

    PubMed

    Ohashi-Ito, Kyoko; Oda, Yoshihisa; Fukuda, Hiroo

    2010-10-01

    Xylem consists of three types of cells: tracheary elements (TEs), parenchyma cells, and fiber cells. TE differentiation includes two essential processes, programmed cell death (PCD) and secondary cell wall formation. These two processes are tightly coupled. However, little is known about the molecular mechanisms underlying these processes. Here, we show that VASCULAR-RELATED NAC-DOMAIN6 (VND6), a master regulator of TEs, regulates some of the downstream genes involved in these processes in a coordinated manner. We first identified genes that are expressed downstream of VND6 but not downstream of SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1), a master regulator of xylem fiber cells, using transformed suspension culture cells in microarray experiments. We found that VND6 and SND1 governed distinct aspects of xylem formation, whereas they regulated a number of genes in common, specifically those related to secondary cell wall formation. Genes involved in TE-specific PCD were upregulated only by VND6. Moreover, we revealed that VND6 directly regulated genes that harbor a TE-specific cis-element, TERE, in their promoters. Thus, we found that VND6 is a direct regulator of genes related to PCD as well as to secondary wall formation.

  20. A gene with domains related to transcription regulation is required for pathogenicity in Colletotrichum acutatum causing Key lime anthracnose.

    PubMed

    Chen, Hui-Qin; Cao, Lihua; Dekkers, Katherine L; Rollins, Jeffrey A; Ko, Nan J; Timmer, L W; Chung, Kuang-Ren

    2005-09-01

    SUMMARY Colletotrichum acutatum causes Key lime anthracnose (KLA) and postbloom fruit drop (PFD) of citrus. We utilized restriction enzyme-mediated integration (REMI) mutagenesis to produce six non-pathogenic mutants from a KLA isolate after screening 1064 transformants on detached Key lime leaves. Subsequently, a gene designated KLAP1 (Key Lime Anthracnose Pathogenicity) was identified from one of the mutants and was demonstrated genetically to be required for pathogenicity to Key lime leaves. The predicted polypeptide encoded by KLAP1 contains a cAMP and cGMP-dependent protein kinase phosphorylation site, and two RGD (Arg-Gly-Asp) cell attachment sequences, a bipartite nuclear targeting sequence, a fungal G-protein alpha subunit signature, a putative metal-binding zinc finger (Cys(2)His(2)) and a putative HMG-I/Y ('high mobility group' non-histone chromatin protein encoding genes) DNA-binding domain (A+T hook), suggesting that KLAP1 may function as a transcription activator in C. acutatum. Sequences homologous to KLAP1 were detected in most C. acutatum isolates examined, and similarity was found in several classes of fungi, animals, plants and bacteria, indicating that KLAP1 is a putative, uncharacterized, conserved transcription activator in fungi. Targeted gene disruption of KLAP1 yielded mutants that were blocked in the penetration stage and were completely defective in pathogenicity on Key lime leaves, but remained pathogenic to flower petals. Complementation of a klap1-null mutant with a full-length KLAP1 gene clone restored complete ability to incite lesions on Key lime. The results indicate that KLAP1 is an important pathogenicity factor in C. acutatum.

  1. Measuring postural-related changes of spontaneous baroreflex sensitivity after repeated long-duration diving: frequency domain approaches.

    PubMed

    Faes, Luca; Masè, Michela; Nollo, Giandomenico; Chon, Ki H; Florian, John P

    2013-11-01

    Sustained water immersion is thought to modulate orthostatic tolerance to an extent dependent on the duration and repetition over consecutive days of the diving sessions. We tested this hypothesis investigating in ten healthy subjects the potential changes in the cardiovascular response to head-up tilt induced by single and multiple resting air dives. Parametric cross-spectral analysis of spontaneous RR interval and systolic arterial pressure variability was performed in three experimental sessions: before diving (BD), after single 6-hour dive (ASD), and after multiple 6-hour dives (AMD, 5 consecutive days with 18-hour surface interval). From this analysis, baroreflex sensitivity (BRS) was computed as spectral power ratio (αBRS), non-causal transfer function gain (tfBRS) and causal transfer function gain (γBRS) evaluated at low frequency (0.04-0.14Hz) in the supine position (su) as well as in the standing upright position in the early tilt (et) and late tilt (lt) epochs. We found that, while αBRS decreased significantly in et and lt compared to su during all sessions, tfBRS and γBRS decreased during ASD and AMD but not during BD; moreover γBRS evidenced a progressive decrease from BD to ASD and to AMD in both et and lt epochs. These results indicate the necessity of following a causal approach for the estimation of BRS in the frequency domain, and suggest a progressive impairment of the baroreflex response to postural stress after single and multiple dives, which may reflect symptoms of increasing orthostatic intolerance.

  2. Evolution of paired domains: Isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6

    PubMed Central

    Sun, Hongmin; Rodin, Andrei; Zhou, Yihong; Dickinson, Douglas P.; Harper, Donald E.; Hewett-Emmett, David; Li, Wen-Hsiung

    1997-01-01

    Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide. PMID:9144207

  3. The Relative Importance of Domain Applicability Metrics for Estimating Prediction Errors in QSAR Varies with Training Set Diversity.

    PubMed

    Sheridan, Robert P

    2015-06-22

    In QSAR, a statistical model is generated from a training set of molecules (represented by chemical descriptors) and their biological activities (an "activity model"). The aim of the field of domain applicability (DA) is to estimate the uncertainty of prediction of a specific molecule on a specific activity model. A number of DA metrics have been proposed in the literature for this purpose. A quantitative model of the prediction uncertainty (an "error model") can be built using one or more of these metrics. A previous publication from our laboratory ( Sheridan , R. P. J. Chem. Inf. 2013 , 53 , 2837 - 2850 ) suggested that QSAR methods such as random forest could be used to build error models by fitting unsigned prediction errors against DA metrics. The QSAR paradigm contains two useful techniques: descriptor importance can determine which DA metrics are most useful, and cross-validation can be used to tell which subset of DA metrics is sufficient to estimate the unsigned errors. Previously we studied 10 large, diverse data sets and seven DA metrics. For those data sets for which it is possible to build a significant error model from those seven metrics, only two metrics were sufficient to account for almost all of the information in the error model. These were TREE_SD (the variation of prediction among random forest trees) and PREDICTED (the predicted activity itself). In this paper we show that when data sets are less diverse, as for example in QSAR models of molecules in a single chemical series, these two DA metrics become less important in explaining prediction error, and the DA metric SIMILARITYNEAREST1 (the similarity of the molecule being predicted to the closest training set compound) becomes more important. Our recommendation is that when the mean pairwise similarity (measured with the Carhart AP descriptor and the Dice similarity index) within a QSAR training set is less than 0.5, one can use only TREE_SD, PREDICTED to form the error model, but

  4. Predicting domain-specific insight of schizophrenia patients from symptomatology, multiple neurocognitive functions, and personality related traits.

    PubMed

    Ritsner, Michael S; Blumenkrantz, Haya

    2007-01-15

    This study examines the contribution of various neurocognitive functions, clinical characteristics, and personality traits to the prediction of three insight dimensions. Clinically stable schizophrenia patients (n=107) residing in the community were evaluated using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Unawareness of Mental Disorder, and a comprehensive battery of instruments to measure personality related variables and neurocognitive functioning. Step-wise multivariate regression analysis indicates significant association of variability in insight dimensions with neurocognitive functioning (20-41%), personality related traits (8-18% temperament factors, 4-7% self-constructs, 10-14% coping styles), severity of symptoms (about 7%), illness duration (6%), and education (about 5%). Poor insight was attributed to impairment in visual and movement skills, sustained attention, executive functions, intensity of autistic preoccupations and positive symptoms, as well as increased novelty seeking behavior, task and emotion oriented coping styles, better self-esteem, self-efficacy, and higher education. Better awareness was related to better performance of neurocognitive tasks, reward dependence behavior, avoidant coping style, and longer illness duration. Aside from common indicators for the various insight dimensions, we defined specific indicators for each insight dimension. Thus, insight dimensions in schizophrenia patients residing in the community were attributed to neurocognitive and personality related factors rather than to psychopathological symptoms. The findings enable better understanding of the multifactorial nature of insight and highlight targets for more effective intervention and rehabilitation.

  5. Chinese Students' Implicit Theories of Intelligence and Other Personal Attributes: Cross-Domain Generality and Age-Related Differences.

    ERIC Educational Resources Information Center

    Cheng, Zi-Juan; Hau, Kit-Tai; Wen, Jian-Bing; Kong, Chit-Kwong

    Using structural equation modeling (SEM), researchers examined whether there was a general dominating factor that governed students' implicit theories of intelligence, morality, personality, creativity, and social intelligence. The possible age-related changes of students' implicit theories were also studied. In all, 1,650 elementary and junior…

  6. Multiple Personality Domains in Relation to Occupational Choice and Performance among Established Teachers. Research Report. ETS RR-04-41

    ERIC Educational Resources Information Center

    Emmerich, Walter; Rock, Donald A.; Trapani, Catherine S.

    2004-01-01

    Does personality impact differently on occupational choice and occupational performance? In a study of established teachers, interests, the Five-Factor Model, and attributions were examined in relation to occupational choice and performance. Attributions were assessed using a new instrument designed for teachers. Choice of teaching specialty was…

  7. Cloning, expression and purification of binding domains of lethal factor and protective antigen of Bacillus anthracis in Escherichia coli and evaluation of their related murine antibody.

    PubMed

    Rezaee, Mehdi; Honari, Hossein; Kooshk, Mohammad Reza Ashrafi

    2014-01-01

    Anthrax is common disease between human and animals caused by Bacillus anthracis. The cell binding domain of protective antigen (PAD4) and the binding domain of lethal factor (LFD1) have high immunogenicity potential and always were considered as a vaccine candidate against anthrax. The aims of this study are cloning and expressing of PAD4 and LFD1 in Escherichia coli, purification of the recombinant proteins and determination of their immunogenicity through evaluating of the relative produced polyclonal antibodies in mice. PAD4 and LFD1 genes were cloned in pET28a(+) vector and expressed in E. coli Bl21(DE3)PlysS. Expression and purification of the two recombinant proteins were confirmed by SDS-PAGE and Western blotting techniques. The PAD4 and LFD1 were purified using Ni(+)-NTA affinity chromatography (95-98 %), yielding 37.5 and 45 mg/l of culture, respectively. The antigens were injected three times into mice and production of relative antibodies was evaluated by ELISA test. The results showed that both PAD4 and LFD1 are immunogenic, but LFD1 has higher potential to stimulate Murine immune system. With regard to the high level of LFD1 and PAD4 expression and also significant increment in produced polyclonal antibodies, these recombinant proteins can be considered as a recombinant vaccine candidate against anthrax.

  8. Health-Related Quality of Life of Adolescent and Young Adult Survivors of Central Nervous System Tumors: Identifying Domains From a Survivor Perspective.

    PubMed

    Kuhlthau, Karen; Luff, Donna; Delahaye, Jennifer; Wong, Alicia; Yock, Torunn; Huang, Mary; Park, Elyse R

    2015-01-01

    This article uses qualitative methods to describe the domains of health-related quality of life (HRQoL) that adolescent and young adult (AYA) survivors of central nervous system (CNS) tumors identify as important. Survivors clearly attributed aspects of their current HRQoL to their disease or its treatment. We identified 7 key domains of AYA CNS tumor survivorship: physical health, social well-being, mental health, cognitive functioning, health behaviors, sexual and reproductive health, and support systems. Although most aspects of HRQoL that survivors discussed represented new challenges, there were several areas where survivors pointed out positive outcomes. There is a need for a HRQoL tool designed for this population of survivors, given their unique treatment and survivorship experience. Aspects of HRQoL related to cognition, sexual and reproductive health, health behaviors, and support systems are not typically included in generic HRQoL tools but should be assessed for this population. Developing HRQoL measurement instruments that capture the most significant aspects of HRQoL will improve the ability to track HRQoL in AYA CNS tumor survivors and in the long-term management of common sequelae from CNS tumors and their treatments. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

  9. The effect of education on age-related changes in three cognitive domains: a cross-sectional study in primary care.

    PubMed

    Martins, Isabel Pavão; Maruta, Carolina; Silva, Cláudia; Rodrigues, Pedro; Chester, Catarina; Ginó, Sandra; Freitas, Vanda; Freitas, Sara; Oliveira, António Gouveia

    2012-01-01

    The present study aims to investigate the protective effect of formal education on age-related changes in different cognitive domains with the hypothesis that it may attenuate the rate of decline. Individuals aged 50 years or older attending primary care physicians without known brain disease (431 participants, mostly [60.3%] female with 66.3 [±9.1] years of age and 7.7 [±4.1] years of education, on average), were evaluated with a neuropsychological battery including 28 cognitive measures. Cognitive domains identified by factor analysis were subject to repeated multiple regression analyses to determine the variance explained by age and education controlling for gender, depressive symptoms, and vascular risk factors. The slope of the regression equation was compared between two educational groups with an average of 4 years and 11 years of education, respectively. Factors identified corresponded to processing ability (Factor 1), memory (Factor 2), and acquired knowledge (Factor 3). Although education improved performance in Factors 1 and 3, it did not change the slope of age-related decline in any factor. This study suggests that in culturally heterogeneous groups, small increments in education enhance cognition but do not modify the rate of decline of executive functioning with age. These results contradict some clinical findings and need to be confirmed in longitudinal studies.

  10. Inhibition deficit in the spatial tendency of the response in multiple-domain amnestic mild cognitive impairment. An event-related potential study

    PubMed Central

    Cespón, Jesús; Galdo-Álvarez, Santiago; Díaz, Fernando

    2015-01-01

    Longitudinal studies have shown that a high percentage of people with amnestic mild cognitive impairment (MCI) develop Alzheimer’s disease (AD). Prodromal AD is known to involve deficits in executive control processes. In the present study, we examined such deficits by recording EEG in 13 single-domain amnestic MCI (sdaMCI), 12 multiple-domain amnestic MCI (mdaMCI) and 18 healthy elderly (control group, CG) participants while they performed a Simon task. The Simon task demands deployment of executive processes because participants have to respond to non-spatial features of a lateralized stimulus and inhibit the more automatic spatial tendency of the response. We specifically focused on the negativity central contralateral (N2cc), an event-related potential (ERP) component related to brain activity that prevents the cross-talk between direction of spatial attention and manual response preparation. The reaction time (RT) was not significantly different among the three groups of participants. The percentage of errors (PE) was higher in mdaMCI than in CG and sdaMCI participants. In addition, N2cc latency was delayed in mdaMCI (i.e., delayed implementation of mechanisms for controlling the spatial tendency of the response). The N2cc latency clearly distinguished among mdaMCI and CG/sdaMCI participants (area under curve: 0.91). Longer N2cc was therefore associated with executive control deficits, which suggests that N2cc latency is a correlate of mdaMCI. PMID:25999853

  11. Mutations activating the yeast eIF-2 alpha kinase GCN2: isolation of alleles altering the domain related to histidyl-tRNA synthetases.

    PubMed Central

    Ramirez, M; Wek, R C; Vazquez de Aldana, C R; Jackson, B M; Freeman, B; Hinnebusch, A G

    1992-01-01

    The protein kinase GCN2 stimulates expression of the yeast transcriptional activator GCN4 at the translational level by phosphorylating the alpha subunit of translation initiation factor 2 (eIF-2 alpha) in amino acid-starved cells. Phosphorylation of eIF-2 alpha reduces its activity, allowing ribosomes to bypass short open reading frames present in the GCN4 mRNA leader and initiate translation at the GCN4 start codon. We describe here 17 dominant GCN2 mutations that lead to derepression of GCN4 expression in the absence of amino acid starvation. Seven of these GCN2c alleles map in the protein kinase moiety, and two in this group alter the presumed ATP-binding domain, suggesting that ATP binding is a regulated aspect of GCN2 function. Six GCN2c alleles map in a region related to histidyl-tRNA synthetases, and two in this group alter a sequence motif conserved among class II aminoacyl-tRNA synthetases that directly interacts with the acceptor stem of tRNA. These results support the idea that GCN2 kinase function is activated under starvation conditions by binding uncharged tRNA to the domain related to histidyl-tRNA synthetase. The remaining GCN2c alleles map at the extreme C terminus, a domain required for ribosome association of the protein. Representative mutations in each domain were shown to depend on the phosphorylation site in eIF-2 alpha for their effects on GCN4 expression and to increase the level of eIF-2 alpha phosphorylation in the absence of amino acid starvation. Synthetic GCN2c double mutations show greater derepression of GCN4 expression than the parental single mutations, and they have a slow-growth phenotype that we attribute to inhibition of general translation initiation. The phenotypes of the GCN2c alleles are dependent on GCN1 and GCN3, indicating that these two positive regulators of GCN4 expression mediate the inhibitory effects on translation initiation associated with activation of the yeast eIF-2 alpha kinase GCN2. Images PMID:1448107

  12. GEm-Related 5 (GER5), an ABA and stress-responsive GRAM domain protein regulating seed development and inflorescence architecture.

    PubMed

    Baron, Kevin N; Schroeder, Dana F; Stasolla, Claudio

    2014-06-01

    We have identified an abscisic acid (ABA) and stress-responsive GRAM (Glucosyltransferases, Rab-like GTPase activators and Myotubularins) domain protein GER5 (GEm-Related 5) closely related to GEM (GLABRA2 Expression Modulator), a novel regulator of cell division and cell fate determination in epidermal cells. A loss-of-function T-DNA line (ger5-2) and transgenic lines silencing (GER5(RNAi)) or overexpressing (GER5(OE)) GER5 displayed several defects in reproductive development affecting seed and embryo development. RNA in situ studies revealed GER5 and related GRAM genes (GEM and GEm-Related 1 (GER1)) have both overlapping and unique expression domains in male and female reproductive organs. Hormone immunolocalization experiments further indicate GER5 transcripts preferentially localize to reproductive tissues which accumulate ABA. Expression analysis revealed members of the GRAM family (GER5, GER1, GEM) display tissue-specific expression patterns and are responsive to phytohormones and abiotic stress, in addition to genetic lesions (aba1, aba2, ctr1) affecting ABA biosynthesis or ethylene signalling. Mature seeds of ger5-2 mutants also exhibit reduced sensitivity to ABA during seed germination assays. Microarray analysis of aborting and developing seeds isolated from ger5-2 mutants revealed underlying transcriptional changes in carbohydrate metabolism, hormone signalling and catabolic processes (e.g. protein degradation, autophagy). Taken together, our results indicate ABA-responsive GRAM genes play a novel role in regulating the reproductive development of plants, and raise intriguing questions regarding the functional relationship between members of the GRAM gene family. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. A Preliminary Prospective Study of an Escalation in 'Maximum Daily Drinks', Fronto-Parietal Circuitry and Impulsivity-Related Domains in Young Adult Drinkers.

    PubMed

    Worhunsky, Patrick D; Dager, Alecia D; Meda, Shashwath A; Khadka, Sabin; Stevens, Michael C; Austad, Carol S; Raskin, Sarah A; Tennen, Howard; Wood, Rebecca M; Fallahi, Carolyn R; Potenza, Marc N; Pearlson, Godfrey D

    2016-05-01

    Excessive alcohol use in young adults is associated with greater impulsivity and neurobiological alterations in executive control systems. The maximum number of drinks consumed during drinking occasions ('MaxDrinks') represents a phenotype linked to vulnerability of alcohol use disorders, and an increase, or 'escalation', in MaxDrinks may be indicative of greater risk for problematic drinking. Thirty-six young adult drinkers performed a Go/No-Go task during fMRI, completed impulsivity-related assessments, and provided monthly reports of alcohol use during a 12-month follow-up period. Participants were characterized by MaxDrinks at baseline and after follow-up, identifying 18 escalating drinkers and 18 constant drinkers. Independent component analysis was used to investigate functional brain networks associated with response inhibition, and relationships with principal component analysis derived impulsivity-related domains were examined. Greater baseline MaxDrinks was associated with an average reduction in the engagement of a right-lateralized fronto-parietal functional network, while an escalation in MaxDrinks was associated with a greater difference in fronto-parietal engagement between successful inhibitions and error trials. Escalating drinkers displayed greater impulsivity/compulsivity-related domain scores that were positively associated with fronto-parietal network engagement and change in MaxDrinks during follow-up. In young adults, an escalating MaxDrinks trajectory was prospectively associated with altered fronto-parietal control mechanisms and greater impulsivity/compulsivity scores. Continued longitudinal studies of MaxDrinks trajectories, functional network activity, and impulsivity/compulsivity-related features may lend further insight into an intermediate phenotype vulnerable for alcohol use and addictive disorders.

  14. An Internet-Mediated Pedometer-Based Program Improves Health-Related Quality-of-Life Domains and Daily Step Counts in COPD

    PubMed Central

    Moy, Marilyn L.; Collins, Riley J.; Martinez, Carlos H.; Kadri, Reema; Roman, Pia; Holleman, Robert G.; Kim, Hyungjin Myra; Nguyen, Huong Q.; Cohen, Miriam D.; Goodrich, David E.; Giardino, Nicholas D.

    2015-01-01

    BACKGROUND: Low levels of physical activity (PA) are associated with poor outcomes in people with COPD. Interventions to increase PA could improve outcomes. METHODS: We tested the efficacy of a novel Internet-mediated, pedometer-based exercise intervention. Veterans with COPD (N = 239) were randomized in a 2:1 ratio to the (1) intervention group (Omron HJ-720 ITC pedometer and Internet-mediated program) or (2) wait-list control group (pedometer). The primary outcome was health-related quality of life (HRQL), assessed by the St. George’s Respiratory Questionnaire (SGRQ), at 4 months. We examined the SGRQ total score (SGRQ-TS) and three domain scores: Symptoms, Activities, and Impact. The secondary outcome was daily step counts. Linear regression models assessed the effect of intervention on outcomes. RESULTS: Participants had a mean age of 67 ± 9 years, and 94% were men. There was no significant between-group difference in mean 4-month SGRQ-TS (2.3 units, P = .14). Nevertheless, a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS, the minimum clinically important difference (53% vs 39%, respectively, P = .05). For domain scores, the intervention group had a lower (reflecting better HRQL) mean than the control group by 4.6 units for Symptoms (P = .046) and by 3.3 units for Impact (P = .049). There was no significant difference in Activities score between the two groups. Compared with the control subjects, intervention participants walked 779 more steps per day at 4 months (P = .005). CONCLUSIONS: An Internet-mediated, pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD. TRIAL REGISTRY: Clinical Trials.gov; No.: NCT01102777; URL: www.clinicaltrials.gov PMID:25811395

  15. In vivo three-dimensional imaging of neovascular age-related macular degeneration using optical frequency domain imaging at 1050 nm.

    PubMed

    de Bruin, Daniel M; Burnes, Daina L; Loewenstein, John; Chen, Yueli; Chang, Susie; Chen, Teresa C; Esmaili, Daniel D; de Boer, Johannes F

    2008-10-01

    To assess the application of optical frequency domain imaging (OFDI) at 1050 nm for the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) and its response to treatment. Three patients presenting with blurred vision and exudative AMD were imaged before and after anti-VEGF treatment with ranibizumab. The patients were imaged with OFDI, a swept-source-based, high-speed optical coherence tomography (OCT) system developed at the Wellman Center for Photomedicine. A center wavelength of 1050 nm was used that has been demonstrated to provide better imaging of the deeper structures of the retina below the RPE, such as the choroidal vasculature. Three-dimensional data sets were acquired in 2 to 4 seconds. En face images were compiled from cross-sectional OFDI data and correlated with color fundus photography (CF) and fluorescein angiograms (FAs). Cross-sectional images were coregistered with CF and FA to obtain depth-resolved information about CNV, CNV volume, retinal thickness, subretinal fluid volume and height of neurosensory detachment before and after treatment with ranibizumab. A band of reduced reflectivity below the RPE was identified in all three subjects that corresponded to areas of confirmed and suspected occult CNV on FA. After treatment, this band was reduced in volume in all patients. High-speed 3-D OFDI at 1050 nm is a promising technology for imaging the retina and choroid in neovascular AMD. The developed system at 1050 nm provides good contrast for occult (type 1) CNV and may have advantages compared with time domain and current state of the art spectral domain OCT systems (SD-OCT) at 850 nm.

  16. Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain.

    PubMed

    Fahsold, R; Hoffmeyer, S; Mischung, C; Gille, C; Ehlers, C; Kücükceylan, N; Abdel-Nour, M; Gewies, A; Peters, H; Kaufmann, D; Buske, A; Tinschert, S; Nürnberg, P

    2000-03-01

    More than 500 unrelated patients with neurofibromatosis type 1 (NF1) were screened for mutations in the NF1 gene. For each patient, the whole coding sequence and all splice sites were studied for aberrations, either by the protein truncation test (PTT), temperature-gradient gel electrophoresis (TGGE) of genomic PCR products, or, most often, by direct genomic sequencing (DGS) of all individual exons. A total of 301 sequence variants, including 278 bona fide pathogenic mutations, were identified. As many as 216 or 183 of the genuine mutations, comprising 179 or 161 different ones, can be considered novel when compared to the recent findings of Upadhyaya and Cooper, or to the NNFF mutation database. Mutation-detection efficiencies of the various screening methods were similar: 47.1% for PTT, 53.7% for TGGE, and 54.9% for DGS. Some 224 mutations (80.2%) yielded directly or indirectly premature termination codons. These mutations showed even distribution over the whole gene from exon 1 to exon 47. Of all sequence variants determined in our study, <20% represent C-->T or G-->A transitions within a CpG dinucleotide, and only six different mutations also occur in NF1 pseudogenes, with five being typical C-->T transitions in a CpG. Thus, neither frequent deamination of 5-methylcytosines nor interchromosomal gene conversion may account for the high mutation rate of the NF1 gene. As opposed to the truncating mutations, the 28 (10.1%) missense or single-amino-acid-deletion mutations identified clustered in two distinct regions, the GAP-related domain (GRD) and an upstream gene segment comprising exons 11-17. The latter forms a so-called cysteine/serine-rich domain with three cysteine pairs suggestive of ATP binding, as well as three potential cAMP-dependent protein kinase (PKA) recognition sites obviously phosphorylated by PKA. Coincidence of mutated amino acids and those conserved between human and Drosophila strongly suggest significant functional relevance of this region

  17. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    DOE PAGES

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; ...

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. Amore » putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.« less

  18. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    SciTech Connect

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.

  19. Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation.

    PubMed

    El Asmar, Zeina; Terrand, Jérome; Jenty, Marion; Host, Lionel; Mlih, Mohamed; Zerr, Aurélie; Justiniano, Hélène; Matz, Rachel L; Boudier, Christian; Scholler, Estelle; Garnier, Jean-Marie; Bertaccini, Diego; Thiersé, Danièle; Schaeffer, Christine; Van Dorsselaer, Alain; Herz, Joachim; Bruban, Véronique; Boucher, Philippe

    2016-03-04

    The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (α) chain of LRP1 mediates TGFβ-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (β) chain of LRP1 suffices to limit cholesterol accumulation in LRP1(-/-) cells. Through binding of Erk2 to the second of its carboxyl-terminal NPXY motifs, LRP1 β-chain positively regulates the expression of ATP binding cassette transporter A1 (ABCA1) and of neutral cholesterol ester hydrolase (NCEH1). These results highlight the unexpected functions of LRP1 and the canonical Wnt5a pathway and new therapeutic potential in cholesterol-associated disorders including cardiovascular diseases.

  20. Multiple classes of transcription factors regulate the expression of VASCULAR-RELATED NAC-DOMAIN7, a master switch of xylem vessel differentiation.

    PubMed

    Endo, Hitoshi; Yamaguchi, Masatoshi; Tamura, Taizo; Nakano, Yoshimi; Nishikubo, Nobuyuki; Yoneda, Arata; Kato, Ko; Kubo, Minoru; Kajita, Shinya; Katayama, Yoshihiro; Ohtani, Misato; Demura, Taku

    2015-02-01

    The secondary cell walls of xylem cells, including vessel elements, provide mechanical strength and contribute to the conduction of water and minerals. VASCULAR-RELATED NAC-DOMAIN7 (VND7) is a NAC-domain transcription factor that regulates the expression of genes required for xylem vessel element formation. Transient expression assays using 68 transcription factors that are expressed during xylem vessel differentiation showed that 14 transcription factors, including VND1-VND7, are putative positive regulators of VND7 expression. Electrophoretic mobility shift assays revealed that all seven VND proteins bound to the VND7 promoter region at its SMBE/TERE motif, indicating that VND7 is a direct target of all of the VND transcription factors. Overexpression of VND1-VND5, GATA12 and ANAC075, newly identified transcription factors that function upstream of VND7, resulted in ectopic xylem vessel element formation. These data suggest that VND7 transcription is a regulatory target of multiple classes of transcription factors.

  1. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

    PubMed

    Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

    2014-05-01

    Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

  2. A truncated fragment of Ov-ASP-1 consisting of the core pathogenesis-related-1 (PR-1) domain maintains adjuvanticity as the full-length protein.

    PubMed

    Guo, Jingjing; Yang, Yi; Xiao, Wenjun; Sun, Weilai; Yu, Hong; Du, Lanying; Lustigman, Sara; Jiang, Shibo; Kou, Zhihua; Zhou, Yusen

    2015-04-15

    The Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has good adjuvanticity for a variety of antigens and vaccines, probably due to its ability activate antigen-processing cells (APCs). However, the functional domain of Ov-ASP-1 as an adjuvant is not clearly defined. Based on the structural prediction of this protein family, we constructed a 16-kDa recombinant protein of Ov-ASP-1 that contains only the core pathogenesis-related-1 (PR-1) domain (residues 10-153), designated ASPPR. We found that ASPPR exhibits adjuvanticity similar to that of the full-length Ov-ASP-1 (residues 10-220) for various antigens, including ovalbumin (OVA), HBsAg protein antigen, and the HIV peptide 5 (Pep5) antigen, but it is more suitable for vaccine design in ASPPR-antigen fusion proteins, and more stable in PBS than Ov-ASP-1 stored at -70 °C. These results suggest that ASPPR might be the functional region of Ov-ASP-1 as an adjuvant, and therefore could be developed as an adjuvant for human use.

  3. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

    PubMed Central

    Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

    2014-01-01

    Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

  4. Influence of image compression on the interpretation of spectral-domain optical coherence tomography in exudative age-related macular degeneration

    PubMed Central

    Kim, J H; Kang, S W; Kim, J-r; Chang, Y S

    2014-01-01

    Purpose To evaluate the effect of image compression of spectral-domain optical coherence tomography (OCT) images in the examination of eyes with exudative age-related macular degeneration (AMD). Methods Thirty eyes from 30 patients who were diagnosed with exudative AMD were included in this retrospective observational case series. The horizontal OCT scans centered at the center of the fovea were conducted using spectral-domain OCT. The images were exported to Tag Image File Format (TIFF) and 100, 75, 50, 25 and 10% quality of Joint Photographic Experts Group (JPEG) format. OCT images were taken before and after intravitreal ranibizumab injections, and after relapse. The prevalence of subretinal and intraretinal fluids was determined. Differences in choroidal thickness between the TIFF and JPEG images were compared with the intra-observer variability. Results The prevalence of subretinal and intraretinal fluids was comparable regardless of the degree of compression. However, the chorio–scleral interface was not clearly identified in many images with a high degree of compression. In images with 25 and 10% quality of JPEG, the difference in choroidal thickness between the TIFF images and the respective JPEG images was significantly greater than the intra-observer variability of the TIFF images (P=0.029 and P=0.024, respectively). Conclusions In OCT images of eyes with AMD, 50% of the quality of the JPEG format would be an optimal degree of compression for efficient data storage and transfer without sacrificing image quality. PMID:24788012

  5. Reliability and reproducibility of spectral and time domain optical coherence tomography images before and after correction for patients with age-related macular degeneration

    PubMed Central

    Sadiq, Mohammad A.; Rashid, Aymen; Channa, Roomasa; Hatef, Elham; Do, Diana V; Nguyen, Quan Dong; Sepah, Yasir J

    2015-01-01

    Purpose: To evaluate the reproducibility and reliability of optical coherence tomography scans obtained using the time domain (TD-OCT) Stratus TM OCT, and the Spectral Domain (SD-OCT) Spectralis TM and Cirrus TM OCT devices before and after manual correction in eyes with either Neovascular (NV-AMD) or Non-Neovascular (NNV-AMD) age-related macular degeneration. Design: Prospective observational study. Methods: Setting: University-based retina practice. Patients: Thirty-six patients (50 eyes) with NV-AMD or NNV-AMD. Procedure: OCT scans were taken simultaneously using one TD-OCT and two SD-OCT devices. Main Outcome Measures: Macular thickness measurements were assessed before and after correction of the algorithm by constructing Bland-Altman plots for agreement and calculating intraclass correlation coefficients (ICCs) and coefficients of repeatability (COR) to evaluate intraclass repeatability. Results: Spectralis had the highest number of images needing manual correction.  All machines had high ICCs, with Spectralis having the highest.  Also, Bland-Altman plots indicated that there was low agreement between Cirrus™ and Stratus™, Spectralis™ and Stratus™, while there was good agreement between the Cirrus™ and Spectralis™.  The CORs were lowest for Spectralis TM and similar and higher for Cirrus TM and Stratus TM.  Agreement, CORs, and ICCs generally improved after manual correction, but only minimally.  Conclusion: Agreement is low between devices, except between both SD-OCT machines.  Manual correction tends to improve results. PMID:26097682

  6. VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.

    PubMed

    Yamaguchi, Masatoshi; Mitsuda, Nobutaka; Ohtani, Misato; Ohme-Takagi, Masaru; Kato, Ko; Demura, Taku

    2011-05-01

    The Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1 nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  7. The NTR module: domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases.

    PubMed Central

    Bányai, L.; Patthy, L.

    1999-01-01

    Using homology search, structure prediction, and structural characterization methods we show that the C-terminal domains of (1) netrins, (2) complement proteins C3, C4, C5, (3) secreted frizzled-related proteins, and (4) type I procollagen C-proteinase enhancer proteins (PCOLCEs) are homologous with the N-terminal domains of (5) tissue inhibitors of metalloproteinases (TIMPs). The proteins harboring this netrin module (NTR module) fulfill diverse biological roles ranging from axon guidance, regulation of Wnt signaling, to the control of the activity of metalloproteases. With the exception of TIMPs, it is not known at present what role the NTR modules play in these processes. In view of the fact that the NTR modules of TIMPs are involved in the inhibition of matrixin-type metalloproteases and that the NTR module of PCOLCEs is involved in the control of the activity of the astacin-type metalloprotease BMP1, it seems possible that interaction with metzincins could be a shared property of NTR modules and could be critical for the biological roles of the host proteins. PMID:10452607

  8. PL3 Amidase, a Tailor-made Lysin Constructed by Domain Shuffling with Potent Killing Activity against Pneumococci and Related Species

    PubMed Central

    Blázquez, Blas; Fresco-Taboada, Alba; Iglesias-Bexiga, Manuel; Menéndez, Margarita; García, Pedro

    2016-01-01

    The emergence and spread of antibiotic-resistant bacteria is pushing the need of alternative treatments. In this context, phage therapy is already a reality to successfully fight certain multiresistant bacteria. Among different phage gene products, murein hydrolases responsible of phage progeny liberation (also called lysins or endolysins) are weapons that target specific peptidoglycan bonds, leading to lysis and death of susceptible bacteria when added from the outside. In the pneumococcal system, all but one phage murein hydrolases reported to date share a choline-binding domain that recognizes cell walls containing choline residues in the (lipo)teichoic acids. Some purified pneumococcal or phage murein hydrolases, as well as several chimeric proteins combining natural catalytic and cell wall-binding domains (CBDs) have been used as effective antimicrobials. In this work we have constructed a novel chimeric N-acetylmuramoyl-L-alanine amidase (PL3) by fusing the catalytic domain of the Pal amidase (a phage-coded endolysin) to the CBD of the LytA amidase, the major pneumococcal autolysin. The physicochemical properties of PL3 and the bacteriolytic effect against several pneumococci (including 48 multiresistant representative strain) and related species, like Streptococcus pseudopneumoniae, Streptococcus mitis, and Streptococcus oralis, have been studied. Results have shown that low doses of PL3, in the range of 0.5–5 μg/ml, are enough to practically sterilize all choline-containing strains tested. Moreover, a single 20-μg dose of PL3 fully protected zebrafish embryos from infection by S. pneumoniae D39 strain. Importantly, PL3 keeps 95% enzymatic activity after 4 weeks at 37°C and can be lyophilized without losing activity, demonstrating a remarkable robustness. Such stability, together with a prominent efficacy against a narrow spectrum of human pathogens, confers to PL3 the characteristic to be an effective therapeutic. In addition, our results demonstrate

  9. A Multivariate Analysis of Age-Related Differences in Default Mode and Task Positive Networks Across Multiple Cognitive Domains

    PubMed Central

    Grady, Cheryl L.; Protzner, Andrea B.; Kovacevic, Natasa; Strother, Stephen C.; Afshin-Pour, Babak; Wojtowicz, Magda; Anderson, John A.E.; Churchill, Nathan; McIntosh, Anthony R.

    2011-01-01

    We explored the effects of aging on two large scale brain networks, the default mode network (DMN) and the task-positive network (TPN). During fMRI scanning, young and older participants carried out four visual tasks: detection, perceptual matching, attentional cueing, and working memory. Accuracy of performance was roughly matched at 80% across tasks and groups. Modulations of activity across conditions were assessed, as well as functional connectivity of both networks. Younger adults showed a broader engagement of the DMN, and older adults a more extensive engagement of the TPN. Functional connectivity in the DMN was reduced in older adults, whereas the main pattern of TPN connectivity was equivalent in the two groups. Age-specific connectivity also was seen in TPN regions. Increased activity in TPN areas predicted worse accuracy on the tasks, but greater expression of a connectivity pattern associated with a right dorsolateral prefrontal TPN region, seen only in older adults, predicted better performance. These results provide further evidence for age-related differences in the DMN, and new evidence of age differences in the TPN. Increased use of the TPN may reflect greater demand on cognitive control processes in older individuals that may be partially offset by alterations in prefrontal functional connectivity. PMID:19789183

  10. Fixation-related FMRI analysis in the domain of reading research: using self-paced eye movements as markers for hemodynamic brain responses during visual letter string processing.

    PubMed

    Richlan, Fabio; Gagl, Benjamin; Hawelka, Stefan; Braun, Mario; Schurz, Matthias; Kronbichler, Martin; Hutzler, Florian

    2014-10-01

    The present study investigated the feasibility of using self-paced eye movements during reading (measured by an eye tracker) as markers for calculating hemodynamic brain responses measured by functional magnetic resonance imaging (fMRI). Specifically, we were interested in whether the fixation-related fMRI analysis approach was sensitive enough to detect activation differences between reading material (words and pseudowords) and nonreading material (line and unfamiliar Hebrew strings). Reliable reading-related activation was identified in left hemisphere superior temporal, middle temporal, and occipito-temporal regions including the visual word form area (VWFA). The results of the present study are encouraging insofar as fixation-related analysis could be used in future fMRI studies to clarify some of the inconsistent findings in the literature regarding the VWFA. Our study is the first step in investigating specific visual word recognition processes during self-paced natural sentence reading via simultaneous eye tracking and fMRI, thus aiming at an ecologically valid measurement of reading processes. We provided the proof of concept and methodological framework for the analysis of fixation-related fMRI activation in the domain of reading research. © The Author 2013. Published by Oxford University Press.

  11. The (lack of) relation between straylight and visual acuity. Two domains of the point-spread-function.

    PubMed

    van den Berg, Thomas J T P

    2017-05-01

    The effect of cataract and other media opacities on functional vision is typically assessed clinically using visual acuity. In both clinical and basic research, straylight (the functional result of light scattering in the eye) is commonly measured. The purpose of the present study was to determine the link between these two measures: is visual acuity in cataract and other media opacities related to straylight? Interdependence between acuity and straylight is addressed from three different points of view: (1) Methodological: can acuity differences affect the measurement value of straylight, and vice versa? (2) Basic optics: does the optical process of light scattering in the human eye affect both straylight and visual acuity? (3) Statistical: how strongly are acuity and straylight correlated in the practice of important clinical conditions? Experimental and theoretical aspects will be considered, with a focus on normal ageing and cataract formation. (1) Methodological: testing potential effects of acuity, artificially manipulated with positive trial lenses, showed no effect on measured straylight values. Since light scattering in the eye involves a low percentage of the light and has large angular spreading, contrast reduction due to straylight is limited, resulting in virtually absent acuity effects. (2) Basic optics: light scattering from the human donor eye lens is found to have virtually no effect in the centre of the point-spread-function, also for cataractous lenses, resulting in virtually absent acuity effects. (3) Statistical: literature data on straylight and visual acuity show a weak correlation for the important groups of normal ageing and cataract populations. The point-spread-function of the normal ageing and cataractous human eye is built upon two rather independent basic parts. Aberrations control the central peak. Light scattering controls the periphery from about 1° onwards. The way acuity and straylight are measured ensures no confounding between

  12. Laboratory permittivity measurements of icy planetary analogs in the millimeter and submillimeter domains, in relation with JUICE mission.

    NASA Astrophysics Data System (ADS)

    Brouet, Y.; Jacob, K.; Murk, A.; Poch, O.; Pommerol, A.; Thomas, N.; Levasseur-Regourd, A. C.

    2015-12-01

    The European Space Agency's JUpiter ICy moons Explorer (JUICE) spacecraft is planned for launch in 2022 and arrival at Jupiter in 2030. It will observe the planet Jupiter and three of its largest moons, Ganymede, Callisto and Europa. One instrument on the JUICE spacecraft is the Sub-millimeter Wave Instrument (SWI), which will measure brightness temperatures from Jupiter's stratosphere and troposphere, and from subsurfaces of Jupiter's icy moons. In the baseline configuration SWI consists of two tunable sub-millimeter wave receivers operating from 530 to 625 GHz. As an alternative one of the receivers could cover the range of 1080 and 1275 GHz. Inversion models are strongly dependent on the knowledge of the complex relative permittivity (hereafter permittivity) of the target material to retrieve the physical properties of the subsurface (e.g. [1][2]). We set up a laboratory experiment allowing us to perform reproducible measurements of the complex scattering parameters S11 and S21 in the ranges of 70 to 110 GHz, of 100 to 160 GHz, of 140 to 220 GHz, of 140 to 220 GHz and of 510 to 715 GHz. These scattering parameters can be used to retrieve the permittivity of icy analogs of the surfaces and subsurfaces of Jupiter's icy moons in order to prepare the data interpretation of SWI [3]. The measurements are performed under laboratory conditions with a quasi-optical bench (Institute of Applied Physics, University of Bern). The icy analogs that we prepare in the Laboratory for Outflow Studies of Sublimating Materials (LOSSy, Physics Institute, University of Bern), include two different porous water ice samples composed of fine-grained ice particles with a size range of 4 to 6 microns and ice particles with a size range of 50 to 100 microns [4][5]; and possibly CO2 ice. We will present the general experimental set-up and the first results in the context to prepare the data interpretation of SWI. [1] Ulaby, F. T., Long, D. G., 2014. Microwave radar and radiometric remote

  13. Characterization of early induced genes in Arabidopsis thaliana responding to bacterial inoculation: identification of centrin and of a novel protein with two regions related to kinase domains.

    PubMed

    Cordeiro, M C; Piqueras, R; de Oliveira, D E; Castresana, C

    1998-09-04

    The early response to bacterial inoculation has been investigated and two Arabidopsis genes, ap3.3a and ap4.3a have been characterized. The AP3.3A protein showed high identity to centrin, a ubiquitous cytoskeletal protein first identified in unicellular green alga. Amino-acid sequence analyses of the AP4.3A protein indicates that the second gene characterized encodes an unusual protein with two putative kinase domains. Expression of ap3.3a and ap4.3a was rapidly induced after pathogen inoculation. A role of ap3.3a in plant defense could be postulated based on its preferential induction during the incompatible interactions analyzed. In contrast, activation of ap4.3a was not specific and could be related to a more general stress response.

  14. Genome cartography through domain annotation

    PubMed Central

    Ponting, Chris P; Dickens, Nicholas J

    2001-01-01

    The evolutionary history of eukaryotic proteins involves rapid sequence divergence, addition and deletion of domains, and fusion and fission of genes. Although the protein repertoires of distantly related species differ greatly, their domain repertoires do not. To account for the great diversity of domain contexts and an unexpected paucity of ortholog conservation, we must categorize the coding regions of completely sequenced genomes into domain families, as well as protein families.

  15. Cross Domain Analogies for Learning Domain Theories

    DTIC Science & Technology

    2007-01-01

    Example Problem and Worked Solution All problems and worked solutions used in this work were taken from the same physics textbook ( Giancoli 1991...domain theory. We close with a discussion of related work and our plans for the future. Representations and Problem Solving Representing physics ...small compared to the 30,000+ concepts and 8,000+ predicates already defined in the KB. Thus, objects, relations, and events that appear in physics

  16. Relative impact of residues at the intracellular and extracellular ends of the human GABAC rho1 receptor M2 domain on picrotoxinin activity.

    PubMed

    Carland, Jane E; Johnston, Graham A R; Chebib, Mary

    2008-02-02

    The relative impact on picrotoxinin activity of residues at the intracellular (2' and 6' residues) and extracellular (15' and 17' residues) ends of the second transmembrane (M2) domain of the human gamma-aminobutyric acid-C (GABA(C)) rho1 receptor was investigated. A series of GABA(C) rho1 subunits were produced containing either single or multiple mutations at the positions of interest. Wild-type and mutant subunits (containing one or more of the following mutations: P2'S, T6'M, I15'N, G17'H) were expressed in Xenopus oocytes and characterized using agonists, partial agonists and antagonists. Changes in agonist activity were observed for mutant receptors. Most notably, mutation at the 2' position resulted in decreased agonist potency, while mutation at the 15' and 17' residues increased agonist potency. The affinity of the competitive antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA) was unchanged compared to wild-type at all mutant receptors. Of the four residues studied, mutation of residues at the 2' and 6' positions had the greatest impact on picrotoxinin activity. Inclusion of the P2'S mutation typically produced receptors with increased picrotoxinin potency, while the T6'M mutation reduced picrotoxinin potency. Picrotoxinin is a mixed antagonist at wild-type and all mutant receptors, with the exception of the double mutant rho1P2'S/T6'M receptors at which the non-competitive component was isolated. It is proposed that the contribution of M2 domain residues to picrotoxinin activity is potentially two-fold: (1) their role as a potential picrotoxinin binding site within the pore; and (2) they are critical for receptor activation properties of the receptor, thus may alter the allosteric mechanism of picrotoxinin.

  17. Is Spectral-Domain Optical Coherence Tomography Essential for Flexible Treatment Regimens with Ranibizumab for Neovascular Age-Related Macular Degeneration?

    PubMed Central

    Ozkaya, Abdullah; Agca, Alper; Ozgurhan, Engin Bilge; Karakucuk, Yalcin; Yazici, Ahmet Taylan; Demirok, Ahmet

    2013-01-01

    Purpose. To evaluate the ability of spectral-domain optical coherence tomography to detect subtle amounts of retinal fluid when the choroidal neovascularization is detected as inactive via time-domain optical coherence tomography and clinical examination in neovascular age-related macular degeneration (nAMD) patients. Methods. Forty-nine eyes of 49 patients with nAMD after ranibizumab treatment were included in this cross-sectional, prospective study. All patients were imaged with TD-OCT and SD-OCT at the same visit one month after a ranibizumab injection. The presence of subretinal, intraretinal, and subretinal pigment epithelium fluid (subRPE) in SD-OCT was evaluated; also mean central retinal thickness (CRT) and the rate of vitreoretinal surface disorders detected via the two devices were evaluated. Results. The mean CRT via TD-OCT and SD-OCT was 218.1 ± 51.3 and 325.7 ± 78.8 microns. Sixteen patients (32.6%) showed any kind of retinal fluid via SD-OCT. In detail, 8 patients (16.3%) showed subretinal fluid, 10 patients (20.4%) showed intraretinal fluid, and 3 patients (6.1%) showed SubRPE fluid. The ability of detecting vitreoretinal surface disorders was comparable between the two devices, except vitreomacular traction. Conclusion. SD-OCT is essential for the nAMD patients who are on an as-needed treatment regimen with ranibizumab. Only TD-OCT and clinical examination may cause insufficient treatment in this group of patients. PMID:24324880

  18. Isolation of a minD-like gene in the hyperthermophilic archaeon Pyrococcus AL585, and phylogenetic characterization of related proteins in the three domains of life.

    PubMed

    Gérard, E; Labedan, B; Forterre, P

    1998-11-05

    The region upstream of the dinF-like gene of the hyperthermophilic archaeon Pyrococcus strain AL585 has been cloned and sequenced. This region contains an open reading frame (ORF) that encodes a polypeptide with a high similarity to MinD proteins and their Mrp paralogues. Transcripts of the dinF-like and the minD-like genes were detected by RT-PCR, indicating that they are both expressed in vivo. The MinD and MinD-like proteins belong to a broad family of ATPases involved in chromosome and plasmid partitioning. MinD-like proteins can be defined by specific amino-acid sequence signatures. A systematic search for proteins sharing these signatures in current databases and newly sequenced genomes show that MinD-like proteins are present in all archaeal genomes sequenced so far, often in several copies. Phylogenetic analysis identifies two groups of MinD-like proteins which are also characterized by more conserved amino-acid motifs. A first group, which includes the Escherichia coli MinD and the Pyrococcus AL585 MinDL protein, contains only procaryotic proteins. This group can be further divided into a subgroup of archaeal proteins and two subgroups of bacterial proteins. A second group includes proteins more related to the E. coli Mrp protein and contains representants of the three domains of life. The conservation of MinD-like proteins in the three domains of life suggests that these proteins play a central role in cellular metabolism.

  19. Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

    PubMed

    Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel

    2015-05-01

    Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder.

  20. Loss of Function of Saccharomyces Cerevisiae Kinesin-Related Cin8 and Kip1 Is Suppressed by Kar3 Motor Domain Mutations

    PubMed Central

    Hoyt, M. A.; He, L.; Totis, L.; Saunders, W. S.

    1993-01-01

    The kinesin-related products of the CIN8 and KIP1 genes of Saccharomyces cerevisiae redundantly perform an essential function in mitosis. The action of either gene-product is required for an outwardly directed force that acts upon the spindle poles. We have selected mutations that suppress the temperature-sensitivity of a cin8-temperature-sensitive kip1-δ strain. The extragenic suppressors analyzed were all found to be alleles of the KAR3 gene. KAR3 encodes a distinct kinesin-related protein whose action antagonizes Cin8p/Kip1p function. All seven alleles analyzed were altered within the region of KAR3 that encodes the putative force-generating (or ``motor'') domain. These mutations also suppressed the inviability associated with the cin8-δ kip1-δ genotype, a property not shared by a deletion of KAR3. Other properties of the suppressing alleles revealed that they were not null for function. Six of the seven were unaffected for the essential karyogamy and meiosis properties of KAR3 and the seventh was dominant for the suppressing trait. Our findings suggest that despite an antagonistic relationship between Cin8p/Kip1p and Kar3p, aspects of their mitotic roles may be similar. PMID:8224825

  1. Self-Esteem is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    PubMed Central

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions, we apply growth modeling to 13-year longitudinal data obtained from by now deceased participants of the Berlin Aging Study (BASE, N = 462; age 70 – 103, M = 86.3 yrs., SD = 8.3; 51% male). Results revealed that self-esteem, on average, does decline in very old age and close to death, but the amount of typical decline is minor. Health-related constraints and disabilities as well as lower control beliefs and higher loneliness were each associated with lower self-esteem late in life. We obtained initial evidence that some of these associations were stronger among the oldest-old participants. Our results corroborate and extend initial reports that self-esteem is, on average, fairly stable into the last years of life. We discuss possible pathways by which common and often severe late-life challenges may undermine an otherwise relatively robust self-esteem system. PMID:25546600

  2. A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes.

    PubMed Central

    Baldwin, A S; LeClair, K P; Singh, H; Sharp, P A

    1990-01-01

    A cDNA from a B-cell library was previously isolated that encodes a sequence-specific DNA-binding protein with affinities for related sites in a class I major histocompatibility complex (MHC) and kappa immunoglobulin gene enhancers. We report here approximately 6.5 kilobases of sequence of the MBP-1 (MHC enhancer binding protein 1) cDNA. MBP-1 protein has a molecular weight predicted to be greater than 200,000. A DNA-binding domain with high affinity for the MHC enhancer sequence TGGGGATTCCCCA was localized to an 118-amino-acid protein fragment containing two zinc fingers of the class Cys2-X12-His2. Analysis of expression of MBP-1 mRNA revealed relatively high expression in HeLa cells and in a human retinal cell line, with lower levels in Jurkat T cells and in two B-cell lines. Interestingly, expression of MBP-1 mRNA was inducible by mitogen and phorbol ester treatment of Jurkat T cells and by serum treatment of confluent serum-deprived human fibroblasts. Images PMID:2108316

  3. The cysteine-rich secretory protein domain of Tpx-1 is related to ion channel toxins and regulates ryanodine receptor Ca2+ signaling.

    PubMed

    Gibbs, Gerard M; Scanlon, Martin J; Swarbrick, James; Curtis, Suzanne; Gallant, Esther; Dulhunty, Angela F; O'Bryan, Moira K

    2006-02-17

    The cysteine-rich secretory proteins (Crisp) are predominantly found in the mammalian male reproductive tract as well as in the venom of reptiles. Crisps are two domain proteins with a structurally similar yet evolutionary diverse N-terminal domain and a characteristic cysteine-rich C-terminal domain, which we refer to as the Crisp domain. We presented the NMR solution structure of the Crisp domain of mouse Tpx-1, and we showed that it contains two subdomains, one of which has a similar fold to the ion channel regulators BgK and ShK. Furthermore, we have demonstrated for the first time that the ion channel regulatory activity of Crisp proteins is attributed to the Crisp domain. Specifically, the Tpx-1 Crisp domain inhibited cardiac ryanodine receptor (RyR) 2 with an IC(50) between 0.5 and 1.0 microM and activated the skeletal RyR1 with an AC(50) between 1 and 10 microM when added to the cytoplasmic domain of the receptor. This activity was nonvoltage-dependent and weakly voltage-dependent, respectively. Furthermore, the Tpx-1 Crisp domain activated both RyR forms at negative bilayer potentials and showed no effect at positive bilayer potentials when added to the luminal domain of the receptor. These data show that the Tpx-1 Crisp domain on its own can regulate ion channel activity and provide compelling evidence for a role for Tpx-1 in the regulation of Ca(2+) fluxes observed during sperm capacitation.

  4. Quantifying behavioural determinants relating to health professional reporting of medication errors: a cross-sectional survey using the Theoretical Domains Framework.

    PubMed

    Alqubaisi, Mai; Tonna, Antonella; Strath, Alison; Stewart, Derek

    2016-11-01

    The aims of this study were to quantify the behavioural determinants of health professional reporting of medication errors in the United Arab Emirates (UAE) and to explore any differences between respondents. A cross-sectional survey of patient-facing doctors, nurses and pharmacists within three major hospitals of Abu Dhabi, the UAE. An online questionnaire was developed based on the Theoretical Domains Framework (TDF, a framework of behaviour change theories). Principal component analysis (PCA) was used to identify components and internal reliability determined. Ethical approval was obtained from a UK university and all hospital ethics committees. Two hundred and ninety-four responses were received. Questionnaire items clustered into six components of knowledge and skills, feedback and support, action and impact, motivation, effort and emotions. Respondents generally gave positive responses for knowledge and skills, feedback and support and action and impact components. Responses were more neutral for the motivation and effort components. In terms of emotions, the component with the most negative scores, there were significant differences in terms of years registered as health professional (those registered longest most positive, p = 0.002) and age (older most positive, p < 0.001) with no differences for gender and health profession. Emotional-related issues are the dominant barrier to reporting and are common to all professions. There is a need to develop, test and implement an intervention to impact health professionals' emotions. Such an intervention should focus on evidence-based behaviour change techniques of reducing negative emotions, focusing on emotional consequences and providing social support. • This research used the Theoretical Domains Framework to quantify the behavioural determinants of health professional reporting of medication errors. • Questionnaire items relating to emotions surrounding reporting generated the most negative responses

  5. Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere

    PubMed Central

    1994-01-01

    Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. To examine the molecular basis for the specification of centromeric chromatin, we have cloned a human cDNA that encodes the 17-kD histone-like centromere antigen, CENP-A. Two domains are evident in the 140 aa CENP-A polypeptide: a unique NH2- terminal domain and a 93-amino acid COOH-terminal domain that shares 62% identity with nucleosomal core protein, histone H3. An epitope tagged derivative of CENP-A was faithfully targeted to centromeres when expressed in a variety of animal cells and this targeting activity was shown to reside in the histone-like COOH-terminal domain of CENP-A. These data clearly indicate that the assembly of centromeres is driven, at least in part, by the incorporation of a novel core histone into centromeric chromatin. PMID:7962047

  6. Development of a high capacity bubble domain memory element and related epitaxial garnet materials for application in spacecraft data recorders. Item 2: The optimization of material-device parameters for application in bubble domain memory elements for spacecraft data recorders

    NASA Technical Reports Server (NTRS)

    Besser, P. J.

    1976-01-01

    Bubble domain materials and devices are discussed. One of the materials development goals was a materials system suitable for operation of 16 micrometer period bubble domain devices at 150 kHz over the temperature range -10 C to +60 C. Several material compositions and hard bubble suppression techniques were characterized and the most promising candidates were evaluated in device structures. The technique of pulsed laser stroboscopic microscopy was used to characterize bubble dynamic properties and device performance at 150 kHz. Techniques for large area LPE film growth were developed as a separate task. Device studies included detector optimization, passive replicator design and test and on-chip bridge evaluation. As a technology demonstration an 8 chip memory cell was designed, tested and delivered. The memory elements used in the cell were 10 kilobit serial registers.

  7. The YTH Domain Is a Novel RNA Binding Domain*

    PubMed Central

    Zhang, Zhaiyi; Theler, Dominik; Kaminska, Katarzyna H.; Hiller, Michael; de la Grange, Pierre; Pudimat, Rainer; Rafalska, Ilona; Heinrich, Bettina; Bujnicki, Janusz M.; Allain, Frédéric H.-T.; Stamm, Stefan

    2010-01-01

    The YTH (YT521-B homology) domain was identified by sequence comparison and is found in 174 different proteins expressed in eukaryotes. It is characterized by 14 invariant residues within an α-helix/β-sheet structure. Here we show that the YTH domain is a novel RNA binding domain that binds to a short, degenerated, single-stranded RNA sequence motif. The presence of the binding motif in alternative exons is necessary for YT521-B to directly influence splice site selection in vivo. Array analyses demonstrate that YT521-B predominantly regulates vertebrate-specific exons. An NMR titration experiment identified the binding surface for single-stranded RNA on the YTH domain. Structural analyses indicate that the YTH domain is related to the pseudouridine synthase and archaeosine transglycosylase (PUA) domain. Our data show that the YTH domain conveys RNA binding ability to a new class of proteins that are found in all eukaryotic organisms. PMID:20167602

  8. Déformation hercynienne et relation socle/couverture dans le domaine du Bas-Draˆa (Anti-Atlas occidental, Maroc)

    NASA Astrophysics Data System (ADS)

    Soulaimani, A.; Le Corre, Cl.; Farazdaq, R.

    1997-04-01

    Hercynian deformations in the western anti-Atlas area are controlled by the reactivation of faults in the Precambrain basement. The Bas-Draˆa anticline zone forms the southernmost Precambian basement massif covered by Infracambrian and Palaeozoic sedimentary formations. Relative motions of basement blocks induce in the cover an heterogeneous ductile deformation associated with a SE vergence. Structural data and finite strain measurements suggest the basement-cover relationships and late Cabboniferous age of the regional tectonics. The uplift of the Bas-Draˆa basement associated with the southeast thrusting induced a punching motion in the cover. A dextral shear component locally involved the rotation of structures or en echelon folding. The deformation is very intense near the basement boundaries, but decreases away from the boundary, as well as upwards within the sedimentary cover. To the southeast the deformation is very weak in the Carboniferous on the Saharan domain. The Bas-Draˆa area represents the last mobile block of Hercynian Belt foreland near the stable West African Craton. Vertical m movements are dominant versus wrench shifting.

  9. Data Resource Profile: Cross-national and cross-study sociodemographic and health-related harmonized domains from SAGE plus ELSA, HRS and SHARE (SAGE+, Wave 1).

    PubMed

    Minicuci, Nadia; Naidoo, Nirmala; Chatterji, Somnath; Kowal, Paul

    2016-10-01

    Four longitudinal studies were included in this rigorous harmonization process: the Study on global AGEing and adult health (SAGE); English Longitudinal Study on Ageing (ELSA); US Health and Retirement Study (HRS); and Survey of Health, Ageing and Retirement in Europe (SHARE). An ex-post harmonized process was applied to nine health-related thematic domains (socio-demographic and economic, health states, overall self-report of health and mental state, health examinations, physical and mental performance tests, risk factors, chronic conditions, social network and subjective well-being) for data from the 2004 wave of each study. Large samples of adults aged 50 years and older were available from each study: SAGE, n = 18 886; ELSA, n = 9181; HRS, n = 19 303; and SHARE, n = 29 917. The microdata, along with further details about the harmonization process and all metadata, are available through the World Health Organization (WHO) data archive at [http://apps.who.int/healthinfo/systems/surveydata/index.php/catalog]. Further information and enquiries can be made to [sagesurvey@who.int] or the corresponding author. The data resource will continue to be updated with data across additional waves of these surveys and new waves.

  10. Data Resource Profile: Cross-national and cross-study sociodemographic and health-related harmonized domains from SAGE plus ELSA, HRS and SHARE (SAGE+, Wave 1)

    PubMed Central

    Minicuci, Nadia; Naidoo, Nirmala; Chatterji, Somnath; Kowal, Paul

    2016-01-01

    Four longitudinal studies were included in this rigorous harmonization process: the Study on global AGEing and adult health (SAGE); English Longitudinal Study on Ageing (ELSA); US Health and Retirement Study (HRS); and Survey of Health, Ageing and Retirement in Europe (SHARE). An ex-post harmonized process was applied to nine health-related thematic domains (socio-demographic and economic, health states, overall self-report of health and mental state, health examinations, physical and mental performance tests, risk factors, chronic conditions, social network and subjective well-being) for data from the 2004 wave of each study. Large samples of adults aged 50 years and older were available from each study: SAGE, n = 18 886; ELSA, n = 9181; HRS, n = 19 303; and SHARE, n = 29 917. The microdata, along with further details about the harmonization process and all metadata, are available through the World Health Organization (WHO) data archive at [http://apps.who.int/healthinfo/systems/surveydata/index.php/catalog]. Further information and enquiries can be made to [sagesurvey@who.int] or the corresponding author. The data resource will continue to be updated with data across additional waves of these surveys and new waves. PMID:27794522

  11. The pipsqueak-domain proteins Distal antenna and Distal antenna-related restrict Hunchback neuroblast expression and early-born neuronal identity

    PubMed Central

    Kohwi, Minoree; Hiebert, Laurel S.; Doe, Chris Q.

    2011-01-01

    A fundamental question in brain development is how precursor cells generate a diverse group of neural progeny in an ordered manner. Drosophila neuroblasts sequentially express the transcription factors Hunchback (Hb), Krüppel (Kr), Pdm1/Pdm2 (Pdm) and Castor (Cas). Hb is necessary and sufficient to specify early-born temporal identity and, thus, Hb downregulation is essential for specification of later-born progeny. Here, we show that distal antenna (dan) and distal antenna-related (danr), encoding pipsqueak motif DNA-binding domain protein family members, are detected in all neuroblasts during the Hb-to-Cas expression window. Dan and Danr are required for timely downregulation of Hb in neuroblasts and for limiting the number of early-born neurons. Dan and Danr function independently of Seven-up (Svp), an orphan nuclear receptor known to repress Hb expression in neuroblasts, because Dan, Danr and Svp do not regulate each other and dan danr svp triple mutants have increased early-born neurons compared with either dan danr or svp mutants. Interestingly, misexpression of Hb can induce Dan and Svp expression in neuroblasts, suggesting that Hb might activate a negative feedback loop to limit its own expression. We conclude that Dan/Danr and Svp act in parallel pathways to limit Hb expression and allow neuroblasts to transition from making early-born neurons to late-born neurons at the proper time. PMID:21429984

  12. Verticillium Infection Triggers VASCULAR-RELATED NAC DOMAIN7–Dependent de Novo Xylem Formation and Enhances Drought Tolerance in Arabidopsis[W

    PubMed Central

    Reusche, Michael; Thole, Karin; Janz, Dennis; Truskina, Jekaterina; Rindfleisch, Sören; Drübert, Christine; Polle, Andrea; Lipka, Volker; Teichmann, Thomas

    2012-01-01

    The soilborne fungal plant pathogen Verticillium longisporum invades the roots of its Brassicaceae hosts and proliferates in the plant vascular system. Typical aboveground symptoms of Verticillium infection on Brassica napus and Arabidopsis thaliana are stunted growth, vein clearing, and leaf chloroses. Here, we provide evidence that vein clearing is caused by pathogen-induced transdifferentiation of chloroplast-containing bundle sheath cells to functional xylem elements. In addition, our findings suggest that reinitiation of cambial activity and transdifferentiation of xylem parenchyma cells results in xylem hyperplasia within the vasculature of Arabidopsis leaves, hypocotyls, and roots. The observed de novo xylem formation correlates with Verticillium-induced expression of the VASCULAR-RELATED NAC DOMAIN (VND) transcription factor gene VND7. Transgenic Arabidopsis plants expressing the chimeric repressor VND7-SRDX under control of a Verticillium infection-responsive promoter exhibit reduced de novo xylem formation. Interestingly, infected Arabidopsis wild-type plants show higher drought stress tolerance compared with noninfected plants, whereas this effect is attenuated by suppression of VND7 activity. Together, our results suggest that V. longisporum triggers a tissue-specific developmental plant program that compensates for compromised water transport and enhances the water storage capacity of infected Brassicaceae host plants. In conclusion, we provide evidence that this natural plant–fungus pathosystem has conditionally mutualistic features. PMID:23023171

  13. Semiautomated segmentation and analysis of retinal layers in three-dimensional spectral-domain optical coherence tomography images of patients with atrophic age-related macular degeneration.

    PubMed

    Hu, Zhihong; Shi, Yue; Nandanan, Kiran; Sadda, Srinivas R

    2017-01-01

    Historically, regular drusen and geographic atrophy (GA) have been recognized as the hallmarks of nonneovascular age-related macular degeneration (AMD). Recent imaging developments have revealed another distinct nonneovascular AMD phenotype, reticular pseudodrusen (RPD). We develop an approach to semiautomatically quantify retinal surfaces associated with various AMD lesions (i.e., regular drusen, RPD, and GA) in spectral domain (SD) optical coherence tomography (OCT) images. More specifically, a graph-based algorithm was used to segment multiple retinal layers in SD-OCT volumes. Varying surface feasibility constraints based on the presegmentation were applied on the double-surface graph search to refine the surface segmentation. The thicknesses of these layers and their correlation with retinal functional measurements, including microperimetry (MP) sensitivity and visual acuity (VA), were investigated. The photoreceptor outer segment layer demonstrated significant thinning with a reduction in MP sensitivity and VA score when atrophic AMD lesions were present. Regular drusen and RPD were separately segmented on SD-OCT images to allow their characteristics and distribution to be studied separately. The mean thickness of regular drusen was found to significantly correlate with the VA score. RPD appeared to be distributed evenly throughout the macula and regular drusen appeared to be more concentrated centrally.

  14. Field Evolution of Antiferromagnetic Domains and Domain Walls

    NASA Astrophysics Data System (ADS)

    Fullerton, Eric E.; Hellwig, Olav; Berger, Andreas K.

    2003-03-01

    We have used magnetron sputtered [Co(4Å)Pt(7Å)]X Co(4Å)Ru(9Å)N multiplayer films to create artificially layered antiferromagnets. In contrast to atomic antiferromagnets our model system has an antiferromagnetic (AF) exchange energy comparable to the Zeemann energy in moderate fields and allows to fine tune the relative magnitude of the different magnetic energy terms by varying the parameters X and N. With increasing X and N we observe a transition from traditionally observed sharp AF domain walls towards AF domain walls with a finite width which consist of ferromagnetic stripes, i.e. the AF domains have zero net moment whereas the domain walls carry a finite magnetic moment. Such AF domain walls have not been observed before and are a direct consequence of balancing out exchange and Zeeman energy. We also show that such domain walls are expected from theoretical energy calculations. In this contribution we study the nature and field evolution of the AF stripe domain walls by Magnetic Force Microscopy (MFM). The surface sensitivity of MFM and the finite moment of the AF domain walls allow us to image AF domains as well as domain walls. We are showing first experiments to study the AF domain wall evolution in real space while applying an external field. O.H. was supported by the Deutsche Forschungsgemeinschaft via a Forschungsstipendium under the contract number HE 3286/1-1.

  15. Domain Validity and Generalizability

    ERIC Educational Resources Information Center

    Kaiser, Henry F.; Michael, William B.

    1975-01-01

    An alternative derivation of Tryon's basic formula for the coefficient of domain validity or the coefficient of generalizability developed by Cronbach, Rajaratnam, and Glaser is provided. This derivation, which is also the generalized Kuder-Richardson coefficient, requires a relatively minimal number of assumptions compared with that in previously…

  16. Identifying health-related quality of life (HRQL) domains for multiple chronic conditions (diabetes, hypertension and dyslipidemia): patient and provider perspectives.

    PubMed

    Bounthavong, Mark; Law, Anandi V

    2008-12-01

    To examine patient and provider perspectives about the impact of having diabetes, hypertension and/or dyslipidemia (DHD) on health-related quality of life (HRQL) in order to identify domains for an HRQL instrument focusing on specific chronic diseases (DHD). Exploratory qualitative design was used to elicit patient and provider responses. Patient survey contained 11 demographic and nine content questions inquiring how the disease(s) affected patient HRQL. Provider survey examined how the disease(s) affected their patient's HRQL and crucial factors for improvement. Patients were included if they had DHD and spoke English. Providers working with DHD patients were identified among university faculty and community practitioners. Thirty-eight patients (24.7%) completed the interviews. Three judges content analysed patient responses and proposed seven categories (patients ranked physical functioning first followed by diet, emotional well-being (E), general well-being, social functioning (S), 'no change in HRQL' and medications). One question about medications had four categories (medication inconvenience, medication side effects, forgetfulness and general well-being). Index for reliability was greater than 80% for all categories. Providers ranked lifestyle modification (LM), first followed by complications, medication, self-care, E, education, S, physical activity and resources (ability to pay) as components that impact HRQL. Patient and provider perspectives were similar in four areas (E, S, medication and diet); however, the differences were in how these impacted HRQL - patients focused on activities relevant to daily life that were affected, while providers based it on processes of therapy management and self-care (education and implementation of LM).

  17. The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis.

    PubMed

    Maheshwar, M M; Cheadle, J P; Jones, A C; Myring, J; Fryer, A E; Harris, P C; Sampson, J R

    1997-10-01

    Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.

  18. Cloning, expression analysis, and RNA interference study of a HORMA domain containing autophagy-related gene 13 (ATG13) from the coleopteran beetle, Tenebrio molitor.

    PubMed

    Lee, Jung Hee; Jo, Yong Hun; Patnaik, Bharat Bhusan; Park, Ki Beom; Tindwa, Hamisi; Seo, Gi Won; Chandrasekar, Raman; Lee, Yong Seok; Han, Yeon Soo

    2015-01-01

    Autophagy is a process that is necessary during starvation, as it replenishes metabolic precursors by eliminating damaged organelles. Autophagy is mediated by more than 35 autophagy-related (Atg) proteins that participate in the nucleation, elongation, and curving of the autophagosome membrane. In a pursuit to address the role of autophagy during development and immune resistance of the mealworm beetle, Tenebrio molitor, we screened ATG gene sequences from the whole-larva transcriptome database. We identified a homolog of ATG13 gene in T. molitor (designated as TmATG13) that comprises a cDNA of 1176 bp open reading frame (ORF) encoding a protein of 391 amino acids. Analyses of the structure-specific features of TmAtg13 showed an intrinsically disordered middle and C-terminal region that was rich in regulatory phosphorylation sites. The N-terminal Atg13 domain had a HORMA (Hop1, Rev7, and Mad2) fold containing amino acid residues conserved across the Atg13 insect orthologs. A quantitative reverse-transcription-polymerase chain reaction analysis revealed that TmATG13 was expressed ubiquitously during all developmental stages of the insect. TmATG13 mRNA expression was high in the fat body and gut of the larval and adult stages of the insect. The TmATG13 transcripts were expressed at a high level until 6 days of ovarian development, followed by a significant decline. Silencing of ATG13 transcripts in T. molitor larvae showed a reduced survivability of 39 and 38% in response to Escherichia coli and Staphylococcus aureus infection. Furthermore, the role of TmAtg13 in initiating autophagy as a part of the host cell autophagic complex of the host cells against the intracellular pathogen Listeria monocytogenes is currently under study and will be critical to unfold the structure-function relationships.

  19. Cloning, expression analysis, and RNA interference study of a HORMA domain containing autophagy-related gene 13 (ATG13) from the coleopteran beetle, Tenebrio molitor

    PubMed Central

    Lee, Jung Hee; Jo, Yong Hun; Patnaik, Bharat Bhusan; Park, Ki Beom; Tindwa, Hamisi; Seo, Gi Won; Chandrasekar, Raman; Lee, Yong Seok; Han, Yeon Soo

    2015-01-01

    Autophagy is a process that is necessary during starvation, as it replenishes metabolic precursors by eliminating damaged organelles. Autophagy is mediated by more than 35 autophagy-related (Atg) proteins that participate in the nucleation, elongation, and curving of the autophagosome membrane. In a pursuit to address the role of autophagy during development and immune resistance of the mealworm beetle, Tenebrio molitor, we screened ATG gene sequences from the whole-larva transcriptome database. We identified a homolog of ATG13 gene in T. molitor (designated as TmATG13) that comprises a cDNA of 1176 bp open reading frame (ORF) encoding a protein of 391 amino acids. Analyses of the structure-specific features of TmAtg13 showed an intrinsically disordered middle and C-terminal region that was rich in regulatory phosphorylation sites. The N-terminal Atg13 domain had a HORMA (Hop1, Rev7, and Mad2) fold containing amino acid residues conserved across the Atg13 insect orthologs. A quantitative reverse-transcription-polymerase chain reaction analysis revealed that TmATG13 was expressed ubiquitously during all developmental stages of the insect. TmATG13 mRNA expression was high in the fat body and gut of the larval and adult stages of the insect. The TmATG13 transcripts were expressed at a high level until 6 days of ovarian development, followed by a significant decline. Silencing of ATG13 transcripts in T. molitor larvae showed a reduced survivability of 39 and 38% in response to Escherichia coli and Staphylococcus aureus infection. Furthermore, the role of TmAtg13 in initiating autophagy as a part of the host cell autophagic complex of the host cells against the intracellular pathogen Listeria monocytogenes is currently under study and will be critical to unfold the structure-function relationships. PMID:26136688

  20. The Toll Interleukin-1 Receptor (IL-1R) 8/Single Ig Domain IL-1R-Related Molecule Modulates the Renal Response to Bacterial Infection

    PubMed Central

    Butter, Loes M.; Teske, Gwendoline J. D.; Stroo, Ingrid; Pulskens, Wilco P.; Florquin, Sandrine

    2012-01-01

    Our immune system has to constantly strike a balance between activation and inhibition of an inflammatory response to combat invading pathogens and avoid inflammation-induced collateral tissue damage. Toll interleukin-1 receptor 8 (IL-1R-8)/single Ig domain IL-1R-related molecule (TIR8/SIGIRR) is an inhibitor of Toll-like receptor (TLR)/IL-1R signaling, which is predominantly expressed in the kidney. The biological role of renal TIR8 during infection is, however, unknown. We therefore evaluated renal TIR8 expression during Escherichia coli pyelonephritis and explored its role in host defense using TIR8−/− versus TIR8+/+ mice. We found that TIR8 protein is abundantly present in the majority of cortical tubular epithelial cells. Pyelonephritis resulted in a significant downregulation of TIR8 mRNA in kidneys of TIR8+/+ mice. TIR8 inhibited an effective host response against E. coli, as indicated by diminished renal bacterial outgrowth and dysfunction in TIR8−/− mice. This correlated with increased amounts of circulating and intrarenal neutrophils at the early phase of infection. TIR8−/− tubular epithelial cells had increased cytokine/chemokine production when stimulated with lipopolysaccharide (LPS) or heat-killed E. coli, suggesting that TIR8 played an anti-inflammatory role during pathogen stimulation by inhibiting LPS signaling. These data suggest that TIR8 is an important negative regulator of an LPS-mediated inflammatory response in tubular epithelial cells and dampens an effective antibacterial host response during pyelonephritis caused by uropathogenic E. coli. PMID:22890991

  1. The toll interleukin-1 receptor (IL-1R) 8/single Ig domain IL-1R-related molecule modulates the renal response to bacterial infection.

    PubMed

    Leemans, Jaklien C; Butter, Loes M; Teske, Gwendoline J D; Stroo, Ingrid; Pulskens, Wilco P; Florquin, Sandrine

    2012-11-01

    Our immune system has to constantly strike a balance between activation and inhibition of an inflammatory response to combat invading pathogens and avoid inflammation-induced collateral tissue damage. Toll interleukin-1 receptor 8 (IL-1R-8)/single Ig domain IL-1R-related molecule (TIR8/SIGIRR) is an inhibitor of Toll-like receptor (TLR)/IL-1R signaling, which is predominantly expressed in the kidney. The biological role of renal TIR8 during infection is, however, unknown. We therefore evaluated renal TIR8 expression during Escherichia coli pyelonephritis and explored its role in host defense using TIR8(-/-) versus TIR8(+/+) mice. We found that TIR8 protein is abundantly present in the majority of cortical tubular epithelial cells. Pyelonephritis resulted in a significant downregulation of TIR8 mRNA in kidneys of TIR8(+/+) mice. TIR8 inhibited an effective host response against E. coli, as indicated by diminished renal bacterial outgrowth and dysfunction in TIR8(-/-) mice. This correlated with increased amounts of circulating and intrarenal neutrophils at the early phase of infection. TIR8(-/-) tubular epithelial cells had increased cytokine/chemokine production when stimulated with lipopolysaccharide (LPS) or heat-killed E. coli, suggesting that TIR8 played an anti-inflammatory role during pathogen stimulation by inhibiting LPS signaling. These data suggest that TIR8 is an important negative regulator of an LPS-mediated inflammatory response in tubular epithelial cells and dampens an effective antibacterial host response during pyelonephritis caused by uropathogenic E. coli.

  2. Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells.

    PubMed

    Cheng, Tsai-Mu; Murad, Yanal M; Chang, Chia-Ching; Yang, Ming-Chi; Baral, Toya Nath; Cowan, Aaron; Tseng, Shin-Hua; Wong, Andrew; Mackenzie, Roger; Shieh, Dar-Bin; Zhang, Jianbing

    2014-03-01

    Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is over-expressed in pancreatic cancer cells, and it is associated with the progression of pancreatic cancer. We tested a single domain antibody (sdAb) targeting CEACAM6, 2A3, which was isolated previously from a llama immune library, and an Fc conjugated version of this sdAb, to determine how they affect the pancreatic cancer cell line BxPC3. We also compared the effects of the antibodies to gemcitabine. Gemcitabine and 2A3 slowed down cancer cell proliferation. However, only 2A3 retarded cancer cell invasion, angiogenesis within the cancer mass and BxPC3 cell MMP-9 activity, three features important for tumour growth and metastasis. The IC50s for 2A3, 2A3-Fc and gemcitabine were determined as 6.5μM, 8μM and 12nM, respectively. While the 2A3 antibody inhibited MMP-9 activity by 33% compared to non-treated control cells, gemcitabine failed to inhibit MMP-9 activity. Moreover, 2A3 and 2A3-Fc inhibited invasion of BxPC3 by 73% compared to non-treated cells. When conditioned media that were produced using 2A3- or 2A3-Fc-treated BxPC3 cells were used in a capillary formation assay, the capillary length was reduced by 21% and 49%, respectively. Therefore 2A3 is an ideal candidate for treating tumours that over-express CEACAM6. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain.

    PubMed

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Beitel, Shawn C; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2015-04-07

    Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs elicit their adverse outcomes through activation of the aryl hydrocarbon receptor (AhR). However, there is limited understanding of the mechanisms that result in differences in sensitivity to DLCs among different species of fishes. Understanding these mechanisms is critical for protection of the diversity of fishes exposed to DLCs, including endangered species. This study investigated specific mechanisms that drive responses of two endangered fishes, white sturgeon (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It determined whether differences in sensitivity to activation of AhRs (AhR1 and AhR2) can be predicted based on identities of key amino acids in the ligand binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were no differences in sensitivity between white sturgeon and lake sturgeon based on activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been shown to be mediated through activation of AhR2, but not AhR1, in all fishes studied to date. This indicates that white sturgeon are likely to have greater sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico mutagenesis suggests that differences in sensitivity to activation of AhR2 result from differences in key amino acids at position 388 in the LBD of AhR2 of white sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of key amino acids in the LBD of AhR2 could be predictive of both in vitro activation by DLCs and in vivo sensitivity to DLCs in these, and potentially other, fishes.

  4. Cetacean distribution and abundance in relation to oceanographic domains on the eastern Bering Sea shelf, June and July of 2002, 2008, and 2010

    NASA Astrophysics Data System (ADS)

    Friday, Nancy A.; Zerbini, Alexandre N.; Waite, Janice M.; Moore, Sue E.; Clapham, Phillip J.

    2013-10-01

    As part of the Bering Sea Project, cetacean surveys were conducted to describe distribution and estimate abundance on the eastern Bering Sea shelf. Three marine mammal observers conducted visual surveys along transect lines sampled during the Alaska Fisheries Science Center walleye pollock assessment survey in June and July of 2008 and 2010. Distribution and abundance in 2008 and 2010 (cold years) are compared with results from a similar survey conducted in 2002 (a warm year), as the only three years that the entire survey area was sampled; patterns largely match those previously observed. Abundance estimates for comparable areas in 2002, 2008 and 2010 were as follows: humpback whales (Megaptera novaeangliae): 231 (CV=0.63), 436 (CV=0.45), and 675 (CV=0.80); fin whales (Balaenoptera physalus): 419 (CV=0.33), 1368 (CV=0.34), and 1061 (CV=0.38); minke whales (Balaenoptera acutorostrata): 389 (CV=0.52), 517 (CV=0.69), and 2020 (CV=0.73); Dall's porpoise (Phocoenoides dalli): 35,303 (CV=0.53), 14,543 (CV=0.32), and 11,143 (CV=0.32); and harbor porpoise (Phocoena phocoena): 1971 (CV=0.46), 4056 (CV=0.40), and 833 (CV=0.66). It should be noted that these abundance estimates are not corrected for biases due to perception, availability, or responsive movement. Estimates for humpback, fin and minke whales increased from 2002 to 2010, while those for harbor and Dall's porpoise decreased; trends were significant for fin whales. It is likely that changes in estimated abundance are due at least in part to shifts in distribution and not just changes in overall population size. Annual abundance estimates were examined by oceanographic domain. Humpback whales were consistently concentrated in coastal waters north of Unimak Pass. Fin whales were broadly distributed in the outer domain and slope in 2008 and 2010, but sightings were sparse in 2002. Minke whales were distributed throughout the study area in 2002 and 2008, but in 2010 they were concentrated in the outer domain and

  5. NON-CONFORMING FINITE ELEMENTS; MESH GENERATION, ADAPTIVITY AND RELATED ALGEBRAIC MULTIGRID AND DOMAIN DECOMPOSITION METHODS IN MASSIVELY PARALLEL COMPUTING ENVIRONMENT

    SciTech Connect

    Lazarov, R; Pasciak, J; Jones, J

    2002-02-01

    Construction, analysis and numerical testing of efficient solution techniques for solving elliptic PDEs that allow for parallel implementation have been the focus of the research. A number of discretization and solution methods for solving second order elliptic problems that include mortar and penalty approximations and domain decomposition methods for finite elements and finite volumes have been investigated and analyzed. Techniques for parallel domain decomposition algorithms in the framework of PETC and HYPRE have been studied and tested. Hierarchical parallel grid refinement and adaptive solution methods have been implemented and tested on various model problems. A parallel code implementing the mortar method with algebraically constructed multiplier spaces was developed.

  6. JMJ27, an Arabidopsis H3K9 histone demethylase, modulates defense against Pseudomonas syringae and flowering time.

    PubMed

    Dutta, Aditya; Choudhary, Pratibha; Caruana, Julie; Raina, Ramesh

    2017-09-01

    Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time. JMJ27 is a nuclear protein containing a zinc-finger motif and a catalytic JmjC domain with conserved Fe(II) and α-ketoglutarate binding sites, and displays H3K9me1/2 demethylase activity both in vitro and in vivo. JMJ27 is induced in response to virulent Pseudomonas syringae pathogens and is required for resistance against these pathogens. JMJ27 is a negative modulator of WRKY25 (a repressor of defense) and a positive modulator of several pathogenesis-related (PR) proteins. Additionally, loss of JMJ27 function leads to early flowering. JMJ27 negatively modulates the major flowering regulator CONSTANS (CO) and positively modulates FLOWERING LOCUS C (FLC). Taken together, our results indicate that JMJ27 functions as a histone demethylase to modulate both physiological (defense) and developmental (flowering time) processes in Arabidopsis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  7. Multifunctionalities driven by ferroic domains

    SciTech Connect

    Yang, J. C.; Huang, Y. L.; Chu, Y. H.; He, Q.

    2014-08-14

    Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.

  8. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Public domain. 120.11 Section 120.11 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.11 Public domain. (a) Public domain means information which is published and which is generally...

  9. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Public domain. 120.11 Section 120.11 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.11 Public domain. (a) Public domain means information which is published and which is generally...

  10. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Public domain. 120.11 Section 120.11 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.11 Public domain. (a) Public domain means information which is published and which is generally...

  11. Convergence in the Domains of Static Spatial Relations and Events of Putting and Taking: Evidence from Bilingual Speakers of Romansh and German

    ERIC Educational Resources Information Center

    Berthele, Raphael

    2015-01-01

    In this article the way bilinguals handle differing semantic categories in their two languages will be investigated. Drawing on bilingual data from multilingual speakers of Romansh as well as from speakers of (Swiss) German, the tensions that emerge from "conflicting habits" in the two languages are analyzed in the semantic domain of…

  12. Self-Esteem Is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    ERIC Educational Resources Information Center

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions,…

  13. Do Nice Guys Really Finish Last? Exploring the Relations between Ethical Conduct, Motivation and Satisfaction among Undergraduates in the Domains of Academics and Athletics

    ERIC Educational Resources Information Center

    Yukhymenko, Mariya A.

    2012-01-01

    This study explored patterns of the ethical conduct of collegiate students in academic and athletic domains employing social cognitive theory (Bandura, 1986, 1997) using non-experimental, comparative and correlational designs. The study explored response patterns on anonymous surveys between varsity (N = 1151) and non-varsity (N = 227)…

  14. Self-Esteem Is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    ERIC Educational Resources Information Center

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions,…

  15. Do Nice Guys Really Finish Last? Exploring the Relations between Ethical Conduct, Motivation and Satisfaction among Undergraduates in the Domains of Academics and Athletics

    ERIC Educational Resources Information Center

    Yukhymenko, Mariya A.

    2012-01-01

    This study explored patterns of the ethical conduct of collegiate students in academic and athletic domains employing social cognitive theory (Bandura, 1986, 1997) using non-experimental, comparative and correlational designs. The study explored response patterns on anonymous surveys between varsity (N = 1151) and non-varsity (N = 227)…

  16. Convergence in the Domains of Static Spatial Relations and Events of Putting and Taking: Evidence from Bilingual Speakers of Romansh and German

    ERIC Educational Resources Information Center

    Berthele, Raphael

    2015-01-01

    In this article the way bilinguals handle differing semantic categories in their two languages will be investigated. Drawing on bilingual data from multilingual speakers of Romansh as well as from speakers of (Swiss) German, the tensions that emerge from "conflicting habits" in the two languages are analyzed in the semantic domain of…

  17. Structural basis for regulation of the human acetyl-CoA thioesterase 12 and interactions with the steroidogenic acute regulatory protein-related lipid transfer (START) domain.

    PubMed

    Swarbrick, Crystall M D; Roman, Noelia; Cowieson, Nathan; Patterson, Edward I; Nanson, Jeffrey; Siponen, Marina I; Berglund, Helena; Lehtiö, Lari; Forwood, Jade K

    2014-08-29

    Acetyl-CoA plays a fundamental role in cell signaling and metabolic pathways, with its cellular levels tightly controlled through reciprocal regulation of enzymes that mediate its synthesis and catabolism. ACOT12, the primary acetyl-CoA thioesterase in the liver of human, mouse, and rat, is responsible for cleavage of the thioester bond within acetyl-CoA, producing acetate and coenzyme A for a range of cellular processes. The enzyme is regulated by ADP and ATP, which is believed to be mediated through the ligand-induced oligomerization of the thioesterase domains, whereby ATP induces active dimers and tetramers, whereas apo- and ADP-bound ACOT12 are monomeric and inactive. Here, using a range of structural and biophysical techniques, it is demonstrated that ACOT12 is a trimer rather than a tetramer and that neither ADP nor ATP exert their regulatory effects by altering the oligomeric status of the enzyme. Rather, the binding site and mechanism of ADP regulation have been determined to occur through two novel regulatory regions, one involving a large loop that links the thioesterase domains (Phe(154)-Thr(178)), defined here as RegLoop1, and a second region involving the C terminus of thioesterase domain 2 (Gln(304)-Gly(326)), designated RegLoop2. Mutagenesis confirmed that Arg(312) and Arg(313) are crucial for this mode of regulation, and novel interactions with the START domain are presented together with insights into domain swapping within eukaryotic thioesterases for substrate recognition. In summary, these experiments provide the first structural insights into the regulation of this enzyme family, revealing an alternate hypothesis likely to be conserved throughout evolution. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. AIDA: ab initio domain assembly server.

    PubMed

    Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

    2014-07-01

    AIDA: ab initio domain assembly server, available at http://ffas.burnham.org/AIDA/ is a tool that can identify domains in multi-domain proteins and then predict their 3D structures and relative spatial arrangements. The server is free and open to all users, and there is an option for a user to provide an e-mail to get the link to result page. Domains are evolutionary conserved and often functionally independent units in proteins. Most proteins, especially eukaryotic ones, consist of multiple domains while at the same time, most experimentally determined protein structures contain only one or two domains. As a result, often structures of individual domains in multi-domain proteins can be accurately predicted, but the mutual arrangement of different domains remains unknown. To address this issue we have developed AIDA program, which combines steps of identifying individual domains, predicting (separately) their structures and assembling them into multiple domain complexes using an ab initio folding potential to describe domain-domain interactions. AIDA server not only supports the assembly of a large number of continuous domains, but also allows the assembly of domains inserted into other domains. Users can also provide distance restraints to guide the AIDA energy minimization. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Magnetic bubble domain memories

    NASA Technical Reports Server (NTRS)

    Ypma, J. E.

    1974-01-01

    Some attractive features of Bubble Domain Memory and its relation to existing technologies are discussed. Two promising applications are block access mass memory and tape recorder replacement. The required chip capabilities for these uses are listed, and the specifications for a block access mass memory designed to fit between core and HPT disk are presented. A feasibility model for a tape recorder replacement is introduced.

  20. Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis

    PubMed Central

    Daskalov, Asen; Habenstein, Birgit; Sabaté, Raimon; Berbon, Mélanie; Martinez, Denis; Chaignepain, Stéphane; Coulary-Salin, Bénédicte; Hofmann, Kay; Loquet, Antoine; Saupe, Sven J.

    2016-01-01

    Recent findings have revealed the role of prion-like mechanisms in the control of host defense and programmed cell death cascades. In fungi, HET-S, a cell death-inducing protein containing a HeLo pore-forming domain, is activated through amyloid templating by a Nod-like receptor (NLR). Here we characterize the HELLP protein behaving analogously to HET-S and bearing a new type of N-terminal cell death-inducing domain termed HeLo-like (HELL) and a C-terminal regulatory amyloid motif known as PP. The gene encoding HELLP is part of a three-gene cluster also encoding a lipase (SBP) and a Nod-like receptor, both of which display the PP motif. The PP motif is similar to the RHIM amyloid motif directing formation of the RIP1/RIP3 necrosome in humans. The C-terminal region of HELLP, HELLP(215-278), encompassing the motif, allows prion propagation and assembles into amyloid fibrils, as demonstrated by X-ray diffraction and FTIR analyses. Solid-state NMR studies reveal a well-ordered local structure of the amyloid core residues and a primary sequence that is almost entirely arranged in a rigid conformation, and confirm a β-sheet structure in an assigned stretch of three amino acids. HELLP is activated by amyloid templating and displays membrane-targeting and cell death-inducing activity. HELLP targets the SBP lipase to the membrane, suggesting a synergy between HELLP and SBP in membrane dismantling. Remarkably, the HeLo-like domain of HELLP is homologous to the pore-forming domain of MLKL, the cell death-execution protein in necroptosis, revealing a transkingdom evolutionary relationship between amyloid-controlled fungal programmed cell death and mammalian necroptosis. PMID:26903619

  1. The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 and participates in adhesion-related functions.

    PubMed

    Dougherty, Gerard W; Chopp, Treasa; Qi, Sheng-Mei; Cutler, Mary Lou

    2005-05-15

    Rsu-1 is a highly conserved leucine rich repeat (LRR) protein that is expressed ubiquitously in mammalian cells. Rsu-1 was identified based on its ability to inhibit transformation by Ras, and previous studies demonstrated that ectopic expression of Rsu-1 inhibited anchorage-independent growth of Ras-transformed cells and human tumor cell lines. Using GAL4-based yeast two-hybrid screening, the LIM domain protein, PINCH1, was identified as the binding partner of Rsu-1. PINCH1 is an adaptor protein that localizes to focal adhesions and it has been implicated in the regulation of adhesion functions. Subdomain mapping in yeast revealed that Rsu-1 binds to the LIM 5 domain of PINCH1, a region not previously identified as a specific binding domain for any other protein. Additional testing demonstrated that PINCH2, which is highly homologous to PINCH1, except in the LIM 5 domain, does not interact with Rsu-1. Glutathione transferase fusion protein binding studies determined that the LRR region of Rsu-1 interacts with PINCH1. Transient expression studies using epitope-tagged Rsu-1 and PINCH1 revealed that Rsu-1 co-immunoprecipitated with PINCH1 and colocalized with vinculin at sites of focal adhesions in mammalian cells. In addition, endogenous P33 Rsu-1 from 293T cells co-immunoprecipitated with transiently expressed myc-tagged PINCH1. Furthermore, RNAi-induced reduction in Rsu-1 RNA and protein inhibited cell attachment, and while previous studies demonstrated that ectopic expression of Rsu-1 inhibited Jun kinase activation, the depletion of Rsu-1 resulted in activation of Jun and p38 stress kinases. These studies demonstrate that Rsu-1 interacts with PINCH1 in mammalian cells and functions, in part, by altering cell adhesion.

  2. Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis.

    PubMed

    Daskalov, Asen; Habenstein, Birgit; Sabaté, Raimon; Berbon, Mélanie; Martinez, Denis; Chaignepain, Stéphane; Coulary-Salin, Bénédicte; Hofmann, Kay; Loquet, Antoine; Saupe, Sven J

    2016-03-08

    Recent findings have revealed the role of prion-like mechanisms in the control of host defense and programmed cell death cascades. In fungi, HET-S, a cell death-inducing protein containing a HeLo pore-forming domain, is activated through amyloid templating by a Nod-like receptor (NLR). Here we characterize the HELLP protein behaving analogously to HET-S and bearing a new type of N-terminal cell death-inducing domain termed HeLo-like (HELL) and a C-terminal regulatory amyloid motif known as PP. The gene encoding HELLP is part of a three-gene cluster also encoding a lipase (SBP) and a Nod-like receptor, both of which display the PP motif. The PP motif is similar to the RHIM amyloid motif directing formation of the RIP1/RIP3 necrosome in humans. The C-terminal region of HELLP, HELLP(215-278), encompassing the motif, allows prion propagation and assembles into amyloid fibrils, as demonstrated by X-ray diffraction and FTIR analyses. Solid-state NMR studies reveal a well-ordered local structure of the amyloid core residues and a primary sequence that is almost entirely arranged in a rigid conformation, and confirm a β-sheet structure in an assigned stretch of three amino acids. HELLP is activated by amyloid templating and displays membrane-targeting and cell death-inducing activity. HELLP targets the SBP lipase to the membrane, suggesting a synergy between HELLP and SBP in membrane dismantling. Remarkably, the HeLo-like domain of HELLP is homologous to the pore-forming domain of MLKL, the cell death-execution protein in necroptosis, revealing a transkingdom evolutionary relationship between amyloid-controlled fungal programmed cell death and mammalian necroptosis.

  3. The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 and participates in adhesion-related functions

    SciTech Connect

    Dougherty, Gerard W.; Chopp, Treasa; Qi Shengmei; Cutler, Mary Lou . E-mail: mcutler@usuhs.mil

    2005-05-15

    Rsu-1 is a highly conserved leucine rich repeat (LRR) protein that is expressed ubiquitously in mammalian cells. Rsu-1 was identified based on its ability to inhibit transformation by Ras, and previous studies demonstrated that ectopic expression of Rsu-1 inhibited anchorage-independent growth of Ras-transformed cells and human tumor cell lines. Using GAL4-based yeast two-hybrid screening, the LIM domain protein, PINCH1, was identified as the binding partner of Rsu-1. PINCH1 is an adaptor protein that localizes to focal adhesions and it has been implicated in the regulation of adhesion functions. Subdomain mapping in yeast revealed that Rsu-1 binds to the LIM 5 domain of PINCH1, a region not previously identified as a specific binding domain for any other protein. Additional testing demonstrated that PINCH2, which is highly homologous to PINCH1, except in the LIM 5 domain, does not interact with Rsu-1. Glutathione transferase fusion protein binding studies determined that the LRR region of Rsu-1 interacts with PINCH1. Transient expression studies using epitope-tagged Rsu-1 and PINCH1 revealed that Rsu-1 co-immunoprecipitated with PINCH1 and colocalized with vinculin at sites of focal adhesions in mammalian cells. In addition, endogenous P33 Rsu-1 from 293T cells co-immunoprecipitated with transiently expressed myc-tagged PINCH1. Furthermore, RNAi-induced reduction in Rsu-1 RNA and protein inhibited cell attachment, and while previous studies demonstrated that ectopic expression of Rsu-1 inhibited Jun kinase activation, the depletion of Rsu-1 resulted in activation of Jun and p38 stress kinases. These studies demonstrate that Rsu-1 interacts with PINCH1 in mammalian cells and functions, in part, by altering cell adhesion.

  4. Cross-sectional and longitudinal correlations between disease progression and different health-related quality of life domains in persons with amyotrophic lateral sclerosis.

    PubMed

    De Groot, Imelda J M; Post, Marcel W M; van Heuveln, Tineke; Van den Berg, Leonard H; Lindeman, Eline

    2007-12-01

    In ALS it would be expected that quality of life (QoL) would be decreased. However, studies to date show diverging results. Our study focuses on how ALS affects QoL on the different domains of the SF-36 cross-sectionally and during progression. The method used was a prospective cohort study, with assessments at baseline, at six months, and at one year. Patients were included with possible, probable or definite ALS according to the revised El Escorial criteria and were between 30 and 70 years of age. ALS functional rating scale was used to establish disease status, SF-36 as QoL scale. At baseline 73 completed ALSFRS forms were available and 62 completed SF-36 forms. The ALSFRS showed disease progression. SF-36 scores showed lower QoL scores of persons with ALS compared to the general population both in cross-sectional and longitudinal aspects in the domains of Physical Functioning, Role Physical, and Social Functioning, but similar compared with the general population in the Mental Health and Role Emotional domains. This study shows deteriorating physical health but stable mental health, thereby illustrating the diverging correlations between ALS severity and HRQoL. The diverging pattern of physical and mental health suggests a frame-shift in the experience of HRQoL.

  5. A new look at the ylidic bond in phosphorus ylides and related compounds: energy decomposition analysis combined with a domain-averaged fermi hole analysis.

    PubMed

    Calhorda, Maria José; Krapp, Andreas; Frenking, Gernot

    2007-04-19

    Geometries and bond dissociation energies of the ylide compounds H2CPH3, H2CPMe3, H2CPF3, (BH2)2CPH3, H2CNH3, H2CAsH3, H2SiPH3, and (BH2)2SiPH3 have been calculated using ab initio (MP2, CBS-QB3) and DFT (B3LYP, BP86) methods. The nature of the ylidic bond R2E1-E2X3 was investigated with an energy decomposition analysis and with the domain-averaged Fermi hole (DAFH) analysis. The results of the latter method indicate that the peculiar features of the ylidic bond can be understood in terms of donor-acceptor interactions between closed-shell R2E1 and E2X3 fragments. The DAFH analysis clearly shows that there are two bonding contributions to the ylidic bond. The strength of the donor and acceptor contributions to the attractive orbital interactions can be estimated from the energy decomposition analysis (EDA) calculations, which give also the contributions of the electrostatic attraction and the Pauli repulsion of the chemical bonding. The EDA and DAFH results clearly show that the orbital interactions take place through the singlet ground state of the R2E1 fragment where the donor orbital of E1 yields pi-type back-donation while the E2X3 lone-pair orbital yields sigma-type bonding. Both bonds are polarized toward E2X3 when E2 = P, while the sigma-type bonding remains more polarized at E2X3 when E2 = N, As. This shows that the phosphorus ylides exhibit a particular bonding situation which is clearly different from that of the nitrogen and arsenic homologues. With ylides built around a P-C linkage, the pi-acceptor strength of phosphorus and the sigma-acceptor strength at carbon contribute to a double bond which is enhanced by electrostatic contributions. The strength of the sigma and pi components and the electrostatic attraction are then fine-tuned by the substituents at C and P, which yields a peculiar type of carbon-phosphorus bonding. The EDA data reveal that the relative strength of the ylidic bond may be determined not only by the R2E1 --> E2X3 pi back

  6. Domain wall orientation and domain shape in KTiOPO4 crystals

    NASA Astrophysics Data System (ADS)

    Shur, V. Ya.; Vaskina, E. M.; Pelegova, E. V.; Chuvakova, M. A.; Akhmatkhanov, A. R.; Kizko, O. V.; Ivanov, M.; Kholkin, A. L.

    2016-09-01

    Domain shape evolution and domain wall motion have been studied in KTiOPO4 (KTP) ferroelectric single crystals using complementary experimental methods. The in situ visualization of domain kinetics has allowed revealing: (1) qualitative change of the domain shape, (2) dependence of the domain wall velocity on its orientation, (3) jump-like domain wall motion caused by domain merging, (4) effect of domain shape stability. The model of domain wall motion driven by generation of elementary steps (kink-pair nucleation) and subsequent kink motion is presented. The decrease in the relative velocity of the approaching parallel domain walls is attributed to electrostatic interaction. The effect of polarization reversal induced by chemical etching is observed. The obtained results are important for the development of domain engineering in the crystals of KTP family.

  7. CDD: a conserved domain database for interactive domain family analysis.

    PubMed

    Marchler-Bauer, Aron; Anderson, John B; Derbyshire, Myra K; DeWeese-Scott, Carol; Gonzales, Noreen R; Gwadz, Marc; Hao, Luning; He, Siqian; Hurwitz, David I; Jackson, John D; Ke, Zhaoxi; Krylov, Dmitri; Lanczycki, Christopher J; Liebert, Cynthia A; Liu, Chunlei; Lu, Fu; Lu, Shennan; Marchler, Gabriele H; Mullokandov, Mikhail; Song, James S; Thanki, Narmada; Yamashita, Roxanne A; Yin, Jodie J; Zhang, Dachuan; Bryant, Stephen H

    2007-01-01

    The conserved domain database (CDD) is part of NCBI's Entrez database system and serves as a primary resource for the annotation of conserved domain footprints on protein sequences in Entrez. Entrez's global query interface can be accessed at http://www.ncbi.nlm.nih.gov/Entrez and will search CDD and many other databases. Domain annotation for proteins in Entrez has been pre-computed and is readily available in the form of 'Conserved Domain' links. Novel protein sequences can be scanned against CDD using the CD-Search service; this service searches databases of CDD-derived profile models with protein sequence queries using BLAST heuristics, at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. Protein query sequences submitted to NCBI's protein BLAST search service are scanned for conserved domain signatures by default. The CDD collection contains models imported from Pfam, SMART and COG, as well as domain models curated at NCBI. NCBI curated models are organized into hierarchies of domains related by common descent. Here we report on the status of the curation effort and present a novel helper application, CDTree, which enables users of the CDD resource to examine curated hierarchies. More importantly, CDD and CDTree used in concert, serve as a powerful tool in protein classification, as they allow users to analyze protein sequences in the context of domain family hierarchies.

  8. Diversity in protein domain superfamilies

    PubMed Central

    Das, Sayoni; Dawson, Natalie L; Orengo, Christine A

    2015-01-01

    Whilst ∼93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain classification resource, the remainder are much more diverse. In this review, we consider how domains in some of the most ubiquitous and promiscuous superfamilies have evolved, in particular the plasticity in their functional sites and surfaces which expands the repertoire of molecules they interact with and actions performed on them. To what extent can we identify a core function for these superfamilies which would allow us to develop a ‘domain grammar of function’ whereby a protein's biological role can be proposed from its constituent domains? Clearly the first step is to understand the extent to which these components vary and how changes in their molecular make-up modifies function. PMID:26451979

  9. Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases.

    PubMed

    Sharma, Prerna; Kaila, Pallavi; Guptasarma, Purnananda

    2016-12-01

    Diverse unrelated enzymes that adopt the beta/alpha (or TIM) barrel topology display similar arrangements of beta/alpha units placed in a radial eight-fold symmetry around the barrel's axis. The TIM barrel was originally thought to be a single structural domain; however, it is now thought that TIM barrels arose from duplication and fusion of smaller half-barrels consisting of four beta/alpha units. We describe here the design, expression and purification, as well as characterization of folding, activity and stability, of chimeras of two TIM barrel glycosyl hydrolases, made by fusing different half-barrel domains derived from an endoglucanase from Clostridium cellulolyticum, CelCCA and a beta-glucosidase from Pyrococcus furiosus, CelB. We show that after refolding following purification from inclusion bodies, the two half-barrel fusion chimeras (CelCCACelB and CelBCelCCA) display catalytic activity although they assemble into large soluble oligomeric aggregated species containing chains of mixed beta and alpha structure. CelBCelCCA displays hyperthermophile-like structural stability as well as significant stability to chemical denaturation (Cm of 2.6 m guanidinium hydrochloride), whereas CelCCACelB displays mesophile-like stability (Tm of ~ 71 °C). The endoglucanase activities of both chimeras are an order of magnitude lower than those of CelB or CelCCA, whereas the beta-glucosidase activity of CelBCelCCA is about two orders of magnitude lower than that of CelB. The chimera CelCCACelB shows no beta-glucosidase activity. Our results demonstrate that half-barrel domains from unrelated sources can fold, assemble and function, with scope for improvement.

  10. The catalytic domains of Clostridium sordellii lethal toxin and related large clostridial glucosylating toxins specifically recognize the negatively charged phospholipids phosphatidylserine and phosphatidic acid.

    PubMed

    Varela Chavez, Carolina; Hoos, Sylviane; Haustant, Georges Michel; Chenal, Alexandre; England, Patrick; Blondel, Arnaud; Pauillac, Serge; Lacy, D Borden; Popoff, Michel Robert

    2015-10-01

    Clostridium sordellii lethal toxin (TcsL) is a potent virulence factor belonging to the large clostridial glucosylating toxin family. TcsL enters target cells via receptor-mediated endocytosis and delivers the N-terminal catalytic domain (TcsL-cat) into the cytosol upon an autoproteolytic process. TcsL-cat inactivates small GTPases including Rac and Ras by glucosylation with uridine-diphosphate (UDP)-glucose as cofactor leading to drastic changes in cytoskeleton and cell viability. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)-containing membranes and to increase the glucosylation of Rac anchored to lipid membrane. We here report binding affinity measurements of TcsL-cat for brain PS-containing membranes by surface plasmon resonance and enzyme-linked immunosorbent assay (ELISA). In addition, TcsL-cat bound to phosphatidic acid (PA) and, to a lesser extent, to other anionic lipids, but not to neutral lipids, sphingolipids or sterol. We further show that the lipid unsaturation status influenced TcsL-cat binding to phospholipids, PS with unsaturated acyl chains and PA with saturated acyl chains being the preferred bindingsubstrates. Phospholipid binding site is localized at the N-terminal four helical bundle structure (1-93 domain). However, TcsL-1-93 bound to a broad range of substrates, whereas TcsL-cat, which is the active domain physiologically delivered into the cytosol, selectively bound to PS and PA. Similar findings were observed with the other large clostridial glucosylating toxins from C. difficile, C. novyi and C. perfringens. © 2015 John Wiley & Sons Ltd.

  11. Duplication of the V3 domain in hepatitis C virus (1b) NS5A protein: Clonal analysis and physicochemical properties related to hepatocellular carcinoma occurrence.

    PubMed

    Petsaris, Odile; Vallet, Sophie; Le Guillou-Guillemette, Hélène; Veillon, Pascal; Gouriou, Stéphanie; Barbier, Georges; Nousbaum, Jean-Baptiste; Saliou, Philippe; NKontchou, Gisèle; Trinchet, Jean-Claude; Lunel-Fabiani, Francoise; Payan, Christopher

    2016-01-01

    Hepatitis C virus non-structural protein 5A is known to play a role in development of hepatocellular carcinoma (HCC) via interactions with host cell pathways. Hepatitis C virus genotype 1b strains presenting a wide insertion of 31 amino acids in the non-structural protein 5A V3 domain (V3 DI) were studied to determine whether this V3-like additional domain (V3 DII) was associated with HCC occurrence. Seventy-four patients' sera were screened for V3 DII presence regarding clinical status. Three strains with duplicated V3 were detected among patients with progression to HCC (n=28), two strains among patients with liver cirrhosis (Ci, n=27) and none among patients with chronic hepatitis (Chr, n=19). Phylogenetic trees built from V3 DI and V3 DII sequences indicated that the latter clustered separately. In between-group clonal analysis, V3 DII sequences from the HCC group were found to be more distant from HCV-J than V3 DI sequences (p<0.0001). Between-group comparisons showed significant differences in genetic distances from HCV-J, in HCC V3 DI and HCC V3 DII compared to Ci V3 DI and Ci V3 DII sequences (p<0.0001). HCC V3 DII domain and its junction with V3 DI exhibited higher Shannon entropy values and enrichment in disorder-promoting residues. Taken together, our results suggest that V3 DII evolution may differ in strains associated with HCC occurrence. The presence of an intrinsically "disordered" V3 duplicate may alter the NS5A protein network. Further investigations are necessary to elucidate the potential impact of V3 duplication in the context of carcinogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Hydrophobic Compounds Reshape Membrane Domains

    PubMed Central

    Barnoud, Jonathan; Rossi, Giulia; Marrink, Siewert J.; Monticelli, Luca

    2014-01-01

    Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, which play an essential role in cellular processes such as signal transduction and protein trafficking. In vivo, perturbations of membrane domains (e.g., by drugs or lipophilic compounds) have major effects on the activity of raft-associated proteins and on signaling pathways, but they are difficult to characterize because of the small size of the domains, typically below optical resolution. Model membranes, instead, can show macroscopic phase separation between liquid-ordered and liquid-disordered domains, and they are often used to investigate the driving forces of membrane lateral organization. Studies in model membranes have shown that some lipophilic compounds perturb membrane domains, but it is not clear which chemical and physical properties determine domain perturbation. The mechanisms of domain stabilization and destabilization are also unknown. Here we describe the effect of six simple hydrophobic compounds on the lateral organization of phase-separated model membranes consisting of saturated and unsaturated phospholipids and cholesterol. Using molecular simulations, we identify two groups of molecules with distinct behavior: aliphatic compounds promote lipid mixing by distributing at the interface between liquid-ordered and liquid-disordered domains; aromatic compounds, instead, stabilize phase separation by partitioning into liquid-disordered domains and excluding cholesterol from the disordered domains. We predict that relatively small concentrations of hydrophobic species can have a broad impact on domain stability in model systems, which suggests possible mechanisms of action for hydrophobic compounds in vivo. PMID:25299598

  13. Supporting multiple domains in a single reuse repository

    NASA Technical Reports Server (NTRS)

    Eichmann, David A.

    1992-01-01

    Domain analysis typically results in the construction of a domain-specific repository. Such a repository imposes artificial boundaries on the sharing of similar assets between related domains. A lattice-based approach to repository modeling can preserve a reuser's domain specific view of the repository, while avoiding replication of commonly used assets and supporting a more general perspective on domain interrelationships.

  14. Supporting multiple domains in a single reuse repository

    NASA Technical Reports Server (NTRS)

    Eichmann, David

    1992-01-01

    Domain analysis typically results in the construction of a domain-specific repository. Such a repository imposes artificial boundaries on the sharing of similar assets between related domains. A lattice-based approach to repository modeling can preserve a reuser's domain specific view of the repository, while avoiding replication of commonly used assets and supporting a more general perspective on domain interrelationships.

  15. Teaching-Learning in the Affective Domain

    ERIC Educational Resources Information Center

    Holt, Brett J.; Hannon, James C.

    2006-01-01

    Affect is an important domain in which children learn. The affective domain of learning in physical education focuses on feelings, values, social behavior, and attitudes as they relate to human movement. Learning in the affective domain in physical education means that students learn such concepts as sportsmanship, "fair play," respect for others,…

  16. Housing satisfaction among chronically homeless adults: identification of its major domains, changes over time, and relation to subjective well-being and functional outcomes.

    PubMed

    Tsai, Jack; Mares, Alvin S; Rosenheck, Robert A

    2012-06-01

    There is limited consensus on the critical domains of housing satisfaction among chronically homeless adults and little information on changes in housing satisfaction over time or whether housing satisfaction at initial entry into housing is correlated with subsequent subjective well-being or other outcomes. The current study tracked housing satisfaction over a 2-year period in a multi-site supported housing initiative and examined the predictive value of clients' housing satisfaction when they were first housed on various subjective and functional outcomes. A total of 756 participants from 11 sites were enrolled in the study. Six domains of housing satisfaction were identified: good environment, control and consumer choice, physical quality, geographic proximity to desirable resources, positive case manager contact, and frequency of landlord interaction. Over 2 years, there were slight declines in housing satisfaction on physical quality of housing and satisfaction with case manager contact, and an increase in satisfaction with landlord interaction. Consistent with some previous research, housing satisfaction was not predictive of housing tenure, clinical outcomes, or duration of program participation. While becoming housed is a significant gain for chronically homeless people, their satisfaction with housing did not predict functional outcomes.

  17. Definition, expression, and characterization of a protein domain in the N-terminus of pregnancy-associated plasma protein-A distantly related to the family of laminin G-like modules.

    PubMed

    Boldt, Henning B; Glerup, Simon; Overgaard, Michael T; Sottrup-Jensen, Lars; Oxvig, Claus

    2006-08-01

    Although pregnancy-associated plasma protein-A (PAPP-A), a modulator of insulin-like growth factor (IGF) activity through its cleavage of IGF-binding protein (IGFBP)-4 and -5, has been known for more than two decades, knowledge about its domain architecture is still incomplete. Using position-specific iterative BLAST, we have identified distant relatives of the PAPP-A N-terminal sequence stretch of 250 residues. We present evidence that a protein domain with weak similarity to known laminin G-like (LG) modules is contained within this region, and we propose that PAPP-A and PAPP-A2 are new and unique members in the group of LG proteins as the pappalysins represent the first examples where LG modules are associated with proteinases. Fourteen beta-strands characteristic for the LG structure were tentatively located within the PAPP-A LG (PA-LG) module using secondary structure prediction and sequence alignment. Upon mammalian expression of PAPP-A truncation mutants, we defined domain boundaries showing that PA-LG is an autonomously folding unit, which spans the first 243 residues. We were unable to express PAPP-A variants which lack the PA-LG module, suggesting a possible role in stabilization of the proteolytic domain. To obtain larger amounts of protein for functional and structural analysis, the defined PA-LG domain was expressed in bacteria and folded in vitro. In addition, the availability of recombinant PA-LG module may potentially improve diagnostic assays based on the measurement of PAPP-A antigen, and also facilitate the study of PAPP-A in animal model systems.

  18. Generic domain models in software engineering

    NASA Technical Reports Server (NTRS)

    Maiden, Neil

    1992-01-01

    This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

  19. Intramuscular injection of mechano growth factor E domain peptide regulated expression of memory-related sod, miR-134 and miR-125b-3p in rat hippocampus under simulated weightlessness.

    PubMed

    Chen, Hailong; Lv, Ke; Dai, Zhongquan; Ji, Guohua; Wang, Tingmei; Wang, Yanli; Zhang, Yongliang; Kan, Guanghan; Li, Yinghui; Qu, Lina

    2016-12-01

    To investigate the expression of memory-related antioxidant genes and miRNAs under simulated weightlessness and the regulation of mechano growth factor (MGF) E domain, the peptide preventing nerve damage. Igf-iea and mgf mRNA levels, expression of antioxidant genes sod1 and sod2 and levels of miR-134 and miR-125b-3p increased in rat hippocampus after 14 days tail suspension to simulate weightlessness which was inhibited with intramuscular injection of E domain peptide. Therefore, administration of MGF E domain peptide could reverse increased expressions of memory-related igf-iea, mgf, sod1, sod2, miR-134 and miR-125b-3p in rat hippocampus under simulated weightlessness. MGF may regulate the redox state and miRNA-targeted NR-CREB signaling, and intramuscular injection may be the alternative administration because of its safety, convenience and ability to pass through the blood brain barrier.

  20. The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism

    PubMed Central

    Calderon-Dominguez, Maria; Gil, Gregorio; Medina, Miguel Angel; Pandak, William M.; Rodríguez-Agudo, Daniel

    2014-01-01

    Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracelular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis. PMID:24440759

  1. Inherent chaperone-like activity of aspartic proteases reveals a distant evolutionary relation to double-ψ barrel domains of AAA-ATPases

    PubMed Central

    Hulko, Michael; Lupas, Andrei N.; Martin, Jörg

    2007-01-01

    Chaperones and proteases share the ability to interact with unfolded proteins. Here we show that enzymatically inactive forms of the aspartic proteases HIV-1 protease and pepsin have inherent chaperone-like activity and can prevent the aggregation of denatured substrate proteins. In contrast to proteolysis, which requires dimeric enzymes, chaperone-like activity could be observed also with monomeric domains. The involvement of the active site cleft in the chaperone-like function was demonstrated by the inhibitory effect of peptide substrate inhibitors. The high structural similarity between aspartic proteases and the N-terminal double-ψ barrels of Cdc48-like proteins, which are involved in the unfolding and dissociation of proteins, suggests that they share a common ancestor. The latent chaperone-like activity in aspartic proteases can be seen as a relic that has further evolved to serve substrate binding in the context of proteolytic activity. PMID:17384229

  2. Mid-infrared pump-related electric-field domains in GaAs/(Al,Ga)As quantum-cascade structures for terahertz lasing without population inversion

    SciTech Connect

    Giehler, M.; Wienold, M.; Schrottke, L.; Hey, R.; Grahn, H. T.; Pavlov, S. G.; Huebers, H.-W.; Winnerl, S.; Schneider, H.

    2011-11-15

    We investigate the effect of mid-infrared (MIR) pumping on the transport properties of GaAs/(Al,Ga)As terahertz (THz) quantum lasers (TQLs), which rely on quantum coherence effects of intersubband transitions. Aiming at THz lasing at elevated temperatures, we extend the concept of THz gain with and without population inversion of a single, MIR-pumped, electrically driven THz stage proposed by Waldmueller et al.[Phys. Rev. Lett. 99, 117401 (2007)] to an entire TQL. However, experiments using a CO{sub 2} as well as a free-electron laser and numerical simulations show that this resonant MIR pumping causes a negative differential conductivity (NDC) in addition to the NDC caused by sequential tunneling. Lasing of these TQLs is prevented by the formation of electric-field domains below the resonance field strength for gain of each single THz stage.

  3. Identification of hormone-interacting amino acid residues within the steroid-binding domain of the glucocorticoid receptor in relation to other steroid hormone receptors

    SciTech Connect

    Carlstedt-Duke, J.; Stroemstedt, P.E.; Persson, B.; Cederlund, E.; Gustafsson, J.A.; Joernvall, H.

    1988-05-15

    Purified rat liver glucocorticoid receptor was covalently charged with (/sup 3/H)glucocorticoid by photoaffinity labeling (UV irradiation of (/sup 3/H)triamcinolone acetonide-glucocorticoid receptor) or affinity labeling (incubation with (/sup 3/H)dexamethasone mesylate). After labeling, separate samples of the denatured receptor were cleaved with trypsin (directly or after prior succinylation), chymotrypsin, and cyanogen bromide. Labeled residues in the peptides obtained were identified by radiosequence analysis. The peaks of radioactivity corresponded to Met-622 and Cys-754 after photoaffinity labeling with (/sup 3/H)triamcinolone acetonide and Cys-656 after affinity labeling with (/sup 3/H)dexamethasone mesylate. The labeled residues are all positioned within hydrophobic segments of the steroid-binding domain. The patterns of hydropathy and secondary structure for the glucocorticoid receptor are highly similar to those for the progestin receptor and similar but less so to those for the estrogen receptor and to those for c-erb A.

  4. Sensing the Coherence of Biology in Contrast to Psychology: Young Children’s Use of Causal Relations to Distinguish Two Foundational Domains

    PubMed Central

    Erickson, Jane E.; Keil, Frank C.; Lockhart, Kristi L.

    2011-01-01

    To what extent do children understand that biological processes fall into 1 coherent domain unified by distinct causal principles? In Experiments 1 and 2 (N = 125) kindergartners are given triads of biological and psychological processes and asked to identify which 2 members of the triad belong together. Results show that 5-year-olds correctly cluster biological processes and separate them from psychological ones. Experiments 3 and 4 (N = 64) examine whether or not children make this distinction because they understand that biological and psychological processes operate according to fundamentally different causal mechanisms. The results suggest that 5-year-olds do possess this understanding, and furthermore, they have intuitions about the nature of these different mechanisms. PMID:20331675

  5. The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism.

    PubMed

    Calderon-Dominguez, Maria; Gil, Gregorio; Medina, Miguel Angel; Pandak, William M; Rodríguez-Agudo, Daniel

    2014-04-01

    Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracellular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis.

  6. Mid-infrared pump-related electric-field domains in GaAs/(Al,Ga)As quantum-cascade structures for terahertz lasing without population inversion

    NASA Astrophysics Data System (ADS)

    Giehler, M.; Wienold, M.; Schrottke, L.; Hey, R.; Grahn, H. T.; Pavlov, S. G.; Hübers, H.-W.; Winnerl, S.; Schneider, H.

    2011-11-01

    We investigate the effect of mid-infrared (MIR) pumping on the transport properties of GaAs/(Al,Ga)As terahertz (THz) quantum lasers (TQLs), which rely on quantum coherence effects of intersubband transitions. Aiming at THz lasing at elevated temperatures, we extend the concept of THz gain with and without population inversion of a single, MIR-pumped, electrically driven THz stage proposed by Waldmueller et al. [Phys. Rev. Lett. 99, 117401 (2007)] to an entire TQL. However, experiments using a CO2 as well as a free-electron laser and numerical simulations show that this resonant MIR pumping causes a negative differential conductivity (NDC) in addition to the NDC caused by sequential tunneling. Lasing of these TQLs is prevented by the formation of electric-field domains below the resonance field strength for gain of each single THz stage.

  7. Health-Related Quality of Life Domains and Household Preparedness for Public Health Emergencies: Behavioral Risk Factor Surveillance System, 2006-2010

    PubMed Central

    Strine, Tara W.; Neff, Linda J.; Crawford, Sara

    2015-01-01

    Background This study examined the association between self-reported levels of household disaster preparedness and a range of physical and mental health quality of life outcomes. Methods Data collected from 14 states participating in a large state-based telephone survey were analyzed (n 5 104 654). Household disaster-preparedness items included having a 3-day supply of food, water, and prescription medications; a working battery-powered radio and flashlight; an evacuation plan; and a willingness to evacuate when instructed to do so. Quality-of-life items were categorized into 2 domains: physical health (general health, unhealthy physical days, and activity-limited days) and mental health (unhealthy mental days, social and emotional support, and life satisfaction). Results Persons with self-reported impaired mental health were generally less likely to report being prepared for a disaster than those who did not report impairment in each domain. Persons with low life satisfaction were among the least likely to be prepared, followed by those with inadequate social and emotional support, and then by those with frequent mental distress. Persons reporting physical impairments also reported deficits in many of the preparedness items. However, after adjusting for sociodemographic characteristics, some of the associations were attenuated and no longer significant Conclusion Persons reporting impaired quality of life are vulnerable to increased mental and physical distress during a disaster, and their vulnerability is compounded if they are ill-prepared. Therefore, persons reporting impaired quality of life should be included in the list of vulnerable populations that need disaster preparedness and response outreach. PMID:24618171

  8. Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior♦

    PubMed Central

    Gee, Christine E.; Peterlik, Daniel; Neuhäuser, Christoph; Bouhelal, Rochdi; Kaupmann, Klemens; Laue, Grit; Uschold-Schmidt, Nicole; Feuerbach, Dominik; Zimmermann, Kaspar; Ofner, Silvio; Cryan, John F.; van der Putten, Herman; Fendt, Markus; Vranesic, Ivo; Glatthar, Ralf; Flor, Peter J.

    2014-01-01

    The metabotropic glutamate receptor subtype 7 (mGlu7) is an important presynaptic regulator of neurotransmission in the mammalian CNS. mGlu7 function has been linked to autism, drug abuse, anxiety, and depression. Despite this, it has been difficult to develop specific blockers of native mGlu7 signaling in relevant brain areas such as amygdala and limbic cortex. Here, we present the mGlu7-selective antagonist 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one (XAP044), which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. There was no effect of XAP044 on LTP of mGlu7-deficient mice, indicating that this pharmacological effect is mGlu7-dependent. Unexpectedly and in contrast to all previous mGlu7-selective drugs, XAP044 does not act via the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding. This was shown by chimeric receptor studies in recombinant cell line assays. XAP044 demonstrates good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy in rodent behavioral paradigms. XAP044 reduces freezing during acquisition of Pavlovian fear and reduces innate anxiety, which is consistent with the phenotypes of mGlu7-deficient mice, the results of mGlu7 siRNA knockdown studies, and the inhibition of amygdala LTP by XAP044. Thus, we present an mGlu7 antagonist with a novel molecular mode of pharmacological action, providing significant application potential in psychiatry. Modeling the selective interaction between XAP044 and mGlu7's Venus flytrap domain, whose three-dimensional structure is already known, will facilitate future drug development supported by computer-assisted drug design. PMID:24596089

  9. Blocking metabotropic glutamate receptor subtype 7 (mGlu7) via the Venus flytrap domain (VFTD) inhibits amygdala plasticity, stress, and anxiety-related behavior.

    PubMed

    Gee, Christine E; Peterlik, Daniel; Neuhäuser, Christoph; Bouhelal, Rochdi; Kaupmann, Klemens; Laue, Grit; Uschold-Schmidt, Nicole; Feuerbach, Dominik; Zimmermann, Kaspar; Ofner, Silvio; Cryan, John F; van der Putten, Herman; Fendt, Markus; Vranesic, Ivo; Glatthar, Ralf; Flor, Peter J

    2014-04-18

    The metabotropic glutamate receptor subtype 7 (mGlu7) is an important presynaptic regulator of neurotransmission in the mammalian CNS. mGlu7 function has been linked to autism, drug abuse, anxiety, and depression. Despite this, it has been difficult to develop specific blockers of native mGlu7 signaling in relevant brain areas such as amygdala and limbic cortex. Here, we present the mGlu7-selective antagonist 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one (XAP044), which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. There was no effect of XAP044 on LTP of mGlu7-deficient mice, indicating that this pharmacological effect is mGlu7-dependent. Unexpectedly and in contrast to all previous mGlu7-selective drugs, XAP044 does not act via the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding. This was shown by chimeric receptor studies in recombinant cell line assays. XAP044 demonstrates good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy in rodent behavioral paradigms. XAP044 reduces freezing during acquisition of Pavlovian fear and reduces innate anxiety, which is consistent with the phenotypes of mGlu7-deficient mice, the results of mGlu7 siRNA knockdown studies, and the inhibition of amygdala LTP by XAP044. Thus, we present an mGlu7 antagonist with a novel molecular mode of pharmacological action, providing significant application potential in psychiatry. Modeling the selective interaction between XAP044 and mGlu7's Venus flytrap domain, whose three-dimensional structure is already known, will facilitate future drug development supported by computer-assisted drug design.

  10. Exploration of relative skill of individual CORDEX South Asia domain experiments (GCM/RCM combinations) for spatiotemporal simulation of temperature and precipitation over the Karakoram sub-region

    NASA Astrophysics Data System (ADS)

    Forsythe, N. D.; Fowler, H.; Pritchard, D.

    2016-12-01

    High mountain Asia (HMA) constitutes one the key "water towers of the world", giving rise to river basins whose resources support hundreds of millions of people. This area will experience rapid demographic growth and socio-economic development for the next few decades compounding pressure on resource managements systems from inevitable climate change. In order to develop climate services to support water resources planning and facilitate adaptive capacity building, it is essential to critically characterise the skill and biases of the evaluation (reanalysis-driven) and control (historical period) components of presently available regional climate model (RCM) experiments. For mountain regions in particular, the ability of RCMs to reasonably reproduce the influence of complex topography, through lapse rates and orographic forcing, on sub-regional climate - notably temperature and precipitation - must be assessed in detail. HMA falls within the South Asia domain of the Coordinated Regional Downscaling Experiment (CORDEX) initiative. Multiple international modelling centres have contributed RCM experiments for the CORDEX South Asia domain. This substantial multi-model ensemble provides a valuable opportunity to explore the spread in model skill at simulation of key characteristics of the present HMA climate. This study focuses geographically on the northwest Upper Indus basin (NW UIB) which covers the bulk of the Karakoram range. Within this subdomain we use climatologies derived from local observations and meteorological reanalyses (ERA-Interim, NASA MERRA-2, HAR)as benchmarks for inter-comparison of individual CORDEX South Asia ensemble members skill in reproducing seasonality and spatial gradients (orographic precipitation profile, temperature lapse rates). Validation of individual CORDEX South Asia ensemble members to this level of detail is indispensable because discontinuities - e.g. differences in latent heat regimes (fusion versus vaporisation) - abound in

  11. Understanding the Public Domain.

    ERIC Educational Resources Information Center

    Russell, Carrie

    2003-01-01

    This overview of the public domain covers: defining the public domain; figuring out if a work is protected by copyright; being sure a work is in the public domain; asserting the copyright protection and term; the Creative Commons initiative; building the Information Commons; when permission is needed for using a public domain work; and special…

  12. Quantitative Analysis of Outer Retinal Tubulation in Age-Related Macular Degeneration From Spectral-Domain Optical Coherence Tomography and Histology

    PubMed Central

    Litts, Katie M.; Ach, Thomas; Hammack, Kristen M.; Sloan, Kenneth R.; Zhang, Yuhua; Freund, K. Bailey; Curcio, Christine A.

    2016-01-01

    Purpose To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 ± 7.9 μm2. The average cone spacing was 7.5 ± 0.6 μm. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6% to 44% of the cones present in a healthy macula. Conclusions These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses. PMID:27177321

  13. Characterization of lipid domains in erythrocyte membranes.

    PubMed

    Rodgers, W; Glaser, M

    1991-02-15

    Fluorescence digital imaging microscopy was used to study the lateral distribution of the lipid components in erythrocyte membranes. Intact erythrocytes labeled with phospholipids containing a fluorophore attached to one fatty acid chain showed an uneven distribution of the phospholipids in the membrane thereby demonstrating the presence of membrane domains. The enrichment of the lipotropic compound chlor-promazine in domains in intact erythrocytes also suggested that the domains are lipid-enriched regions. Similar membrane domains were present in erythrocyte ghosts. The phospholipid enrichment was increased in the domains by inducing membrane protein aggregation. Double-labeling experiments were done to determine the relative distributions of different phospholipids in the membrane. Vesicles made from extracted lipids did not show the presence of domains consistent with the conclusion that membrane proteins were responsible for creating the domains. Overall, it was found that large domains exist in the red blood cell membrane with unequal enrichment of the different phospholipid species.

  14. FILAMENTOUS FLOWER, a meristem and organ identity gene of Arabidopsis, encodes a protein with a zinc finger and HMG-related domains.

    PubMed

    Sawa, S; Watanabe, K; Goto, K; Liu, Y G; Shibata, D; Kanaya, E; Morita, E H; Okada, K

    1999-05-01

    Distinctive from that of the animal system, the basic plan of the plant body is the continuous formation of a structural unit, composed of a stem with a meristem at the top and lateral organs continuously forming at the meristem. Therefore, mechanisms controlling the formation, maintenance, and development of a meristem will be a key to understanding the body plan of higher plants. Genetic analyses of filamentous flower (fil) mutants have indicated that FIL is required for the maintenance and growth of inflorescence and floral meristems, and of floral organs of Arabidopsis thaliana. FIL encodes a protein carrying a zinc finger and a HMG box-like domain, which is known to work as a transcription regulator. As expected, the FIL protein was shown to have a nuclear location. In situ hybridization clearly demonstrated that FIL is expressed only at the abaxial side of primordia of leaves and floral organs. Transgenic plants, ectopically expressing FIL, formed filament-like leaves with randomly arranged cells at the leaf margin. Our results indicate that cells at the abaxial side of the lateral organs are responsible for the normal development of the organs as well as for maintaining the activity of meristems.

  15. Depletion of the Trypanosome Pumilio Domain Protein PUF2 or of Some Other Essential Proteins Causes Transcriptome Changes Related to Coding Region Length

    PubMed Central

    Jha, Bhaskar Anand; Fadda, Abeer; Merce, Clementine; Mugo, Elisha; Droll, Dorothea

    2014-01-01

    Pumilio domain RNA-binding proteins are known mainly as posttranscriptional repressors of gene expression that reduce mRNA translation and stability. Trypanosoma brucei has 11 PUF proteins. We show here that PUF2 is in the cytosol, with roughly the same number of molecules per cell as there are mRNAs. Although PUF2 exhibits a low level of in vivo RNA binding, it is not associated with polysomes. PUF2 also decreased reporter mRNA levels in a tethering assay, consistent with a repressive role. Depletion of PUF2 inhibited growth of bloodstream-form trypanosomes, causing selective loss of mRNAs with long open reading frames and increases in mRNAs with shorter open reading frames. Reexamination of published RNASeq data revealed the same trend in cells depleted of some other proteins. We speculate that these length effects could be caused by inhibition of the elongation phase of transcription or by an influence of translation status or polysomal conformation on mRNA decay. PMID:24681684

  16. Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members

    PubMed Central

    Iyer, Lakshminarayan M.; Koonin, Eugene V.; Leipe, Detlef D.; Aravind, L.

    2005-01-01

    We report an in-depth computational study of the protein sequences and structures of the superfamily of archaeo-eukaryotic primases (AEPs). This analysis greatly expands the range of diversity of the AEPs and reveals the unique active site shared by all members of this superfamily. In particular, it is shown that eukaryotic nucleo-cytoplasmic large DNA viruses, including poxviruses, asfarviruses, iridoviruses, phycodnaviruses and the mimivirus, encode AEPs of a distinct family, which also includes the herpesvirus primases whose relationship to AEPs has not been recognized previously. Many eukaryotic genomes, including chordates and plants, encode previously uncharacterized homologs of these predicted viral primases, which might be involved in novel DNA repair pathways. At a deeper level of evolutionary connections, structural comparisons indicate that AEPs, the nucleases involved in the initiation of rolling circle replication in plasmids and viruses, and origin-binding domains of papilloma and polyoma viruses evolved from a common ancestral protein that might have been involved in a protein-priming mechanism of initiation of DNA replication. Contextual analysis of multidomain protein architectures and gene neighborhoods in prokaryotes and viruses reveals remarkable parallels between AEPs and the unrelated DnaG-type primases, in particular, tight associations with the same repertoire of helicases. These observations point to a functional equivalence of the two classes of primases, which seem to have repeatedly displaced each other in various extrachromosomal replicons. PMID:16027112

  17. Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

    PubMed Central

    Cordeiro, Tiago N.; Schmidt, Holger; Madrid, Cristina; Juárez, Antonio; Bernadó, Pau; Griesinger, Christian; García, Jesús; Pons, Miquel

    2011-01-01

    Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family. PMID:22114557

  18. Inhibition of Cu2+-mediated generation of reactive oxygen species by the small heat shock protein αB-crystallin: the relative contributions of the N- and C-terminal domains.

    PubMed

    Prabhu, Sankaralingam; Srinivas, Volety; Ramakrishna, Tangirala; Raman, Bakthisaran; Rao, Ch Mohan

    2011-08-01

    Oxidative stress, Cu(2+) homeostasis, and small heat shock proteins (sHsp's) have important implications in several neurodegenerative diseases. The ubiquitous sHsp αB-crystallin is an oligomeric protein that binds Cu(2+). We have investigated the relative contributions of the N- and C-terminal (C-TDαB-crystallin) domains of αB-crystallin to its Cu(2+)-binding and redox-attenuation properties and mapped the Cu(2+)-binding regions. C-TDαB-crystallin binds Cu(2+) with slightly less affinity and inhibits Cu(2+)-catalyzed, ascorbate-mediated generation of ROS to a lesser extent than αB-crystallin. [Cu(2+)]/[subunit] stoichiometries for redox attenuation by αB-crystallin and C-TDαB-crystallin are 5 and 2, respectively. Both αB-crystallin and C-TDαB-crystallin also inhibit the Fenton reaction of hydroxyl radical formation. Trypsinization of αB-crystallin bound to a Cu(2+)-NTA column and MALDI-TOF analysis of column-bound peptides yielded three peptides located in the N-terminal domain, and in-solution trypsinization of αB-crystallin followed by Cu(2+)-NTA column chromatography identified four additional Cu(2+)-binding peptides located in the C-terminal domain. Thus, Cu(2+)-binding regions are distributed in the N- and C-terminal domains. Small-angle X-ray scattering and sedimentation-velocity measurements indicate quaternary structural changes in αB-crystallin upon Cu(2+) binding. Our study indicates that an oligomer of αB-crystallin can sequester a large number (~150) of Cu(2+) ions. It acts like a "Cu(2+) sponge," exhibits redox attenuation of Cu(2+), and has potential roles in Cu(2+) homeostasis and in preventing oxidative stress. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. High Affinity Binding of the Receptor-associated Protein D1D2 Domains with the Low Density Lipoprotein Receptor-related Protein (LRP1) Involves Bivalent Complex Formation

    PubMed Central

    Prasad, Joni M.; Young, Patricia A.; Strickland, Dudley K.

    2016-01-01

    The LDL receptor-related protein 1 (LRP1) is a large endocytic receptor that binds and mediates the endocytosis of numerous structurally diverse ligands. Currently, the basis for ligand recognition by LRP1 is not well understood. LRP1 requires a molecular chaperone, termed the receptor-associated protein (RAP), to escort the newly synthesized receptor from the endoplasmic reticulum to the Golgi. RAP is a three-domain protein that contains the following two high affinity binding sites for LRP1: one is located within domains 1 and 2, and one is located in its third domain. Studies on the interaction of the RAP third domain with LRP1 reveal critical contributions by lysine 256 and lysine 270 for this interaction. From these studies, a model for ligand recognition by this class of receptors has been proposed. Here, we employed surface plasmon resonance to investigate the binding of RAP D1D2 to LRP1. Our results reveal that the high affinity of D1D2 for LRP1 results from avidity effects mediated by the simultaneous interactions of lysine 60 in D1 and lysine 191 in D2 with sites on LRP1 to form a bivalent D1D2-LRP1 complex. When lysine 60 and 191 are both mutated to alanine, the binding of D1D2 to LRP1 is ablated. Our data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors, which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor. PMID:27402839

  20. GsmR, a response regulator with an HD-related output domain in Xanthomonas campestris, is positively controlled by Clp and is involved in the expression of genes responsible for flagellum synthesis.

    PubMed

    Liu, Yu-Fan; Liao, Chao-Tsai; Song, Wan-Ling; Hsu, Pei-Chi; Du, Shin-Chiao; Lo, Hsueh-Hsia; Hsiao, Yi-Min

    2013-01-01

    In prokaryotes, two-component signal transduction systems, consisting of a histidine kinase and a response regulator, play a critical role in regulating a range of cellular functions. A recent study suggests that XCC3315, a response regulator with a CheY-like receiver domain attached to an uncharacterized HD-related output domain (HDOD domain), plays a role in the general stress response of the Gram-negative bacterium Xanthomonas campestris pv. campestris (Xcc), the causal agent of black rot in cruciferous plants. Here, we demonstrated genetically that XCC3315, designated as gsmR (general stress and motility regulator), is involved in the expression of genes responsible for flagellum synthesis, including rpoN2, flhF, flhB, and fliC. Site-directed mutagenesis revealed that Glu9 and Arg100 in the receiver domain and Gly205, Asp263, His287, Trp298 and His311 in the HDOD are critical amino acids for GsmR function in cell motility regulation. The gsmR transcription initiation site was mapped. Promoter analysis and gel retardation assay revealed that the expression of gsmR is positively controlled by the global transcriptional regulator Clp in a direct manner, and is subject to catabolite repression. Our findings not only extend the previous work on Clp regulation to show that it influences the expression of gsmR in Xcc, but are also the first to characterize the expression of this response regulator gene in this phytopathogen. Furthermore, GsmR is the first HDOD-containing protein of bacteria in which key amino acids have been experimentally identified and characterized.

  1. NLR family pyrin domain containing 3 (NLRP3) inflammasome gene polymorphism rs7512998 (C>T) predicts aging-related increase of blood pressure, the TAMRISK study.

    PubMed

    Kunnas, Tarja; Määttä, Kirsi; Nikkari, Seppo T

    2015-01-01

    The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome by cellular stress leads to activation of the inflammasome, and NLRP3 gene polymorphisms have been associated with autoinflammatory diseases. Inflammasomes have also been implicated in the initiation or progression of metabolic disorders such as atherosclerosis, type 2 diabetes and obesity. The association of NLRP3 genetic variant rs7512998 with blood pressure and hypertension was studied in a 50-year-old Finnish cohort with a subpopulation who had available data on blood pressure measurements also at the age of 45 years. NLRP3 gene polymorphism rs7512998 C-allele was associated with higher systolic (p = 0.006) and diastolic (p = 0.011) blood pressure compared to the TT-genotype carriers in 50-year-old subjects. In addition, by analysis of variance for repeated measures between ages of 45- and 50 years there was a significant time by genotype interaction; blood pressure increased more in subjects with the C-allele both in systolic (p = 0.035) and diastolic (p = 0.012) values. However, no association with diagnosed hypertension was found. We report for the first time that NLRP3 gene polymorphism rs7512998 was associated with systolic and diastolic blood pressure in 50-year-old subjects. In addition, an effect of this variation upon blood pressure was seen in these same subjects in a 5-year follow-up from a 45-year-old cohort to 50 years of age.

  2. Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site

    PubMed Central

    Velho, Renata Voltolini; De Pace, Raffaella; Klünder, Sarah; Sperb-Ludwig, Fernanda; Lourenço, Charles Marques; Schwartz, Ida V. D.; Braulke, Thomas; Pohl, Sandra

    2015-01-01

    Mucolipidosis II (MLII) and III alpha/beta are autosomal-recessive diseases of childhood caused by mutations in GNPTAB encoding the α/β-subunit precursor protein of the GlcNAc-1-phosphotransferase complex. This enzyme modifies lysosomal hydrolases with mannose 6-phosphate targeting signals. Upon arrival in the Golgi apparatus, the newly synthesized α/β-subunit precursor is catalytically activated by site-1 protease (S1P). Here we performed comprehensive expression studies of GNPTAB mutations, including two novel mutations T644M and T1223del, identified in Brazilian MLII/MLIII alpha/beta patients. We show that the frameshift E757KfsX1 and the non-sense R587X mutations result in the retention of enzymatically inactive truncated precursor proteins in the endoplasmic reticulum (ER) due to loss of cytosolic ER exit motifs consistent with a severe clinical phenotype in homozygosity. The luminal missense mutations, C505Y, G575R and T644M, partially impaired ER exit and proteolytic activation in accordance with less severe MLIII alpha/beta disease symptoms. Analogous to the previously characterized S399F mutant, we found that the missense mutation I403T led to retention in the ER and loss of catalytic activity. Substitution of further conserved residues in stealth domain 2 (I346 and W357) revealed similar biochemical properties and allowed us to define a putative binding site for accessory proteins required for ER exit of α/β-subunit precursors. Interestingly, the analysis of the Y937_M972del mutant revealed partial Golgi localization and formation of abnormal inactive β-subunits generated by S1P which correlate with a clinical MLII phenotype. Expression analyses of mutations identified in patients underline genotype–phenotype correlations in MLII/MLIII alpha/beta and provide novel insights into structural requirements of proper GlcNAc-1-phosphotransferase activity. PMID:25788519

  3. A single mutation in framework 2 of the heavy variable domain improves the properties of a diabody and a related single-chain antibody.

    PubMed

    Rodríguez-Rodríguez, Everardo Remi; Ledezma-Candanoza, Luis M; Contreras-Ferrat, Luis Gabriel; Olamendi-Portugal, Timoteo; Possani, Lourival D; Becerril, Baltazar; Riaño-Umbarila, Lidia

    2012-10-26

    Excellent results regarding improved therapeutic properties have been often obtained through the conversion of a single-chain variable fragment (scFv) into a noncovalent dimeric antibody (diabody) via peptide linker shortening. We utilized this approach to obtain a dimeric version of the human scFv 6009F, which was originally engineered to neutralize the Cn2 toxin of Centruroides noxius scorpion venom. However, some envenoming symptoms remained with diabody 6009F. Diabody 6009F was subjected to directed evolution to obtain a variant capable of eliminating envenoming symptoms. After two rounds of biopanning, diabody D4 was isolated. It exhibited a single mutation (E43G) in framework 2 of the heavy-chain variable domain. Diabody D4 displayed an increase in T(m) (thermal transition midpoint temperature) of 6.3°C compared with its dimeric precursor. The importance of the E43G mutation was tested in the context of the human scFv LR, a highly efficient antibody against Cn2, which was previously generated by our group [Riaño-Umbarila, L., Contreras-Ferrat, G., Olamendi-Portugal, T., Morelos-Juárez, C., Corzo, G., Possani, L. D. and Becerril, B. (2011). J. Biol. Chem.286, 6143-6151]. The new variant, scFv LER, displayed an increase in T(m) of 3.4°C and was capable of neutralizing 2 LD(50) of Cn2 toxin with no detectable symptoms when injected into mice at a 1:1 toxin-to-antibody molar ratio. These results showed that the E43G mutation might increase the therapeutic properties of these antibody fragments. Molecular modeling and dynamics results suggest that the rearrangement of the hydrogen-bonding network near the E43G mutation could explain the improved functional stability and neutralization properties of both the diabody D4 and scFv LER.

  4. Domain walls riding the wave.

    SciTech Connect

    Karapetrov, G.; Novosad, V.; Materials Science Division

    2010-11-01

    the preferred method, as it combines manipulation and readout of the domain-wall state. The electrons that take part in the process of readout and manipulation of the domain-wall structure in the nanowire do so through the so-called spin transfer torque: When spin-polarized electrons in the ferromagnet nanowire pass through the domain wall they experience a nonuniform magnetization, and they try to align their spins with the local magnetic moments. The force that the electrons experience has a reaction force counterpart that 'pushes' the local magnetic moments, resulting in movement of the domain wall in the direction of the electron flow through the spin-transfer torque. The forces between the electrons and the local magnetic moments in the ferromagnet also create additional electrical resistance for the electrons passing through the domain wall. By measuring resistance across a segment of the nanowire, one determines if a domain wall is present; i.e., one can read the stored information. The interaction of the spin-polarized electrons with the domain wall in the ferromagnetic nanowire is not very efficient. Even for materials achieving high polarization of the free electrons, it is very difficult to move the magnetic domain wall. Several factors contribute to this problem, with imperfections of the ferromagnetic nanowire that cause domain-wall pinning being the dominant one. Permalloy nanowires, one of the best candidates for domain-wall-based memory and logic devices, require current densities of the order of 10{sup 8} A/cm{sup 2} in order to move a domain wall from a pinning well. Considering that this current has to pass through a relatively long wire, it is not very difficult to imagine that most of the energy will go to Joule heating. The efficiency of the process - the ratio of the energy converted to domain-wall motion to the total energy consumed - is comparable to that of an incandescent light bulb converting electricity to light. A step towards more

  5. Domains in multiband superconductors

    NASA Astrophysics Data System (ADS)

    Tanaka, Y.; Yanagisawa, T.; Crisan, A.; Shirage, P. M.; Iyo, A.; Tokiwa, K.; Nishio, T.; Sundaresan, A.; Terada, N.

    2011-11-01

    Multiband superconductors can have several types of domains that are inhibited in conventional single-band superconductors. These domains are phase domains and chiral domains and their domain wall are an interband phase difference soliton. In a superconductor with an odd number of electronic bands (five or more) and with positive interband Josephson interactions, we find other types of domains with different interband phase differences. We call these domains configuration domains because pseudo-order parameters for each band are dispersed in the complex plain and several configurations, which have several local minima. Fractional vortices serve as hubs for phase difference solitons (configuration domain walls). The divergence of the number of configurations with local minima would pose a serious problem for the stability of superconductivity.

  6. The Temporal Context Model in Spatial Navigation and Relational Learning: Toward a Common Explanation of Medial Temporal Lobe Function Across Domains

    ERIC Educational Resources Information Center

    Howard, Marc W.; Fotedar, Mrigankka S.; Datey, Aditya V.; Hasselmo, Michael E.

    2005-01-01

    The medial temporal lobe (MTL) has been studied extensively at all levels of analysis, yet its function remains unclear. Theory regarding the cognitive function of the MTL has centered along 3 themes. Different authors have emphasized the role of the MTL in episodic recall, spatial navigation, or relational memory. Starting with the temporal…

  7. The Temporal Context Model in Spatial Navigation and Relational Learning: Toward a Common Explanation of Medial Temporal Lobe Function Across Domains

    ERIC Educational Resources Information Center

    Howard, Marc W.; Fotedar, Mrigankka S.; Datey, Aditya V.; Hasselmo, Michael E.

    2005-01-01

    The medial temporal lobe (MTL) has been studied extensively at all levels of analysis, yet its function remains unclear. Theory regarding the cognitive function of the MTL has centered along 3 themes. Different authors have emphasized the role of the MTL in episodic recall, spatial navigation, or relational memory. Starting with the temporal…

  8. Students' tripartite efficacy beliefs in high school physical education: within- and cross-domain relations with motivational processes and leisure-time physical activity.

    PubMed

    Jackson, Ben; Whipp, Peter R; Chua, K L Peter; Dimmock, James A; Hagger, Martin S

    2013-02-01

    Within instructional settings, individuals form relational efficacy appraisals that complement their self-efficacy beliefs. In high school physical education (PE), for instance, students develop a level of confidence in their teacher's capabilities, as well as estimating how confident they think their teacher is in their (i.e., the students') ability. Grounded in existing transcontextual work, we examined the motivational pathways through which students' relational efficacy and self-efficacy beliefs in PE were predictive of their leisure-time physical activity. Singaporean students (N = 990; age M = 13.95, SD = 1.02) completed instruments assessing efficacy beliefs, perceptions of teacher relatedness support, and autonomous motivation toward PE, and 2 weeks later they reported their motivation toward, and engagement in, leisure-time physical activity. Structural equation modeling revealed that students reported stronger other-efficacy and RISE beliefs when they felt that their teacher created a highly relatedness-supportive environment. In turn, their relational efficacy beliefs (a) supported their confidence in their own ability, (b) directly and indirectly predicted more autonomous motives for participation in PE, and (c) displayed prospective transcontextual effects in relation to leisure-time variables. By emphasizing the adaptive motivational effects associated with the tripartite constructs, these findings highlight novel pathways linking students' efficacy perceptions with leisure-time outcomes.

  9. The Temporal Context Model in spatial navigation and relational learning: Toward a common explanation of medial temporal lobe function across domains

    PubMed Central

    Howard, Marc W.; Fotedar, Mrigankka S.; Datey, Aditya V.; Hasselmo, Michael E.

    2005-01-01

    The medial temporal lobe (MTL) has been studied extensively at all levels of analysis, yet its function remains unclear. Theory regarding the cognitive function of the MTL has centered along 3 themes. Different authors have emphasized the role of the MTL in episodic recall, spatial navigation, or relational memory. Starting with the temporal context model (M. W. Howard and M. J. Kahana, 2002), a distributed memory model that has been applied to benchmark data from episodic recall tasks, the authors propose that the entorhinal cortex supports a gradually changing representation of temporal context and the hippocampus proper enables retrieval of these contextual states. Simulation studies show this hypothesis explains the firing of place cells in the entorhinal cortex and the behavioral effects of hippocampal lesion in relational memory tasks. These results constitute a first step towards a unified computational theory of MTL function that integrates neurophysiological, neuropsychological and cognitive findings. PMID:15631589

  10. HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels.

    PubMed

    Flamme, I; Fröhlich, T; von Reutern, M; Kappel, A; Damert, A; Risau, W

    1997-04-01

    Transcription factors of the bHLH-PAS protein family are important regulators of developmental processes such as neurogenesis and tracheal development in invertebrates. Recently a bHLH-PAS protein, named trachealess (trl) was identified as a master regulator of tracheogenesis. Hypoxia-inducible factor, HIF-1 alpha, is a vertebrate relative of trl which is likely to be involved in growth of blood vessels by the induction of vascular endothelial growth factor (VEGF) in response to hypoxia. In the present study we describe mRNA cloning and mRNA expression pattern of mouse HIF-related factor (HRF), a novel close relative of HIF-1 alpha which is expressed most prominently in brain capillary endothelial cells and other blood vessels as well as in bronchial epithelium in the embryo and the adult. In addition, smooth muscle cells of the uterus, neurons, brown adipose tissue and various epithelial tissues express HRF mRNA as well. High expression levels of HRF mRNA in embryonic choroid plexus and kidney glomeruli, places where VEGF is highly expressed, suggest a role of this factor in VEGF gene activation similar to that of HIF-1 alpha. Given the similarity between morphogenesis of the tracheal system and the vertebrate vascular system, the expression pattern of HRF in the vasculature and the bronchial tree raises the possibility that this family of transcription factors may be involved in tubulogenesis.

  11. Definition and identification of homology domains.

    PubMed

    Lawrence, C B; Goldman, D A

    1988-03-01

    A method is described for identifying and evaluating regions of significant similarity between two sequences. The notion of a 'homology domain' is employed which defines the boundaries of a region of sequence homology containing no insertions or deletions. The relative significance of different potential homology domains is evaluated using a non-linear similarity score related to the probability of finding the observed level of similarity in the region by chance. The sensitivity of the method is demonstrated by simulating the evolution of homology domains and applying the method to their detection. Several examples of the use of homology domain identification are given.

  12. AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

    PubMed Central

    Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

    2015-01-01

    Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568

  13. Internationalized Domain Names.

    ERIC Educational Resources Information Center

    Wielansky, Marc D.

    2002-01-01

    Reports on an investigation of what may appear at first to be an arcane topic--the internationalization of domain names on the Internet. Concludes that expanding domain names internationally poses challenges to the inherent open structure of the Internet; to its ease of use for those accustomed to Latin-alphabet-only domain names; and to corporate…

  14. Learning to remember: cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains.

    PubMed

    Talboom, Joshua S; West, Stephen G; Engler-Chiurazzi, Elizabeth B; Enders, Craig K; Crain, Ian; Bimonte-Nelson, Heather A

    2014-12-01

    Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6 to 18 months old on the same T-maze; Group one received a version testing spatial reference memory, and Group two received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats, respectively. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. Group five of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects, since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which were related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. Published by Elsevier Inc.

  15. Learning to remember: Cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains

    PubMed Central

    Talboom, Joshua S.; West, Stephen G.; Engler-Chiurazzi, Elizabeth B.; Enders, Craig K.; Crain, Ian; Bimonte-Nelson, Heather A.

    2014-01-01

    Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6-18 months old on the same T-maze; one group received a version testing spatial reference memory, and the other group received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. The fifth group of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which was related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. PMID:25104561

  16. Patterns of Depressive Symptoms and Social Relating Behaviors Differ Over Time From Other Behavioral Domains for Young People With Down Syndrome

    PubMed Central

    Foley, Kitty-Rose; Bourke, Jenny; Einfeld, Stewart L.; Tonge, Bruce J.; Jacoby, Peter; Leonard, Helen

    2015-01-01

    Abstract People with intellectual disabilities are at a higher risk for experiencing behavioral, emotional, and psychiatric problems in comparison with the general population. People with Down syndrome have been reported as experiencing fewer behavioral problems than others with intellectual disability, although still at a greater level than the non-intellectually disabled population, except for depression and Alzheimer disease. The aim of this study was to describe the trajectories of subscales of behavior, including depressive symptoms, communication disturbance, anxiety, disruptiveness, and social relating abilities, for young adults with Down syndrome. Families of young adults with Down syndrome living in Perth, Western Australia, participated in a questionnaire study over 8 years, 2004 (n = 255), 2009 (n = 191), and 2011 (n = 188). Questionnaires collected information about young person characteristics and family functioning. The parent-completed Developmental Behavior Checklist-Adult (DBC-A) and Developmental Behavior Checklist-Primary Carer Version (DBC-P) were used to measure emotional and behavioral problems. These measures include the following subscales: disruptive, communication and anxiety disturbances, self-absorbed, antisocial, depressive, and social relating. DBC score declined from 2004 to 2011 reflecting an improvement in behavior in the self-absorbed (coeff −0.011, 95% confidence interval (CI) −0.031, −0.008), anxiety (coef −0.009 95%CI −0.129, −0.006), communication disturbances (coeff −0.008, 95% CI −0.012, −0.005) and disruptive/antisocial behavior (coeff −0.013, 95% CI −0.016, −0.009) subscales. Subscales for depressive symptoms and social relating problems decreased less (coeff −0.003, 95% CI −0.007, −0.0001) (coeff −0.003 95% CI −0.007, 0.001). Young people who were lower functioning were reported as exhibiting significantly more behavioral problems across every subscale when compared with those

  17. Tomato yellow leaf curl Sardinia virus-resistant tomato plants expressing the multifunctional N-terminal domain of the replication-associated protein show transcriptional changes resembling stress-related responses.

    PubMed

    Lucioli, Alessandra; Berardi, Alessandra; Gatti, Francesca; Tavazza, Raffaela; Pizzichini, Daniele; Tavazza, Mario

    2014-01-01

    The N-terminal domain (amino acids 1-130) of the replication-associated protein (Rep130 ) of Tomato yellow leaf curl Sardinia virus (TYLCSV) retains the ability of full-length Rep to localize to the nucleus and to down-regulate C1 transcription when ectopically expressed in plants, both functions being required to inhibit homologous viral replication. In this study, we analysed the effect of Rep130 expression on virus resistance and the plant transcriptome in the natural and agronomically important host species of TYLCSV, Solanum lycopersicum. Tomato plants accumulating high levels of Rep130 were generated and proved to be resistant to TYLCSV. Using an in vitro assay, we showed that plant-expressed Rep130 also retains the catalytic activity of Rep, thus supporting the notion that this protein domain is fully functional. Interestingly, Rep130 -expressing tomatoes were characterized by an altered transcriptional profile resembling stress-related responses. Notably, the serine-type protease inhibitor (Ser-PI) category was over-represented among the 20 up-regulated genes. The involvement of Rep130 in the alteration of host mRNA steady-state levels was confirmed using a distinct set of virus-resistant transgenic tomato plants expressing the same TYLCSV Rep130 , but from a different, synthetic, gene. Eight genes were found to be up-regulated in both types of transgenic tomato and two encoded Ser-PIs. Four of these eight genes were also up-regulated in TYLCSV-infected wild-type tomato plants. Implications with regard to the ability of this Rep domain to interfere with viral infections and to alter the host transcriptome are discussed. © 2013 BSPP AND JOHN WILEY & SONS LTD.

  18. Crystallization of the receptor-binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragment

    SciTech Connect

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, Thomas J.; Parker, Michael W.

    2009-04-01

    Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography. In this study, a monoclonal antibody Fab fragment which recognizes the same region of PTHrP as its receptor, PTH1R, was used to aid in the crystallization of PTHrP. The resultant protein complex was crystallized using the hanging-drop vapour-diffusion method with polyethylene glycol as a precipitant. The crystals belonged to the orthorhombic space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.6, b = 96.3, c = 88.5 {angstrom}, and diffracted to 2.0 {angstrom} resolution using synchrotron radiation. The crystal structure will shed light on the nature of the key residues of PTHrP that interact with the antibody and will provide insights into how the antibody is able to discriminate between PTHrP and the related molecule parathyroid homone.

  19. Crystallization of the receptor-binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragment.

    PubMed

    McKinstry, William J; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T; Martin, Thomas J; Parker, Michael W

    2009-04-01

    Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography. In this study, a monoclonal antibody Fab fragment which recognizes the same region of PTHrP as its receptor, PTH1R, was used to aid in the crystallization of PTHrP. The resultant protein complex was crystallized using the hanging-drop vapour-diffusion method with polyethylene glycol as a precipitant. The crystals belonged to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 72.6, b = 96.3, c = 88.5 A, and diffracted to 2.0 A resolution using synchrotron radiation. The crystal structure will shed light on the nature of the key residues of PTHrP that interact with the antibody and will provide insights into how the antibody is able to discriminate between PTHrP and the related molecule parathyroid homone.

  20. Predicting students' physical activity and health-related well-being: a prospective cross-domain investigation of motivation across school physical education and exercise settings.

    PubMed

    Standage, Martyn; Gillison, Fiona B; Ntoumanis, Nikos; Treasure, Darren C

    2012-02-01

    A three-wave prospective design was used to assess a model of motivation guided by self-determination theory (Ryan & Deci, 2008) spanning the contexts of school physical education (PE) and exercise. The outcome variables examined were health-related quality of life (HRQoL), physical self-concept (PSC), and 4 days of objectively assessed estimates of activity. Secondary school students (n = 494) completed questionnaires at three separate time points and were familiarized with how to use a sealed pedometer. Results of structural equation modeling supported a model in which perceptions of autonomy support from a PE teacher positively predicted PE-related need satisfaction (autonomy, competence, and relatedness). Competence predicted PSC, whereas relatedness predicted HRQoL. Autonomy and competence positively predicted autonomous motivation toward PE, which in turn positively predicted autonomous motivation toward exercise (i.e., 4-day pedometer step count). Autonomous motivation toward exercise positively predicted step count, HRQoL, and PSC. Results of multisample structural equation modeling supported gender invariance. Suggestions for future work are discussed.

  1. Enhanced protein domain discovery using taxonomy

    PubMed Central

    Coin, Lachlan; Bateman, Alex; Durbin, Richard

    2004-01-01

    Background It is well known that different species have different protein domain repertoires, and indeed that some protein domains are kingdom specific. This information has not yet been incorporated into statistical methods for finding domains in sequences of amino acids. Results We show that by incorporating our understanding of the taxonomic distribution of specific protein domains, we can enhance domain recognition in protein sequences. We identify 4447 new instances of Pfam domains in the SP-TREMBL database using this technique, equivalent to the coverage increase given by the last 8.3% of Pfam families and to a 0.7% increase in the number of domain predictions. We use PSI-BLAST to cross-validate our new predictions. We also benchmark our approach using a SCOP test set of proteins of known structure, and demonstrate improvements relative to standard Hidden Markov model techniques. Conclusions Explicitly including knowledge about the taxonomic distribution of protein domains can enhance protein domain recognition. Our method can also incorporate other context-specific domain distributions – such as domain co-occurrence and protein localisation. PMID:15137915

  2. A highly convergent synthesis of the C1-C31 polyol domain of amphidinol 3 featuring a TST-RCM reaction: confirmation of the revised relative stereochemistry.

    PubMed

    Grisin, Aleksandr; Evans, P Andrew

    2015-11-13

    The concise enantioselective synthesis of the revised C1-C31 fragment of the polyketide amphidinol 3 was accomplished in 16 steps and 12.8% overall yield. Salient features of the strategy include chemoselective Weinreb amide coupling and concomitant CBS reduction for the preparation of the C1-C15 tris-syn-1,5-diol motif and a temporary silicon-tethered ring-closing metathesis (TST-RCM) reaction in combination with a diastereoselective hydroboration for the construction of the C16-C31 polypropionate fragment. The union of the fragments was accomplished by a regioselective ring-opening of the terminal epoxide with a phenyl sulfone stabilized carbanion, which upon reduction and deprotection permits a comparison of the relative configuration with the natural product.

  3. The Inventory of Personality Organization: psychometric properties, factorial composition, and criterion relations with affect, aggressive dyscontrol, psychosis proneness, and self-domains in a nonclinical sample.

    PubMed

    Lenzenweger, M F; Clarkin, J F; Kernberg, O F; Foelsch, P A

    2001-12-01

    This report describes 2 studies of the psychometric characteristics of the primary clinical scales of the Inventory of Personality Organization (IPO; O. F. Kernberg & J. F. Clarkin, 1995), which assess reality testing, primitive psychological defenses, and identity diffusion, in a nonclinical sample. The 3 IPO scales display adequate internal consistency and good test-retest reliability. Item-level confirmatory factor analysis supported a two-factor structure of the IPO consistent with O. F. Kernberg's (1984, 1996) model of borderline personality organization. Each of the 3 IPO scales was associated with increased negative affect, aggressive dyscontrol, and dysphoria as well as lower levels of positive affect consistent with Kernberg's model of borderline personality organization. The IPO Reality Testing scale is closely related to various measures of psychotic-like phenomena.

  4. Large-scale brain networks in board game experts: insights from a domain-related task and task-free resting state.

    PubMed

    Duan, Xujun; Liao, Wei; Liang, Dongmei; Qiu, Lihua; Gao, Qing; Liu, Chengyi; Gong, Qiyong; Chen, Huafu

    2012-01-01

    Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior.

  5. C2-Domain Abscisic Acid-Related Proteins Mediate the Interaction of PYR/PYL/RCAR Abscisic Acid Receptors with the Plasma Membrane and Regulate Abscisic Acid Sensitivity in Arabidopsis[C][W

    PubMed Central

    Rodriguez, Lesia; Diaz, Maira; Rodrigues, Americo; Izquierdo-Garcia, Ana C.; Peirats-Llobet, Marta; Fernandez, Maria A.; Antoni, Regina; Fernandez, Daniel; Marquez, Jose A.; Mulet, Jose M.; Albert, Armando; Rodriguez, Pedro L.

    2014-01-01

    Membrane-delimited abscisic acid (ABA) signal transduction plays a critical role in early ABA signaling, but the molecular mechanisms linking core signaling components to the plasma membrane are unclear. We show that transient calcium-dependent interactions of PYR/PYL ABA receptors with membranes are mediated through a 10-member family of C2-domain ABA-related (CAR) proteins in Arabidopsis thaliana. Specifically, we found that PYL4 interacted in an ABA-independent manner with CAR1 in both the plasma membrane and nucleus of plant cells. CAR1 belongs to a plant-specific gene family encoding CAR1 to CAR10 proteins, and bimolecular fluorescence complementation and coimmunoprecipitation assays showed that PYL4-CAR1 as well as other PYR/PYL-CAR pairs interacted in plant cells. The crystal structure of CAR4 was solved, which revealed that, in addition to a classical calcium-dependent lipid binding C2 domain, a specific CAR signature is likely responsible for the interaction with PYR/PYL receptors and their recruitment to phospholipid vesicles. This interaction is relevant for PYR/PYL function and ABA signaling, since different car triple mutants affected in CAR1, CAR4, CAR5, and CAR9 genes showed reduced sensitivity to ABA in seedling establishment and root growth assays. In summary, we identified PYR/PYL-interacting partners that mediate a transient Ca2+-dependent interaction with phospholipid vesicles, which affects PYR/PYL subcellular localization and positively regulates ABA signaling. PMID:25465408

  6. C2-domain abscisic acid-related proteins mediate the interaction of PYR/PYL/RCAR abscisic acid receptors with the plasma membrane and regulate abscisic acid sensitivity in Arabidopsis.

    PubMed

    Rodriguez, Lesia; Gonzalez-Guzman, Miguel; Diaz, Maira; Rodrigues, Americo; Izquierdo-Garcia, Ana C; Peirats-Llobet, Marta; Fernandez, Maria A; Antoni, Regina; Fernandez, Daniel; Marquez, Jose A; Mulet, Jose M; Albert, Armando; Rodriguez, Pedro L

    2014-12-01

    Membrane-delimited abscisic acid (ABA) signal transduction plays a critical role in early ABA signaling, but the molecular mechanisms linking core signaling components to the plasma membrane are unclear. We show that transient calcium-dependent interactions of PYR/PYL ABA receptors with membranes are mediated through a 10-member family of C2-domain ABA-related (CAR) proteins in Arabidopsis thaliana. Specifically, we found that PYL4 interacted in an ABA-independent manner with CAR1 in both the plasma membrane and nucleus of plant cells. CAR1 belongs to a plant-specific gene family encoding CAR1 to CAR10 proteins, and bimolecular fluorescence complementation and coimmunoprecipitation assays showed that PYL4-CAR1 as well as other PYR/PYL-CAR pairs interacted in plant cells. The crystal structure of CAR4 was solved, which revealed that, in addition to a classical calcium-dependent lipid binding C2 domain, a specific CAR signature is likely responsible for the interaction with PYR/PYL receptors and their recruitment to phospholipid vesicles. This interaction is relevant for PYR/PYL function and ABA signaling, since different car triple mutants affected in CAR1, CAR4, CAR5, and CAR9 genes showed reduced sensitivity to ABA in seedling establishment and root growth assays. In summary, we identified PYR/PYL-interacting partners that mediate a transient Ca(2+)-dependent interaction with phospholipid vesicles, which affects PYR/PYL subcellular localization and positively regulates ABA signaling.

  7. Oral health related quality of life in pregnant and post partum women in two social network domains; predominantly home-based and work-based networks

    PubMed Central

    2012-01-01

    Background Individuals connected to supportive social networks have better general and oral health quality of life. The objective of this study was to assess whether there were differences in oral health related quality of life (OHRQoL) between women connected to either predominantly home-based and work-based social networks. Methods A follow-up prevalence study was conducted on 1403 pregnant and post-partum women (mean age of 25.2 ± 6.3 years) living in two cities in the State of Rio de Janeiro, Brazil. Women were participants in an established cohort followed from pregnancy (baseline) to post-partum period (follow-up). All participants were allocated to two groups; 1. work-based social network group - employed women with paid work, and, 2. home-based social network group - women with no paid work, housewives or unemployed women. Measures of social support and social network were used as well as questions on sociodemographic characteristics and OHRQoL and health related behaviors. Multinomial logistic regression was performed to obtain OR of relationships between occupational contexts, affectionate support and positive social interaction on the one hand, and oral health quality of life, using the Oral Health Impacts Profile (OHIP) measure, adjusted for age, ethnicity, family income, schooling, marital status and social class. Results There was a modifying effect of positive social interaction on the odds of occupational context on OHRQoL. The odds of having a poorer OHIP score, ≥4, was significantly higher for women with home-based social networks and moderate levels of positive social interactions [OR 1.64 (95% CI: 1.08-2.48)], and for women with home-based social networks and low levels of positive social interactions [OR 2.15 (95% CI: 1.40-3.30)] compared with women with work-based social networks and high levels of positive social interactions. Black ethnicity was associated with OHIP scores ≥4 [OR 1.73 (95% CI: 1.23-2.42)]. Conclusions Pregnant and post

  8. Oral health related quality of life in pregnant and post partum women in two social network domains; predominantly home-based and work-based networks.

    PubMed

    Lamarca, Gabriela A; Leal, Maria do C; Leao, Anna T T; Sheiham, Aubrey; Vettore, Mario V

    2012-01-13

    Individuals connected to supportive social networks have better general and oral health quality of life. The objective of this study was to assess whether there were differences in oral health related quality of life (OHRQoL) between women connected to either predominantly home-based and work-based social networks. A follow-up prevalence study was conducted on 1403 pregnant and post-partum women (mean age of 25.2 ± 6.3 years) living in two cities in the State of Rio de Janeiro, Brazil. Women were participants in an established cohort followed from pregnancy (baseline) to post-partum period (follow-up). All participants were allocated to two groups; 1. work-based social network group--employed women with paid work, and, 2. home-based social network group--women with no paid work, housewives or unemployed women. Measures of social support and social network were used as well as questions on sociodemographic characteristics and OHRQoL and health related behaviors. Multinomial logistic regression was performed to obtain OR of relationships between occupational contexts, affectionate support and positive social interaction on the one hand, and oral health quality of life, using the Oral Health Impacts Profile (OHIP) measure, adjusted for age, ethnicity, family income, schooling, marital status and social class. There was a modifying effect of positive social interaction on the odds of occupational context on OHRQoL. The odds of having a poorer OHIP score, ≥ 4, was significantly higher for women with home-based social networks and moderate levels of positive social interactions [OR 1.64 (95% CI: 1.08-2.48)], and for women with home-based social networks and low levels of positive social interactions [OR 2.15 (95% CI: 1.40-3.30)] compared with women with work-based social networks and high levels of positive social interactions. Black ethnicity was associated with OHIP scores ≥ 4 [OR 1.73 (95% CI: 1.23-2.42)]. Pregnant and post-partum Brazilian women in paid

  9. Functional domain walls in multiferroics.

    PubMed

    Meier, Dennis

    2015-11-25

    During the last decade a wide variety of novel and fascinating correlation phenomena has been discovered at domain walls in multiferroic bulk systems, ranging from unusual electronic conductance to inseparably entangled spin and charge degrees of freedom. The domain walls represent quasi-2D functional objects that can be induced, positioned, and erased on demand, bearing considerable technological potential for future nanoelectronics. Most of the challenges that remain to be solved before turning related device paradigms into reality, however, still fall in the field of fundamental condensed matter physics and materials science. In this topical review seminal experimental findings gained on electric and magnetic domain walls in multiferroic bulk materials are addressed. A special focus is put on the physical properties that emerge at so-called charged domain walls and the added functionality that arises from coexisting magnetic order. The research presented in this review highlights that we are just entering a whole new world of intriguing nanoscale physics that is yet to be explored in all its details. The goal is to draw attention to the persistent challenges and identify future key directions for the research on functional domain walls in multiferroics.

  10. Association of Piebaldism, multiple café-au-lait macules, and intertriginous freckling: clinical evidence of a common pathway between KIT and sprouty-related, ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1 (SPRED1).

    PubMed

    Chiu, Yvonne E; Dugan, Stefanie; Basel, Donald; Siegel, Dawn H

    2013-01-01

    Piebaldism is a rare genodermatosis caused by KIT mutations. We report the case of a 5-year-old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café-au-lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty-related, Ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1 (SPRED1) mutations that also has multiple café-au-lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café-au-lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1.

  11. Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain.

    PubMed

    Prasad, Joni M; Migliorini, Mary; Galisteo, Rebeca; Strickland, Dudley K

    2015-07-10

    The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the low density lipoprotein receptor family and plays important roles in a number of physiological and pathological processes. Expression of LRP1 requires the receptor-associated protein (RAP), a molecular chaperone that binds LRP1 and other low density lipoprotein receptor family members in the endoplasmic reticulum and traffics with them to the Golgi where the acidic environment causes its dissociation. Exogenously added RAP is a potent LRP1 antagonist and binds to LRP1 on the cell surface, preventing ligands from binding. Following endocytosis, RAP dissociates in the acidic endosome, allowing LRP1 to recycle back to the cell surface. The acid-induced dissociation of RAP is mediated by its D3 domain, a relatively unstable three-helical bundle that denatures at pH <6.2 due to protonation of key histidine residues on helices 2 and 3. To develop an LRP1 inhibitor that does not dissociate at low pH, we introduced a disulfide bond between the second and third helices in the RAP D3 domain. By combining this disulfide bond with elimination of key histidine residues, we generated a stable RAP molecule that is resistant to both pH- and heat-induced denaturation. This molecule bound to LRP1 with high affinity at both neutral and acidic pH and proved to be a potent inhibitor of LRP1 function both in vitro and in vivo, suggesting that our stable RAP molecule may be useful in multiple pathological settings where LRP1 blockade has been shown to be effective. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain*

    PubMed Central

    Prasad, Joni M.; Migliorini, Mary; Galisteo, Rebeca; Strickland, Dudley K.

    2015-01-01

    The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the low density lipoprotein receptor family and plays important roles in a number of physiological and pathological processes. Expression of LRP1 requires the receptor-associated protein (RAP), a molecular chaperone that binds LRP1 and other low density lipoprotein receptor family members in the endoplasmic reticulum and traffics with them to the Golgi where the acidic environment causes its dissociation. Exogenously added RAP is a potent LRP1 antagonist and binds to LRP1 on the cell surface, preventing ligands from binding. Following endocytosis, RAP dissociates in the acidic endosome, allowing LRP1 to recycle back to the cell surface. The acid-induced dissociation of RAP is mediated by its D3 domain, a relatively unstable three-helical bundle that denatures at pH <6.2 due to protonation of key histidine residues on helices 2 and 3. To develop an LRP1 inhibitor that does not dissociate at low pH, we introduced a disulfide bond between the second and third helices in the RAP D3 domain. By combining this disulfide bond with elimination of key histidine residues, we generated a stable RAP molecule that is resistant to both pH- and heat-induced denaturation. This molecule bound to LRP1 with high affinity at both neutral and acidic pH and proved to be a potent inhibitor of LRP1 function both in vitro and in vivo, suggesting that our stable RAP molecule may be useful in multiple pathological settings where LRP1 blockade has been shown to be effective. PMID:26013822

  13. JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells.

    PubMed

    Boeckel, Jes-Niels; Derlet, Anja; Glaser, Simone F; Luczak, Annika; Lucas, Tina; Heumüller, Andreas W; Krüger, Marcus; Zehendner, Christoph M; Kaluza, David; Doddaballapur, Anuradha; Ohtani, Kisho; Treguer, Karine; Dimmeler, Stefanie

    2016-07-01

    Jumonji C (JmjC) domain-containing proteins modify histone and nonhistone proteins thereby controlling cellular functions. However, the role of JmjC proteins in angiogenesis is largely unknown. Here, we characterize the expression of JmjC domain-containing proteins after inducing endothelial differentiation of murine embryonic stem cells and study the function of JmjC domain-only proteins in endothelial cell (EC) functions. We identified a large number of JmjC domain-containing proteins regulated by endothelial differentiation of murine embryonic stem cells. Among the family of JmjC domain-only proteins, Jmjd8 was significantly upregulated on endothelial differentiation. Knockdown of Jmjd8 in ECs significantly decreased in vitro network formation and sprouting in the spheroid assay. JMJD8 is exclusively detectable in the cytoplasm, excluding a function as a histone-modifying enzyme. Mass spectrometry analysis revealed JMJD8-interacting proteins with known functions in cellular metabolism like pyruvate kinase M2. Accordingly, knockdown of pyruvate kinase M2 in human umbilical vein ECs decreased endothelial sprouting in the spheroid assay. Knockdown of JMJD8 caused a reduction of EC metabolism as measured by Seahorse Bioscience extracellular flux analysis. Conversely, overexpression of JMJD8 enhanced cellular oxygen consumption rate of ECs, reflecting an increased mitochondrial respiration. Jmjd8 is upregulated during endothelial differentiation and regulates endothelial sprouting and metabolism by interacting with pyruvate kinase M2. © 2016 American Heart Association, Inc.

  14. Frequency domain FIR and IIR adaptive filters

    NASA Technical Reports Server (NTRS)

    Lynn, D. W.

    1990-01-01

    A discussion of the LMS adaptive filter relating to its convergence characteristics and the problems associated with disparate eigenvalues is presented. This is used to introduce the concept of proportional convergence. An approach is used to analyze the convergence characteristics of block frequency-domain adaptive filters. This leads to a development showing how the frequency-domain FIR adaptive filter is easily modified to provide proportional convergence. These ideas are extended to a block frequency-domain IIR adaptive filter and the idea of proportional convergence is applied. Experimental results illustrating proportional convergence in both FIR and IIR frequency-domain block adaptive filters is presented.

  15. Domains and Naive Theories.

    PubMed

    Gelman, Susan A; Noles, Nicholaus S

    2011-09-01

    Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This review examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children's classification of biological and non-biological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning.

  16. Domains and Naive Theories

    PubMed Central

    Gelman, Susan A.; Noles, Nicholaus S.

    2013-01-01

    Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This review examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children’s classification of biological and non-biological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning. PMID:24187603

  17. Phantom domain walls

    NASA Astrophysics Data System (ADS)

    Avelino, P. P.; Ferreira, V. M. C.; Menezes, J.; Sousa, L.

    2017-08-01

    We consider a model with two real scalar fields which admits phantom domain wall solutions. We investigate the structure and evolution of these phantom domain walls in an expanding homogeneous and isotropic universe. In particular, we show that the increase of the tension of the domain walls with cosmic time, associated to the evolution of the phantom scalar field, is responsible for an additional damping term in their equations of motion. We describe the macroscopic dynamics of phantom domain walls, showing that extended phantom defects whose tension varies on a cosmological time scale cannot be the dark energy.

  18. Relativity

    NASA Astrophysics Data System (ADS)

    Stephani, Hans

    2004-02-01

    Preface; Notation; Part I. Special Relativity: 1. Introduction: inertial systems and Galilei invariance of classical mechanics; 2. Light propagation in moving coordinate systems and Lorentz transformations; 3. Our world as a Minkowski space; 4. Mechanics of special relativity; 5. Optics of plane waves; 6. Four-dimensional vectors and tensors; 7. Electrodynamics in vacuo; 8. Transformation properties of electromagnetic fields: examples; 9. Null vectors and the algebraic properties of electromagnetic field tensors; 10. Charged point particles and their field; 11. Pole-dipole particles and their field; 12. Electrodynamics in media; 13. Perfect fluids and other physical theories; Part II. Riemannian Geometry: 14. Introduction: the force-free motion of particles in Newtonian mechanics; 15. Why Riemannian geometry?; 16. Riemannian space; 17. Tensor algebra; 18. The covariant derivative and parallel transport; 19. The curvature tensor; 20. Differential operators, integrals and integral laws; 21. Fundamental laws of physics in Riemannian spaces; Part III. Foundations of Einstein's Theory of Gravitation: 22. The fundamental equations of Einstein's theory of gravitation; 23. The Schwarzschild solution; 24. Experiments to verify the Schwarzschild metric; 25. Gravitational lenses; 26. The interior Schwarzschild solution; Part IV. Linearized Theory of Gravitation, Far Fields and Gravitational Waves: 27. The linearized Einstein theory of gravity; 28. Far fields due to arbitrary matter distributions and balance equations for momentum and angular momentum; 29. Gravitational waves; 30. The Cauchy problem for the Einstein field equations; Part V. Invariant Characterization of Exact Solutions: 31. Preferred vector fields and their properties; 32. The Petrov classification; 33. Killing vectors and groups of motion; 34. A survey of some selected classes of exact solutions; Part VI. Gravitational Collapse and Black Holes: 35. The Schwarzschild singularity; 36. Gravitational collapse

  19. Visualizing domain wall and reverse domain superconductivity.

    PubMed

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  20. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

    Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

    2014-01-01

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

  1. Bias/Variance Analysis for Relational Domains

    DTIC Science & Technology

    2007-08-15

    EDtr ,Dte,t[L(t, y)] = EDtr ,Dte,t[(t − y)2] = Et[(t − E[t])2] + EDtr ,Dte...y − E[t])2] = NT (x) + EDtr ,Dte[(y − EDtr ,Dte[y] + EDtr ,Dte[y]− E[t])2] = NT (x) + EDtr ,Dte[(y − EDtr ,Dte[y])2 + ( EDtr ,Dte[y]− E[t])2 + 2(y − EDtr ,Dte...y]) · ( EDtr ,Dte[y]− E[t])] = NT (x) + EDtr ,Dte[(y − EDtr ,Dte[y])2] + ( EDtr ,Dte[y]− E[t])2 = NT (x) + VT (x) + BT (x) In this decomposition the

  2. Three genes expressing Kunitz domains in the epididymis are related to genes of WFDC-type protease inhibitors and semen coagulum proteins in spite of lacking similarity between their protein products

    PubMed Central

    2011-01-01

    Background We have previously identified a locus on human chromosome 20q13.1, encompassing related genes of postulated WFDC-type protease inhibitors and semen coagulum proteins. Three of the genes with WFDC motif also coded for the Kunitz-type protease inhibitor motif. In this report, we have reinvestigated the locus for homologous genes encoding Kunitz motif only. The identified genes have been analyzed with respect to structure, expression and function. Results We identified three novel genes; SPINT3, SPINT4 and SPINT5, and the structure of their transcripts were determined by sequencing of DNA generated by rapid amplification of cDNA ends. Each gene encodes a Kunitz domain preceded by a typical signal peptide sequence, which indicates that the proteins of 7.6, 8.7, and 9.7 kDa are secreted. Analysis of transcripts in 26 tissues showed that the genes predominantly are expressed in the epididymis. The recombinantly produced proteins could not inhibit the amidolytic activity of trypsin, chymotrypsin, plasmin, thrombin, coagulation factor Xa, elastase, urokinase and prostate specific antigen, whereas similarly made bovine pancreatic trypsin inhibitor (BPTI) had the same bioactivity as the protein isolated from bovine pancreas. Conclusions The similar organization, chromosomal location and site of expression, suggests that the novel genes are homologous with the genes of WFDC-type protease inhibitors and semen coagulum proteins, despite the lack of similarity in primary structure of their protein products. Their restricted expression to the epididymis suggests that they could be important for male reproduction. The recombinantly produced proteins are presumably bioactive, as demonstrated with similarly made BPTI, but may have a narrower spectrum of inhibition, as indicated by the lacking activity against eight proteases with differing specificity. Another possibility is that they have lost the protease inhibiting properties, which is typical of Kunitz domains, in

  3. Causal Learning Across Domains

    ERIC Educational Resources Information Center

    Schulz, Laura E.; Gopnik, Alison

    2004-01-01

    Five studies investigated (a) children's ability to use the dependent and independent probabilities of events to make causal inferences and (b) the interaction between such inferences and domain-specific knowledge. In Experiment 1, preschoolers used patterns of dependence and independence to make accurate causal inferences in the domains of…

  4. A Domain Analysis Bibliography

    DTIC Science & Technology

    1990-06-01

    Bauhaus , a prototype CASE workstation for D-SAPS development. [ARAN88A] Guillermo F. Arango. Domain Engineering for Software Reuse. PhD thesis...34 VITA90B: Domain Analysis within the ISEC Rapid Center 48 CMU/SEI-90-SR-3 Appendix III Alphabetical by Organization/Project BAUHAUS * ALLE87A

  5. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  6. Domains of Learning.

    ERIC Educational Resources Information Center

    Gagne, Robert M.

    In planning educational research, recognition needs to be made of five domains of learning: (1) motor skills, (2) verbal information, (3) intellectual skills, (4) cognitive strategies, and (5) attitudes. In being cognizant of these domains, the researcher is able to distinguish the parts of a content area which are subject to different…

  7. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  8. Domain wall filters

    SciTech Connect

    Baer, Oliver; Narayanan, Rajamani; Neuberger, Herbert; Witzel, Oliver

    2007-03-15

    We propose using the extra dimension separating the domain walls carrying lattice quarks of opposite handedness to gradually filter out the ultraviolet fluctuations of the gauge fields that are felt by the fermionic excitations living in the bulk. This generalization of the homogeneous domain wall construction has some theoretical features that seem nontrivial.

  9. Sac phosphatase domain proteins.

    PubMed Central

    Hughes, W E; Cooke, F T; Parker, P J

    2000-01-01

    Advances in our understanding of the roles of phosphatidylinositol phosphates in controlling cellular functions such as endocytosis, exocytosis and the actin cytoskeleton have included new insights into the phosphatases that are responsible for the interconversion of these lipids. One of these is an entirely novel class of phosphatase domain found in a number of well characterized proteins. Proteins containing this Sac phosphatase domain include the yeast Saccharomyces cerevisiae proteins Sac1p and Fig4p. The Sac phosphatase domain is also found within the mammalian phosphoinositide 5-phosphatase synaptojanin and the yeast synaptojanin homologues Inp51p, Inp52p and Inp53p. These proteins therefore contain both Sac phosphatase and 5-phosphatase domains. This review describes the Sac phosphatase domain-containing proteins and their actions, with particular reference to the genetic and biochemical insights provided by study of the yeast Saccharomyces cerevisiae. PMID:10947947

  10. Domains of Awareness in Schizophrenia

    PubMed Central

    Gilleen, J.; Greenwood, K.; David, A. S.

    2011-01-01

    Patients with schizophrenia are often characterized as lacking insight or awareness into their illness and symptoms, yet despite considerable research, we still lack a full understanding of the factors involved in causing poor awareness. Within schizophrenia, there has been shown to be a fractionation across dimensions of awareness into mental illness: of being ill, of symptoms, and of treatment compliance. Recently, attention has turned to evidence of a fractionation between awareness of illness and of cognitive impairments and functioning. The current study investigated the degree of fractionation across a broad range of domains of function in schizophrenia and how each domain may be associated with neuropsychological functioning, clinical, mood, and demographic variables. Thirty-one mostly chronic stable patients with schizophrenia completed a battery of neuropsychological tests and measures of psychopathology, including mood. Cognitive insight and awareness of illness, symptoms, memory, and behavioral functioning were also measured. Insight and awareness were assessed using a combination of semistructured interview, observer-rated, self-rated, and objective measures, and included measures of the discrepancy between carer and self-ratings of impairment. Results revealed that awareness of functioning in each domain was largely independent and that awareness in each domain was predicted by different factors. Insight into symptoms was relatively poor while insight into cognitive deficits was preserved. Relative to neuropsychological variables, cognitive insight, comprising self-certainty and self-reflexivity, was a greater predictor of awareness. In conclusion, awareness is multiply fractionated and multiply determined. Therapeutic interventions could, therefore, produce beneficial changes within specific domains of awareness. PMID:20851850

  11. Cooperative interactions between paired domain and homeodomain.

    PubMed

    Jun, S; Desplan, C

    1996-09-01

    The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.

  12. Domain Transfer Learning for MCI Conversion Prediction

    PubMed Central

    Cheng, Bo; Liu, Mingxia; Zhang, Daoqiang; Munsell, Brent C.; Shen, Dinggang

    2015-01-01

    Machine learning methods have been increasingly used to predict the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD), by classifying MCI converters (MCI-C) from MCI non-converters (MCI-NC). However, most of existing methods construct classifiers using only data from one particular target domain (e.g., MCI), and ignore data in the other related domains (e.g., AD and normal control (NC)) that could provide valuable information to promote the performance of MCI conversion prediction. To this end, we develop a novel domain transfer learning method for MCI conversion prediction, which can use data from both the target domain (i.e., MCI) and the auxiliary domains (i.e., AD and NC). Specifically, the proposed method consists of three key components: 1) a domain transfer feature selection (DTFS) component that selects the most informative feature-subset from both target domain and auxiliary domains with different imaging modalities, 2) a domain transfer sample selection (DTSS) component that selects the most informative sample-subset from the same target and auxiliary domains with different data modalities, and 3) a domain transfer support vector machine (DTSVM) classification component that fuses the selected features and samples to separate MCI-C and MCI-NC patients. We evaluate our method on 202 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with MRI, FDG-PET and CSF data. The experimental results show that the proposed method can classify MCI-C patients from MCI-NC patients with an accuracy of 79.4%, with the aid of additional domain knowledge learned from AD and NC. PMID:25751861

  13. Domain Transfer Learning for MCI Conversion Prediction.

    PubMed

    Cheng, Bo; Liu, Mingxia; Zhang, Daoqiang; Munsell, Brent C; Shen, Dinggang

    2015-07-01

    Machine learning methods have successfully been used to predict the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD), by classifying MCI converters (MCI-C) from MCI nonconverters (MCI-NC). However, most existing methods construct classifiers using data from one particular target domain (e.g., MCI), and ignore data in other related domains (e.g., AD and normal control (NC)) that may provide valuable information to improve MCI conversion prediction performance. To address is limitation, we develop a novel domain transfer learning method for MCI conversion prediction, which can use data from both the target domain (i.e., MCI) and auxiliary domains (i.e., AD and NC). Specifically, the proposed method consists of three key components: 1) a domain transfer feature selection component that selects the most informative feature-subset from both target domain and auxiliary domains from different imaging modalities; 2) a domain transfer sample selection component that selects the most informative sample-subset from the same target and auxiliary domains from different data modalities; and 3) a domain transfer support vector machine classification component that fuses the selected features and samples to separate MCI-C and MCI-NC patients. We evaluate our method on 202 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that have MRI, FDG-PET, and CSF data. The experimental results show the proposed method can classify MCI-C patients from MCI-NC patients with an accuracy of 79.4%, with the aid of additional domain knowledge learned from AD and NC.

  14. Extra domains in secondary transport carriers and channel proteins.

    PubMed

    Barabote, Ravi D; Tamang, Dorjee G; Abeywardena, Shannon N; Fallah, Neda S; Fu, Jeffrey Yu Chung; Lio, Jeffrey K; Mirhosseini, Pegah; Pezeshk, Ronnie; Podell, Sheila; Salampessy, Marnae L; Thever, Mark D; Saier, Milton H

    2006-10-01

    "Extra" domains in members of the families of secondary transport carrier and channel proteins provide secondary functions that expand, amplify or restrict the functional nature of these proteins. Domains in secondary carriers include TrkA and SPX domains in DASS family members, DedA domains in TRAP-T family members (both of the IT superfamily), Kazal-2 and PDZ domains in OAT family members (of the MF superfamily), USP, IIA(Fru) and TrkA domains in ABT family members (of the APC superfamily), ricin domains in OST family members, and TrkA domains in AAE family members. Some transporters contain highly hydrophilic domains consisting of multiple repeat units that can also be found in proteins of dissimilar function. Similarly, transmembrane alpha-helical channel-forming proteins contain unique, conserved, hydrophilic domains, most of which are not found in carriers. In some cases the functions of these domains are known. They may be ligand binding domains, phosphorylation domains, signal transduction domains, protein/protein interaction domains or complex carbohydrate-binding domains. These domains mediate regulation, subunit interactions, or subcellular targeting. Phylogenetic analyses show that while some of these domains are restricted to closely related proteins derived from specific organismal types, others are nearly ubiquitous within a particular family of transporters and occur in a tremendous diversity of organisms. The former probably became associated with the transporters late in the evolutionary process; the latter probably became associated with the carriers much earlier. These domains can be located at either end of the transporter or in a central region, depending on the domain and transporter family. These studies provide useful information about the evolution of extra domains in channels and secondary carriers and provide novel clues concerning function.

  15. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    PubMed

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  16. A new principle technic for the transformation from frequency domain to time domain

    NASA Astrophysics Data System (ADS)

    Gao, Ben-Qing

    2017-03-01

    A principle technic for the transformation from frequency domain to time domain is presented. Firstly, a special type of frequency domain transcendental equation is obtained for an expected frequency domain parameter which is a rational or irrational fraction expression. Secondly, the inverse Laplace transformation is performed. When the two time-domain factors corresponding to the two frequency domain factors at two sides of frequency domain transcendental equation are known quantities, a time domain transcendental equation is reached. At last, the expected time domain parameter corresponding to the expected frequency domain parameter can be solved by the inverse convolution process. Proceeding from rational or irrational fraction expression, all solving process is provided. In the meantime, the property of time domain sequence is analyzed and the strategy for choosing the parameter values is described. Numerical examples are presented to verify the proposed theory and technic. Except for rational or irrational fraction expressions, examples of complex relative permittivity of water and plasma are used as verification method. The principle method proposed in the paper can easily solve problems which are difficult to be solved by Laplace transformation.

  17. XML Based Markup Languages for Specific Domains

    NASA Astrophysics Data System (ADS)

    Varde, Aparna; Rundensteiner, Elke; Fahrenholz, Sally

    A challenging area in web based support systems is the study of human activities in connection with the web, especially with reference to certain domains. This includes capturing human reasoning in information retrieval, facilitating the exchange of domain-specific knowledge through a common platform and developing tools for the analysis of data on the web from a domain expert's angle. Among the techniques and standards related to such work, we have XML, the eXtensible Markup Language. This serves as a medium of communication for storing and publishing textual, numeric and other forms of data seamlessly. XML tag sets are such that they preserve semantics and simplify the understanding of stored information by users. Often domain-specific markup languages are designed using XML, with a user-centric perspective. Standardization bodies and research communities may extend these to include additional semantics of areas within and related to the domain. This chapter outlines the issues to be considered in developing domain-specific markup languages: the motivation for development, the semantic considerations, the syntactic constraints and other relevant aspects, especially taking into account human factors. Illustrating examples are provided from domains such as Medicine, Finance and Materials Science. Particular emphasis in these examples is on the Materials Markup Language MatML and the semantics of one of its areas, namely, the Heat Treating of Materials. The focus of this chapter, however, is not the design of one particular language but rather the generic issues concerning the development of domain-specific markup languages.

  18. Phylogenetic Analysis of Brassica rapa MATH-Domain Proteins

    PubMed Central

    Zhao, Liming; Huang, Yong; Hu, Yan; He, Xiaoli; Shen, Wenhui; Liu, Chunlin; Ruan, Ying

    2013-01-01

    The MATH (meprin and TRAF-C homology) domain is a fold of seven anti-parallel β-helices involved in protein-protein interaction. Here, we report the identification and characterization of 90 MATH-domain proteins from the Brassica rapa genome. By sequence analysis together with MATH-domain proteins from other species, the B. rapa MATH-domain proteins can be grouped into 6 classes. Class-I protein has one or several MATH domains without any other recognizable domain; Class-II protein contains a MATH domain together with a conserved BTB (Broad Complex, Tramtrack, and Bric-a-Brac ) domain; Class-III protein belongs to the MATH/Filament domain family; Class-IV protein contains a MATH domain frequently combined with some other domains; Class-V protein has a relative long sequence but contains only one MATH domain; Class-VI protein is characterized by the presence of Peptidase and UBQ (Ubiquitinylation) domains together with one MATH domain. As part of our study regarding seed development of B. rapa, six genes are screened by SSH (Suppression Subtractive Hybridization) and their expression levels are analyzed in combination with seed developmental stages, and expression patterns suggested that Bra001786, Bra03578 and Bra036572 may be seed development specific genes, while Bra001787, Bra020541 and Bra040904 may be involved in seed and flower organ development. This study provides the first characterization of the MATH domain proteins in B. rapa PMID:24179444

  19. Requirements analysis, domain knowledge, and design

    NASA Technical Reports Server (NTRS)

    Potts, Colin

    1988-01-01

    Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.

  20. Visualizing Knowledge Domains.

    ERIC Educational Resources Information Center

    Borner, Katy; Chen, Chaomei; Boyack, Kevin W.

    2003-01-01

    Reviews visualization techniques for scientific disciplines and information retrieval and classification. Highlights include historical background of scientometrics, bibliometrics, and citation analysis; map generation; process flow of visualizing knowledge domains; measures and similarity calculations; vector space model; factor analysis;…

  1. Misexpression of AtTX12 encoding a Toll/interleukin-1 receptor domain induces growth defects and expression of defense-related genes partially independently of EDS1 in Arabidopsis

    PubMed Central

    Song, Sang-Kee

    2016-01-01

    In this study, a tissue-specific GAL4/UAS activation tagging system was used for the characterization of genes which could induce lethality when ubiquitously expressed. A dominant mutant exhibiting stunted growth was isolated and named defective root development 1-D (drd1-D). The T-DNA tag was located within the promoter region of AtTX12, which is predicted to encode a truncated nucleotide-binding leucine-rich repeat (NLR) protein, containing a Toll/interleukin-1 receptor (TIR) domain. The transcript levels of AtTX12 and defense-related genes were elevated in drd1-D, and the misexpression of AtTX12 recapitulated the drd1-D phenotypes. In the presence of ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), a key transducer of signals triggered by TIR-type NLRs, a low-level of AtTX12 misexpression induced strong defective phenotypes including seedling lethality whereas, in the absence of EDS1, a high-level of AtTX12 misexpression induced weak growth defects like dwarfism, suggesting that AtTX12 might function mainly in an EDS1-dependent and partially in an EDS1-independent manner. [BMB Reports 2016; 49(12): 693–698] PMID:27802841

  2. SOT1, a pentatricopeptide repeat protein with a small MutS-related domain, is required for correct processing of plastid 23S-4.5S rRNA precursors in Arabidopsis thaliana.

    PubMed

    Wu, Wenjuan; Liu, Sheng; Ruwe, Hannes; Zhang, Delin; Melonek, Joanna; Zhu, Yajuan; Hu, Xupeng; Gusewski, Sandra; Yin, Ping; Small, Ian D; Howell, Katharine A; Huang, Jirong

    2016-03-01

    Ribosomal RNA processing is essential for plastid ribosome biogenesis, but is still poorly understood in higher plants. Here, we show that SUPPRESSOR OF THYLAKOID FORMATION1 (SOT1), a plastid-localized pentatricopeptide repeat (PPR) protein with a small MutS-related domain, is required for maturation of the 23S-4.5S rRNA dicistron. Loss of SOT1 function leads to slower chloroplast development, suppression of leaf variegation, and abnormal 23S and 4.5S processing. Predictions based on the PPR motif sequences identified the 5' end of the 23S-4.5S rRNA dicistronic precursor as a putative SOT1 binding site. This was confirmed by electrophoretic mobility shift assay, and by loss of the abundant small RNA 'footprint' associated with this site in sot1 mutants. We found that more than half of the 23S-4.5S rRNA dicistrons in sot1 mutants contain eroded and/or unprocessed 5' and 3' ends, and that the endonucleolytic cleavage product normally released from the 5' end of the precursor is absent in a sot1 null mutant. We postulate that SOT1 binding protects the 5' extremity of the 23S-4.5S rRNA dicistron from exonucleolytic attack, and favours formation of the RNA structure that allows endonucleolytic processing of its 5' and 3' ends. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  3. Stability of domain structures in multi-domain proteins

    PubMed Central

    Bhaskara, Ramachandra M.; Srinivasan, Narayanaswamy

    2011-01-01

    Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR. PMID:22355559

  4. Software architecture design domain

    SciTech Connect

    White, S.A.

    1996-12-31

    Software architectures can provide a basis for the capture and subsequent reuse of design knowledge. The goal of software architecture is to allow the design of a system to take place at a higher level of abstraction; a level concerned with components, connections, constraints, rationale. This architectural view of software adds a new layer of abstraction to the traditional design phase of software development. It has resulted in a flurry of activity towards techniques, tools, and architectural design languages developed specifically to assist with this activity. An analysis of architectural descriptions, even though they differ in notation, shows a common set of key constructs that are present across widely varying domains. These common aspects form a core set of constructs that should belong to any ADL in order to for the language to offer the ability to specify software systems at the architectural level. This analysis also revealed a second set of constructs which served to expand the first set thereby improving the syntax and semantics. These constructs are classified according to whether they provide representation and analysis support for architectures belonging to many varying application domains (domain-independent construct class) or to a particular application domain (domain-dependent constructs). This paper presents the constructs of these two classes, their placement in the architecture design domain and shows how they may be used to classify, select, and analyze proclaimed architectural design languages (ADLs).

  5. Certifying Domain-Specific Policies

    NASA Technical Reports Server (NTRS)

    Lowry, Michael; Pressburger, Thomas; Rosu, Grigore; Koga, Dennis (Technical Monitor)

    2001-01-01

    Proof-checking code for compliance to safety policies potentially enables a product-oriented approach to certain aspects of software certification. To date, previous research has focused on generic, low-level programming-language properties such as memory type safety. In this paper we consider proof-checking higher-level domain -specific properties for compliance to safety policies. The paper first describes a framework related to abstract interpretation in which compliance to a class of certification policies can be efficiently calculated Membership equational logic is shown to provide a rich logic for carrying out such calculations, including partiality, for certification. The architecture for a domain-specific certifier is described, followed by an implemented case study. The case study considers consistency of abstract variable attributes in code that performs geometric calculations in Aerospace systems.

  6. Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.

    PubMed

    Rose, Nathan R; Woon, Esther C Y; Tumber, Anthony; Walport, Louise J; Chowdhury, Rasheduzzaman; Li, Xuan Shirley; King, Oliver N F; Lejeune, Clarisse; Ng, Stanley S; Krojer, Tobias; Chan, Mun Chiang; Rydzik, Anna M; Hopkinson, Richard J; Che, Ka Hing; Daniel, Michelle; Strain-Damerell, Claire; Gileadi, Carina; Kochan, Grazyna; Leung, Ivanhoe K H; Dunford, James; Yeoh, Kar Kheng; Ratcliffe, Peter J; Burgess-Brown, Nicola; von Delft, Frank; Muller, Susanne; Marsden, Brian; Brennan, Paul E; McDonough, Michael A; Oppermann, Udo; Klose, Robert J; Schofield, Christopher J; Kawamura, Akane

    2012-07-26

    The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal that daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups.

  7. The Plant Growth Regulator Daminozide is a Selective Inhibitor of the Human KDM2/7 Histone Demethylases

    PubMed Central

    Rose, Nathan R.; Woon, Esther C.Y.; Tumber, Anthony; Walport, Louise J.; Chowdhury, Rasheduzzaman; Li, Xuan Shirley; King, Oliver N.F.; Lejeune, Clarisse; Ng, Stanley S.; Krojer, Tobias; Chan, Mun Chiang; Rydzik, Anna M.; Hopkinson, Richard J.; Che, Ka Hing; Daniel, Michelle; Strain-Damerell, Claire; Gileadi, Carina; Kochan, Grazyna; Leung, Ivanhoe K. H.; Dunford, James; Yeoh, Kar Kheng; Ratcliffe, Peter J.; Burgess-Brown, Nicola; von Delft, Frank; Muller, Susanne; Marsden, Brian; Brennan, Paul E.; McDonough, Michael A.; Oppermann, Udo; Klose, Robert J.; Schofield, Christopher J.; Kawamura, Akane

    2015-01-01

    The JmjC oxygenases catalyse the N-demethylation of Nε-methyl lysine residues in histones and are current therapeutic targets. A set of 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups. PMID:22724510

  8. La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability.

    PubMed

    Yang, Ruiqing; Gaidamakov, Sergei A; Xie, Jingwei; Lee, Joowon; Martino, Luigi; Kozlov, Guennadi; Crawford, Amanda K; Russo, Amy N; Conte, Maria R; Gehring, Kalle; Maraia, Richard J

    2011-02-01

    The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them against 3'-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and reciprocal immunoprecipitations (IPs) from HeLa cells revealed that LARP4 interacts with RACK1, a 40S ribosome- and mRNA-associated protein. LARP4 cosediments with 40S ribosome subunits and polyribosomes, and its knockdown decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs decrease LARP4 association with polysomes. Several translation and mRNA metabolism-related proteins use a PAM2 sequence containing a critical invariant phenylalanine to make direct contact with the MLLE domain of PABP, and their competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all ∼150 previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 (PAM2w) with tryptophan in place of the phenylalanine. Binding and nuclear magnetic resonance (NMR) studies have shown that a peptide representing LARP4 PAM2w interacts with the MLLE of PABP within the affinity range measured for other PAM2 motif peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4 expression stimulates luciferase reporter activity by promoting mRNA stability, as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis.

  9. Domain transfer learning for MCI conversion prediction.

    PubMed

    Cheng, Bo; Zhang, Daoqiang; Shen, Dinggang

    2012-01-01

    In recent studies of Alzheimer's disease (AD), it has increasing attentions in identifying mild cognitive impairment (MCI) converters (MCI-C) from MCI non-converters (MCI-NC). Note that MCI is a prodromal stage of AD, with possibility to convert to AD. Most traditional methods for MCI conversion prediction learn information only from MCI subjects (including MCI-C and MCI-NC), not from other related subjects, e.g., AD and normal controls (NC), which can actually aid the classification between MCI-C and MCI-NC. In this paper, we propose a novel domain-transfer learning method for MCI conversion prediction. Different from most existing methods, we classify MCI-C and MCI-NC with aid from the domain knowledge learned with AD and NC subjects as auxiliary domain to further improve the classification performance. Our method contains two key components: (1) the cross-domain kernel learning for transferring auxiliary domain knowledge, and (2) the adapted support vector machine (SVM) decision function construction for cross-domain and auxiliary domain knowledge fusion. Experimental results on the Alzheimer's Disease neuroimaging initiative (ADNI) database show that the proposed method can significantly improve the classification performance between MCI-C and MCI-NC, with aid of domain knowledge learned from AD and NC subjects.

  10. The BAH domain of Rsc2 is a histone H3 binding domain

    PubMed Central

    Chambers, Anna L.; Pearl, Laurence H.; Oliver, Antony W.; Downs, Jessica A.

    2013-01-01

    Bromo-adjacent homology (BAH) domains are commonly found in chromatin-associated proteins and fall into two classes; Remodels the Structure of Chromatin (RSC)-like or Sir3-like. Although Sir3-like BAH domains bind nucleosomes, the binding partners of RSC-like BAH domains are currently unknown. The Rsc2 subunit of the RSC chromatin remodeling complex contains an RSC-like BAH domain and, like the Sir3-like BAH domains, we find Rsc2 BAH also interacts with nucleosomes. However, unlike Sir3-like BAH domains, we find that Rsc2 BAH can bind to recombinant purified H3 in vitro, suggesting that the mechanism of nucleosome binding is not conserved. To gain insight into the Rsc2 BAH domain, we determined its crystal structure at 2.4 Å resolution. We find that it differs substantially from Sir3-like BAH domains and lacks the motifs in these domains known to be critical for making contacts with histones. We then go on to identify a novel motif in Rsc2 BAH that is critical for efficient H3 binding in vitro and show that mutation of this motif results in defective Rsc2 function in vivo. Moreover, we find this interaction is conserved across Rsc2-related proteins. These data uncover a binding target of the Rsc2 family of BAH domains and identify a novel motif that mediates this interaction. PMID:23907388

  11. Biology and Beyond: Domain Specificity in a Broader Developmental Context

    ERIC Educational Resources Information Center

    Keil, Frank C.

    2007-01-01

    The assumption of domain specificity has been invaluable to the study of the emergence of biological thought in young children. Yet, domains of thought must be understood within a broader context that explains how those domains relate to the surrounding cultures, to different kinds of cognitive constraints, to framing effects, to abilities to…

  12. Changing Your Domain Name in 25 Nail-Biting Steps

    ERIC Educational Resources Information Center

    Hassler, Carol

    2012-01-01

    When staff at the Wisconsin State Law Library began compiling a wish list for a new website, the topic of a new domain name came up almost immediately. Their old website was located at http://wsll.state.wi.us. Spelling that relatively complex domain over the phone day after day provided the impetus to explore other options. Whatever domain name…

  13. Changing Your Domain Name in 25 Nail-Biting Steps

    ERIC Educational Resources Information Center

    Hassler, Carol

    2012-01-01

    When staff at the Wisconsin State Law Library began compiling a wish list for a new website, the topic of a new domain name came up almost immediately. Their old website was located at http://wsll.state.wi.us. Spelling that relatively complex domain over the phone day after day provided the impetus to explore other options. Whatever domain name…

  14. Domains in Ferroelectric Nanostructures

    NASA Astrophysics Data System (ADS)

    Gregg, Marty

    2010-03-01

    Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device

  15. Extending Protein Domain Boundary Predictors to Detect Discontinuous Domains

    PubMed Central

    Xue, Zhidong; Jang, Richard; Govindarajoo, Brandon; Huang, Yichu; Wang, Yan

    2015-01-01

    A variety of protein domain predictors were developed to predict protein domain boundaries in recent years, but most of them cannot predict discontinuous domains. Considering nearly 40% of multidomain proteins contain one or more discontinuous domains, we have developed DomEx to enable domain boundary predictors to detect discontinuous domains by assembling the continuous domain segments. Discontinuous domains are predicted by matching the sequence profile of concatenated continuous domain segments with the profiles from a single-domain library derived from SCOP and CATH, and Pfam. Then the matches are filtered by similarity to library templates, a symmetric index score and a profile-profile alignment score. DomEx recalled 32.3% discontinuous domains with 86.5% precision when tested on 97 non-homologous protein chains containing 58 continuous and 99 discontinuous domains, in which the predicted domain segments are within ±20 residues of the boundary definitions in CATH 3.5. Compared with our recently developed predictor, ThreaDom, which is the state-of-the-art tool to detect discontinuous-domains, DomEx recalled 26.7% discontinuous domains with 72.7% precision in a benchmark with 29 discontinuous-domain chains, where ThreaDom failed to predict any discontinuous domains. Furthermore, combined with ThreaDom, the method ranked number one among 10 predictors. The source code and datasets are available at https://github.com/xuezhidong/DomEx. PMID:26502173

  16. Inhalational anesthetics disrupt postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 domain protein interactions critical to action of several excitatory receptor channels related to anesthesia

    PubMed Central

    Tao, Feng; Chen, Qiang; Sato, Yuko; Skinner, John; Tang, Pei; Johns, Roger A.

    2015-01-01

    Background We have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. Our data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated. Methods Glutathione S-transferase pull-down assay, co-immunoprecipitation and yeast two-hybrid analysis were used to assess PDZ domain-mediated protein-protein interactions in different conditions. Nuclear magnetic resonance spectroscopy was used to investigate isoflurane-induced chemical shift changes in the PDZ1–3 domains of PSD-95. A surface plasmon resonance-based BIAcore assay was used to examine the ability of isoflurane to inhibit the PDZ domain-mediated protein-protein interactions in real time. Results Halothane and isoflurane dose dependently inhibited PDZ domain-mediated interactions between PSD-95 and Shaker-type potassium channel Kv1.4 and between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluA2 and its interacting proteins— glutamate receptor interacting protein or protein interacting with c kinase 1. However, halothane and isoflurane had no effect on PDZ domain-mediated interactions between γ-aminobutyric acid, type B receptor and its interacting proteins. The inhaled anesthetic isoflurane mostly affected the residues close to or in the peptide binding groove of PSD-95 PDZ1 and PDZ2 (especially PDZ2), while barely affecting the peptide binding groove of PSD-95 PDZ3. Conclusion These results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia and pain processing. PMID:25654436

  17. Mapping knowledge domains: Characterizing PNAS

    PubMed Central

    Boyack, Kevin W.

    2004-01-01

    A review of data mining and analysis techniques that can be used for the mapping of knowledge domains is given. Literature mapping techniques can be based on authors, documents, journals, words, and/or indicators. Most mapping questions are related to research assessment or to the structure and dynamics of disciplines or networks. Several mapping techniques are demonstrated on a data set comprising 20 years of papers published in PNAS. Data from a variety of sources are merged to provide unique indicators of the domain bounded by PNAS. By using funding source information and citation counts, it is shown that, on an aggregate basis, papers funded jointly by the U.S. Public Health Service (which includes the National Institutes of Health) and non-U.S. government sources outperform papers funded by other sources, including by the U.S. Public Health Service alone. Grant data from the National Institute on Aging show that, on average, papers from large grants are cited more than those from small grants, with performance increasing with grant amount. A map of the highest performing papers over the 20-year period was generated by using citation analysis. Changes and trends in the subjects of highest impact within the PNAS domain are described. Interactions between topics over the most recent 5-year period are also detailed. PMID:14963238

  18. Axion domain wall baryogenesis

    SciTech Connect

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu

    2015-07-28

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m≃10{sup 8}–10{sup 13} GeV and f≃10{sup 13}–10{sup 16} GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  19. Axion domain wall baryogenesis

    SciTech Connect

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu E-mail: kitajima@tuhep.phys.tohoku.ac.jp

    2015-07-01

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m ≅ 10{sup 8}–10{sup 13} GeV and f ≅ 10{sup 13}–10{sup 16} GeV . Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  20. The ASH1-RELATED3 SET-