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Sample records for extended phenotypes structure

  1. On the origins of parasite-extended phenotypes.

    PubMed

    Hughes, David P

    2014-07-01

    Parasites that adaptively manipulate the behavior of their host are among the most exciting adaptations that we can find in nature. The behavior of the host can become an extended phenotype of the parasites within animals such that the success and failure of the parasite's genome rely on precise change of the host's behavior. Evolutionary biology was borne from the close attention of naturalists such as Wallace and Darwin to phenotypic variation in seeking to understand the origins of new species. In this essay, I argue that we also need to think about the origins of parasite-extended phenotypes. This is a more difficult task than understanding the evolution of textbook examples of novelty such as the eyes of vertebrates or the hooves of horses. However, new tools such as phylogenomics provide an important opportunity to make significant progress in understanding the extended phenotypes of parasites. Knowing the origins of parasite-extended phenotypes is important as a goal all by itself. But the knowledge gained will also help us understand why complex manipulation is so rare and to identify the evolutionary tipping points driving its appearance.

  2. Could the Extended Phenotype Extend to the Cellular and Subcellular Levels in Insect-Induced Galls?

    PubMed

    Carneiro, Renê Gonçalves da Silva; Pacheco, Priscilla; Isaias, Rosy Mary dos Santos

    2015-01-01

    Neo-ontogenesis of plant galls involves redifferentiation of host plant tissues to express new phenotypes, when new cell properties are established via structural-functional remodeling. Herein, Psidium cattleianum leaves and Nothotrioza cattleiani galls are analyzed by developmental anatomy, cytometry and immunocytochemistry of cell walls. We address hypothesis-driven questions concerning the organogenesis of globoid galls in the association of P. cattleianum-N. cattleianum, and P. myrtoides-N. myrtoidis. These double co-generic systems represent good models for comparing final gall shapes and cell lineages functionalities under the perspective of convergent plant-dependent or divergent insect-induced characteristics. Gall induction, and growth and development are similar in both galls, but homologous cell lineages exhibit divergent degrees of cell hypertrophy and directions of elongation. Median cortical cells in P. cattleianum galls hypertrophy the most, while in P. myrtoides galls there is a centrifugal gradient of cell hypertrophy. Cortical cells in P. cattleianum galls tend to anisotropy, while P. myrtoidis galls have isotropically hypertrophied cells. Immunocytochemistry evidences the chemical identity and functional traits of cell lineages: epidermal cells walls have homogalacturonans (HGAs) and galactans, which confer rigidity to sites of enhanced cell division; oil gland cell walls have arabinogalactan proteins (AGPs) that help avoiding cell death; and parenchyma cell walls have HGAs, galactans and arabinans, which confer porosity. Variations in such chemical identities are related to specific sites of hypertrophy. Even though the double co-generic models have the same macroscopic phenotype, the globoid morphotype, current analyses indicate that the extended phenotype of N. cattleiani is substantiated by cellular and subcellular specificities. PMID:26053863

  3. Could the Extended Phenotype Extend to the Cellular and Subcellular Levels in Insect-Induced Galls?

    PubMed Central

    Carneiro, Renê Gonçalves da Silva; Pacheco, Priscilla; Isaias, Rosy Mary dos Santos

    2015-01-01

    Neo-ontogenesis of plant galls involves redifferentiation of host plant tissues to express new phenotypes, when new cell properties are established via structural-functional remodeling. Herein, Psidium cattleianum leaves and Nothotrioza cattleiani galls are analyzed by developmental anatomy, cytometry and immunocytochemistry of cell walls. We address hypothesis-driven questions concerning the organogenesis of globoid galls in the association of P. cattleianum - N. cattleianum, and P. myrtoides - N. myrtoidis. These double co-generic systems represent good models for comparing final gall shapes and cell lineages functionalities under the perspective of convergent plant-dependent or divergent insect-induced characteristics. Gall induction, and growth and development are similar in both galls, but homologous cell lineages exhibit divergent degrees of cell hypertrophy and directions of elongation. Median cortical cells in P. cattleianum galls hypertrophy the most, while in P. myrtoides galls there is a centrifugal gradient of cell hypertrophy. Cortical cells in P. cattleianum galls tend to anisotropy, while P. myrtoidis galls have isotropically hypertrophied cells. Immunocytochemistry evidences the chemical identity and functional traits of cell lineages: epidermal cells walls have homogalacturonans (HGAs) and galactans, which confer rigidity to sites of enhanced cell division; oil gland cell walls have arabinogalactan proteins (AGPs) that help avoiding cell death; and parenchyma cell walls have HGAs, galactans and arabinans, which confer porosity. Variations in such chemical identities are related to specific sites of hypertrophy. Even though the double co-generic models have the same macroscopic phenotype, the globoid morphotype, current analyses indicate that the extended phenotype of N. cattleiani is substantiated by cellular and subcellular specificities. PMID:26053863

  4. Could the Extended Phenotype Extend to the Cellular and Subcellular Levels in Insect-Induced Galls?

    PubMed

    Carneiro, Renê Gonçalves da Silva; Pacheco, Priscilla; Isaias, Rosy Mary dos Santos

    2015-01-01

    Neo-ontogenesis of plant galls involves redifferentiation of host plant tissues to express new phenotypes, when new cell properties are established via structural-functional remodeling. Herein, Psidium cattleianum leaves and Nothotrioza cattleiani galls are analyzed by developmental anatomy, cytometry and immunocytochemistry of cell walls. We address hypothesis-driven questions concerning the organogenesis of globoid galls in the association of P. cattleianum-N. cattleianum, and P. myrtoides-N. myrtoidis. These double co-generic systems represent good models for comparing final gall shapes and cell lineages functionalities under the perspective of convergent plant-dependent or divergent insect-induced characteristics. Gall induction, and growth and development are similar in both galls, but homologous cell lineages exhibit divergent degrees of cell hypertrophy and directions of elongation. Median cortical cells in P. cattleianum galls hypertrophy the most, while in P. myrtoides galls there is a centrifugal gradient of cell hypertrophy. Cortical cells in P. cattleianum galls tend to anisotropy, while P. myrtoidis galls have isotropically hypertrophied cells. Immunocytochemistry evidences the chemical identity and functional traits of cell lineages: epidermal cells walls have homogalacturonans (HGAs) and galactans, which confer rigidity to sites of enhanced cell division; oil gland cell walls have arabinogalactan proteins (AGPs) that help avoiding cell death; and parenchyma cell walls have HGAs, galactans and arabinans, which confer porosity. Variations in such chemical identities are related to specific sites of hypertrophy. Even though the double co-generic models have the same macroscopic phenotype, the globoid morphotype, current analyses indicate that the extended phenotype of N. cattleiani is substantiated by cellular and subcellular specificities.

  5. The social and ecological costs of an ‘over-extended' phenotype

    PubMed Central

    Maguire, Sean M.; Hofmann, Hans A.; Kohda, Masanori

    2016-01-01

    Extended phenotypes offer a unique opportunity to experimentally manipulate and identify sources of selection acting on traits under natural conditions. The social cichlid fish Neolamprologus multifasciatus builds nests by digging up aquatic snail shells, creating an extended sexual phenotype that is highly amenable to experimental manipulation through addition of extra shells. Here, we find sources of both positive sexual selection and opposing natural selection acting on this trait; augmenting shell nests increases access to mates, but also increases social aggression and predation risk. Increasing the attractiveness of one male also changed social interactions throughout the social network and altered the entire community structure. Manipulated males produced and received more displays from neighbouring females, who also joined augmented male territories at higher rates than unmanipulated groups. However, males in more attractive territories received more aggression from neighbouring males, potentially as a form of social policing. We also detected a significant ecological cost of the ‘over-extended' phenotype; heterospecific predators usurped augmented nests at higher rates, using them as breeding sites and displacing residents. Using these natural experiments, we find that both social and ecological interactions generate clear sources of selection mediating the expression of an extended phenotype in the wild. PMID:26740619

  6. Stellar structures in Extended Gravity

    NASA Astrophysics Data System (ADS)

    Capozziello, S.; De Laurentis, M.

    2016-09-01

    Stellar structures are investigated by considering the modified Lané-Emden equation coming out from Extended Gravity. In particular, this equation is obtained in the Newtonian limit of f ( R) -gravity by introducing a polytropic relation between the pressure and the density into the modified Poisson equation. The result is an integro-differential equation, which, in the limit f ( R) → R , becomes the standard Lané-Emden equation usually adopted in the stellar theory. We find the radial profiles of gravitational potential by solving for some values of the polytropic index. The solutions are compatible with those coming from General Relativity and could be physically relevant in order to address peculiar and extremely massive objects.

  7. Extended phenotypic spectrum of KIF5A mutations

    PubMed Central

    Liu, Yo-Tsen; Laurá, Matilde; Hersheson, Joshua; Horga, Alejandro; Jaunmuktane, Zane; Brandner, Sebastian; Pittman, Alan; Hughes, Deborah; Polke, James M.; Sweeney, Mary G.; Proukakis, Christos; Janssen, John C.; Auer-Grumbach, Michaela; Zuchner, Stephan; Shields, Kevin G.; Reilly, Mary M.

    2014-01-01

    Objective: To establish the phenotypic spectrum of KIF5A mutations and to investigate whether KIF5A mutations cause axonal neuropathy associated with hereditary spastic paraplegia (HSP) or typical Charcot-Marie-Tooth disease type 2 (CMT2). Methods: KIF5A sequencing of the motor-domain coding exons was performed in 186 patients with the clinical diagnosis of HSP and in 215 patients with typical CMT2. Another 66 patients with HSP or CMT2 with pyramidal signs were sequenced for all exons of KIF5A by targeted resequencing. One additional patient was genetically diagnosed by whole-exome sequencing. Results: Five KIF5A mutations were identified in 6 unrelated patients: R204W and D232N were novel mutations; R204Q, R280C, and R280H have been previously reported. Three patients had CMT2 as the predominant and presenting phenotype; 2 of them also had pyramidal signs. The other 3 patients presented with HSP but also had significant axonal neuropathy or other additional features. Conclusion: This is currently the largest study investigating KIF5A mutations. By combining next-generation sequencing and conventional sequencing, we confirm that KIF5A mutations can cause variable phenotypes ranging from HSP to CMT2. The identification of mutations in CMT2 broadens the phenotypic spectrum and underlines the importance of KIF5A mutations, which involve degeneration of both the central and peripheral nervous systems and should be tested in HSP and CMT2. PMID:25008398

  8. The life of a dead ant: the expression of an adaptive extended phenotype.

    PubMed

    Andersen, Sandra B; Gerritsma, Sylvia; Yusah, Kalsum M; Mayntz, David; Hywel-Jones, Nigel L; Billen, Johan; Boomsma, Jacobus J; Hughes, David P

    2009-09-01

    Specialized parasites are expected to express complex adaptations to their hosts. Manipulation of host behavior is such an adaptation. We studied the fungus Ophiocordyceps unilateralis, a locally specialized parasite of arboreal Camponotus leonardi ants. Ant-infecting Ophiocordyceps are known to make hosts bite onto vegetation before killing them. We show that this represents a fine-tuned fungal adaptation: an extended phenotype. Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings approximately 25 cm above the soil, where temperature and humidity conditions were optimal for fungal growth. Experimental relocation confirmed that parasite fitness was lower outside this manipulative zone. Host resources were rapidly colonized and further secured by extensive internal structuring. Nutritional composition analysis indicated that such structuring allows the parasite to produce a large fruiting body for spore production. Our findings suggest that the osmotrophic lifestyle of fungi may have facilitated novel exploitation strategies. PMID:19627240

  9. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture.

    PubMed

    Minter, Nicholas J; Franks, Nigel R; Brown, Katharine A Robson

    2012-03-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures. PMID:21849386

  10. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture

    PubMed Central

    Minter, Nicholas J.; Franks, Nigel R.; Robson Brown, Katharine A.

    2012-01-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures. PMID:21849386

  11. Altering an extended phenotype reduces intraspecific male aggression and can maintain diversity in cichlid fish

    PubMed Central

    Croft, Guy E.; Joyce, Domino A.

    2013-01-01

    Reduced male aggression towards different phenotypes generating negative frequency-dependent intrasexual selection has been suggested as a mechanism to facilitate the invasion and maintenance of novel phenotypes in a population. To date, the best empirical evidence for the phenomenon has been provided by laboratory studies on cichlid fish with different colour polymorphisms. Here we experimentally tested the hypothesis in a natural population of Lake Malawi cichlid fish, in which males build sand-castles (bowers) to attract females during seasonal leks. We predicted that if bower shape plays an important role in male aggressive interactions, aggression among conspecific males should decrease when their bower shape is altered. Accordingly, we allocated randomly chosen bowers in a Nyassachromis cf. microcephalus lek into three treatments: control, manipulated to a different shape, and simulated manipulation. We then measured male behaviours and bower shape before and after these treatments. We found that once bower shape was altered, males were involved in significantly fewer aggressive interactions with conspecific males than before manipulation. Mating success was not affected. Our results support the idea that an extended phenotype, such as bower shape, can be important in maintaining polymorphic populations. Specifically, reduced male conspecific aggression towards males with different extended phenotypes (here, bower shapes) may cause negative frequency-dependent selection, allowing the invasion and establishment of a new phenotype (bower builder). This could help our understanding of mechanisms of diversification within populations, and in particular, the overall diversification of bower shapes within Lake Malawi cichlids. PMID:24349896

  12. A molecular genetic study of autism and related phenotypes in extended pedigrees

    PubMed Central

    2013-01-01

    Background Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. Methods We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. Results Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. Conclusions These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears

  13. Extended hydrogen-bonded structures of phosphatidylethanolamine.

    PubMed

    Sen, A; Yang, P W; Mantsch, H H; Hui, S W

    1988-06-01

    The structure of phosphatidylethanolamine in pure dry hexane was studied. Viscosity measurements show that the hexane solution of PE has a very high viscosity, while freeze fracture electron microscopy revealed extensive fibre-like structures. These extended structures are disrupted by the addition of small amounts of water or organic solvents which are capable of hydrogen-bonding. The Fourier transform infrared spectra of the lipid solutions in dry and hydrated hexane show considerable differences in the phosphate and ethanolamine absorption bands, and demonstrate that the viscous fibre-like structures formed by phosphatidylethanolamine in dry hexane consist of extended intermolecular hydrogen-bonds, similar to those found in the solid lipid, with the ammonium group as the hydrogen-donor and the phosphate group as the hydrogen-acceptor. The high viscosity is not observed in hexane solution of phosphatidylcholine.

  14. Extendable retractable telescopic mast for deployable structures

    NASA Technical Reports Server (NTRS)

    Schmid, M.; Aguirre, M.

    1986-01-01

    The Extendable and Retractable Mast (ERM) which is presently developed by Dornier in the frame of an ESA-contract, will be used to deploy and retract large foldable structures. The design is based on a telescopic carbon-fiber structure with high stiffness, strength and pointing accuracy. To verify the chosen design, a breadboard model of an ERM was built and tested under thermal vacuum (TV)-conditions. It is planned as a follow-on development to manufacture and test an Engineering Model Mast. The Engineering Model will be used to establish the basis for an ERM-family covering a wide range of requirements.

  15. Extending Injury- and Disease-Resistant CNS Phenotypes by Repetitive Epigenetic Conditioning

    PubMed Central

    Gidday, Jeffrey M.

    2015-01-01

    Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist – in effect, expanding conditioning’s “therapeutic window” – would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1–3 days) protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances post-ischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neuroplasticity remain largely unstudied, accumulating empirical evidence supports the contention that all of these adaptive phenotypes are epigenetically mediated. Going forward, additional preclinical demonstrations of the ability to induce sustained beneficial phenotypes that reduce the burden of acute and chronic neurodegeneration, and experimental interrogations of the regulatory constructs responsible for these epigenetic responses, will accelerate the identification of not only efficacious but also practical, adaptive epigenetics-based treatments for individuals with neurological disease. PMID:25784897

  16. Angle-resolved photoemission extended fine structure

    SciTech Connect

    Barton, J.J.

    1985-03-01

    Measurements of the Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) from the S(1s) core level of a c(2 x 2)S/Ni(001) are analyzed to determine the spacing between the S overlayer and the first and second Ni layers. ARPEFS is a type of photoelectron diffraction measurement in which the photoelectron kinetic energy is swept typically from 100 to 600 eV. By using this wide range of intermediate energies we add high precision and theoretical simplification to the advantages of the photoelectron diffraction technique for determining surface structures. We report developments in the theory of photoelectron scattering in the intermediate energy range, measurement of the experimental photoemission spectra, their reduction to ARPEFS, and the surface structure determination from the ARPEFS by combined Fourier and multiple-scattering analyses. 202 refs., 67 figs., 2 tabs.

  17. Silylated carbodiimides in molecular and extended structures

    NASA Astrophysics Data System (ADS)

    Kroll, Peter; Riedel, Ralf; Hoffmann, Roald

    1999-08-01

    This work studies the ternary Si-C-N phases SiC2N4 and Si2CN4,exploiting an analogy between the NCN and O groups. Starting from the molecular model of N,N'-bis(trimethylsilyl)-carbodiimide and proceeding to extended models, we calculate that the energy hypersurface associated with the Si-N=C bond angle φN is very shallow, for both molecular and extended structures. We propose a crystal structure for the low-temperature modification α-SiC2N4 in space group P4322 (95), which is 40 meV (~4 kJ/mol) lower in energy than an ideal cubic arrangement in space group Pn3¯m.A second structure, β-SiC2N4 [space group P4¯n2 (118)], is slightly higher in energy than α-SiC2N4,but still more stable than the cubic structure, and may be the high-temperature structure of SiC2N4.Both variants of SiC2N4 show a small bulk modulus of about 8 GPa (~0.13 Mbar),suggesting a high compressibility of these nonoxide covalently bonded materials. For Si2CN4 we refined the crystal structure of the compound within the experimentally determined space group Aba2 (41). We also found a second candidate nearly equal in energy, with space group Cmc21,differing only in the connection pattern of the SiN2 layered sheets. Both ternary compounds appear to be thermodynamically unstable with respect to decomposition into Si3N4,C, and molecular N2.

  18. Extended culture of macrophages from different sources and maturation results in a common M2 phenotype.

    PubMed

    Chamberlain, Lisa M; Holt-Casper, Dolly; Gonzalez-Juarrero, Mercedes; Grainger, David W

    2015-09-01

    Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign-body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely used in short-term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development toward an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign-body response and encapsulation in vivo often elicit a shift toward an analogous M2 macrophage phenotype. In vitro "default" of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized, but has important implications to in vitro modeling of in vivo host response.

  19. EXTENDED CULTURE OF MACROPHAGES FROM DIFFERENT SOURCES AND MATURATION RESULTS IN A COMMON M2 PHENOTYPE

    PubMed Central

    Chamberlain, Lisa M.; Holt-Casper, Dolly; Gonzalez-Juarrero, Mercedes; Grainger, David W.

    2015-01-01

    Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely employed in short term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development towards an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign body response and encapsulation in vivo often elicit a shift towards an analogous M2 macrophage phenotype. In vitro “default” of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized but has important implications to in vitro modeling of in vivo host response. PMID:25684281

  20. Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes

    PubMed Central

    Reid, Emma S.; Papandreou, Apostolos; Drury, Suzanne; Boustred, Christopher; Yue, Wyatt W.; Wedatilake, Yehani; Beesley, Clare; Jacques, Thomas S.; Anderson, Glenn; Abulhoul, Lara; Broomfield, Alex; Cleary, Maureen; Grunewald, Stephanie; Varadkar, Sophia M.; Lench, Nick; Rahman, Shamima; Gissen, Paul; Clayton, Peter T.

    2016-01-01

    Neurometabolic disorders are markedly heterogeneous, both clinically and genetically, and are characterized by variable neurological dysfunction accompanied by suggestive neuroimaging or biochemical abnormalities. Despite early specialist input, delays in diagnosis and appropriate treatment initiation are common. Next-generation sequencing approaches still have limitations but are already enabling earlier and more efficient diagnoses in these patients. We designed a gene panel targeting 614 genes causing inborn errors of metabolism and tested its diagnostic efficacy in a paediatric cohort of 30 undiagnosed patients presenting with variable neurometabolic phenotypes. Genetic defects that could, at least partially, explain observed phenotypes were identified in 53% of cases. Where biochemical abnormalities pointing towards a particular gene defect were present, our panel identified diagnoses in 89% of patients. Phenotypes attributable to defects in more than one gene were seen in 13% of cases. The ability of in silico tools, including structure-guided prediction programmes to characterize novel missense variants were also interrogated. Our study expands the genetic, clinical and biochemical phenotypes of well-characterized (POMGNT1, TPP1) and recently identified disorders (PGAP2, ACSF3, SERAC1, AFG3L2, DPYS). Overall, our panel was accurate and efficient, demonstrating good potential for applying similar approaches to clinically and biochemically diverse neurometabolic disease cohorts. PMID:27604308

  1. Extended region of nodulation genes in Rhizobium meliloti 1021. I. Phenotypes of Tn5 insertion mutants

    SciTech Connect

    Swanson, J.A.; Tu, J.K.; Ogawa, J.; Sanga, R.; Fisher, R.F.; Long, S.R.

    1987-10-01

    Rhizobium meliloti Nod/sup -/ mutant WL131, a derivative of wild-type strain 102F51, was complemented by a clone bank of wild-type R. meliloti 1021 DNA, and clone pRmJT5 was recovered. Transfer of pRmJT5 conferred alfalfa nodulation on other Rhizobium species, indicating a role in host range determination for pRmJT5. Mutagenesis of pRmJT5 revealed several segments in which transposon insertion causes delay in nodulation, and/or marked reduction of the number of nodules formed on host alfalfa plants. The set of mutants indicated five regions in which nod genes are located; one mutant, nod-216, is located in a region not previously reported to encode a nodulation gene. Other mutant phenotypes correlated with the positions of open reading frames for nodH, nodF and nodE, and with a 2.2-kb EcoRI fragment. A mutant in nodG had no altered phenotype in this strain. One nodulation mutant was shown to be a large deletion of the common nod gene region. The authors present a discussion comparing the various studies made on this extended nod gene region.

  2. Detection of extended-spectrum β-lactamases in Klebsiella pneumoniae: comparison of phenotypic characterization methods

    PubMed Central

    Ejaz, Hasan; ul-Haq, Ikram; Mahmood, Saqib; Zafar, Aizza; Mohsin Javed, Muhammad

    2013-01-01

    Objective: Extended-spectrum β-lactamase producing K. pneumoniae is a serious threat to the patients. This manuscript shows the comparison of phenotypic characterization methods used for ESBL K. pneumoniae and frequency distribution of these isolates in various clinical samples. Methodology: Eleven different types of pathological samples collected on various time intervals were analyzed. K. pneumoniae were identified with API 20E system (bioMerieux) and initial screening of ESBL K. pneumoniae was performed using the ceftazidime antimicrobial disc. Double-disc synergy test (DDST) and CLSI confirmatory test were compared for the phenotypic detection of ESBL K. pneumoniae. Results: A total number of 214 ESBL producing K. pneumoniae were isolated from various clinical samples. Frequency distribution of ESBL producing K. pneumoniae was found to be highest among blood 117 (54.7%) and urine 46 (21.5%) samples. Data regarding the use of various interventions among these patients showed most common presence of intravenous line 209 (97.7%) and urinary catheters 46 (21.5%). Comparison of DDST and CLSI confirmatory test showed that the DDST detected 145 (67.8%) isolates while 213 (99.5%) ESBL K. pneumoniae were characterized by CLSI confirmatory test. Conclusion: The use of CLSI confirmatory test is very efficient in the early detection of ESBL K. pneumoniae especially when the facilities for molecular characterization are not available. PMID:24353625

  3. Next-generation Sequencing Extends the Phenotypic Spectrum for LCA5 Mutations: Novel LCA5 Mutations in Cone Dystrophy

    PubMed Central

    Chen, Xue; Sheng, Xunlun; Sun, Xiantao; Zhang, Yuxin; Jiang, Chao; Li, Huiping; Ding, Sijia; Liu, Yani; Liu, Wenzhou; Li, Zili; Zhao, Chen

    2016-01-01

    We aim to characterize the clinical features and genetic causes for two affected siblings from a Chinese family with cone dystrophy (CD). Two patients and four unaffected family members were recruited and received complete ophthalmic examinations. Genomic DNA was isolated from the peripheral blood samples from all patients. Targeted next-generation sequencing (NGS) approach followed by intrafamilal cosegregation and in silico analyses were employed to determine the genetic defects. Ophthalmic evaluations finalized the clinical diagnosis of CD for the two patients in this family, both of whom presented macular atrophy with no remarkable changes in the peripheral retina. Comprehensive genetic screening approach revealed biallelic missense mutations in the Leber congenital amaurosis 5 (LCA5) gene, p.[Ala212Pro];[Tyr441Cys], as disease causative for this family. Both mutations were novel. The first substitution was predicted to eliminate a hydrogen bond and alter the tertiary structure of lebercilin, protein encoded by LCA5. We for the first time report novel biallelic LCA5 mutations in causing CD. Our study extends the phenotypic and genotypic spectrums for LCA5-associated retinopathies and better illustrates its genotype-phenotype correlations, which would help with better genetic diagnosis, prognosis, and personalized treatment for CD patients. PMID:27067258

  4. Targeted next-generation sequencing extends the phenotypic and mutational spectrums for EYS mutations

    PubMed Central

    Gu, Shun; Tian, Yuanyuan; Chen, Xue

    2016-01-01

    Purpose We aim to determine genetic lesions with a phenotypic correlation in four Chinese families with autosomal recessive retinitis pigmentosa (RP). Methods Medical histories were carefully reviewed. All patients received comprehensive ophthalmic evaluations. The next-generation sequencing (NGS) approach targeting a panel of 205 retinal disease–relevant genes and 15 candidate genes was selectively performed on probands from the four recruited families for mutation detection. Online predictive software and crystal structure modeling were also applied to test the potential pathogenic effects of identified mutations. Results Of the four families, two were diagnosed with RP sino pigmento (RPSP). Patients with RPSP claimed to have earlier RP age of onset but slower disease progression. Five mutations in the eyes shut homolog (EYS) gene, involving two novel (c.7228+1G>A and c.9248G>A) and three recurrent mutations (c.4957dupA, c.6416G>A and c.6557G>A), were found as RP causative in the four families. The missense variant c.5093T>C was determined to be a variant of unknown significance (VUS) due to the variant’s colocalization in the same allele with the reported pathogenic mutation c.6416G>A. The two novel variants were further confirmed absent in 100 unrelated healthy controls. Online predictive software indicated potential pathogenicity of the three missense mutations. Further, crystal structural modeling suggested generation of two abnormal hydrogen bonds by the missense mutation p.G2186E (c.6557G>A) and elongation of its neighboring β-sheet induced by p.G3083D (c.9248G>A), which could alter the tertiary structure of the eys protein and thus interrupt its physicochemical properties. Conclusions Taken together, with the targeted NGS approach, we reveal novel EYS mutations and prove the efficiency of targeted NGS in the genetic diagnoses of RP. We also first report the correlation between EYS mutations and RPSP. The genotypic-phenotypic relationship in all

  5. The structure of phenotypic personality traits.

    PubMed

    Goldberg, L R

    1993-01-01

    This personal historical article traces the development of the Big-Five factor structure, whose growing acceptance by personality researchers has profoundly influenced the scientific study of individual differences. The roots of this taxonomy lie in the lexical hypothesis and the insights of Sir Francis Galton, the prescience of L. L. Thurstone, the legacy of Raymond B. Cattell, and the seminal analyses of Tupes and Christal. Paradoxically, the present popularity of this model owes much to its many critics, each of whom tried to replace it, but failed. In reaction, there have been a number of attempts to assimilate other models into the five-factor structure. Lately, some practical implications of the emerging consensus can be seen in such contexts as personnel selection and classification. PMID:8427480

  6. The structure of phenotypic personality traits.

    PubMed

    Goldberg, L R

    1993-01-01

    This personal historical article traces the development of the Big-Five factor structure, whose growing acceptance by personality researchers has profoundly influenced the scientific study of individual differences. The roots of this taxonomy lie in the lexical hypothesis and the insights of Sir Francis Galton, the prescience of L. L. Thurstone, the legacy of Raymond B. Cattell, and the seminal analyses of Tupes and Christal. Paradoxically, the present popularity of this model owes much to its many critics, each of whom tried to replace it, but failed. In reaction, there have been a number of attempts to assimilate other models into the five-factor structure. Lately, some practical implications of the emerging consensus can be seen in such contexts as personnel selection and classification.

  7. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

    PubMed Central

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat

    2016-01-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete’s heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation.

  8. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes.

    PubMed

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat; Saguner, Ardan M

    2016-08-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete's heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation. PMID:27617087

  9. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

    PubMed Central

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat

    2016-01-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete’s heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation. PMID:27617087

  10. Extended phenotypes in a boy and his mother with oto-palato-digital-syndrome type II

    PubMed Central

    Kaissi, Ali Al; Kraschl, Raimund; Kaulfersch, Wilhelm; Grill, Franz; Ganger, Rudolf

    2015-01-01

    Key Clinical Message We describe additional phenotypic features in a boy and his mother. Both manifested the phenotypic/genotypic correlation of oto-palato-digital syndrome type II. The mother′s radiographs showed wormian bones of the skull, and paranasal bossing, her feet showed bilateral fusion of the cuboid with the lateral cuneiform bone with subsequent development of metatarsus varus associated with dysplastic distal phalanges. PMID:26401283

  11. Structural Phenotyping of Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Pasqualini, Francesco Silvio; Sheehy, Sean Paul; Agarwal, Ashutosh; Aratyn-Schaus, Yvonne; Parker, Kevin Kit

    2015-01-01

    Summary Structural phenotyping based on classical image feature detection has been adopted to elucidate the molecular mechanisms behind genetically or pharmacologically induced changes in cell morphology. Here, we developed a set of 11 metrics to capture the increasing sarcomere organization that occurs intracellularly during striated muscle cell development. To test our metrics, we analyzed the localization of the contractile protein α-actinin in a variety of primary and stem-cell derived cardiomyocytes. Further, we combined these metrics with data mining algorithms to unbiasedly score the phenotypic maturity of human-induced pluripotent stem cell-derived cardiomyocytes. PMID:25733020

  12. Evolution of sexual dimorphism in phenotypic covariance structure in Phymata.

    PubMed

    Punzalan, David; Rowe, Locke

    2015-06-01

    Sexual dimorphism is a consequence of both sex-specific selection and potential constraints imposed by a shared genetic architecture underlying sexually homologous traits. However, genetic architecture is expected to evolve to mitigate these constraints, allowing the sexes to approach their respective optimal mean phenotype. In addition, sex-specific selection is expected to generate sexual dimorphism of trait covariance structure (e.g., the phenotypic covariance matrix, P), but previous empirical work has not fully addressed this prediction. We compared patterns of phenotypic divergence, for three traits in seven taxa in the insect genus Phymata (Reduviidae), to ask whether sexual dimorphism in P is common and whether its magnitude relates to the extent of sexual dimorphism in trait means. We found that sexual dimorphism in both mean and covariance structure was pervasive but also that the multivariate distance between sex-specific means was correlated with sex differences in the leading eigenvector of P, while accounting for uncertainty in phylogenetic relationships. Collectively, our findings suggest that sexual dimorphism in covariance structure may be a common but underappreciated feature of dioecious populations.

  13. Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome

    PubMed Central

    Rider, Nicholas L.; Boisson, Bertrand; Jyonouchi, Soma; Hanson, Eric P.; Rosenzweig, Sergio D.; Casanova, Jean-Laurent; Orange, Jordan S.

    2015-01-01

    Unbiased genetic diagnosis has increasingly associated seemingly unrelated somatic and immunological phenotypes. We report a male infant who presented within the first year of life with physical growth impairment, feeding difficulties, hyperemesis without diarrhea, and abnormal hair findings suggestive of trichorrhexis nodosa. With advancing age, moderate global developmental delay, susceptibility to frequent viral illnesses, otitis media, and purulent conjunctivitis were identified. Because of the repeated infections, an immunological evaluation was pursued and identified impaired antibody memory responses following pneumococcal vaccine administration. Immunoglobulin replacement therapy and nutritional support were employed as mainstays of therapy. The child is now aged 12 years and still without diarrhea. Whole exome sequencing identified compound heterozygous mutations in the TTC37 gene, a known cause of the trichohepatoenteric syndrome (THES). This case extends the known phenotype of THES and defines a potential subset for inclusion as an immune overlap syndrome. PMID:25688341

  14. Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome.

    PubMed

    Rider, Nicholas L; Boisson, Bertrand; Jyonouchi, Soma; Hanson, Eric P; Rosenzweig, Sergio D; Cassanova, Jean-Laurent; Orange, Jordan S

    2015-01-01

    Unbiased genetic diagnosis has increasingly associated seemingly unrelated somatic and immunological phenotypes. We report a male infant who presented within the first year of life with physical growth impairment, feeding difficulties, hyperemesis without diarrhea, and abnormal hair findings suggestive of trichorrhexis nodosa. With advancing age, moderate global developmental delay, susceptibility to frequent viral illnesses, otitis media, and purulent conjunctivitis were identified. Because of the repeated infections, an immunological evaluation was pursued and identified impaired antibody memory responses following pneumococcal vaccine administration. Immunoglobulin replacement therapy and nutritional support were employed as mainstays of therapy. The child is now aged 12 years and still without diarrhea. Whole exome sequencing identified compound heterozygous mutations in the TTC37 gene, a known cause of the trichohepatoenteric syndrome (THES). This case extends the known phenotype of THES and defines a potential subset for inclusion as an immune overlap syndrome. PMID:25688341

  15. The Unexpected Anabolic Phenotype and Extended Longevity of Skin Fibroblasts after Chronic Glucocorticoid Excess

    PubMed Central

    Pratsinis, Harris; Tsagarakis, Stylianos; Zervolea, Irene; Stathakos, Dimitri; Thalassinos, Nikos; Kletsas, Dimitris

    2006-01-01

    Intense stress can challenge tissue homeostasis and accelerate the ageing process. However, several lines of evidence indicate that repeated mild stresses can have beneficial and even life-prolonging effects. Hypersecretion of glucocorticoids (GC) represents the major hormonal response to stress. Besides its life-sustaining role, GC excess, usually due to several side-effects that promote a “catabolic” phenotype, can be detrimental for several tissues. Cushing's syndrome patients are characterized by chronic endogenous GC excess and consequently at the time of diagnosis they have an atrophic elderly-like skin. Interestingly, when Cushing's syndrome fibroblasts were removed from the high-GC milieu in vivo and cultured in vitro under standard conditions they express an “anabolic” phenotype, i.e. they restore their ability for collagen synthesis, they secrete reduced levels of metalloproteases (MMP-1 and MMP-2) and have an increased proliferative capacity and contractility. Furthermore, these cells exhibit a significant extension of their proliferative lifespan, while they respond better to exogenous stress by producing significantly higher levels of heat-shock protein-70 (HSP70). These results imply that long-term hypercortisolism in vivo can have beneficial consequences on fibroblast physiology in vitro. PMID:18648637

  16. Distal 15q trisomy: phenotypic comparison of nine cases in an extended family.

    PubMed Central

    Schnatterly, P; Bono, K L; Robinow, M; Wyandt, H E; Kardon, N; Kelly, T E

    1984-01-01

    Nine related individuals have been identified as being trisomic for the distal part of the long arm of chromosome 15 (15q23 to 15qter). The physical characteristics, especially the facial features, of these nine cases are similar and distinctive. These include: facial asymmetry, down-slanting palpebral fissures, ptosis, prominent nose, long philtrum, down-turned mouth, midline crease in the lower lip, puffy cheeks, and micrognathia. By comparing related individuals with the same translocation, the variability due to different breakpoints can be eliminated. Clinical similarities between unrelated individuals with similar duplicated 15q material, but differing second chromosomes, suggest that the phenotype is due to the extra distal 15q chromosomal material. We conclude that distal 15q trisomy produces a clinically recognizable syndrome. Images Fig. 2 Fig. 4 PMID:6711563

  17. Distal 15q trisomy: phenotypic comparison of nine cases in an extended family.

    PubMed

    Schnatterly, P; Bono, K L; Robinow, M; Wyandt, H E; Kardon, N; Kelly, T E

    1984-03-01

    Nine related individuals have been identified as being trisomic for the distal part of the long arm of chromosome 15 (15q23 to 15qter). The physical characteristics, especially the facial features, of these nine cases are similar and distinctive. These include: facial asymmetry, down-slanting palpebral fissures, ptosis, prominent nose, long philtrum, down-turned mouth, midline crease in the lower lip, puffy cheeks, and micrognathia. By comparing related individuals with the same translocation, the variability due to different breakpoints can be eliminated. Clinical similarities between unrelated individuals with similar duplicated 15q material, but differing second chromosomes, suggest that the phenotype is due to the extra distal 15q chromosomal material. We conclude that distal 15q trisomy produces a clinically recognizable syndrome.

  18. Sexual and natural selection in the evolution of extended phenotypes: the use of green nesting material in starlings.

    PubMed

    Rubalcaba, J G; Polo, V; Maia, R; Rubenstein, D R; Veiga, J P

    2016-08-01

    Although sexual selection is typically considered the predominant force driving the evolution of ritualized sexual behaviours, natural selection may also play an important and often underappreciated role. The use of green aromatic plants among nesting birds has been interpreted as a component of extended phenotype that evolved either via natural selection due to potential sanitary functions or via sexual selection as a signal of male attractiveness. Here, we compared both hypotheses using comparative methods in starlings, a group where this behaviour is widespread. We found that the use of green plants was positively related to male-biased size dimorphism and that it was most likely to occur among cavity-nesting species. These results suggest that this behaviour is likely favoured by sexual selection, but also related to its sanitary use in response to higher parasite loads in cavities. We speculate that the use of green plants in starlings may be facilitated by cavity nesting and was subsequently co-opted as a sexual signal by males. Our results represent an example of how an extended phenotypic component of males becomes sexually selected by females. Thus, both natural selection and sexual selection are necessary to fully understand the evolution of ritualized behaviours involved in courtship. PMID:27168035

  19. Cosmetics as a feature of the extended human phenotype: modulation of the perception of biologically important facial signals.

    PubMed

    Etcoff, Nancy L; Stock, Shannon; Haley, Lauren E; Vickery, Sarah A; House, David M

    2011-01-01

    Research on the perception of faces has focused on the size, shape, and configuration of inherited features or the biological phenotype, and largely ignored the effects of adornment, or the extended phenotype. Research on the evolution of signaling has shown that animals frequently alter visual features, including color cues, to attract, intimidate or protect themselves from conspecifics. Humans engage in conscious manipulation of visual signals using cultural tools in real time rather than genetic changes over evolutionary time. Here, we investigate one tool, the use of color cosmetics. In two studies, we asked viewers to rate the same female faces with or without color cosmetics, and we varied the style of makeup from minimal (natural), to moderate (professional), to dramatic (glamorous). Each look provided increasing luminance contrast between the facial features and surrounding skin. Faces were shown for 250 ms or for unlimited inspection time, and subjects rated them for attractiveness, competence, likeability and trustworthiness. At 250 ms, cosmetics had significant positive effects on all outcomes. Length of inspection time did not change the effect for competence or attractiveness. However, with longer inspection time, the effect of cosmetics on likability and trust varied by specific makeup looks, indicating that cosmetics could impact automatic and deliberative judgments differently. The results suggest that cosmetics can create supernormal facial stimuli, and that one way they may do so is by exaggerating cues to sexual dimorphism. Our results provide evidence that judgments of facial trustworthiness and attractiveness are at least partially separable, that beauty has a significant positive effect on judgment of competence, a universal dimension of social cognition, but has a more nuanced effect on the other universal dimension of social warmth, and that the extended phenotype significantly influences perception of biologically important signals at first

  20. Cosmetics as a feature of the extended human phenotype: modulation of the perception of biologically important facial signals.

    PubMed

    Etcoff, Nancy L; Stock, Shannon; Haley, Lauren E; Vickery, Sarah A; House, David M

    2011-01-01

    Research on the perception of faces has focused on the size, shape, and configuration of inherited features or the biological phenotype, and largely ignored the effects of adornment, or the extended phenotype. Research on the evolution of signaling has shown that animals frequently alter visual features, including color cues, to attract, intimidate or protect themselves from conspecifics. Humans engage in conscious manipulation of visual signals using cultural tools in real time rather than genetic changes over evolutionary time. Here, we investigate one tool, the use of color cosmetics. In two studies, we asked viewers to rate the same female faces with or without color cosmetics, and we varied the style of makeup from minimal (natural), to moderate (professional), to dramatic (glamorous). Each look provided increasing luminance contrast between the facial features and surrounding skin. Faces were shown for 250 ms or for unlimited inspection time, and subjects rated them for attractiveness, competence, likeability and trustworthiness. At 250 ms, cosmetics had significant positive effects on all outcomes. Length of inspection time did not change the effect for competence or attractiveness. However, with longer inspection time, the effect of cosmetics on likability and trust varied by specific makeup looks, indicating that cosmetics could impact automatic and deliberative judgments differently. The results suggest that cosmetics can create supernormal facial stimuli, and that one way they may do so is by exaggerating cues to sexual dimorphism. Our results provide evidence that judgments of facial trustworthiness and attractiveness are at least partially separable, that beauty has a significant positive effect on judgment of competence, a universal dimension of social cognition, but has a more nuanced effect on the other universal dimension of social warmth, and that the extended phenotype significantly influences perception of biologically important signals at first

  1. Cosmetics as a Feature of the Extended Human Phenotype: Modulation of the Perception of Biologically Important Facial Signals

    PubMed Central

    Etcoff, Nancy L.; Stock, Shannon; Haley, Lauren E.; Vickery, Sarah A.; House, David M.

    2011-01-01

    Research on the perception of faces has focused on the size, shape, and configuration of inherited features or the biological phenotype, and largely ignored the effects of adornment, or the extended phenotype. Research on the evolution of signaling has shown that animals frequently alter visual features, including color cues, to attract, intimidate or protect themselves from conspecifics. Humans engage in conscious manipulation of visual signals using cultural tools in real time rather than genetic changes over evolutionary time. Here, we investigate one tool, the use of color cosmetics. In two studies, we asked viewers to rate the same female faces with or without color cosmetics, and we varied the style of makeup from minimal (natural), to moderate (professional), to dramatic (glamorous). Each look provided increasing luminance contrast between the facial features and surrounding skin. Faces were shown for 250 ms or for unlimited inspection time, and subjects rated them for attractiveness, competence, likeability and trustworthiness. At 250 ms, cosmetics had significant positive effects on all outcomes. Length of inspection time did not change the effect for competence or attractiveness. However, with longer inspection time, the effect of cosmetics on likability and trust varied by specific makeup looks, indicating that cosmetics could impact automatic and deliberative judgments differently. The results suggest that cosmetics can create supernormal facial stimuli, and that one way they may do so is by exaggerating cues to sexual dimorphism. Our results provide evidence that judgments of facial trustworthiness and attractiveness are at least partially separable, that beauty has a significant positive effect on judgment of competence, a universal dimension of social cognition, but has a more nuanced effect on the other universal dimension of social warmth, and that the extended phenotype significantly influences perception of biologically important signals at first

  2. Association between brain structure and phenotypic characteristics in pedophilia.

    PubMed

    Poeppl, Timm B; Nitschke, Joachim; Santtila, Pekka; Schecklmann, Martin; Langguth, Berthold; Greenlee, Mark W; Osterheider, Michael; Mokros, Andreas

    2013-05-01

    Studies applying structural neuroimaging to pedophiles are scarce and have shown conflicting results. Although first findings suggested reduced volume of the amygdala, pronounced gray matter decreases in frontal regions were observed in another group of pedophilic offenders. When compared to non-sexual offenders instead of community controls, pedophiles revealed deficiencies in white matter only. The present study sought to test the hypotheses of structurally compromised prefrontal and limbic networks and whether structural brain abnormalities are related to phenotypic characteristics in pedophiles. We compared gray matter volume of male pedophilic offenders and non-sexual offenders from high-security forensic hospitals using voxel-based morphometry in cross-sectional and correlational whole-brain analyses. The significance threshold was set to p < .05, corrected for multiple comparisons. Compared to controls, pedophiles exhibited a volume reduction of the right amygdala (small volume corrected). Within the pedophilic group, pedosexual interest and sexual recidivism were correlated with gray matter decrease in the left dorsolateral prefrontal cortex (r = -.64) and insular cortex (r = -.45). Lower age of victims was strongly associated with gray matter reductions in the orbitofrontal cortex (r = .98) and angular gyri bilaterally (r = .70 and r = .93). Our findings of specifically impaired neural networks being related to certain phenotypic characteristics might account for the heterogeneous results in previous neuroimaging studies of pedophilia. The neuroanatomical abnormalities in pedophilia seem to be of a dimensional rather than a categorical nature, supporting the notion of a multifaceted disorder.

  3. Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy

    PubMed Central

    Weninger, Wolfgang J.; Geyer, Stefan H.; Martineau, Alexandrine; Galli, Antonella; Adams, David J.; Wilson, Robert; Mohun, Timothy J.

    2014-01-01

    The arrival of simple and reliable methods for 3D imaging of mouse embryos has opened the possibility of analysing normal and abnormal development in a far more systematic and comprehensive manner than has hitherto been possible. This will not only help to extend our understanding of normal tissue and organ development but, by applying the same approach to embryos from genetically modified mouse lines, such imaging studies could also transform our knowledge of gene function in embryogenesis and the aetiology of developmental disorders. The International Mouse Phenotyping Consortium is coordinating efforts to phenotype single gene knockouts covering the entire mouse genome, including characterising developmental defects for those knockout lines that prove to be embryonic lethal. Here, we present a pilot study of 34 such lines, utilising high-resolution episcopic microscopy (HREM) for comprehensive 2D and 3D imaging of homozygous null embryos and their wild-type littermates. We present a simple phenotyping protocol that has been developed to take advantage of the high-resolution images obtained by HREM and that can be used to score tissue and organ abnormalities in a reliable manner. Using this approach with embryos at embryonic day 14.5, we show the wide range of structural abnormalities that are likely to be detected in such studies and the variability in phenotypes between sibling homozygous null embryos. PMID:25256713

  4. A cubic extended interior penalty function for structural optimization

    NASA Technical Reports Server (NTRS)

    Prasad, B.; Haftka, R. T.

    1979-01-01

    This paper describes an optimization procedure for the minimum weight design of complex structures. The procedure is based on a new cubic extended interior penalty function (CEIPF) used with the sequence of unconstrained minimization technique (SUMT) and Newton's method. The Hessian matrix of the penalty function is approximated using only constraints and their derivatives. The CEIPF is designed to minimize the error in the approximation of the Hessian matrix, and as a result the number of structural analyses required is small and independent of the number of design variables. Three example problems are reported. The number of structural analyses is reduced by as much as 50 per cent below previously reported results.

  5. Baculovirus-induced tree-top disease: how extended is the role of egt as a gene for the extended phenotype?

    PubMed

    Ros, Vera I D; van Houte, Stineke; Hemerik, Lia; van Oers, Monique M

    2015-01-01

    Many parasites alter host behaviour to enhance their chance of transmission. Recently, the ecdysteroid UDP-glucosyl transferase (egt) gene from the baculovirus Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) was identified to induce tree-top disease in L. dispar larvae. Infected gypsy moth larvae died at elevated positions (hence the term tree-top disease), which is thought to promote dissemination of the virus to lower foliage. It is, however, unknown whether egt has a conserved role among baculoviruses in inducing tree-top disease. Here, we studied tree-top disease induced by the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in two different host insects, Trichoplusia ni and Spodoptera exigua, and we investigated the role of the viral egt gene therein. AcMNPV induced tree-top disease in both T. ni and S. exigua larvae, although in S. exigua a moulting-dependent effect was seen. Those S. exigua larvae undergoing a larval moult during the infection process died at elevated positions, while larvae that did not moult after infection died at low positions. For both T. ni and S. exigua, infection with a mutant AcMNPV lacking egt did not change the position where the larvae died. We conclude that egt has no highly conserved role in inducing tree-top disease in lepidopteran larvae. The conclusion that egt is a 'gene for an extended phenotype' is therefore not generally applicable for all baculovirus-host interactions. We hypothesize that in some baculovirus-host systems (including LdMNPV in L. dispar), an effect of egt on tree-top disease can be observed through indirect effects of egt on moulting-related climbing behaviour. PMID:25443568

  6. Concomitant Hamiltonian and topological structures of extended magnetohydrodynamics

    NASA Astrophysics Data System (ADS)

    Lingam, Manasvi; Miloshevich, George; Morrison, Philip J.

    2016-07-01

    The paper describes the unique geometric properties of ideal magnetohydrodynamics (MHD), and demonstrates how such features are inherited by extended MHD, viz. models that incorporate two-fluid effects (the Hall term and electron inertia). The generalized helicities, and other geometric expressions for these models are presented in a topological context, emphasizing their universal facets. Some of the results presented include: the generalized Kelvin circulation theorems; the existence of two Lie-dragged 2-forms; and two concomitant helicities that can be studied via the Jones polynomial, which is widely utilized in Chern-Simons theory. The ensuing commonality is traced to the existence of an underlying Hamiltonian structure for all the extended MHD models, exemplified by the presence of a unique noncanonical Poisson bracket, and its associated energy.

  7. Small cell lung cancer: Circulating tumor cells of extended stage patients express a mesenchymal-epithelial transition phenotype.

    PubMed

    Hamilton, Gerhard; Hochmair, Maximilian; Rath, Barbara; Klameth, Lukas; Zeillinger, Robert

    2016-07-01

    Small cell lung cancer (SCLC) is distinguished by aggressive growth, early dissemination and a poor prognosis at advanced stage. The remarkably high count of circulating tumor cells (CTCs) of SCLC allowed for the establishment of permanent CTC cultures at our institution for the first time. CTCs are assumed to have characteristics of cancer stem cells (CSCs) and an epithelial-mesenchymal transition (EMT) phenotype, but extravasation of tumors at distal sites is marked by epithelial features. Two SCLC CTC cell lines, namely BHGc7 and BHGc10, as well as SCLC cell lines derived from primary tumors and metastases were analyzed for the expression of pluripotent stem cell markers and growth factors. Expression of E-cadherin and β-Catenin were determined by flow cytometry. Stem cell-associated markers SOX17, α-fetoprotein, OCT-3/4, KDR, Otx2, GATA-4, Nanog, HCG, TP63 and Goosecoid were not expressed in the 2 CTC lines. In contrast, high expression was found for HNF-3β/FOXA2, SOX2, PDX-1/IPF1 and E-cadherin. E-cadherin expression was restricted to the 2 CTCs and 2 cell lines derived from pleural effusion (SCLC26A) and bone metastases (NCI-H526), respectively. Thus, these SCLC CTCs established from extended disease SCLC patients lack expression of stem cell markers which suppress the epithelial phenotype. Instead they express high levels of E-cadherin consistent with a mesenchymal-epithelial transition (MET or EMrT) and form large tumorospheres possibly in response to the selection pressure of first-line chemotherapy. HNF-3β/FOXA2 and PDX-1/IPF1 expression seem to be related to growth factor dependence on insulin/IGF-1 receptors and IGF-binding proteins. PMID:26919626

  8. Characterization of Extended-Spectrum β-Lactamase-Producing Salmonella typhimurium by Phenotypic and Genotypic Typing Methods

    PubMed Central

    Ait Mhand, Rajaa; Brahimi, Naima; Moustaoui, Najat; El Mdaghri, Naima; Amarouch, Hamid; Grimont, Francine; Bingen, Edouard; Benbachir, Mohamed

    1999-01-01

    During 1994, 10 isolates of extended-spectrum β-lactamase-producing Salmonella typhimurium were recovered from children transferred to our hospital from two different centers. Two additional isolates were recovered from two nurses from one of these centers. The aim of this study was to determine if there is any relationship between these isolates. The characterization was done by phenotypic and genotypic methods: biotyping, phage typing, antibiotic susceptibility pattern determination, plasmid analysis, ribotyping (by the four endonucleases EcoRI, SmaI, BglII, and PvuII), pulsed-field gel electrophoresis (PFGE) of genome macrorestriction patterns with XbaI, and randomly amplified polymorphic DNA (RAPD) pattern determination (with the three primers 217 d2, B1, and A3). The same biotype, the same serotype, and an identical antibiotype were found. All isolates were resistant to oxyimino-β-lactams, gentamicin, tobramycin, and sulfamethoxazole-trimethoprim. All isolates showed an indistinguishable pattern by ribotyping and very similar patterns by PFGE and RAPD. The overall results indicated the spread of a closely related strain of S. typhimurium in children and nurses. PMID:10523599

  9. Conflict between biotic and climatic selective pressures acting on an extended phenotype in a subarctic, but not temperate, environment.

    PubMed

    Rohwer, V G; Bonier, F; Martin, P R

    2015-10-22

    Climatic selective pressures are thought to dominate biotic selective pressures at higher latitudes. However, few studies have experimentally tested how these selective pressures differentially act on traits across latitudes because traits can rarely be manipulated independently of the organism in nature. We overcame this challenge by using an extended phenotype-active bird nests-and conducted reciprocal transplant experiments between a subarctic and temperate site, separated by 14° of latitude. At the subarctic site, biotic selective pressures (nest predation) favoured smaller, non-local temperate nests, whereas climatic selective pressures (temperature) favoured larger local nests, particularly at colder temperatures. By contrast, at the temperate site, climatic and biotic selective pressures acted similarly on temperate and subarctic nests. Our results illustrate a functional trade-off in the subarctic between nest morphologies favoured by biotic versus climatic selective pressures, with climate favouring local nest morphologies. At our temperate site, however, allocative trade-offs in the time and effort devoted to nest construction favour smaller, local nests. Our findings illustrate a conflict between biotic and climatic selective pressures at the northern extremes of a species geographical range, and suggest that trade-offs between trait function and trait elaboration act differentially across latitude to create broad geographic variation in traits.

  10. The extended phenotypes of marine symbioses: ecological and evolutionary consequences of intraspecific genetic diversity in coral–algal associations

    PubMed Central

    Parkinson, John E.; Baums, Iliana B.

    2014-01-01

    Reef-building corals owe much of their success to a symbiosis with dinoflagellate microalgae in the genus Symbiodinium. In this association, the performance of each organism is tied to that of its partner, and together the partners form a holobiont that can be subject to selection. Climate change affects coral reefs, which are declining globally as a result. Yet the extent to which coral holobionts will be able to acclimate or evolve to handle climate change and other stressors remains unclear. Selection acts on individuals and evidence from terrestrial systems demonstrates that intraspecific genetic diversity plays a significant role in symbiosis ecology and evolution. However, we have a limited understanding of the effects of such diversity in corals. As molecular methods have advanced, so too has our recognition of the taxonomic and functional diversity of holobiont partners. Resolving the major components of the holobiont to the level of the individual will help us assess the importance of intraspecific diversity and partner interactions in coral–algal symbioses. Here, we hypothesize that unique combinations of coral and algal individuals yield functional diversity that affects not only the ecology and evolution of the coral holobiont, but associated communities as well. Our synthesis is derived from reviewing existing evidence and presenting novel data. By incorporating the effects of holobiont extended phenotypes into predictive models, we may refine our understanding of the evolutionary trajectory of corals and reef communities responding to climate change. PMID:25202306

  11. Structure of the extended emission in the infrared celestial background

    SciTech Connect

    Price, S.D.

    1988-01-01

    The extended infrared celestial emission is due to three main sources: zodiacal dust, large discrete objects in the galaxy, and interstellar dust. As viewed from earth orbit, the thermal reradiation of sunlight absorbed by dust in the solar system produces a pervasive IR background that peaks roughly along the ecliptic plane, where the density of dust is highest. Much-smaller-scale structure was also observed in both the visual and infrared. Between 7 and 30 micrometers, H II regions are the brightest discrete objects in the galaxy. An additional emission mechanism is needed, however, to account for the shorter-wavelength observations. The galactic sources combine along the line of sight to produce an intense band of emission, centered on the galactic plane. Structure in all of these backgrounds creates a clutter problem for an orbiting IR telescope.

  12. Extended structure of rat islet amyloid polypeptide in solution.

    PubMed

    Wei, Lei; Jiang, Ping; Manimekalai, Malathy Sony Subramanian; Hunke, Cornelia; Grüber, Gerhard; Pervushin, Konstantin; Mu, Yuguang

    2015-01-01

    The process of islet amyloid polypeptide (IAPP) formation and the prefibrillar oligomers are supposed to be one of the pathogenic agents causing pancreatic β-cell dysfunction. The human IAPP (hIAPP) aggregates easily and therefore, it is difficult to characterize its structural features by standard biophysical tools. The rat version of IAPP (rIAPP) that differs by six amino acids when compared with hIAPP, is not prone to aggregation and does not form amyloid fibrils. Similar to hIAPP it also demonstrates random-coiled nature in solution. The structural propensity of rIAPP has been studied as a hIAPP mimic in recent works. However, the overall shape of it in solution still remains elusive. Using small angle X-ray scattering (SAXS) measurements combined with nuclear magnetic resonance (NMR) and molecular dynamics simulations (MD) the solution structure of rIAPP was studied. An unambiguously extended structural model with a radius of gyration of 1.83 nm was determined from SAXS data. Consistent with previous studies, an overall random-coiled feature with residual helical propensity in the N-terminus was confirmed. Combined efforts are necessary to unambiguously resolve the structural features of intrinsic disordered proteins.

  13. A tractable genotype-phenotype map modelling the self-assembly of protein quaternary structure.

    PubMed

    Greenbury, Sam F; Johnston, Iain G; Louis, Ard A; Ahnert, Sebastian E

    2014-06-01

    The mapping between biological genotypes and phenotypes is central to the study of biological evolution. Here, we introduce a rich, intuitive and biologically realistic genotype-phenotype (GP) map that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a two-dimensional lattice and exhibits a number of properties: redundancy (genotypes vastly outnumber phenotypes), phenotype bias (genotypic redundancy varies greatly between phenotypes), genotype component disconnectivity (phenotypes consist of disconnected mutational networks) and shape space covering (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales very roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the hydrophobic-polar (HP) lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps.

  14. A tractable genotype–phenotype map modelling the self-assembly of protein quaternary structure

    PubMed Central

    Greenbury, Sam F.; Johnston, Iain G.; Louis, Ard A.; Ahnert, Sebastian E.

    2014-01-01

    The mapping between biological genotypes and phenotypes is central to the study of biological evolution. Here, we introduce a rich, intuitive and biologically realistic genotype–phenotype (GP) map that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a two-dimensional lattice and exhibits a number of properties: redundancy (genotypes vastly outnumber phenotypes), phenotype bias (genotypic redundancy varies greatly between phenotypes), genotype component disconnectivity (phenotypes consist of disconnected mutational networks) and shape space covering (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales very roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the hydrophobic-polar (HP) lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps. PMID:24718456

  15. The extended structure of the dwarf irregular galaxy Sagittarius

    NASA Astrophysics Data System (ADS)

    Beccari, G.; Bellazzini, M.; Fraternali, F.; Battaglia, G.; Perina, S.; Sollima, A.; Oosterloo, T. A.; Testa, V.; Galleti, S.

    2014-10-01

    We present a detailed study of the stellar and H i structure of the dwarf irregular galaxy Sagittarius. We use new deep and wide field photometry to trace the surface brightness profile of the galaxy out to ≃5.0' (corresponding to ≃1600 pc) and down to μV ≃ 30.0 mag/arcsec2, thus showing that the stellar body of the galaxy is much more extended than previously believed, and it is similarly (or more) extended than the overall H i distribution. The whole major-axis profile is consistent with a pure exponential, with a scale radius of ≃340 pc. The surface density maps reveal that the distribution of old and intermediate-age stars is smooth and remarkably flattened out to its edges, while the associated H i has a much rounder shape, is off-centred and presents multiple density maxima and a significant hole. No clear sign of systemic rotation is detectable in the complex H i velocity field. No metallicity gradient is detected in the old and intermediate age population of the galaxy, and we confirm that this population has a much more extended distribution than young stars (age ≲ 1 Gyr). Based on data obtained with the European Southern Observatory Very Large Telescope, Paranal, Chile, under the Program 089.D-0052(A).Table of stellar photometry (IN6) is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/570/A78

  16. Integrative phenomics reveals insight into the structure of phenotypic diversity in budding yeast

    PubMed Central

    Skelly, Daniel A.; Merrihew, Gennifer E.; Riffle, Michael; Connelly, Caitlin F.; Kerr, Emily O.; Johansson, Marnie; Jaschob, Daniel; Graczyk, Beth; Shulman, Nicholas J.; Wakefield, Jon; Cooper, Sara J.; Fields, Stanley; Noble, William S.; Muller, Eric G.D.; Davis, Trisha N.; Dunham, Maitreya J.; MacCoss, Michael J.; Akey, Joshua M.

    2013-01-01

    To better understand the quantitative characteristics and structure of phenotypic diversity, we measured over 14,000 transcript, protein, metabolite, and morphological traits in 22 genetically diverse strains of Saccharomyces cerevisiae. More than 50% of all measured traits varied significantly across strains [false discovery rate (FDR) = 5%]. The structure of phenotypic correlations is complex, with 85% of all traits significantly correlated with at least one other phenotype (median = 6, maximum = 328). We show how high-dimensional molecular phenomics data sets can be leveraged to accurately predict phenotypic variation between strains, often with greater precision than afforded by DNA sequence information alone. These results provide new insights into the spectrum and structure of phenotypic diversity and the characteristics influencing the ability to accurately predict phenotypes. PMID:23720455

  17. Extended model of the channel diffusivity in the rutile structure

    NASA Astrophysics Data System (ADS)

    Ruebenbauer, K.; Wdowik, U. D.; Kwater, M.; Kowalik, J. T.

    1996-11-01

    A model describing the diffusivity of a highly diluted and randomly distributed substitutional cationic impurity via the open and almost empty <001> channels in the rutile structure has been developed recently. The above model is based upon the assumption that the insignificant fraction of the impurities resides in the channels. An extended model is developed that allows for a significant fraction of the impurities to stay within channels, and it is used to evaluate emission Mössbauer spectra originating from the diffusing impurities embedded in single-crystalline samples. Final results are shown for the 14.4-keV Mössbauer line in 57Co(Fe). It is shown that spectral line positions depend upon the wave-vector transfer to the system, and that the data are sensitive to the fraction of both parent and daughter impurities residing in the channels.

  18. FOURIER ANALYSIS OF EXTENDED FINE STRUCTURE WITH AUTOREGRESSIVE PREDICTION

    SciTech Connect

    Barton, J.; Shirley, D.A.

    1985-01-01

    Autoregressive prediction is adapted to double the resolution of Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) Fourier transforms. Even with the optimal taper (weighting function), the commonly used taper-and-transform Fourier method has limited resolution: it assumes the signal is zero beyond the limits of the measurement. By seeking the Fourier spectrum of an infinite extent oscillation consistent with the measurements but otherwise having maximum entropy, the errors caused by finite data range can be reduced. Our procedure developed to implement this concept applies autoregressive prediction to extrapolate the signal to an extent controlled by a taper width. Difficulties encountered when processing actual ARPEFS data are discussed. A key feature of this approach is the ability to convert improved measurements (signal-to-noise or point density) into improved Fourier resolution.

  19. The extended evolutionary synthesis: its structure, assumptions and predictions

    PubMed Central

    Laland, Kevin N.; Uller, Tobias; Feldman, Marcus W.; Sterelny, Kim; Müller, Gerd B.; Moczek, Armin; Jablonka, Eva; Odling-Smee, John

    2015-01-01

    Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the ‘extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism–environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology. PMID:26246559

  20. Structure of the extended emission in the infrared celestial background

    SciTech Connect

    Price, S.D.

    1986-09-30

    The extended emission in the infrared celestial background may be divided into three main components: the zodiacal background, the large discrete sources in the galaxy, and the interstellar dust. The zodiacal background is due to the thermal reradiation of sunlight absorbed by the dust in the solar system. An earth-orbiting infrared telescope will detect the diffuse emission from this dust in all directions with maximum intensity lying roughly along the ecliptic plane where the density of dust is highest. Structure with scale lengths of 10/sup 0/ was measured in both the visual and infrared; finer structure was detected in the infrared by the Infrared Astronomy Satellite. H II regions, areas of ionized gas mixed with and surrounded by dust, are the brightest discrete objects in the galaxy in the long wavelength infrared re-emitted in the infrared with a range of temperatures characteristic of the thermal equilibrium for the surroundings of the dust. The emission from the interstellar dust produces a filimentary structured background, the infrared cirrus. The observed far-infrared color temperature of about 20-35K for the cirrus is consistent with emission-form graphite and silicate grains which absorb the interstellar radiation field. The much-larger LWIR color temperature is likely due to a greater abundance of sub-micron particles in the interstellar medium and, perhaps, from band emission due to polycyclic aromatic hydrocarbons. These galactic planes have full width at half maxima of about 2/sup 0/.

  1. The extended evolutionary synthesis: its structure, assumptions and predictions.

    PubMed

    Laland, Kevin N; Uller, Tobias; Feldman, Marcus W; Sterelny, Kim; Müller, Gerd B; Moczek, Armin; Jablonka, Eva; Odling-Smee, John

    2015-08-22

    Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the 'extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism-environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology.

  2. Visibility of Extended Coronal Structures and CMEs in the EUV

    NASA Astrophysics Data System (ADS)

    Schanche, Nicole; Golub, Leon

    2014-06-01

    Extended coronal structures around active regions and coronal mass ejections (CMEs) have often been seen in the extreme-ultraviolet (EUV) channels to the full extent of the AIA and SWAP field of views 1.3 and 1.7 Rsun). Using off-pointed comet data in AIA we sum a large number of frames to evaluate the off-limb distance to which streamers can be detected. For CMEs, we compared the events classified as halo CMEs in the white-light LASCO CACTus catalog from July-September 2013 to the AIA and SWAP data collected around those events. We discovered that roughly 80% of events could be seen in the EUV using both regular and running difference movies, with the most effective channels being the 193 and 304Å channels. By projecting out the signal strength of several of these events, we conclude that these EUV events can in many cases be detected to over 2.5 Rsun. A larger field-of-view telescope would make it possible to track the development of these structures and events from the disk out to several solar radii, complementing the traditional white-light methods.

  3. The extended interacting wind structure of Eta Carinae

    NASA Astrophysics Data System (ADS)

    Gull, T. R.; Nielsen, K. E.; Corcoran, M. F.; Madura, T. I.; Owocki, S. P.; Russell, C. M. P.; Hillier, D. J.; Hamaguchi, K.; Kober, G. V.; Weis, K.; Stahl, O.; Okazaki, A. T.

    2009-07-01

    The highly eccentric binary system, η Car, provides clues to the transition of massive stars from hydrogen-burning via the CNO cycle to a helium-burning evolutionary state. The fast-moving wind of η Car B creates a cavity in η Car A's slower, but more massive, stellar wind, providing an in situ probe. The Hubble Space Telescope/Space Telescope Imaging Spectrograph (HST/STIS), with its high spatial and spectral resolutions, is well matched to follow temporal spatial and velocity variations of multiple wind features. We use observations obtained across 1998-2004 to produce a rudimentary three-dimensional model of the wind interaction in the η Car system. Broad (+/-500 km s-1) [FeII] emission line structures extend 0.7arcsec (~1600 au) from the stellar core. In contrast, [FeIII], [ArIII], [NeIII] and [SIII] lines extend only 0.3arcsec (700 au) from NE to SW and are blue shifted from -500 to +200 km s-1. All observed spectral features vary with the 5.54-year orbital period. The highly ionized, forbidden emission disappears during the low state, associated with periastron passage. The high-ionization emission originates in the outer wind interaction region that is directly excited by the far-ultraviolet radiation from η Car B. The HST/STIS spectra reveal a time-varying, distorted paraboloidal structure, caused by the interaction of the massive stellar winds. The model and observations are consistent with the orbital plane aligned with the skirt of the Homunculus. However, the axis of the distorted paraboloid, relative to the major axis of the binary orbit, is shifted in a prograde rotation along the plane, which projected on the sky is from NE to NW. Based on observations made with the National Aeronautics and Space Agency/European Space Agency (NASA/ESA) HST. Support for Programme numbers 7302, 8036, 8483, 8619, 9083, 9337, 9420, 9973, 10957 and 11273 was provided by NASA directly to the Space Telescope Imaging Spectrograph Science Team and through grants from the

  4. Discrepancy between genotypic and phenotypic extended-spectrum β-lactamase rates in Escherichia coli from intra-abdominal infections in the USA.

    PubMed

    Lob, Sibylle H; Biedenbach, Douglas J; Badal, Robert E; Kazmierczak, Krystyna M; Sahm, Daniel F

    2016-09-01

    Varying rates of false-positive results of phenotypic extended-spectrum β-lactamase (ESBL) tests have been reported for different methods in different settings, species and geographic locations. This report describes discrepancies in Escherichia coli genotypic and phenotypic ESBL rates observed in a surveillance study of 29 US hospitals that participated in the Study for Monitoring Antimicrobial Resistance Trends (SMART). The ESBL phenotype was determined with the Clinical and Laboratory Standards Institute confirmatory broth microdilution test using cefotaxime and ceftazidime with and without clavulanate. Genes encoding ESBLs, carbapenemases and plasmidic AmpC β-lactamases were detected using a combination of microarray and multiplex PCR assays. Among 168 molecularly characterized phenotypically ESBL-positive E. coli isolates from intra-abdominal infections, 4.8 % were genotypically negative from 2009 to 2012 and 29.5 % in 2013. Because of the high rate of false-positive phenotypic ESBL results in 2013, the 5-year phenotypic ESBL trend was skewed and showed a statistically significant increase (P<0.05) in ESBL-positive E. coli in the USA, which was not seen using the genotypic ESBL rates. The majority of false-positive phenotypic profiles had ceftazidime MICs of 2 µg ml-1 and a ≥3 doubling dilution decrease in MIC for only one of the two antimicrobial agents. False-positive ESBL results can adversely impact epidemiological surveillance and patient care (including inappropriate treatment, unnecessary patient isolation and higher costs). Careful evaluation and comparison of phenotypic and genotypic test results can yield the greatest insight, but the most accurate (and faster) detection of ESBL producers is usually based on molecular data.

  5. Population structure and genotype-phenotype associations in a collection of oat landraces and historic cultivars.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a partic...

  6. Understanding the Phenotypic Structure of Adult Retrospective ADHD Symptoms during Childhood in the United States

    ERIC Educational Resources Information Center

    Ranby, Krista W.; Boynton, Marcella H.; Kollins, Scott H.; McClernon, F. Joseph; Yang, Chongming; Fuemmeler, Bernard F.

    2012-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous disorder, and the phenotypic structure comprising inattentive and hyperactive-impulsive type symptoms has been the focus of a growing body of recent research. Methodological studies are needed to better characterize phenotypes to advance research as well as clinical…

  7. Structural studies of amorphous titanium diboride thin films by extended x-ray-absorption fine-structure and extended electron-energy-loss fine-structure techniques

    NASA Astrophysics Data System (ADS)

    Kaloyeros, Alain E.; Hoffman, Mark P.; Williams, Wendell S.; Greene, Alex E.; McMillan, Joyce A.

    1988-10-01

    The local atomic structure of amorphous titanium diboride thin films, prepared by electron-beam vaporization (EBV) of the crystalline compound onto liquid-nitrogen-cooled substrates, was studied using extended x-ray-absorption fine-structure (EXAFS) and extended energy-loss fine-structure (EXELFS) techniques. From a comparison of the extended fine-structure spectra of the amorphous films with corresponding spectra of crystalline titanium diboride, accurate information was derived on the nature of the local structure, or short-range order, and on the coordination numbers, interatomic distances, and nanostructural atomic disorder in amorphous TiB2. A relaxation of the interatomic spacing and a reduction of coordination number for the nearest-neighbor atoms was inferred for the amorphous state. Local prismatic coordination with random 90° rotations about prismatic planes is proposed as a likely atomic structure consistent with the data for the amorphous form. Finally, EXAFS and EXELFS were employed to examine in detail the structural changes induced in amorphous TiB2 by variations in the EBV deposition parameters, and to determine a set of optimized parameters for the EBV deposition of a TiB2 stable amorphous phase.

  8. Extended Kalman filter based structural damage detection for MR damper controlled structures

    NASA Astrophysics Data System (ADS)

    Jin, Chenhao; Jang, Shinae; Sun, Xiaorong; Jiang, Zhaoshuo; Christenson, Richard

    2016-04-01

    The Magneto-rheological (MR) dampers have been widely used in many building and bridge structures against earthquake and wind loadings due to its advantages including mechanical simplicity, high dynamic range, low power requirements, large force capacity, and robustness. However, research about structural damage detection methods for MR damper controlled structures is limited. This paper aims to develop a real-time structural damage detection method for MR damper controlled structures. A novel state space model of MR damper controlled structure is first built by combining the structure's equation of motion and MR damper's hyperbolic tangent model. In this way, the state parameters of both the structure and MR damper are added in the state vector of the state space model. Extended Kalman filter is then used to provide prediction for state variables from measurement data. The two techniques are synergistically combined to identify parameters and track the changes of both structure and MR damper in real time. The proposed method is tested using response data of a three-floor MR damper controlled linear building structure under earthquake excitation. The testing results show that the adaptive extended Kalman filter based approach is capable to estimate not only structural parameters such as stiffness and damping of each floor, but also the parameters of MR damper, so that more insights and understanding of the damage can be obtained. The developed method also demonstrates high damage detection accuracy and light computation, as well as the potential to implement in a structural health monitoring system.

  9. OBESITY/HYPERLEPTINEMIC PHENOTYPE IMPAIRS STRUCTURAL AND FUNCTIONAL PLASTICITY IN THE RAT HIPPOCAMPUS

    PubMed Central

    Grillo, Claudia A.; Piroli, Gerardo G.; Junor, Lorain; Wilson, Steven P.; Mott, David D.; Wilson, Marlene A.; Reagan, Lawrence P.

    2011-01-01

    Epidemiological studies estimate that greater than 60% of the adult US population may be categorized as either overweight or obese and there is a growing appreciation that the complications of obesity extend to the central nervous system (CNS). While the vast majority of these studies have focused upon the hypothalamus, more recent studies suggest that the complications of obesity may also affect the structural and functional integrity of the hippocampus. A potential contributor to obesity-related CNS abnormalities is the adipocyte-derived hormone leptin. In this regard, decreases in CNS leptin activity may contribute to deficits in hippocampal synaptic plasticity and suggest that leptin resistance, a well described phenomenon in the hypothalamus, may also be observed in the hippocampus. Unfortunately, the myriad of metabolic and endocrine abnormalities in diabetes/obesity phenotypes makes it challenging to assess the role of leptin in hippocampal neuroplasticity deficits associated with obesity models. To address this question, we examined hippocampal morphological and behavioral plasticity following lentivirus-mediated downregulation of hypothalamic insulin receptors (hypo-IRAS). Hypo-IRAS rats exhibit increases in body weight, adiposity, plasma leptin and triglyceride levels. As such, hypo-IRAS rats develop a phenotype that is consistent with features of the metabolic syndrome. In addition, hippocampal morphological plasticity and performance of hippocampal-dependent tasks are adversely affected in hypo-IRAS rats. Leptin-mediated signaling is also decreased in hypo-IRAS rats. We will discuss these findings in the context of how hyperleptinemia and hypertriglyceridemia may represent mechanistic mediators of the neurological consequences of impaired hippocampal synaptic plasticity in obesity. PMID:21354191

  10. A Hunter Patient with a Severe Phenotype Reveals Two Large Deletions and Two Duplications Extending 1.2 Mb Distally to IDS Locus.

    PubMed

    Zanetti, Alessandra; Tomanin, Rosella; Rampazzo, Angelica; Rigon, Chiara; Gasparotto, Nicoletta; Cassina, Matteo; Clementi, Maurizio; Scarpa, Maurizio

    2014-01-01

    Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an X-linked lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS), an enzyme involved in the glycosaminoglycans (GAGs) degradation. We here report the case of a 9-year-old boy who was diagnosed with an extremely severe form of MPS II at 10 months of age. Sequencing of the IDS gene revealed the deletion of exons 1-7, extending distally and removing the entire pseudogene IDSP1. The difficulty to define the boundaries of the deletion and the particular severity of the patient phenotype suggested to verify the presence of pathological copy number variations (CNVs) in the genome, by the array CGH (aCGH) technology. The examination revealed the presence of two deletions alternate with two duplications, overall affecting a region of about 1.2 Mb distally to IDS gene. This is the first complex rearrangement involving IDS and extending to a large region located distally to it described in a severe Hunter patient, as evidenced by the CNVs databases interrogated. The analysis of the genes involved in the rearrangement and of the disorders correlated with them did not help to clarify the phenotype observed in our patient, except for the deletion of the IDS gene, which explains per se the Hunter phenotype. However, this cannot exclude a potential "contiguous gene syndrome" as well as the future rising of additional pathological symptoms associated with the other extra genes involved in the identified rearrangement.

  11. Simple surface structure determination from Fourier transforms of angle-resolved photoemission extended fine structure

    SciTech Connect

    Zheng, Y. |; Shirley, D.A.

    1995-02-01

    The authors show by Fourier analyses of experimental data, with no further treatment, that the positions of all the strong peaks in Fourier transforms of angle-resolved photoemission extended fine structure (ARPEFS) from adsorbed surfaces can be explicitly predicted from a trial structure with an accuracy of about {+-} 0.3 {angstrom} based on a single-scattering cluster model together with the concept of a strong backscattering cone, and without any additional analysis. This characteristic of ARPEFS Fourier transforms can be developed as a simple method for determining the structures of adsorbed surfaces to an accuracy of about {+-} 0.1 {angstrom}.

  12. Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum

    PubMed Central

    Maria, Maleeha; Lamers, Ideke J. C.; Schmidts, Miriam; Ajmal, Muhammad; Jaffar, Sulman; Ullah, Ehsan; Mustafa, Bilal; Ahmad, Shakeel; Nazmutdinova, Katia; Hoskins, Bethan; van Wijk, Erwin; Koster-Kamphuis, Linda; Khan, Muhammad Imran; Beales, Phil L.; Cremers, Frans P. M.; Roepman, Ronald; Azam, Maleeha; Arts, Heleen H.; Qamar, Raheel

    2016-01-01

    Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder that is both genetically and clinically heterogeneous. To date 19 genes have been associated with BBS, which encode proteins active at the primary cilium, an antenna-like organelle that acts as the cell’s signaling hub. In the current study, a combination of mutation screening, targeted sequencing of ciliopathy genes associated with BBS, and whole-exome sequencing was used for the genetic characterization of five families including four with classic BBS symptoms and one BBS-like syndrome. This resulted in the identification of novel mutations in BBS genes ARL6 and BBS5, and recurrent mutations in BBS9 and CEP164. In the case of CEP164, this is the first report of two siblings with a BBS-like syndrome with mutations in this gene. Mutations in this gene were previously associated with nephronophthisis 15, thus the current results expand the CEP164-associated phenotypic spectrum. The clinical and genetic spectrum of BBS and BBS-like phenotypes is not fully defined in Pakistan. Therefore, genetic studies are needed to gain insights into genotype-phenotype correlations, which will in turn improve the clinician’s ability to make an early and accurate diagnosis, and facilitate genetic counseling, leading to directly benefiting families with affected individuals. PMID:27708425

  13. Population structure of deep-sea chemolithoautotrophs: identification of phenotypic and genotypic correlations

    NASA Astrophysics Data System (ADS)

    Mino, S.; Nakagawa, S.; Sawabe, T.; Miyazaki, J.; Makita, H.; Nunoura, T.; Yamamoto, M.; Takai, K.

    2012-12-01

    Deep-sea hydrothermal fields are areas on the seafloor of high biological productivity fueled primarily by microbial chemosynthesis. Chemolithoautotrophic Epsilonproteobacteria and Persephonella with an ability to utilize inorganic substrates such as elemental sulfur and hydrogen are important members in wide range of temperature conditions in deep-sea hydrothermal vents. However, little is known about their population genetic structure such as intraspecific genetic diversity, distribution pattern, and phenotypic characteristics. Previously, using genetic approach based on multi-locus sequence analysis (MLSA), we clarified that Epsilonproteobacteria Group A, B, F, and Persephonella populations were geographically separated, and Epsilonproteobacteria appeared to diverge by mutation rather than recombination. Contrary to genetic evidence for allopatric segregation in deep-sea chemoautotrophs, however, phenotypic evidence has never been found. In addition, analyzing such a phenotypic characteristic may lead to a better understanding of the interactions microbes have with their environment. In this study, we present a metabolomic approach based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to reveal phenotypic biogeographical discrimination. We demonstrated the whole-cell MALDI-TOF MS method on Epsilonproteobacteria and Persephonella populations. These chemoautotrophic strains used in this study were isolated from chimney structures, vent fluids, and hydrothermal sediments. These hydrothermal samples were collected from geographically separated hydrothermal areas of the South Mariana Trough, Okinawa Trough and Central Indian Ridge. Based on mass peaks (signal/noise >10) within the m/z range of 2000-14000, phenotypic analysis was carried out by cluster analysis. The result of phenotypic analysis was compared with the genotypic clusters. The whole-cell MALDI-TOF MS revealed that Persephonella population was identified to

  14. Band structures extending to very high spin in Xe126

    NASA Astrophysics Data System (ADS)

    Rønn Hansen, C.; Sletten, G.; Hagemann, G. B.; Herskind, B.; Jensen, D. R.; Bringel, P.; Engelhardt, C.; Hübel, H.; Neußer-Neffgen, A.; Singh, A. K.; Carpenter, M. P.; Janssens, R. V. F.; Khoo, T. L.; Lauritsen, T.; Bednarczyk, P.; Byrski, T.; Curien, D.; Benzoni, G.; Bracco, A.; Camera, F.; Leoni, S.; Clark, R. M.; Fallon, P.; Korichi, A.; Roccaz, J.; Maj, A.; Wilson, J. N.; Lisle, J. C.; Steinhardt, T.; Thelen, O.; Ødegård, S. W.

    2007-09-01

    High-spin states in Xe126 have been populated in the Se82(Ca48,4n)Xe126 reaction in two experiments, one at the VIVITRON accelerator in Strasbourg using the Euroball detector array, and a subsequent one with ATLAS at Argonne using the Gammasphere Ge-detector array. Levels and assignments made previously for Xe126 up to I=20 have been confirmed and extended. Four regular bands extending to a spin of almost I=60, which are interpreted as two pairs of signature partners with opposite parity, are identified for the first time. The α = 0 partner of each pair is connected to the lower-lying levels, whereas the two α = 1 partners remain floating. A fractional Doppler shift analysis of transitions in the strongest populated (π,α)=(-,0) band provides a value of 5.20.50.4 b for the transition quadrupole moment, which can be related to a minimum in the potential-energy surface calculated by the ULTIMATE CRANKER cranked shell-model code at ɛ≈0.35 and γ≈5°. The four lowest bands calculated for this minimum compare well with the two signature pairs experimentally observed over a wide spin range. A sharp upbend at ℏω~1170 keV is interpreted as a crossing with a band involving the j15/2 neutron orbital, for which pairing correlations are expected to be totally quenched. The four long bands extend to within ˜5 spin units of a crossing with an yrast line defined by calculated hyperdeformed transitions and will serve as important stepping stones into the spin region beyond 60ħ for future experiments.

  15. Structural and functional genome analysis using extended chromatin

    SciTech Connect

    Heaf, T.; Ward, D.C.

    1994-09-01

    Highly extended linear chromatin fibers (ECFs) produced by detergent and high-salt lysis and stretching of nuclear chromatin across the surface of a glass slide can by hybridized over physical distances of at least several Mb. This allows long-range FISH analysis of the human genome with excellent DNA resolution (<10 kb/{mu}m). The insertion of Alu elements which are more than 50-fold underrepresented in centromeres can be seen within and near long tandem arrays of alpha-satellite DNA. Long tracts of trinucleotide repeats, i.e. (CCA){sub n}, can be localized within larger genomic regions. The combined application of BrdU incorporation and ECFs allows one to study the spatio-temporal distribution of DNA replication sites in finer detail. DNA synthesis occurs at multiple discrete sites within Mb arrays of alpha-satellite. Replicating DNA is tightly associated with the nuclear matrix and highly resistant to stretching out, while ECFs containing newly replicated DNA are easily released. Asynchrony in replication timing is accompanied by differences in condensation of homologous DNA segments. Extended chromatin reveals differential packaging of active and inactive DNA. Upon transcriptional inactivation by AMD, the normally compact rRNA genes become much more susceptible to decondensation procedures. By extending the chromatin from pachytene spermatocytes, meiotic pairing and genetic exchange between homologs can be visualized directly. Histone depletion by high salt and detergent produces loop chromatin surrounding the nuclear matrix in a halo-like fashion. DNA halos can be used to map nuclear matrix attachment sites in somatic cells and in mature sperm. Alpha-satellite containing DNA loops appear to be attached to the sperm-cell matrix by CENP-B boxes, short 17 bp sequences found in a subset of alpha satellite monomers. Sperm telomeres almost always appear as hybridization doublets, suggesting the presence of already replicated chromosome ends.

  16. Extending the phenotype of monosomy 1p36 syndrome and mapping of a critical region for obesity and hyperphagia.

    PubMed

    D'Angelo, Carla S; Kohl, Ilana; Varela, Monica Castro; de Castro, Cláudia I E; Kim, Chong A; Bertola, Débora R; Lourenço, Charles M; Koiffmann, Célia P

    2010-01-01

    Rearrangements of 1p36 are the most frequently detected abnormalities in diagnostic testing for chromosomal cryptic imbalances and include variably sized simple terminal deletions, derivative chromosomes, interstitial deletions, and complex rearrangements. These rearrangements result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no individual gene within this region has been conclusively determined to be causative of any component of the phenotype. Nor is it known if the rearrangements convey phenotypes via a haploinsufficiency mechanism or through a position effect. We have used multiplex ligation-dependent probe amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and overweight/obese, PWS negative individuals, and in a separate group of 83 patients initially sent to investigate a variety of other conditions. The strategy allowed the identification and delineation of rearrangements in nine subjects with a wide spectrum of clinical presentations. Our work reinforces the association of monosomy 1p36 and obesity and hyperphagia, and further suggests that these features may be associated with non-classical manifestations of this disorder in addition to a submicroscopic deletion of approximately 2-3 Mb in size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome-specific kit coupled to the subtelomeric kit is an effective approach to identify and delineate rearrangements at 1p36.

  17. Can structural neuroimaging be used to define phenotypes and course of schizophrenia?

    PubMed

    Kerns, John G; Lauriello, John

    2012-09-01

    This article examines whether structural neuroimaging measures have been found to predict outcome in schizophrenia and whether changes in neuroimaging measures have been found to correlate with poor outcome in the disorder. Overall, there is little compelling evidence that structural neuroimaging measures in either first-episode or chronic patients predict future outcome. Progressive brain changes might reflect a neuroimaging phenotype associated with a worse course of the disorder. At the same time, there are many fruitful avenues that future research could take in an attempt to better predict future outcome or to identify specific imaging phenotypes associated with outcome. PMID:22929870

  18. Structural mapping: how to study the genetic architecture of a phenotypic trait through its formation mechanism.

    PubMed

    Tong, Chunfa; Shen, Lianying; Lv, Yafei; Wang, Zhong; Wang, Xiaoling; Feng, Sisi; Li, Xin; Sui, Yihan; Pang, Xiaoming; Wu, Rongling

    2014-01-01

    Traditional approaches for genetic mapping are to simply associate the genotypes of a quantitative trait locus (QTL) with the phenotypic variation of a complex trait. A more mechanistic strategy has emerged to dissect the trait phenotype into its structural components and map specific QTLs that control the mechanistic and structural formation of a complex trait. We describe and assess such a strategy, called structural mapping, by integrating the internal structural basis of trait formation into a QTL mapping framework. Electrical impedance spectroscopy (EIS) has been instrumental for describing the structural components of a phenotypic trait and their interactions. By building robust mathematical models on circuit EIS data and embedding these models within a mixture model-based likelihood for QTL mapping, structural mapping implements the EM algorithm to obtain maximum likelihood estimates of QTL genotype-specific EIS parameters. The uniqueness of structural mapping is to make it possible to test a number of hypotheses about the pattern of the genetic control of structural components. We validated structural mapping by analyzing an EIS data collected for QTL mapping of frost hardiness in a controlled cross of jujube trees. The statistical properties of parameter estimates were examined by simulation studies. Structural mapping can be a powerful alternative for genetic mapping of complex traits by taking account into the biological and physical mechanisms underlying their formation.

  19. Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

    PubMed

    Mensah, F; Bansal, A; Berkovitz, S; Sharma, A; Reddy, V; Leandro, M J; Cambridge, G

    2016-05-01

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19⁺ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD⁺ subsets. Within memory subsets, a higher frequency of CD21⁺ CD38⁻ B cells (> 20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy. PMID:26646713

  20. Trade-Offs in Relative Limb Length among Peruvian Children: Extending the Thrifty Phenotype Hypothesis to Limb Proportions

    PubMed Central

    Pomeroy, Emma; Stock, Jay T.; Stanojevic, Sanja; Miranda, J. Jaime; Cole, Tim J.; Wells, Jonathan C. K.

    2012-01-01

    Background and Methods Both the concept of ‘brain-sparing’ growth and associations between relative lower limb length, childhood environment and adult disease risk are well established. Furthermore, tibia length is suggested to be particularly plastic under conditions of environmental stress. The mechanisms responsible are uncertain, but three hypotheses may be relevant. The ‘thrifty phenotype’ assumes that some components of growth are selectively sacrificed to preserve more critical outcomes, like the brain. The ‘distal blood flow’ hypothesis assumes that blood nutrients decline with distance from the heart, and hence may affect limbs in relation to basic body geometry. Temperature adaptation predicts a gradient of decreased size along the limbs reflecting decreasing tissue temperature/blood flow. We examined these questions by comparing the size of body segments among Peruvian children born and raised in differentially stressful environments. In a cross-sectional sample of children aged 6 months to 14 years (n = 447) we measured head circumference, head-trunk height, total upper and lower limb lengths, and zeugopod (ulna and tibia) and autopod (hand and foot) lengths. Results Highland children (exposed to greater stress) had significantly shorter limbs and zeugopod and autopod elements than lowland children, while differences in head-trunk height were smaller. Zeugopod elements appeared most sensitive to environmental conditions, as they were relatively shorter among highland children than their respective autopod elements. Discussion The results suggest that functional traits (hand, foot, and head) may be partially protected at the expense of the tibia and ulna. The results do not fit the predictions of the distal blood flow and temperature adaptation models as explanations for relative limb segment growth under stress conditions. Rather, our data support the extension of the thrifty phenotype hypothesis to limb growth, and suggest that certain

  1. Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.

    PubMed

    Hamilton, Mark J; Newbury-Ecob, Ruth; Holder-Espinasse, Muriel; Yau, Shu; Lillis, Suzanne; Hurst, Jane A; Clement, Emma; Reardon, William; Joss, Shelagh; Hobson, Emma; Blyth, Moira; Al-Shehhi, Maryam; Lynch, Sally A; Suri, Mohnish

    2016-10-01

    Rubinstein-Taybi syndrome (RTS) is an autosomal dominant neurodevelopmental disorder characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Mutations in CREBBP account for around 55% of cases, with a further 8% attributed to the paralogous gene EP300. Comparatively few reports exist describing the phenotype of Rubinstein-Taybi because of EP300 mutations. Clinical and genetic data were obtained from nine patients from the UK and Ireland with pathogenic EP300 mutations, identified either by targeted testing or by exome sequencing. All patients had mild or moderate intellectual impairment. Behavioural or social difficulties were noted in eight patients, including three with autistic spectrum disorders. Typical dysmorphic features of Rubinstein-Taybi were only variably present. Additional observations include maternal pre-eclampsia (2/9), syndactyly (3/9), feeding or swallowing issues (3/9), delayed bone age (2/9) and scoliosis (2/9). Six patients had truncating mutations in EP300, with pathogenic missense mutations identified in the remaining three. The findings support previous observations that microcephaly, maternal pre-eclampsia, mild growth restriction and a mild to moderate intellectual disability are key pointers to the diagnosis of EP300-related RTS. Variability in the presence of typical facial features of Rubinstein-Taybi further highlights clinical heterogeneity, particularly among patients identified by exome sequencing. Features that overlap with Floating-Harbor syndrome, including craniofacial dysmorphism and delayed osseous maturation, were observed in three patients. Previous reports have only described mutations predicted to cause haploinsufficiency of EP300, whereas this cohort includes the first described pathogenic missense mutations in EP300.

  2. Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.

    PubMed

    Hamilton, Mark J; Newbury-Ecob, Ruth; Holder-Espinasse, Muriel; Yau, Shu; Lillis, Suzanne; Hurst, Jane A; Clement, Emma; Reardon, William; Joss, Shelagh; Hobson, Emma; Blyth, Moira; Al-Shehhi, Maryam; Lynch, Sally A; Suri, Mohnish

    2016-10-01

    Rubinstein-Taybi syndrome (RTS) is an autosomal dominant neurodevelopmental disorder characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Mutations in CREBBP account for around 55% of cases, with a further 8% attributed to the paralogous gene EP300. Comparatively few reports exist describing the phenotype of Rubinstein-Taybi because of EP300 mutations. Clinical and genetic data were obtained from nine patients from the UK and Ireland with pathogenic EP300 mutations, identified either by targeted testing or by exome sequencing. All patients had mild or moderate intellectual impairment. Behavioural or social difficulties were noted in eight patients, including three with autistic spectrum disorders. Typical dysmorphic features of Rubinstein-Taybi were only variably present. Additional observations include maternal pre-eclampsia (2/9), syndactyly (3/9), feeding or swallowing issues (3/9), delayed bone age (2/9) and scoliosis (2/9). Six patients had truncating mutations in EP300, with pathogenic missense mutations identified in the remaining three. The findings support previous observations that microcephaly, maternal pre-eclampsia, mild growth restriction and a mild to moderate intellectual disability are key pointers to the diagnosis of EP300-related RTS. Variability in the presence of typical facial features of Rubinstein-Taybi further highlights clinical heterogeneity, particularly among patients identified by exome sequencing. Features that overlap with Floating-Harbor syndrome, including craniofacial dysmorphism and delayed osseous maturation, were observed in three patients. Previous reports have only described mutations predicted to cause haploinsufficiency of EP300, whereas this cohort includes the first described pathogenic missense mutations in EP300. PMID:27465822

  3. Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

    PubMed

    Mensah, F; Bansal, A; Berkovitz, S; Sharma, A; Reddy, V; Leandro, M J; Cambridge, G

    2016-05-01

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19⁺ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD⁺ subsets. Within memory subsets, a higher frequency of CD21⁺ CD38⁻ B cells (> 20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.

  4. Correlates across the Structural, Functional, and Molecular Phenotypes of Fragile X Syndrome

    ERIC Educational Resources Information Center

    Beckel-Mitchener, Andrea; Greenough, William T.

    2004-01-01

    Fragile X syndrome (FXS) is characterized by a pattern of morphological, functional, and molecular characteristics with, in at least some cases, apparent relationships among phenotypic features at different levels. Gross morphology differences in the sizes of some human brain regions are accompanied by fine structural alterations in the shapes and…

  5. Extending the lifespan of nuclear power plant structures

    SciTech Connect

    Naus, D.J.; Oland, C.B.; Ellingwood, B.

    1995-04-01

    By the end of this decade, 63 of the 111 commercial nuclear power plants in the United States will be more than 20 years old, with some nearing the end of their 40-year operating license term. Faced with the prospect of having to replace lost generating capacity from other sources and substantial shutdown and decommissioning costs, many utilities are expected to apply to continue the service of their plants past the initial licensing period. In support of such applications, evidence should be provided that the capacity of the safety-related systems and structures to mitigate potential extreme events has not deteriorated unacceptably due to either aging or environmental stressor effects during the previous service history.

  6. The Extended Granin Family: Structure, Function, and Biomedical Implications

    PubMed Central

    Bartolomucci, Alessandro; Possenti, Roberta; Mahata, Sushil K.; Fischer-Colbrie, Reiner; Loh, Y. Peng

    2011-01-01

    The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers. PMID:21862681

  7. Phosphorenes with Non-Honeycomb Structures: A Much Extended Family

    NASA Astrophysics Data System (ADS)

    Wu, Menghao; Fu, Huahua; Zhou, Ling; Yao, Kailun; Zeng, Xiao Cheng; Huazhong University of Science; Technology Team; University of Nebraska-Lincoln Team

    We predict a new class of monolayer phosphorous allotropes, namely, ɛ-P, ζ-P, η-P and θ-P. Distinctly different from the monolayer α-P (black) and previously predicted β-P (Phys. Rev. Lett. 112, 176802 (2014)), γ-P and δ-P (Phys. Rev. Lett. 113, 046804 (2014)) with buckled honeycomb lattice, the new allotropes are composed of P4 square or P5 pentagon units that favor tricoordination for P atoms. The new four phases, together with 5 hybrid phases, are confirmed stable by first-principles calculations. In particularly, the θ-P is shown to be equally stable as the α-P (black) and more stable than all previously reported phosphorene allotropes. Prediction of nonvolatile ferroelastic switching and structural transformation among different phases under strains points out their potential applications via strain engineering. MHW was supported by start-up fund from Huazhong University of Science and Technology.

  8. Complexation thermodynamics of modified cyclodextrins: extended cavities and distorted structures.

    PubMed

    Schönbeck, Christian; Westh, Peter; Holm, René

    2014-08-28

    Inclusion complexes between two bile salts and a range of differently methylated β-cyclodextrins were studied in an attempt to rationalize the complexation thermodynamics of modified cyclodextrins. Calorimetric titrations at a range of temperatures provided precise values of the enthalpies (ΔH°), entropies (ΔS°), and heat capacities (ΔCp) of complexation, while molecular dynamics simulations assisted the interpretation of the obtained thermodynamic parameters. As previously observed for several types of modified cyclodextrins, the substituents at the rims of the cyclodextrin induced large changes in ΔH° and ΔS°, but due to enthalpy-entropy compensation the changes in Gibbs free energy, and the binding constant, were much smaller. For the methylated β-cyclodextrins, the substituent-induced increments in ΔH° and ΔS° were nonmonotonic with an initial strong increase in both ΔH° and ΔS° and then a strong decrease when the degree of substitution exceeded some threshold. Exactly the same trend was observed for ΔCp. The dehydration of nonpolar surface, as quantified by the simulations, can to a large extent explain the variation in the thermodynamic parameters. The methyl substituents form additional hydrophobic contacts with the bile salt, but at high degrees of methylation they also cause significant distortion of the otherwise circular cyclodextrin structure. These two opposing contributions to the dehydration are the major causes for the observed variations in the thermodynamic functions. The structural effects are not expected to be specific for methylated cyclodextrins but should be observed for most modified cyclodextrins. An even more general conclusion is that variations in the extent of hydration are an important underlying reason for the commonly observed phenomenon termed enthalpy-entropy compensation and also for the less frequent reports of entropy convergence around 110 °C.

  9. The Arches Cluster: Extended Structure and Tidal Radius

    NASA Astrophysics Data System (ADS)

    Hosek, Matthew W., Jr.; Lu, Jessica R.; Anderson, Jay; Ghez, Andrea M.; Morris, Mark R.; Clarkson, William I.

    2015-11-01

    At a projected distance of ˜26 pc from Sgr A*, the Arches cluster provides insight into star formation in the extreme Galactic center (GC) environment. Despite its importance, many key properties, such as the cluster’s internal structure and orbital history, are not well known. We present an astrometric and photometric study of the outer region of the Arches cluster (R > 6.″25) using Hubble Space Telescope WFC3IR. Using proper motions, we calculate membership probabilities for stars down to F153M = 20 mag (˜2.5 M⊙) over a 120″ × 120″ field of view, an area 144 times larger than previous astrometric studies of the cluster. We construct the radial profile of the Arches to a radius of 75″ (˜3 pc at 8 kpc), which can be well described by a single power law. From this profile we place a 3σ lower limit of 2.8 pc on the observed tidal radius, which is larger than the predicted tidal radius (1-2.5 pc). Evidence of mass segregation is observed throughout the cluster, and no tidal tail structures are apparent along the orbital path. The absence of breaks in the profile suggests that the Arches has not likely experienced its closest approach to the GC between ˜0.2 and 1 Myr ago. If accurate, this constraint indicates that the cluster is on a prograde orbit and is located in front of the sky plane that intersects Sgr A*. However, further simulations of clusters in the GC potential are required to interpret the observed profile with more confidence.

  10. Evaluation of high temperature structural adhesives for extended service

    NASA Technical Reports Server (NTRS)

    Hill, S. G.; Peters, P. D.; Hendricks, C. L.

    1982-01-01

    The evaluation, selection, and demonstration of structural adhesive systems for supersonic cruise research applications, and establishment of environmental durability of selected systems for up to 20,000 hours is described. Ten candidate adhesives were initially evaluated. During screening and evaluation, these candidates were narrowed to three of the most promising for environmental durability testing. The three adhesives were LARC-13, PPQ, and NR056X. The LARC-13 was eliminated because of a lack of stability at 505 K. The NRO56X was removed from the market. The LARC-TPI was added after preliminary evaluation and an abbreviated screening test. Only PPQ and LARC-TPI remained as the reasonable candidates late into the durability testing. Large area bond panels were fabricated to demonstrate the processibility of the selected systems. Specifications were prepared to assure control over critical material and process parameters. Surface characterization concentrated primarily upon titanium surface treatments of 10 volt chronic acid anodize, 5 volt chromic acid anodize and PASA-JELL. Failure analysis was conducted on lap shear adhesive bond failures which occurred in PPQ and LARC-13 test specimens after 10,000 hours at 505 K.

  11. Conflict between biotic and climatic selective pressures acting on an extended phenotype in a subarctic, but not temperate, environment

    PubMed Central

    Rohwer, V. G.; Bonier, F.; Martin, P. R.

    2015-01-01

    Climatic selective pressures are thought to dominate biotic selective pressures at higher latitudes. However, few studies have experimentally tested how these selective pressures differentially act on traits across latitudes because traits can rarely be manipulated independently of the organism in nature. We overcame this challenge by using an extended phenotype—active bird nests—and conducted reciprocal transplant experiments between a subarctic and temperate site, separated by 14° of latitude. At the subarctic site, biotic selective pressures (nest predation) favoured smaller, non-local temperate nests, whereas climatic selective pressures (temperature) favoured larger local nests, particularly at colder temperatures. By contrast, at the temperate site, climatic and biotic selective pressures acted similarly on temperate and subarctic nests. Our results illustrate a functional trade-off in the subarctic between nest morphologies favoured by biotic versus climatic selective pressures, with climate favouring local nest morphologies. At our temperate site, however, allocative trade-offs in the time and effort devoted to nest construction favour smaller, local nests. Our findings illustrate a conflict between biotic and climatic selective pressures at the northern extremes of a species geographical range, and suggest that trade-offs between trait function and trait elaboration act differentially across latitude to create broad geographic variation in traits. PMID:26490789

  12. Structural and Genetic Assessment of the ABCA4-Associated Optical Gap Phenotype

    PubMed Central

    Nõupuu, Kalev; Lee, Winston; Zernant, Jana; Tsang, Stephen H.; Allikmets, Rando

    2014-01-01

    Purpose. To investigate the developmental stages and genetic etiology of the optical gap phenotype in recessive Stargardt disease (STGD1). Methods. Single and longitudinal data points from 15 patients, including four sibling pairs, exhibiting an optical gap phenotype on spectral-domain optical coherence tomography (SD-OCT) with confirmed disease-causing ABCA4 alleles were retrospectively analyzed. Fundus images with corresponding SD-OCT scans were collected with a confocal scanning laser ophthalmoscope. Structural phenotypes were assigned to three developmental stages according to SD-OCT. The ABCA4 gene was screened in all patients. Results. At least two disease-causing ABCA4 variants where identified in each patient; all except one (91%) were compound heterozygous for the p.G1961E mutation. All patients exhibited structural findings on SD-OCT that grouped into three progressive developmental stages over several years. Stage 1 was characterized by mild disruptions of the ellipsoid zone (EZ) band over the fovea. Stage 2 was a progressive expansion of the EZ band loss resulting in an empty lesion devoid of photoreceptors. Stage 3 observed a structural collapse of the inner retinal layers into the optical gap space leading to involvement and atrophy of the RPE thereafter. Conclusions. The optical gap phenotype in STGD1 can be structurally divided into three progressive stages spanning several years. This particular phenotype also appears to be highly associated with the p.G1961E mutation of ABCA4. Taken together, it appears that a focal loss of photoreceptors sequentially precedes RPE dysfunction in the early development of ABCA4-associated optical gap lesions. PMID:25301883

  13. Phenotypic variation and water selection potential in the stem structure of invasive alligator weed

    NASA Astrophysics Data System (ADS)

    Du, Leshan; Yang, Beifen; Guan, Wenbin; Li, Junmin

    2016-02-01

    The morphological and anatomical characteristics of stems have been found to be related to drought resistance in plants. Testing the phenotypic selection of water availability on stem anatomical traits would be useful for exploring the evolutionary potential of the stem in response to water availability. To test the phenotypic variation of the stem anatomical traits of an invasive plant in response to water availability, we collected a total of 320 individuals of Alternanthera philoxeroides from 16 populations from terrestrial and aquatic habitats in 8 plots in China and then analyzed the variation, differentiation, plasticity and selection potential of water availability on the stem anatomical traits. We found that except for the thickness of the cortex, all of the examined phenotypic parameters of the A. philoxeroides stem were significantly and positively correlated with soil water availability. The phenotypic differentiation coefficient for all of the anatomical structural parameters indicated that most of the variation existed between habitats within the same plot, whereas there was little variation among plots or among individuals within the same habitat except for variation in the thickness of the cortex. A significant phenotypic plasticity response to water availability was found for all of the anatomical traits of A. philoxeroides stem except for the thickness of the cortex. The associations between fitness and some of the anatomical traits, such as the stem diameter, the cortex area-to-stem area ratio, the pith cavity area-to-stem area ratio and the density of vascular bundles, differed with heterogeneous water availability. In both the aquatic and terrestrial habitats, no significant directional selection gradient was found for the stem diameter, the cortex area-to-stem area ratio or the density of vascular bundles. These results indicated that the anatomical structure of the A. philoxeroides stem may play an important role in the adaptation to changes

  14. Plant phenotyping using multi-view stereo vision with structured lights

    NASA Astrophysics Data System (ADS)

    Nguyen, Thuy Tuong; Slaughter, David C.; Maloof, Julin N.; Sinha, Neelima

    2016-05-01

    A multi-view stereo vision system for true 3D reconstruction, modeling and phenotyping of plants was created that successfully resolves many of the shortcomings of traditional camera-based 3D plant phenotyping systems. This novel system incorporates several features including: computer algorithms, including camera calibration, excessive-green based plant segmentation, semi-global stereo block matching, disparity bilateral filtering, 3D point cloud processing, and 3D feature extraction, and hardware consisting of a hemispherical superstructure designed to hold five stereo pairs of cameras and a custom designed structured light pattern illumination system. This system is nondestructive and can extract 3D features of whole plants modeled from multiple pairs of stereo images taken at different view angles. The study characterizes the systems phenotyping performance for 3D plant features: plant height, total leaf area, and total leaf shading area. For plants having specified leaf spacing and size, the algorithms used in our system yielded satisfactory experimental results and demonstrated the ability to study plant development where the same plants were repeatedly imaged and phenotyped over the time.

  15. Hypertrophic phenotype in cardiac cell assemblies solely by structural cues and ensuing self-organization

    PubMed Central

    Chung, Chiung-yin; Bien, Harold; Sobie, Eric A.; Dasari, Vikram; McKinnon, David; Rosati, Barbara; Entcheva, Emilia

    2011-01-01

    In vitro models of cardiac hypertrophy focus exclusively on applying “external” dynamic signals (electrical, mechanical, and chemical) to achieve a hypertrophic state. In contrast, here we set out to demonstrate the role of “self-organized” cellular architecture and activity in reprogramming cardiac cell/tissue function toward a hypertrophic phenotype. We report that in neonatal rat cardiomyocyte culture, subtle out-of-plane microtopographic cues alter cell attachment, increase biomechanical stresses, and induce not only structural remodeling, but also yield essential molecular and electrophysiological signatures of hypertrophy. Increased cell size and cell binucleation, molecular up-regulation of released atrial natriuretic peptide, altered expression of classic hypertrophy markers, ion channel remodeling, and corresponding changes in electrophysiological function indicate a state of hypertrophy on par with other in vitro and in vivo models. Clinically used antihypertrophic pharmacological treatments partially reversed hypertrophic behavior in this in vitro model. Partial least-squares regression analysis, combining gene expression and functional data, yielded clear separation of phenotypes (control: cells grown on flat surfaces; hypertrophic: cells grown on quasi-3-dimensional surfaces and treated). In summary, structural surface features can guide cardiac cell attachment, and the subsequent syncytial behavior can facilitate trophic signals, unexpectedly on par with externally applied mechanical, electrical, and chemical stimulation.—Chung, C., Bien, H., Sobie, E. A., Dasari, V., McKinnon, D., Rosati, B., Entcheva, E. Hypertrophic phenotype in cardiac cell assemblies solely by structural cues and ensuing self-organization. PMID:21084696

  16. Effects of phenotype and genotype on methods for detection of extended-spectrum-beta-lactamase-producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in Norway.

    PubMed

    Tofteland, Ståle; Haldorsen, Bjørg; Dahl, Kristin H; Simonsen, Gunnar S; Steinbakk, Martin; Walsh, Timothy R; Sundsfjord, Arnfinn

    2007-01-01

    Consecutive clinical isolates of Escherichia coli (n = 87) and Klebsiella pneumoniae (n = 25) with reduced susceptibilities to oxyimino-cephalosporins (MICs > 1 mg/liter) from 18 Norwegian laboratories during March through October 2003 were examined for bla(TEM/SHV/CTX-M) extended-spectrum-beta-lactamase (ESBL) genes, oxyimino-cephalosporin MIC profiles, ESBL phenotypes (determined by the ESBL Etest and the combined disk and double-disk synergy [DDS] methods), and susceptibility to non-beta-lactam antibiotics. Multidrug-resistant CTX-M-15-like (n = 23) and CTX-M-9-like (n = 15) ESBLs dominated among the 50 ESBL-positive E. coli isolates. SHV-5-like (n = 9) and SHV-2-like (n = 4) ESBLs were the most prevalent in 19 ESBL-positive K. pneumoniae isolates. Discrepant ESBL phenotype test results were observed for one major (CTX-M-9) and several minor (TEM-128 and SHV-2/-28) ESBL groups and in SHV-1/-11-hyperproducing isolates. Negative or borderline ESBL results were observed when low-MIC oxyimino-cephalosporin substrates were used to detect clavulanic acid (CLA) synergy. CLA synergy was detected by the ESBL Etest and the DDS method but not by the combined disk method in SHV-1/-11-hyperproducing strains. The DDS method revealed unexplained CLA synergy in combination with aztreonam and cefpirome in three E. coli strains. The relatively high proportion of ESBL-producing E. coli organisms with a low ceftazidime MIC in Norway emphasizes that cefpodoxime alone or both cefotaxime and ceftazidime should be used as substrates for ESBL detection. PMID:17079502

  17. Structural Properties of Gene Promoters Highlight More than Two Phenotypes of Diabetes

    PubMed Central

    Guja, Cristian

    2015-01-01

    Genome-wide association studies (GWAS) published in the last decade raised the number of loci associated with type 1 (T1D) and type 2 diabetes (T2D) to more than 50 for each of these diabetes phenotypes. The environmental factors seem to play an important role in the expression of these genes, acting through transcription factors that bind to promoters. Using the available databases we examined the promoters of various genes classically associated with the two main diabetes phenotypes. Our comparative analyses have revealed significant architectural differences between promoters of genes classically associated with T1D and T2D. Nevertheless, five gene promoters (about 16%) belonging to T1D and six gene promoters (over 19%) belonging to T2D have shown some intermediary structural properties, suggesting a direct relationship to either LADA (Latent Autoimmune Diabetes in Adults) phenotype or to non-autoimmune type 1 phenotype. The distribution of these promoters in at least three separate classes seems to indicate specific pathogenic pathways. The image-based patterns (DNA patterns) generated by promoters of genes associated with these three phenotypes support the clinical observation of a smooth link between specific cases of typical T1D and T2D. In addition, a global distribution of these DNA patterns suggests that promoters of genes associated with T1D appear to be evolutionary more conserved than those associated with T2D. Though, the image based patterns obtained by our method might be a new useful parameter for understanding the pathogenetic mechanism and the diabetogenic gene networks. PMID:26379145

  18. Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia.

    PubMed

    Haider, Shozeb; Islam, Barira; D'Atri, Valentina; Sgobba, Miriam; Poojari, Chetan; Sun, Li; Yuen, Tony; Zaidi, Mone; New, Maria I

    2013-02-12

    Mutations in the cytochrome p450 (CYP)21A2 gene, which encodes the enzyme steroid 21-hydroxylase, cause the majority of cases in congenital adrenal hyperplasia, an autosomal recessive disorder. To date, more than 100 CYP21A2 mutations have been reported. These mutations can be associated either with severe salt-wasting or simple virilizing phenotypes or with milder nonclassical phenotypes. Not all CYP21A2 mutations have, however, been characterized biochemically, and the clinical consequences of these mutations remain unknown. Using the crystal structure of its bovine homolog as a template, we have constructed a humanized model of CYP21A2 to provide comprehensive structural explanations for the clinical manifestations caused by each of the known disease-causing missense mutations in CYP21A2. Mutations that affect membrane anchoring, disrupt heme and/or substrate binding, or impair stability of CYP21A2 cause complete loss of function and salt-wasting disease. In contrast, mutations altering the transmembrane region or conserved hydrophobic patches cause up to a 98% reduction in enzyme activity and simple virilizing disease. Mild nonclassical disease can result from interference in oxidoreductase interactions, salt-bridge and hydrogen-bonding networks, and nonconserved hydrophobic clusters. A simple in silico evaluation of previously uncharacterized gene mutations could, thus, potentially help predict the often diverse phenotypes of a monogenic disorder.

  19. The Drosophila phenotype ontology

    PubMed Central

    2013-01-01

    Background Phenotype ontologies are queryable classifications of phenotypes. They provide a widely-used means for annotating phenotypes in a form that is human-readable, programatically accessible and that can be used to group annotations in biologically meaningful ways. Accurate manual annotation requires clear textual definitions for terms. Accurate grouping and fruitful programatic usage require high-quality formal definitions that can be used to automate classification. The Drosophila phenotype ontology (DPO) has been used to annotate over 159,000 phenotypes in FlyBase to date, but until recently lacked textual or formal definitions. Results We have composed textual definitions for all DPO terms and formal definitions for 77% of them. Formal definitions reference terms from a range of widely-used ontologies including the Phenotype and Trait Ontology (PATO), the Gene Ontology (GO) and the Cell Ontology (CL). We also describe a generally applicable system, devised for the DPO, for recording and reasoning about the timing of death in populations. As a result of the new formalisations, 85% of classifications in the DPO are now inferred rather than asserted, with much of this classification leveraging the structure of the GO. This work has significantly improved the accuracy and completeness of classification and made further development of the DPO more sustainable. Conclusions The DPO provides a set of well-defined terms for annotating Drosophila phenotypes and for grouping and querying the resulting annotation sets in biologically meaningful ways. Such queries have already resulted in successful function predictions from phenotype annotation. Moreover, such formalisations make extended queries possible, including cross-species queries via the external ontologies used in formal definitions. The DPO is openly available under an open source license in both OBO and OWL formats. There is good potential for it to be used more broadly by the Drosophila

  20. Linking amphibian call structure to the environment: the interplay between phenotypic flexibility and individual attributes.

    PubMed

    Ziegler, Lucía; Arim, Matías; Narins, Peter M

    2011-05-01

    The structure of the environment surrounding signal emission produces different patterns of degradation and attenuation. The expected adjustment of calls to ensure signal transmission in an environment was formalized in the acoustic adaptation hypothesis. Within this framework, most studies considered anuran calls as fixed attributes determined by local adaptations. However, variability in vocalizations as a product of phenotypic expression has also been reported. Empirical evidence supporting the association between environment and call structure has been inconsistent, particularly in anurans. Here, we identify a plausible causal structure connecting environment, individual attributes, and temporal and spectral adjustments as direct or indirect determinants of the observed variation in call attributes of the frog Hypsiboas pulchellus. For that purpose, we recorded the calls of 40 males in the field, together with vegetation density and other environmental descriptors of the calling site. Path analysis revealed a strong effect of habitat structure on the temporal parameters of the call, and an effect of site temperature conditioning the size of organisms calling at each site and thus indirectly affecting the dominant frequency of the call. Experimental habitat modification with a styrofoam enclosure yielded results consistent with field observations, highlighting the potential role of call flexibility on detected call patterns. Both, experimental and correlative results indicate the need to incorporate the so far poorly considered role of phenotypic plasticity in the complex connection between environmental structure and individual call attributes.

  1. Linking amphibian call structure to the environment: the interplay between phenotypic flexibility and individual attributes.

    PubMed

    Ziegler, Lucía; Arim, Matías; Narins, Peter M

    2011-05-01

    The structure of the environment surrounding signal emission produces different patterns of degradation and attenuation. The expected adjustment of calls to ensure signal transmission in an environment was formalized in the acoustic adaptation hypothesis. Within this framework, most studies considered anuran calls as fixed attributes determined by local adaptations. However, variability in vocalizations as a product of phenotypic expression has also been reported. Empirical evidence supporting the association between environment and call structure has been inconsistent, particularly in anurans. Here, we identify a plausible causal structure connecting environment, individual attributes, and temporal and spectral adjustments as direct or indirect determinants of the observed variation in call attributes of the frog Hypsiboas pulchellus. For that purpose, we recorded the calls of 40 males in the field, together with vegetation density and other environmental descriptors of the calling site. Path analysis revealed a strong effect of habitat structure on the temporal parameters of the call, and an effect of site temperature conditioning the size of organisms calling at each site and thus indirectly affecting the dominant frequency of the call. Experimental habitat modification with a styrofoam enclosure yielded results consistent with field observations, highlighting the potential role of call flexibility on detected call patterns. Both, experimental and correlative results indicate the need to incorporate the so far poorly considered role of phenotypic plasticity in the complex connection between environmental structure and individual call attributes. PMID:22479134

  2. Phenotypic and Molecular Characterisation of Extended-Spectrum Beta-Lactamase Producing Escherichia coli Obtained from Animal Fecal Samples in Ado Ekiti, Nigeria

    PubMed Central

    Olowe, Olugbenga Adekunle; Adewumi, Olufunmilayo; Odewale, Gbolabo; Ojurongbe, Olusola; Adefioye, Olusolabomi Jose

    2015-01-01

    Production of extended-spectrum β-lactamases (ESBLs) producing E. coli in animals and different methods of identifications from Ado Ekiti, Ekiti State, Nigeria, were investigated. Three hundred and fifty fecal samples, collected from apparently healthy cattle and pigs, were cultured and identified following standard procedures. ESBL phenotypic detection was carried out using combination disc test, double disc synergism test, and ESBL brilliance agar screening. Molecular detection of TEM, SHV, and CTX-M genes was carried out using standard molecular method. One hundred and fourteen E. coli isolates were recovered from the 350 samples processed, out of which 72 (63.2%) isolates were positive for ESBLs with multiple resistance to the antibiotics used. Eighty-one (71%) isolates were positive for ESBL by combination disc test, 90 (78.9%) were positive for double disc synergism test, and 93 (81.6%) were positive for ESBL brilliance agar. TEM and CTX-M genes were detected in 48 (42.1%) and 51 (44.7%) isolates, respectively. SHV gene was not detected in any of the isolates while TEM and CTX-M were detected in 33 (28.9%) isolates. This study showed high resistance of E. coli to antibiotics, particularly to the third generation cephalosporins. Regular monitoring and regulated use of antibiotics in livestock should be encouraged. PMID:26417371

  3. Phenotype, Sex of Rearing, Gender Re-Assignment, and Response to Medical Treatment in Extended Family Members with a Novel Mutation in the SRD5A2 Gene.

    PubMed

    Deeb, Asma; Al Suwaidi, Hana; Ibukunoluwa, Fakunle; Attia, Salima

    2016-06-01

    Deficiency of steroid 5-alpha reductase-2 (5ARD2) is an inborn error of metabolism causing a disorder of sexual differentiation. It is caused by a mutation in the SRD5A2 gene in which various mutation types have been reported. Affected individuals have a broad spectrum of presentation ranging from normal female-appearing genitalia, cliteromegaly, microphallus, hypospadias, to completely male-appearing genitalia. We report an extended Emirati family with 11 affected members. The family displayed various phenotypes on presentation leading to different sex of rearing. Some family members were reassigned gender at various stages of life. The index case was born with severe undervirilization with bilaterally palpable gonads and was raised as male from birth. He had a 46,XY karyotype and a high testosterone/dihydrotestosterone ratio. Genetic investigation revealed a novel homozygous deletion of exon 2 of the SRD5A2 gene. Both parents were found to be carriers for the gene deletion. The patient had masculinizing surgery and a course of topical dihydrotestosterone. No beneficial effect of the hormone application was noted over 3 months and the treatment was discontinued. The findings on this kindred indicate that deletion of exon 2 in the SRD5A2 gene causes various degrees of genital ambiguity leading to different sex of rearing in affected family members. Gender reassignment may be done at various ages even in conservative communities like the Gulf region.

  4. Mutations of the AMH type II receptor in two extended families with persistent Müllerian duct syndrome: lack of phenotype/genotype correlation.

    PubMed

    Abduljabbar, Mohammad; Taheini, Khalid; Picard, Jean-Yves; Cate, Richard L; Josso, Nathalie

    2012-01-01

    Our goal was to compare phenotype and genotype in two extended Middle-Eastern families affected by persistent Müllerian duct syndrome due to mutations of the type II anti-Müllerian hormone receptor (AMHR-II). The first, consanguineous, family consisted of 6 boys and 2 girls, the second consisted of 4 girls and 2 boys. In family I, 4 boys and 1 girl were homozygous for a stop mutation in the 9th exon of AMHR-II, removing part of the intracellular domain of the protein. In family II, 1 girl and 1 boy were homozygous for a transversion changing conserved histidine 254 into a glutamine. Both homozygous girls were normal. In the homozygous males, the degree of development of Müllerian derivatives was variable. The uterus was well developed in 2 boys of family I and in the patient from family II; however, in 1 subject from family I, Müllerian derivatives were undetectable. Taken together, the diversity of clinical symptoms within the same sibship and the lack of correlation between the development of the Müllerian derivatives and the severity of the molecular defects suggest highly variable penetrance of the abnormal alleles and/or the existence of other genetic or epigenetic modifiers of gene expression. PMID:22584735

  5. Phenotypic and Molecular Characterisation of Extended-Spectrum Beta-Lactamase Producing Escherichia coli Obtained from Animal Fecal Samples in Ado Ekiti, Nigeria.

    PubMed

    Olowe, Olugbenga Adekunle; Adewumi, Olufunmilayo; Odewale, Gbolabo; Ojurongbe, Olusola; Adefioye, Olusolabomi Jose

    2015-01-01

    Production of extended-spectrum β-lactamases (ESBLs) producing E. coli in animals and different methods of identifications from Ado Ekiti, Ekiti State, Nigeria, were investigated. Three hundred and fifty fecal samples, collected from apparently healthy cattle and pigs, were cultured and identified following standard procedures. ESBL phenotypic detection was carried out using combination disc test, double disc synergism test, and ESBL brilliance agar screening. Molecular detection of TEM, SHV, and CTX-M genes was carried out using standard molecular method. One hundred and fourteen E. coli isolates were recovered from the 350 samples processed, out of which 72 (63.2%) isolates were positive for ESBLs with multiple resistance to the antibiotics used. Eighty-one (71%) isolates were positive for ESBL by combination disc test, 90 (78.9%) were positive for double disc synergism test, and 93 (81.6%) were positive for ESBL brilliance agar. TEM and CTX-M genes were detected in 48 (42.1%) and 51 (44.7%) isolates, respectively. SHV gene was not detected in any of the isolates while TEM and CTX-M were detected in 33 (28.9%) isolates. This study showed high resistance of E. coli to antibiotics, particularly to the third generation cephalosporins. Regular monitoring and regulated use of antibiotics in livestock should be encouraged. PMID:26417371

  6. Population Structure and Genotype–Phenotype Associations in a Collection of Oat Landraces and Historic Cultivars

    PubMed Central

    Winkler, Louisa R.; Michael Bonman, J.; Chao, Shiaoman; Admassu Yimer, B.; Bockelman, Harold; Esvelt Klos, Kathy

    2016-01-01

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent, with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace) was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color, and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae) resistance, days to anthesis, and growth habit (winter/spring). In addition, two novel loci were identified for

  7. Intraspecific phenotypic variation in a fish predator affects multitrophic lake metacommunity structure

    PubMed Central

    Howeth, Jennifer G; Weis, Jerome J; Brodersen, Jakob; Hatton, Elizabeth C; Post, David M

    2013-01-01

    Contemporary insights from evolutionary ecology suggest that population divergence in ecologically important traits within predators can generate diversifying ecological selection on local community structure. Many studies acknowledging these effects of intraspecific variation assume that local populations are situated in communities that are unconnected to similar communities within a shared region. Recent work from metacommunity ecology suggests that species dispersal among communities can also influence species diversity and composition but can depend upon the relative importance of the local environment. Here, we study the relative effects of intraspecific phenotypic variation in a fish predator and spatial processes related to plankton species dispersal on multitrophic lake plankton metacommunity structure. Intraspecific diversification in foraging traits and residence time of the planktivorous fish alewife (Alosa pseudoharengus) among coastal lakes yields lake metacommunities supporting three lake types which differ in the phenotype and incidence of alewife: lakes with anadromous, landlocked, or no alewives. In coastal lakes, plankton community composition was attributed to dispersal versus local environmental predictors, including intraspecific variation in alewives. Local and beta diversity of zooplankton and phytoplankton was additionally measured in response to intraspecific variation in alewives. Zooplankton communities were structured by species sorting, with a strong influence of intraspecific variation in A. pseudoharengus. Intraspecific variation altered zooplankton species richness and beta diversity, where lake communities with landlocked alewives exhibited intermediate richness between lakes with anadromous alewives and without alewives, and greater community similarity. Phytoplankton diversity, in contrast, was highest in lakes with landlocked alewives. The results indicate that plankton dispersal in the region supplied a migrant pool that was

  8. Population Structure and Genotype-Phenotype Associations in a Collection of Oat Landraces and Historic Cultivars.

    PubMed

    Winkler, Louisa R; Michael Bonman, J; Chao, Shiaoman; Admassu Yimer, B; Bockelman, Harold; Esvelt Klos, Kathy

    2016-01-01

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent, with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace) was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color, and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae) resistance, days to anthesis, and growth habit (winter/spring). In addition, two novel loci were identified for

  9. Population Structure and Genotype-Phenotype Associations in a Collection of Oat Landraces and Historic Cultivars.

    PubMed

    Winkler, Louisa R; Michael Bonman, J; Chao, Shiaoman; Admassu Yimer, B; Bockelman, Harold; Esvelt Klos, Kathy

    2016-01-01

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent, with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace) was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color, and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae) resistance, days to anthesis, and growth habit (winter/spring). In addition, two novel loci were identified for

  10. Structural studies of molecular and metallic overlayers using angle- resolved photoemission extended fine structure

    SciTech Connect

    Huang, Z.

    1992-10-01

    Angle-resolved photoemission extended fine structure (ARPEFS) was used to study molecular and metallic overlayers on metal surfaces through analysis of p2mg(2[times]1)CO/Ni(110) and the p(2[times]2)K/Ni(111) adsorption. For the dense p2mg(2[times]1)CO/Ni(110) surface layer, photoemission intensities from C 1s level were measured in three directions at photoelectron kinetic energies 60-400 eV. Using multiple-scattering spherical-wave (MSSW) modeling, it was found that CO molecules are adsorbed on short-bridge sites, with adjacent CO along the [110] direction displaced alternatively in opposite directions towards the [001] azimuths to form a zigzag chain geometry. The tilt angle is 16[plus minus]2[degree] from the surface normal for the direction linking the C atom and the center of the Ni bridge. The carbon C-Ni interatomic distance was determined to be 1.94[plus minus]0.02[Angstrom]. The first- to second-layer spacing of Ni is 1.27[plus minus]0.04[Angstrom], up from 1.10[Angstrom] for the clean Ni(110) surface, but close to the 1.25[Angstrom] Ni interlayer spacing in the bulk. The C-O bond length and tilt angle were varied within small ranges (1.10--1.20[Angstrom] and 15--23[degrees]) in our MSSW simulations. Best agreement between experiment and simulations was achieved at 1.16[Angstrom] and 19[degrees]. This yields an O-O distance of 2.95[Angstrom] for the two nearest CO molecules, (van der Waals' radius [approximately] 1.5 [Angstrom] for oxygen). Two different partial-wave phase-shifts were used in MSSW, and structural results from both are in very good agreement. For the p(2[times]2)K/Ni(111) overlayer, ARPEFS [chi](k) curves from K 1s level measured along [111] and [771] at 130K showed that the K atoms are preferentially adsorbed on the atop sites, in agreement with a LEED study of the same system.

  11. Structural studies of molecular and metallic overlayers using angle- resolved photoemission extended fine structure

    SciTech Connect

    Huang, Z.

    1992-10-01

    Angle-resolved photoemission extended fine structure (ARPEFS) was used to study molecular and metallic overlayers on metal surfaces through analysis of p2mg(2{times}1)CO/Ni(110) and the p(2{times}2)K/Ni(111) adsorption. For the dense p2mg(2{times}1)CO/Ni(110) surface layer, photoemission intensities from C 1s level were measured in three directions at photoelectron kinetic energies 60-400 eV. Using multiple-scattering spherical-wave (MSSW) modeling, it was found that CO molecules are adsorbed on short-bridge sites, with adjacent CO along the [110] direction displaced alternatively in opposite directions towards the [001] azimuths to form a zigzag chain geometry. The tilt angle is 16{plus_minus}2{degree} from the surface normal for the direction linking the C atom and the center of the Ni bridge. The carbon C-Ni interatomic distance was determined to be 1.94{plus_minus}0.02{Angstrom}. The first- to second-layer spacing of Ni is 1.27{plus_minus}0.04{Angstrom}, up from 1.10{Angstrom} for the clean Ni(110) surface, but close to the 1.25{Angstrom} Ni interlayer spacing in the bulk. The C-O bond length and tilt angle were varied within small ranges (1.10--1.20{Angstrom} and 15--23{degrees}) in our MSSW simulations. Best agreement between experiment and simulations was achieved at 1.16{Angstrom} and 19{degrees}. This yields an O-O distance of 2.95{Angstrom} for the two nearest CO molecules, (van der Waals` radius {approximately} 1.5 {Angstrom} for oxygen). Two different partial-wave phase-shifts were used in MSSW, and structural results from both are in very good agreement. For the p(2{times}2)K/Ni(111) overlayer, ARPEFS {chi}(k) curves from K 1s level measured along [111] and [771] at 130K showed that the K atoms are preferentially adsorbed on the atop sites, in agreement with a LEED study of the same system.

  12. Packaging and structural phenotype of brome mosaic virus capsid protein with altered N-terminal {beta}-hexamer structure

    SciTech Connect

    Wispelaere, Melissanne de; Chaturvedi, Sonali; Wilkens, Stephan; Rao, A.L.N.

    2011-10-10

    The first 45 amino acid region of brome mosaic virus (BMV) capsid protein (CP) contains RNA binding and structural domains that are implicated in the assembly of infectious virions. One such important structural domain encompassing amino acids {sup 28}QPVIV{sup 32}, highly conserved between BMV and cowpea chlorotic mottle virus (CCMV), exhibits a {beta}-hexamer structure. In this study we report that alteration of the {beta}-hexamer structure by mutating {sup 28}QPVIV{sup 32} to {sup 28}AAAAA{sup 32} had no effect either on symptom phenotype, local and systemic movement in Chenopodium quinoa and RNA profile of in vivo assembled virions. However, sensitivity to RNase and assembly phenotypes distinguished virions assembled with CP subunits having {beta}-hexamer from those of wild type. A comparison of 3-D models obtained by cryo electron microscopy revealed overall similar structural features for wild type and mutant virions, with small but significant differences near the 3-fold axes of symmetry.

  13. SCOPe: Structural Classification of Proteins--extended, integrating SCOP and ASTRAL data and classification of new structures.

    PubMed

    Fox, Naomi K; Brenner, Steven E; Chandonia, John-Marc

    2014-01-01

    Structural Classification of Proteins-extended (SCOPe, http://scop.berkeley.edu) is a database of protein structural relationships that extends the SCOP database. SCOP is a manually curated ordering of domains from the majority of proteins of known structure in a hierarchy according to structural and evolutionary relationships. Development of the SCOP 1.x series concluded with SCOP 1.75. The ASTRAL compendium provides several databases and tools to aid in the analysis of the protein structures classified in SCOP, particularly through the use of their sequences. SCOPe extends version 1.75 of the SCOP database, using automated curation methods to classify many structures released since SCOP 1.75. We have rigorously benchmarked our automated methods to ensure that they are as accurate as manual curation, though there are many proteins to which our methods cannot be applied. SCOPe is also partially manually curated to correct some errors in SCOP. SCOPe aims to be backward compatible with SCOP, providing the same parseable files and a history of changes between all stable SCOP and SCOPe releases. SCOPe also incorporates and updates the ASTRAL database. The latest release of SCOPe, 2.03, contains 59 514 Protein Data Bank (PDB) entries, increasing the number of structures classified in SCOP by 55% and including more than 65% of the protein structures in the PDB.

  14. Thermal Expansion Behaviour of Silver Examined by Extended X-Ray Absorption Fine Structure Spectroscopy

    SciTech Connect

    Dubiel, M.; Chasse, A.; Haug, J.; Schneider, R.; Kruth, H.

    2007-02-02

    EXAFS (extended X-ray absorption fine structure) investigations are reported concerning the thermal expansion behaviour of silver in an extended range of temperature from 10 K to about 950 K measured in transmission mode. Both the ratio method and an EXAFS fitting procedure were applied to reveal the temperature dependence of EXAFS parameters. Models based on quantum and classical thermodynamic perturbation theory have been used to interpret experimental data and compared to XRD (X-ray diffraction) results of bulk silver material. The description of thermodynamic data of thermal expansion of silver in the complete range of temperature by EXAFS Spectroscopy was successful by first calculations using third order quantum perturbation theory.

  15. On implementation of the extended interior penalty function. [optimum structural design

    NASA Technical Reports Server (NTRS)

    Cassis, J. H.; Schmit, L. A., Jr.

    1976-01-01

    The extended interior penalty function formulation is implemented. A rational method for determining the transition between the interior and extended parts is set forth. The formulation includes a straightforward method for avoiding design points with some negative components, which are physically meaningless in structural analysis. The technique, when extended to problems involving parametric constraints, can facilitate closed form integration of the penalty terms over the most important parts of the parameter interval. The method lends itself well to the use of approximation concepts, such as design variable linking, constraint deletion and Taylor series expansions of response quantities in terms of design variables. Examples demonstrating the algorithm, in the context of planar orthogonal frames subjected to ground motion, are included.

  16. DETERMINING THE NATURE OF THE EXTENDED H I STRUCTURE AROUND LITTLE THINGS DWARF GALAXY NGC 1569

    SciTech Connect

    Johnson, Megan

    2013-06-15

    This work presents an extended, neutral hydrogen emission map around Magellanic-type dwarf irregular galaxy (dIm) NGC 1569. In the spring of 2010, the Robert C. Byrd Green Bank Telescope was used to map a 9 Degree-Sign Multiplication-Sign 2 Degree-Sign region in H I line emission that includes NGC 1569 and IC 342 as well as two other dwarf galaxies. The primary objective for these observations was to search for structures potentially connecting NGC 1569 with IC 342 group members in order to trace previous interactions and thus, provide an explanation for the starburst and peculiar kinematics prevalent in NGC 1569. A large, half-degree diameter H I cloud was detected that shares the same position and velocity as NGC 1569. Also, two long structures were discovered that are reminiscent of intergalactic filaments extending out in a V-shaped manner from NGC 1569 toward UGCA 92, a nearby dwarf galaxy. These filamentary structures extend for about 1. Degree-Sign 5, which is 77 kpc at NGC 1569. There is a continuous velocity succession with the 0. Degree-Sign 5 H I cloud, filaments, and main body of the galaxy. The 0. Degree-Sign 5 H I cloud and filamentary structures may be foreground Milky Way, but are suggestive as possible remnants of an interaction between NGC 1569 and UGCA 92. The data also show two tidal tails extending from UGCA 86 and IC 342, respectively. These structures may be part of a continuous H I bridge but more data are needed to determine if this is the case.

  17. Novel Intronic RNA Structures Contribute to Maintenance of Phenotype in Saccharomyces cerevisiae

    PubMed Central

    Hooks, Katarzyna B.; Naseeb, Samina; Parker, Steven; Griffiths-Jones, Sam; Delneri, Daniela

    2016-01-01

    The Saccharomyces cerevisiae genome has undergone extensive intron loss during its evolutionary history. It has been suggested that the few remaining introns (in only 5% of protein-coding genes) are retained because of their impact on function under stress conditions. Here, we explore the possibility that novel noncoding RNA structures (ncRNAs) are embedded within intronic sequences and are contributing to phenotype and intron retention in yeast. We employed de novo RNA structure prediction tools to screen intronic sequences in S. cerevisiae and 36 other fungi. We identified and validated 19 new intronic RNAs via RNA sequencing (RNA-seq) and RT-PCR. Contrary to the common belief that excised introns are rapidly degraded, we found that, in six cases, the excised introns were maintained intact in the cells. In another two cases we showed that the ncRNAs were further processed from their introns. RNA-seq analysis confirmed that introns in ribosomal protein genes are more highly expressed when they contain predicted RNA structures. We deleted the novel intronic RNA structure within the GLC7 intron and showed that this region, rather than the intron itself, is responsible for the cell’s ability to respond to salt stress. We also showed a direct association between the in cis presence of the intronic RNA and GLC7 expression. Overall, these data support the notion that some introns may have been maintained in the genome because they harbor functional RNA structures. PMID:27194751

  18. Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype

    PubMed Central

    Marques, Mayra de A.; de Oliveira, Guilherme A. P.

    2016-01-01

    Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the “disease of the sarcomere.” The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53), seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We highlight the

  19. Genomic structural variation contributes to phenotypic change of industrial bioethanol yeast Saccharomyces cerevisiae.

    PubMed

    Zhang, Ke; Zhang, Li-Jie; Fang, Ya-Hong; Jin, Xin-Na; Qi, Lei; Wu, Xue-Chang; Zheng, Dao-Qiong

    2016-03-01

    Genomic structural variation (GSV) is a ubiquitous phenomenon observed in the genomes of Saccharomyces cerevisiae strains with different genetic backgrounds; however, the physiological and phenotypic effects of GSV are not well understood. Here, we first revealed the genetic characteristics of a widely used industrial S. cerevisiae strain, ZTW1, by whole genome sequencing. ZTW1 was identified as an aneuploidy strain and a large-scale GSV was observed in the ZTW1 genome compared with the genome of a diploid strain YJS329. These GSV events led to copy number variations (CNVs) in many chromosomal segments as well as one whole chromosome in the ZTW1 genome. Changes in the DNA dosage of certain functional genes directly affected their expression levels and the resultant ZTW1 phenotypes. Moreover, CNVs of large chromosomal regions triggered an aneuploidy stress in ZTW1. This stress decreased the proliferation ability and tolerance of ZTW1 to various stresses, while aneuploidy response stress may also provide some benefits to the fermentation performance of the yeast, including increased fermentation rates and decreased byproduct generation. This work reveals genomic characters of the bioethanol S. cerevisiae strain ZTW1 and suggests that GSV is an important kind of mutation that changes the traits of industrial S. cerevisiae strains.

  20. Where is the extended phenotype in the wild? The community composition of arthropods on mature oak trees does not depend on the oak genotype.

    PubMed

    Gossner, Martin M; Brändle, Martin; Brandl, Roland; Bail, Johannes; Müller, Jörg; Opgenoorth, Lars

    2015-01-01

    Through a series of common garden experiments, it has been shown that heritable phenotypic differences between individual trees can affect arthropod communities. However, field studies under heterogeneous environmental conditions remain rare. In the present study, we investigated the genetic constitution of 121 mature oak host trees at different trophic levels from 10 sites across Bavaria, southern Germany and their associated insect communities. A total of 23,576 individuals representing 395 species of beetles and true bugs were evaluated. In particular, we determined whether the composition of arthropod communities is related to the oak genotype and whether the strength of the relationships decreases from lower to higher trophic levels, such as for phytophagous, xylophagous, zoophagous, and mycetophagous species. The genetic differentiation of oaks was assessed using eight microsatellite markers. We found no significant influence of the oak genotype on neither the full beetle and true bug community nor on any of the analyzed trophic guilds. In contrast, the community composition of the insects was highly related to the space and climate, such that the community similarity decreased with increases in spatial distance and climatic differences. The relationship with space and climate was much stronger in beetles than in true bugs, particularly in mycetophagous species. Our results suggest that spatial processes override the genetic effects of the host plant in structuring arthropod communities on oak trees. Because we used neutral markers, we cannot exclude the possibility that trait-specific markers may reveal a genetic imprint of the foundation tree species on the composition of the arthropod community. However, based on the strength of the spatial patterns in our data set, we assume that genetic differences among oaks are less important in the structuring of arthropod communities. Future whole-genome studies are required to draw a final conclusion.

  1. Where Is the Extended Phenotype in the Wild? The Community Composition of Arthropods on Mature Oak Trees Does Not Depend on the Oak Genotype

    PubMed Central

    Gossner, Martin M.; Brändle, Martin; Brandl, Roland; Bail, Johannes; Müller, Jörg; Opgenoorth, Lars

    2015-01-01

    Through a series of common garden experiments, it has been shown that heritable phenotypic differences between individual trees can affect arthropod communities. However, field studies under heterogeneous environmental conditions remain rare. In the present study, we investigated the genetic constitution of 121 mature oak host trees at different trophic levels from 10 sites across Bavaria, southern Germany and their associated insect communities. A total of 23,576 individuals representing 395 species of beetles and true bugs were evaluated. In particular, we determined whether the composition of arthropod communities is related to the oak genotype and whether the strength of the relationships decreases from lower to higher trophic levels, such as for phytophagous, xylophagous, zoophagous, and mycetophagous species. The genetic differentiation of oaks was assessed using eight microsatellite markers. We found no significant influence of the oak genotype on neither the full beetle and true bug community nor on any of the analyzed trophic guilds. In contrast, the community composition of the insects was highly related to the space and climate, such that the community similarity decreased with increases in spatial distance and climatic differences. The relationship with space and climate was much stronger in beetles than in true bugs, particularly in mycetophagous species. Our results suggest that spatial processes override the genetic effects of the host plant in structuring arthropod communities on oak trees. Because we used neutral markers, we cannot exclude the possibility that trait-specific markers may reveal a genetic imprint of the foundation tree species on the composition of the arthropod community. However, based on the strength of the spatial patterns in our data set, we assume that genetic differences among oaks are less important in the structuring of arthropod communities. Future whole-genome studies are required to draw a final conclusion. PMID:25635387

  2. Structural transformations from point to extended defects in silicon: A molecular dynamics study

    SciTech Connect

    Marques, Luis A.; Pelaz, Lourdes; Santos, Ivan; Lopez, Pedro; Aboy, Maria

    2008-11-15

    We use classical molecular dynamics simulation techniques to study how point defects aggregate to form extended defects in silicon. We have found that <110> chains of alternating interstitials and bond defects, a generalization of the Si di-interstitial structure, are metastable at room temperature but spontaneously transform into (311) defects when annealed at higher temperatures. Obtained atomic configurations and energetics are in good agreement with experiments and previous theoretical calculations. We have found a (311) structural unit which consists of two interstitial chains along <110> but arranged differently with respect to the known (311) units.

  3. Optical coherence tomography for live phenotypic analysis of embryonic ocular structures in mouse models

    NASA Astrophysics Data System (ADS)

    Larina, Irina V.; Syed, Saba H.; Sudheendran, Narendran; Overbeek, Paul A.; Dickinson, Mary E.; Larin, Kirill V.

    2012-08-01

    Mouse models of ocular diseases provide a powerful resource for exploration of molecular regulation of eye development and pre-clinical studies. Availability of a live high-resolution imaging method for mouse embryonic eyes would significantly enhance longitudinal analyses and high-throughput morphological screening. We demonstrate that optical coherence tomography (OCT) can be used for live embryonic ocular imaging throughout gestation. At all studied stages, the whole eye is within the imaging distance of the system and there is a good optical contrast between the structures. We also performed OCT eye imaging in the embryonic retinoblastoma mouse model Pax6-SV40 T-antigen, which spontaneously forms lens and retinal lesions, and demonstrate that OCT allows us to clearly differentiate between the mutant and wild type phenotypes. These results demonstrate that OCTin utero imaging is a potentially useful tool to study embryonic ocular diseases in mouse models.

  4. Extending CATH: increasing coverage of the protein structure universe and linking structure with function.

    PubMed

    Cuff, Alison L; Sillitoe, Ian; Lewis, Tony; Clegg, Andrew B; Rentzsch, Robert; Furnham, Nicholas; Pellegrini-Calace, Marialuisa; Jones, David; Thornton, Janet; Orengo, Christine A

    2011-01-01

    CATH version 3.3 (class, architecture, topology, homology) contains 128,688 domains, 2386 homologous superfamilies and 1233 fold groups, and reflects a major focus on classifying structural genomics (SG) structures and transmembrane proteins, both of which are likely to add structural novelty to the database and therefore increase the coverage of protein fold space within CATH. For CATH version 3.4 we have significantly improved the presentation of sequence information and associated functional information for CATH superfamilies. The CATH superfamily pages now reflect both the functional and structural diversity within the superfamily and include structural alignments of close and distant relatives within the superfamily, annotated with functional information and details of conserved residues. A significantly more efficient search function for CATH has been established by implementing the search server Solr (http://lucene.apache.org/solr/). The CATH v3.4 webpages have been built using the Catalyst web framework.

  5. Hamiltonian structure for two-dimensional extended Green-Naghdi equations

    NASA Astrophysics Data System (ADS)

    Matsuno, Yoshimasa

    2016-06-01

    The two-dimensional Green-Naghdi (GN) shallow-water model for surface gravity waves is extended to incorporate the arbitrary higher-order dispersive effects. This can be achieved by developing a novel asymptotic analysis applied to the basic nonlinear water wave problem. The linear dispersion relation for the extended GN system is then explored in detail. In particular, we use its characteristics to discuss the well-posedness of the linearized problem. As illustrative examples of approximate model equations, we derive a higher-order model that is accurate to the fourth power of the dispersion parameter in the case of a flat bottom topography, and address the related issues such as the linear dispersion relation, conservation laws and the pressure distribution at the fluid bottom on the basis of this model. The original Green-Naghdi (GN) model is then briefly described in the case of an uneven bottom topography. Subsequently, the extended GN system presented here is shown to have the same Hamiltonian structure as that of the original GN system. Last, we demonstrate that Zakharov's Hamiltonian formulation of surface gravity waves is equivalent to that of the extended GN system by rewriting the former system in terms of the momentum density instead of the velocity potential at the free surface.

  6. Family Structure and Adolescent Alcohol Use Problems: Extending Popular Explanations to American Indiansc

    PubMed Central

    Eitle, Tamela McNulty; Johnson-Jennings, Michelle; Eitle, David J.

    2013-01-01

    Competing explanations of the relationship between family structure and alcohol use problems are examined using a sample of American Indian adolescents from the National Longitudinal Study of Adolescent Health. Living in a single-parent family is found to be a marker for the unequal distribution of stress exposure and parental alcohol use, but the effects of other family structures like non-parent families and the presence of under 21-year-old extended family or non-family members emerge or remain as risk or protective factors for alcohol use problems after a consideration of SES, family processes, peer socialization, and social stress. In particular, a non-parent family structure that has not been considered in prior research emerged as a protective family structure for American Indian adolescent alcohol use problems. PMID:24014896

  7. Structural and functional roles of the N- and C-terminal extended modules in channelrhodopsin-1.

    PubMed

    Doi, Satoko; Mori, Arisa; Tsukamoto, Takashi; Reissig, Louisa; Ihara, Kunio; Sudo, Yuki

    2015-09-26

    Channelrhodopsins have become a focus of interest because of their ability to control neural activity by light, used in a technology called optogenetics. The channelrhodopsin in the eukaryote Chlamydomonas reinhardtii (CrChR-1) is a light-gated cation channel responsible for motility changes upon photo-illumination and a member of the membrane-embedded retinal protein family. Recent crystal structure analysis revealed that CrChR-1 has unique extended modules both at its N- and C-termini compared to other microbial retinal proteins. This study reports the first successful expression of a ChR-1 variant in Escherichia coli as a holoprotein: the ChR-1 variant lacking both the N- and C-termini (CrChR-1_82-308). However, compared to ChR-1 having the extended modules (CrChR-1_1-357), truncation of the termini greatly altered the absorption maximum and photochemical properties, including the pKa values of its charged residues around the chromophore, the reaction rates in the photocycle and the photo-induced ion channeling activity. The results of some experiments regarding ion transport activity suggest that CrChR-1_82-308 has a proton channeling activity even in the dark. On the basis of these results, we discuss the structural and functional roles of the N- and C-terminal extended modules in CrChR-1. PMID:26098533

  8. Split mandrel versus split sleeve coldworking: Dual methods for extending the fatigue life of metal structures

    NASA Technical Reports Server (NTRS)

    Rodman, Geoffrey A.; Creager, Matthew

    1994-01-01

    It is common practice to use split sleeve coldworking of fastener holes as a means of extending the fatigue life of metal structures. In search of lower manufacturing costs, the aerospace industry is examining the split mandrel (sleeveless) coldworking process as an alternative method of coldworking fastener holes in metal structures. The split mandrel process (SpM) significantly extends the fatigue life of metal structures through the introduction of a residual compressive stress in a manner that is very similar to the split sleeve system (SpSl). Since the split mandrel process is significantly less expensive than the split sleeve process and more adaptable to robotic automation, it will have a notable influence upon other new manufacture of metal structures which require coldworking a significant number of holes, provided the aerospace community recognizes that the resulting residual stress distributions and fatigue life improvement are the same for both processes. Considerable testing has validated the correctness of that conclusion. The findings presented in this paper represent the results of an extensive research and development program, comprising data collected from over 400 specimens fabricated from 2024-T3 and 7075-T651 aluminum alloys in varied configurations, which quantify the benefits (fatigue enhancement and cost savings) of automating a sleeveless coldworking system.

  9. Reconstruction of magnetic domain structure using the reverse Monte Carlo method with an extended Fourier image

    PubMed Central

    Tokii, Maki; Kita, Eiji; Mitsumata, Chiharu; Ono, Kanta; Yanagihara, Hideto

    2015-01-01

    Visualization of the magnetic domain structure is indispensable to the investigation of magnetization processes and the coercivity mechanism. It is necessary to develop a reconstruction method from the reciprocal-space image to the real-space image. For this purpose, it is necessary to solve the problem of missing phase information in the reciprocal-space image. We propose the method of extend Fourier image with mean-value padding to compensate for the phase information. We visualized the magnetic domain structure using the Reverse Monte Carlo method with simulated annealing to accelerate the calculation. With this technique, we demonstrated the restoration of the magnetic domain structure, obtained magnetization and magnetic domain width, and reproduced the characteristic form that constitutes a magnetic domain. PMID:25991875

  10. Structural damage detection using extended Kalman filter combined with statistical process control

    NASA Astrophysics Data System (ADS)

    Jin, Chenhao; Jang, Shinae; Sun, Xiaorong

    2015-04-01

    Traditional modal-based methods, which identify damage based upon changes in vibration characteristics of the structure on a global basis, have received considerable attention in the past decades. However, the effectiveness of the modalbased methods is dependent on the type of damage and the accuracy of the structural model, and these methods may also have difficulties when applied to complex structures. The extended Kalman filter (EKF) algorithm which has the capability to estimate parameters and catch abrupt changes, is currently used in continuous and automatic structural damage detection to overcome disadvantages of traditional methods. Structural parameters are typically slow-changing variables under effects of operational and environmental conditions, thus it would be difficult to observe the structural damage and quantify the damage in real-time with EKF only. In this paper, a Statistical Process Control (SPC) is combined with EFK method in order to overcome this difficulty. Based on historical measurements of damage-sensitive feathers involved in the state-space dynamic models, extended Kalman filter (EKF) algorithm is used to produce real-time estimations of these features as well as standard derivations, which can then be used to form control ranges for SPC to detect any abnormality of the selected features. Moreover, confidence levels of the detection can be adjusted by choosing different times of sigma and number of adjacent out-of-range points. The proposed method is tested using simulated data of a three floors linear building in different damage scenarios, and numerical results demonstrate high damage detection accuracy and light computation of this presented method.

  11. Crystal structure of two CD46 domains reveals an extended measles virus-binding surface.

    PubMed Central

    Casasnovas, J M; Larvie, M; Stehle, T

    1999-01-01

    Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 A resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46. PMID:10357804

  12. A testosterone-related structural brain phenotype predicts aggressive behavior from childhood to adulthood.

    PubMed

    Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Ducharme, Simon

    2016-01-01

    Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here, we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6-22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. PMID:26431805

  13. Drug repositioning by kernel-based integration of molecular structure, molecular activity, and phenotype data.

    PubMed

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems.

  14. Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies.

    PubMed Central

    Templeton, A R; Weiss, K M; Nickerson, D A; Boerwinkle, E; Sing, C F

    2000-01-01

    Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3' region should have general utility in most human populations, but the 5' SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region. PMID:11063700

  15. Allosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure

    PubMed Central

    Moraga-Cid, Gustavo; Sauguet, Ludovic; Huon, Christèle; Malherbe, Laurie; Girard-Blanc, Christine; Petres, Stéphane; Murail, Samuel; Taly, Antoine; Baaden, Marc; Delarue, Marc; Corringer, Pierre-Jean

    2015-01-01

    The glycine receptor (GlyR) is a pentameric ligand-gated ion channel (pLGIC) mediating inhibitory transmission in the nervous system. Its transmembrane domain (TMD) is the target of allosteric modulators such as general anesthetics and ethanol and is a major locus for hyperekplexic congenital mutations altering the allosteric transitions of activation or desensitization. We previously showed that the TMD of the human α1GlyR could be fused to the extracellular domain of GLIC, a bacterial pLGIC, to form a functional chimera called Lily. Here, we overexpress Lily in Schneider 2 insect cells and solve its structure by X-ray crystallography at 3.5 Å resolution. The TMD of the α1GlyR adopts a closed-channel conformation involving a single ring of hydrophobic residues at the center of the pore. Electrophysiological recordings show that the phenotypes of key allosteric mutations of the α1GlyR, scattered all along the pore, are qualitatively preserved in this chimera, including those that confer decreased sensitivity to agonists, constitutive activity, decreased activation kinetics, or increased desensitization kinetics. Combined structural and functional data indicate a pore-opening mechanism for the α1GlyR, suggesting a structural explanation for the effect of some key hyperekplexic allosteric mutations. The first X-ray structure of the TMD of the α1GlyR solved here using GLIC as a scaffold paves the way for mechanistic investigation and design of allosteric modulators of a human receptor. PMID:25730860

  16. Evaluation of intrauterine structural pathology by three-dimensional sonohysterography using an extended imaging method.

    PubMed

    Zafarani, Fatemeh; Ahmadi, Firoozeh

    2013-04-01

    Structural intrauterine abnormalities are an important cause of infertility, recurrent pregnancy loss and bleeding or pain associated with a poor reproductive outcome. Various diagnostic methods have been applied to detect these lesions such as hysterosalpingography, hysteroscopy and sonohysterography. More recently, three-dimensional extended imaging (3DXI) provides the ability to obtain sequential sections of acquired volume scans in A, B and C planes. Here, we briefly discuss the technique of saline infusion sonography, followed by a review of sonohysterographic characteristics of intracavitary pathologies with more focus on some definitions and measurements.

  17. Applications of a quadratic extended interior penalty function for structural optimization

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Starnes, J. H., Jr.

    1975-01-01

    A quadratic extended interior penalty function formulation especially well suited for second-order unconstrained optimization procedures is presented. Analytical derivatives of constraints and an approximate analysis technique are used. Minimum-mass design results are presented which indicate that the combination of these procedures can help make mathematical programming a useful optimization tool for large-order structural design problems with a large number of design variables and multiple constraints. Examples include statically loaded high- and low-aspect-ratio wings simultaneously subjected to stress, displacement, minimum gage and, in some cases, maximum strain constraints.

  18. The effects of extended clinorotation on potato minituber formation and structure

    NASA Astrophysics Data System (ADS)

    Nedukha, O. M.; Vasyltsov, I. V.

    Formation and structure of potato minitubers grown aseptically for 30 days on a horizontal clinostat and in stationary control have been studied by light and electron microscopy. It was demonstrated that the number of plants that formed minitubers, their size and fresh weight, was higher when clino-rotated than in the stationary control. It was revealed that the amount of amyloplasts in parenchyma cell sections was doubled in minitubers formed under clino-rotation. Other factors (shape of minitubers and size of reserve parenchyma cells) did not differ from the stationary control. The changes in amyloplast ultrastructure suggest accelerated cell maturity of potato reserve parenchyma in extended clino-rotation.

  19. Extended X-ray absorption fine structure (EXAFS) study of CaSO 4:Dy phosphors

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, D.; Bakshi, A. K.; Ciatto, G.; Aquilanti, G.; Pradhan, A. S.; Pascarelli, S.

    2006-03-01

    Extended X-ray absorption fine structure (EXAFS) measurements have been carried out on CaSO 4:Dy phosphors at the Dy L 3 edge with synchrotron radiation. The data have been analysed to find out the Dy-S and Dy-O bond lengths in the neighborhood of the Dy atoms. Measurements have been carried out over several samples thermally annealed for different cycles at 400 °C in air for 1 h and the change in bond lengths in samples with increasing number of annealing cycles have been studied by analyzing the EXAFS data.

  20. Surface extended x-ray absorption fine structure of low-Z absorbates using fluorescence detection

    SciTech Connect

    Stoehr, J.; Kollin, E.B.; Fischer, D.A.; Hastings, J.B.; Zaera, F.; Sette, F.

    1985-05-01

    Comparison of x-ray fluorescence yield (FY) and electron yield surface extended x-ray absorption fine structure spectra above the S K-edge for c(2 x 2) S on Ni(100) reveals an order of magnitude higher sensitivity of the FY technique. Using FY detection, thiophene (C/sub 4/H/sub 4/S) chemisorption on Ni(100) is studied with S coverages down to 0.08 monolayer. The molecule dissociates at temperatures as low as 100K by interaction with fourfold hollow Ni sites. Blocking of these sites by oxygen leaves the molecule intact.

  1. Improved self-absorption correction for extended x-ray absorption fine-structure measurements

    SciTech Connect

    Booth, C.H.; Bridges, F.

    2003-06-04

    Extended x-ray absorption fine-structure (EXAFS) data collected in the fluorescence mode are susceptible to an apparent amplitude reduction due to the self-absorption of the fluorescing photon by the sample before it reaches a detector. Previous treatments have made the simplifying assumption that the effect of the EXAFS on the correction term is negligible, and that the samples are in the thick limit. We present a nearly exact treatment that can be applied for any sample thickness or concentration, and retains the EXAFS oscillations in the correction term.

  2. Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

    PubMed

    Sukegawa, K; Nakamura, H; Kato, Z; Tomatsu, S; Montaño, A M; Fukao, T; Toietta, G; Tortora, P; Orii, T; Kondo, N

    2000-05-22

    Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype and phenotype has remained unclear. We studied 17 missense mutations using biochemical approaches and 32 missense mutations, using structural analyses. Fifteen missense mutations and two newly engineered active site mutations (C79S, C79T) were characterized by transient expression analysis. Mutant proteins, except for C79S and C79T, were destabilized and detected as insoluble precursor forms while the C79S and C79T mutants were of a soluble mature size. Mutants found in the severe phenotype had no activity. Mutants found in the mild phenotype had a considerable residual activity (1.3-13.3% of wild-type GALNS activity). Sulfatases, including GALNS, are members of a highly conserved gene family sharing an extensive sequence homology. Thus, a tertiary structural model of human GALNS was constructed from the X-ray crystal structure of N -acetylgalacto-samine-4-sulfatase and arylsulfatase A, using homology modeling, and 32 missense mutations were investigated. Consequently, we propose that there are at least three different reasons for the severe phenotype: (i) destruction of the hydrophobic core or modification of the packing; (ii) removal of a salt bridge to destabilize the entire conformation; (iii) modification of the active site. In contrast, mild mutations were mostly located on the surface of the GALNS protein. These studies shed further light on the genotype-phenotype correlation of MPS IVA and structure-function relationship in the sulfatase family. PMID:10814710

  3. HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship.

    PubMed

    Bode, Heiko; Bourquin, Florence; Suriyanarayanan, Saranya; Wei, Yu; Alecu, Irina; Othman, Alaa; Von Eckardstein, Arnold; Hornemann, Thorsten

    2016-03-01

    Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a rare autosomal dominant inherited peripheral neuropathy caused by mutations in the SPTLC1 and SPTLC2 subunits of serine palmitoyltransferase (SPT). The mutations induce a permanent shift in the substrate preference from L-serine to L-alanine, which results in the pathological formation of atypical and neurotoxic 1-deoxy-sphingolipids (1-deoxySL). Here we compared the enzymatic properties of 11 SPTLC1 and six SPTLC2 mutants using a uniform isotope labelling approach. In total, eight SPT mutants (STPLC1p.C133W, p.C133Y, p.S331F, p.S331Y and SPTLC2p.A182P, p.G382V, p.S384F, p.I504F) were associated with increased 1-deoxySL synthesis. Despite earlier reports, canonical activity with l-serine was not reduced in any of the investigated SPT mutants. Three variants (SPTLC1p.S331F/Y and SPTLC2p.I505Y) showed an increased canonical activity and increased formation of C20 sphingoid bases. These three mutations are associated with an exceptionally severe HSAN1 phenotype, and increased C20 sphingosine levels were also confirmed in plasma of patients. A principal component analysis of the analysed sphingoid bases clustered the mutations into three separate entities. Each cluster was related to a distinct clinical outcome (no, mild and severe HSAN1 phenotype). A homology model based on the protein structure of the prokaryotic SPT recapitulated the same grouping on a structural level. Mutations associated with the mild form clustered around the active site, whereas mutations associated with the severe form were located on the surface of the protein. In conclusion, we showed that HSAN1 mutations in SPT have distinct biochemical properties, which allowed for the prediction of the clinical symptoms on the basis of the plasma sphingoid base profile. PMID:26681808

  4. Deep skin structural and microcirculation imaging with extended-focus OCT

    NASA Astrophysics Data System (ADS)

    Blatter, Cedric; Grajciar, Branislav; Huber, Robert; Leitgeb, Rainer A.

    2012-02-01

    We present an extended focus OCT system for dermatologic applications that maintains high lateral resolution over a large depth range by using Bessel beam illumination. More, Bessel beams exhibit a self-reconstruction property that is particularly useful to avoid shadowing from surface structures such as hairs. High lateral resolution and high-speed measurement, thanks to a rapidly tuning swept source, allows not only for imaging of small skin structures in depth but also for comprehensive visualization of the small capillary network within the human skin in-vivo. We use this information for studying temporal vaso-responses to hypothermia. In contrast to other perfusion imaging methods such as laser Doppler imaging (LDI), OCT gives specific access to vascular responses in different vascular beds in depth.

  5. Negative thermal expansion in CuCl: An extended x-ray absorption fine structure study

    SciTech Connect

    Vaccari, M.; Grisenti, R.; Fornasini, P.; Rocca, F.; Sanson, A.

    2007-05-01

    Extended x-ray absorption fine structure (EXAFS) has been measured from liquid helium to ambient temperature at the Cu K edge of copper chloride (CuCl) to investigate the local origin of negative thermal expansion. A quantitative analysis of the first coordination shell, performed by the cumulant method, reveals that the nearest-neighbor Cu-Cl interatomic distance undergoes a strong positive expansion, contrasting with the much weaker negative expansion of the crystallographic distance between average atomic positions below 100 K. The anisotropy of relative thermal vibrations, monitored by the ratio {gamma} between perpendicular and parallel mean square relative displacements, is considerably high, while the diffraction thermal factors are isotropic. The relative perpendicular vibrations measured by EXAFS are related to the tension mechanism and to the transverse acoustic modes, which are considered responsible for negative thermal expansion in zinc-blende structures.

  6. Extending the ICRF to Higher Radio Frequencies: Imaging and Source Structure

    NASA Technical Reports Server (NTRS)

    Boboltz, David A.; Fey, Alan L.; Charlot, Patrick; Fomalont, Edward B.; Lanyi, Gabor E.; Zhang, Li-Wei

    2004-01-01

    We present imaging results and source structure analysis of extragalactic radio sources observed using the Very Long Baseline Array (VLBA) at 24 GHz and 43 GHz as part of an ongoing NASA, USNO, NRAO and Bordeaux Observatory collaboration to extend the International Celestial Reference Frame (ICRF) to higher radio frequencies. The K/Q-band image database now includes images of 108 sources at 43 GHz (Q-braid) and images of 230 sources at 24 GHz (K-band). Preliminary analysis of the observations taken to date shows that the sources are generally more compact as one goes from the ICRF frequency of 8.4 GHz to 24 GHz. This result is consistent with the standard theory of compact extragalactic radio sources and suggests that reference frames defined at these higher radio frequencies will be less susceptible to the effects of intrinsic source structure than those defined at lower frequencies.

  7. An extended structure-based model based on a stochastic eddy-axis evolution equation

    NASA Technical Reports Server (NTRS)

    Kassinos, S. C.; Reynolds, W. C.

    1995-01-01

    We have proposed and implemented an extension of the structure-based model for weak deformations. It was shown that the extended model will correctly reduce to the form of standard k-e models for the case of equilibrium under weak mean strain. The realizability of the extended model is guaranteed by the method of its construction. The predictions of the proposed model were very good for rotating homogeneous shear flows and for irrotational axisymmetric contraction, but were seriously deficient in the case of plane strain and axisymmetric expansion. We have concluded that the problem behind these difficulties lies in the algebraic constitutive equation relating the Reynolds stresses to the structure parameters rather than in the slow model developed here. In its present form, this equation assumes that under irrotational strain the principal axes of the Reynolds stresses remain locked onto those of the eddy-axis tensor. This is correct in the RDT limit, but inappropriate under weaker mean strains, when the non-linear eddy-eddy interactions tend to misalign the two sets of principal axes and create some non-zero theta and gamma.

  8. Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer.

    PubMed

    Schauder, Curtis M; Wu, Xudong; Saheki, Yasunori; Narayanaswamy, Pradeep; Torta, Federico; Wenk, Markus R; De Camilli, Pietro; Reinisch, Karin M

    2014-06-26

    Growing evidence suggests that close appositions between the endoplasmic reticulum (ER) and other membranes, including appositions with the plasma membrane (PM), mediate exchange of lipids between these bilayers. The mechanisms of such exchange, which allows lipid transfer independently of vesicular transport, remain poorly understood. The presence of a synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain, a proposed lipid-binding module, in several proteins localized at membrane contact sites has raised the possibility that such domains may be implicated in lipid transport. SMP-containing proteins include components of the ERMES complex, an ER–mitochondrial tether, and the extended synaptotagmins (known as tricalbins in yeast), which are ER–PM tethers. Here we present at 2.44 Å resolution the crystal structure of a fragment of human extended synaptotagmin 2 (E-SYT2), including an SMP domain and two adjacent C2 domains. The SMP domain has a β-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Å-long cylinder traversed by a channel lined entirely with hydrophobic residues, with the two C2A–C2B fragments forming arched structures flexibly linked to the SMP domain. Importantly, structural analysis complemented by mass spectrometry revealed the presence of glycerophospholipids in the E-SYT2 SMP channel, indicating a direct role for E-SYTs in lipid transport. These findings provide strong evidence for a role of SMP-domain-containing proteins in the control of lipid transfer at membrane contact sites and have broad implications beyond the field of ER-to-PM appositions. PMID:24847877

  9. Genetic diversity and structuring across the range of a widely distributed ladybird: focus on rear-edge populations phenotypically divergent.

    PubMed

    Lecompte, Émilie; Bouanani, Mohand-Ameziane; Magro, Alexandra; Crouau-Roy, Brigitte

    2016-08-01

    Population genetics and phenotypic structures are often predicted to vary along the geographic range of a species. This phenomenon would be accentuated for species with large range areas, with discontinuities and marginal populations. We herein compare the genetic patterns of central populations of Coccinella septempunctata L. with those of two phenotypically differentiated populations considered as rear-edge populations and subspecies based on phenotype (Algeria and Japan). According to the central-marginal model and expected characteristics of rear-edge populations, we hypothesize that these rear-edge populations have (1) a reduced genetic diversity, resulting from their relative isolation over long periods of time, (2) a higher population genetic differentiation, explained by low contemporary gene flow levels, and (3) a relationship between genetic diversity characteristics and phenotypes, due to historical isolation and/or local adaptation. Based on genotyping of 28 populations for 18 microsatellite markers, several levels of regional genetic diversity and differentiation are observed between and within populations, according to their localization: low within-population genetic diversity and higher genetic differentiation of rear-edge populations. The genetic structuring clearly dissociates the Algerian and Eastern Asia populations from the others. Geographical patterns of genetic diversity and differentiation support the hypothesis of the central-marginal model. The pattern observed is in agreement with the phenotypic structure across species range. A clear genetic break between populations of Algeria, the Eastern Asia, and the remaining populations is a dominant feature of the data. Differential local adaptations, absence of gene flow between marginal and central populations, and/or incapacity to mate after colonization, have contributed to their distinct genotypic and phenotypic characteristics. PMID:27551401

  10. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

    SciTech Connect

    Tainer, John; Fan, Li; Fuss, Jill O.; Cheng, Quen J.; Arvai, Andrew S.; Hammel, Michal; Roberts, Victoria A.; Cooper, Priscilla K.; Tainer, John A.

    2008-06-02

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  11. XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

    SciTech Connect

    Fan, L.; Fuss, J.O.; Cheng, Q.J.; Arvai, A.S.; Hammel, M.; Roberts, V.A.; Cooper, P.K.; Tainer, J.A.

    2009-05-18

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  12. Structural Basis for the Trembler-J Phenotype of Charcot-Marie-Tooth Disease

    PubMed Central

    Sakakura, Masayoshi; Hadziselimovic, Arina; Wang, Zhen; Schey, Kevin L.; Sanders, Charles R.

    2011-01-01

    Summary Mutations in peripheral myelin protein 22 (PMP22) can result in the common peripheral neuropathy, Charcot-Marie-Tooth disease (CMTD). The Leu16Pro mutation in PMP22 results in misassembly of the protein, which causes the Trembler-J (TrJ) disease phenotype. Here we elucidate the structural defects present in a partially folded state of TrJ PMP22 that are decisive in promoting CMTD-causing misfolding. In this state transmembrane helices 2-4 (TM2-4) form a molten-globular bundle while transmembrane helix 1 (TM1) is dissociated from this bundle. The TrJ mutation was seen to profoundly disrupt the TM1 helix, resulting in increased backbone dynamics and changes in the tertiary interactions of TM1 with the PMP22 TM2-4 core in the folded state. Consequently, TM1 undergoes enhanced dissociation from the other transmembrane segments in TrJ PMP22, becoming available for recognition and sequestration by protein folding quality control, leading to loss of function and toxic accumulation of aggregates that results in CMTD. PMID:21827951

  13. Phenotypic covariance structure and its divergence for acoustic mate attraction signals among four cricket species

    PubMed Central

    Bertram, Susan M; Fitzsimmons, Lauren P; McAuley, Emily M; Rundle, Howard D; Gorelick, Root

    2012-01-01

    The phenotypic variance–covariance matrix (P) describes the multivariate distribution of a population in phenotypic space, providing direct insight into the appropriateness of measured traits within the context of multicollinearity (i.e., do they describe any significant variance that is independent of other traits), and whether trait covariances restrict the combinations of phenotypes available to selection. Given the importance of P, it is therefore surprising that phenotypic covariances are seldom jointly analyzed and that the dimensionality of P has rarely been investigated in a rigorous statistical framework. Here, we used a repeated measures approach to quantify P separately for populations of four cricket species using seven acoustic signaling traits thought to enhance mate attraction. P was of full or almost full dimensionality in all four species, indicating that all traits conveyed some information that was independent of the other traits, and that phenotypic trait covariances do not constrain the combinations of signaling traits available to selection. P also differed significantly among species, although the dominant axis of phenotypic variation (pmax) was largely shared among three of the species (Acheta domesticus, Gryllus assimilis, G. texensis), but different in the fourth (G. veletis). In G. veletis and A. domesticus, but not G. assimilis and G. texensis, pmax was correlated with body size, while pmax was not correlated with residual mass (a condition measure) in any of the species. This study reveals the importance of jointly analyzing phenotypic traits. PMID:22408735

  14. A Phenotypic Structure and Neural Correlates of Compulsive Behaviors in Adolescents

    PubMed Central

    Montigny, Chantale; Castellanos-Ryan, Natalie; Whelan, Robert; Banaschewski, Tobias; Barker, Gareth J.; Büchel, Christian; Gallinat, Jürgen; Flor, Herta; Mann, Karl; Paillère-Martinot, Marie-Laure; Nees, Frauke; Lathrop, Mark; Loth, Eva; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Schumann, Gunter; Smolka, Michael N.; Struve, Maren; Robbins, Trevor W.; Garavan, Hugh; Conrod, Patricia J.

    2013-01-01

    Background A compulsivity spectrum has been hypothesized to exist across Obsessive-Compulsive disorder (OCD), Eating Disorders (ED), substance abuse (SA) and binge-drinking (BD). The objective was to examine the validity of this compulsivity spectrum, and differentiate it from an externalizing behaviors dimension, but also to look at hypothesized personality and neural correlates. Method A community-sample of adolescents (N=1938; mean age 14.5 years), and their parents were recruited via high-schools in 8 European study sites. Data on adolescents’ psychiatric symptoms, DSM diagnoses (DAWBA) and substance use behaviors (AUDIT and ESPAD) were collected through adolescent- and parent-reported questionnaires and interviews. The phenotypic structure of compulsive behaviors was then tested using structural equation modeling. The model was validated using personality variables (NEO-FFI and TCI), and Voxel-Based Morphometry (VBM) analysis. Results Compulsivity symptoms best fit a higher-order two factor model, with ED and OCD loading onto a compulsivity factor, and BD and SA loading onto an externalizing factor, composed also of ADHD and conduct disorder symptoms. The compulsivity construct correlated with neuroticism (r=0.638; p≤0.001), conscientiousness (r=0.171; p≤0.001), and brain gray matter volume in left and right orbitofrontal cortex, right ventral striatum and right dorsolateral prefrontal cortex. The externalizing factor correlated with extraversion (r=0.201; p≤0.001), novelty-seeking (r=0.451; p≤0.001), and negatively with gray matter volume in the left inferior and middle frontal gyri. Conclusions Results suggest that a compulsivity spectrum exists in an adolescent, preclinical sample and accounts for variance in both OCD and ED, but not substance-related behaviors, and can be differentiated from an externalizing spectrum. PMID:24244633

  15. [POLYMORPHISM IN THE PHENOTYPIC STRUCTURE OF A POPULATION OF TAIGA TICK AND ITS EPIDEMIOLOGICAL SIGNIFICANCE].

    PubMed

    Morozov, I M; Alekseev, A N; Dubinina, E V; Nikitin, A Ya; Melnikova, O V; Andaev, E I

    2015-01-01

    The paper presents the results of 10-year (2005-2014) observations of an Ixodespersulcatus Schulze population. The purpose of this investigation was to trace long-term changes in the structure of the taiga tick population from the proportion of specimens with external skeletal anomalies and to assess a relationship between the pattern of imago phenotypic variation and the virus percentage of a carrier. There were a total of reports of the external skeletal structure of 1123 females gathered from plants to a flag in an area at 43 km from the Baikal Road connecting Irkutsk and the settlement of Listvyanka (Irkutsk Region). The proportion of specimens with anomalies averaged 37.8 +/- 1.88%. Four-to-seven varying anomalies were annually recorded. There was a preponderance of scutum impairment (an average of 17.0 +/- 3.08% of all females) that was a conglomerate of prominences and indentations along the entire clypeus surface and that was denoted P9. The nature of a change in the proportion of ticks with two anomalies (average monthly registration rate, 2.5 +/- 0.66%) is exhibited by three-year high-frequency oscillations whereas the specimens with P9 anomalies fail to show so clear cycling. The percentage of virus-containing taiga ticks was individually determined estimating the level of tick-borne encephalitis virus antigen by an enzyme immunoassay. A total of 4022 ticks were examined. The male and female data were pooled. There was a positive correlation between the change in the proportion of females with P9 anomaly and the infection of ticks in the examined population (Spearman's correlation coefficient, 0.88; P < 0.01). This supports the earlier observation of the greater epidemiological significance of the imago of a taiga tick with external skeletal anomalies particularly with considerably marked ones.

  16. [POLYMORPHISM IN THE PHENOTYPIC STRUCTURE OF A POPULATION OF TAIGA TICK AND ITS EPIDEMIOLOGICAL SIGNIFICANCE].

    PubMed

    Morozov, I M; Alekseev, A N; Dubinina, E V; Nikitin, A Ya; Melnikova, O V; Andaev, E I

    2015-01-01

    The paper presents the results of 10-year (2005-2014) observations of an Ixodespersulcatus Schulze population. The purpose of this investigation was to trace long-term changes in the structure of the taiga tick population from the proportion of specimens with external skeletal anomalies and to assess a relationship between the pattern of imago phenotypic variation and the virus percentage of a carrier. There were a total of reports of the external skeletal structure of 1123 females gathered from plants to a flag in an area at 43 km from the Baikal Road connecting Irkutsk and the settlement of Listvyanka (Irkutsk Region). The proportion of specimens with anomalies averaged 37.8 +/- 1.88%. Four-to-seven varying anomalies were annually recorded. There was a preponderance of scutum impairment (an average of 17.0 +/- 3.08% of all females) that was a conglomerate of prominences and indentations along the entire clypeus surface and that was denoted P9. The nature of a change in the proportion of ticks with two anomalies (average monthly registration rate, 2.5 +/- 0.66%) is exhibited by three-year high-frequency oscillations whereas the specimens with P9 anomalies fail to show so clear cycling. The percentage of virus-containing taiga ticks was individually determined estimating the level of tick-borne encephalitis virus antigen by an enzyme immunoassay. A total of 4022 ticks were examined. The male and female data were pooled. There was a positive correlation between the change in the proportion of females with P9 anomaly and the infection of ticks in the examined population (Spearman's correlation coefficient, 0.88; P < 0.01). This supports the earlier observation of the greater epidemiological significance of the imago of a taiga tick with external skeletal anomalies particularly with considerably marked ones. PMID:26720971

  17. Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics

    PubMed Central

    Li, Dong; Shao, Lin; Chen, Bi-Chang; Zhang, Xi; Zhang, Mingshu; Moses, Brian; Milkie, Daniel E.; Beach, Jordan R.; Hammer, John A.; Pasham, Mithun; Kirchhausen, Tomas; Baird, Michelle A.; Davidson, Michael W.; Xu, Pingyong; Betzig, Eric

    2015-01-01

    Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and a-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions. PMID:26315442

  18. Synchrotron x-ray fluorescence and extended x-ray absorption fine structure analysis

    SciTech Connect

    Chen, J.R.; Gordon, B.M.; Hanson, A.L.; Jones, K.W.; Kraner, H.W.; Chao, E.C.T.; Minkin, J.A.

    1984-01-01

    The advent of dedicated synchrotron radiation sources has led to a significant increase in activity in many areas of science dealing with the interaction of x-rays with matter. Synchrotron radiation provides intense, linearly polarized, naturally collimated, continuously tunable photon beams, which are used to determine not only the elemental composition of a complex, polyatomic, dilute material but also the chemical form of the elements with improved accuracy. Examples of the application of synchrotron radiation include experiments in synchrotron x-ray fluorescence (SXRF) analysis and extended x-ray absorption fine structure (EXAFS) analysis. New synchrotron radiation x-ray microprobes for elemental analysis in the parts per billion range are under construction at several laboratories. 76 references, 24 figures.

  19. Extended x-ray absorption fine structure studies of the atomic structure of nanoparticles in different metallic matrices.

    PubMed

    Baker, S H; Roy, M; Gurman, S J; Binns, C

    2009-05-01

    It has been appreciated for some time that the novel properties of particles in the size range 1-10 nm are potentially exploitable in a range of applications. In order to ultimately produce commercial devices containing nanosized particles, it is necessary to develop controllable means of incorporating them into macroscopic samples. One way of doing this is to embed the nanoparticles in a matrix of a different material, by co-deposition for example, to form a nanocomposite film. The atomic structure of the embedded particles can be strongly influenced by the matrix. Since some of the key properties of materials, including magnetism, strongly depend on atomic structure, the ability to determine atomic structure in embedded nanoparticles is very important. This review focuses on nanoparticles, in particular magnetic nanoparticles, embedded in different metal matrices. Extended x-ray absorption fine structure (EXAFS) provides an excellent means of probing atomic structure in nanocomposite materials, and an overview of this technique is given. Its application in probing catalytic metal clusters is described briefly, before giving an account of the use of EXAFS in determining atomic structure in magnetic nanocomposite films. In particular, we focus on cluster-assembled films comprised of Fe and Co nanosized particles embedded in various metal matrices, and show how the crystal structure of the particles can be changed by appropriate choice of the matrix material. The work discussed here demonstrates that combining the results of structural and magnetic measurements, as well as theoretical calculations, can play a significant part in tailoring the properties of new magnetic cluster-assembled materials.

  20. Further delineation of novel 1p36 rearrangements by array-CGH analysis: narrowing the breakpoints and clarifying the "extended" phenotype.

    PubMed

    Giannikou, Krinio; Fryssira, Helen; Oikonomakis, Vasilis; Syrmou, Areti; Kosma, Konstantina; Tzetis, Maria; Kitsiou-Tzeli, Sofia; Kanavakis, Emmanouel

    2012-09-15

    High resolution oligonucleotide array Comparative Genome Hybridization technology (array-CGH) has greatly assisted the recognition of the 1p36 contiguous gene deletion syndrome. The 1p36 deletion syndrome is considered to be one of the most common subtelomeric microdeletion syndromes and has an incidence of ~1 in 5000 live births, while respectively the "pure" 1p36 microduplication has not been reported so far. We present seven new patients who were referred for genetic evaluation due to Developmental Delay (DD), Mental Retardation (MR), and distinct dysmorphic features. They all had a wide phenotypic spectrum. In all cases previous standard karyotypes were negative. Array-CGH analysis revealed five patients with interstitial 1p36 microdeletion (four de novo and one maternal) and two patients with de novo reciprocal duplication of different sizes. These were the first reported "pure" 1p36 microduplication cases so far. Three of our patients carrying the 1p36 microdeletion syndrome were also found to have additional pathogenetic aberrations. These findings (del 3q27.1; del 4q21.22-q22.1; del 16p13.3; dup 21q21.2-q21.3; del Xp22.12) might contribute to the patients' severe phenotype, acting as additional modifiers of their clinical manifestations. We review and compare the clinical and array-CGH findings of our patients to previously reported cases with the aim of clearly delineating more accurate genotype-phenotype correlations for the 1p36 syndrome that could allow for a more precise prognosis.

  1. Asymmetric Dust Jets and Extended Structure of 22P/Kopff Observed During 2009 Appearance

    NASA Astrophysics Data System (ADS)

    Hanayama, Hidekazu; Ishiguro, Masateru; Watanabe, Jun-Ichi; Sarugaku, Yuki; Fukushima, Hideo; Miyaji, Takeshi; Yanagisawa, Kenshi; Kuroda, Daisuke; Yoshida, Michitoshi; Ohta, Kouji; Nobuyuki, Kawai

    2012-12-01

    22P/Kopff images were taken with Multicolor Imaging Telescopes for Survey and Monstrous Explosions (MITSuME) 3ch simultaneous CCD cameras on the Ishigakijima astronomical observatory 105-cm telescope and a 2kCCD camera on the Kiso 105-cm Schmidt telescope from 2009 August to December after the passage of its perihelion on 2009 May 25. We confirmed that the near-nuclear fan-shaped jet structure extended toward the south. Whereas we detected a dust trail structure on the project orbit of the parent nucleus, we could not confirm the obvious neck-line structure. We deduced a pole orientation of (αp1, δp1) = (302°±30°, 62°±10°) or (αp1, δp1) = (122°±30°, -62°±10°) in the case of prograde or retrograde rotation, based on the fan-shaped jet. In addition, we conducted a model simulation of the dust orbital evolution, and found that the observed dust morphology of the fan-shaped jet and dust trail can well explain the dust emission near the south polar region. Finally, we conclude that the surface of 22P/Kopff is becoming largely dormant, but the polar region is still active, as we saw in the Deep Space 1 image of 19P/Borrelly.

  2. Crystal Structure of a Super Leucine Zipper an Extended Two-Stranded Super Long Coiled Coil

    SciTech Connect

    J Diao

    2011-12-31

    Coiled coil is a ubiquitous structural motif in proteins, with two to seven alpha helices coiled together like the strands of a rope, and coiled coil folding and assembly is not completely understood. A GCN4 leucine zipper mutant with four mutations of K3A, D7A, Y17W, and H18N has been designed, and the crystal structure has been determined at 1.6 {angstrom} resolution. The peptide monomer shows a helix trunk with short curved N- and C-termini. In the crystal, two monomers cross in 35{sup o} and form an X-shaped dimer, and each X-shaped dimer is welded into the next one through sticky hydrophobic ends, thus forming an extended two-stranded, parallel, super long coiled coil rather than a discrete, two-helix coiled coil of the wild-type GCN4 leucine zipper. Leucine residues appear at every seventh position in the super long coiled coil, suggesting that it is an extended super leucine zipper. Compared to the wild-type leucine zipper, the N-terminus of the mutant has a dramatic conformational change and the C-terminus has one more residue Glu 32 determined. The mutant X-shaped dimer has a large crossing angle of 35{sup o} instead of 18{sup o} in the wild-type dimer. The results show a novel assembly mode and oligomeric state of coiled coil, and demonstrate that mutations may affect folding and assembly of the overall coiled coil. Analysis of the formation mechanism of the super long coiled coil may help understand and design self-assembling protein fibers.

  3. The Relative Influence of Competition and Prey Defenses on the Phenotypic Structure of Insectivorous Bat Ensembles in Southern Africa

    PubMed Central

    Schoeman, M. Corrie; Jacobs, David S.

    2008-01-01

    Deterministic filters such as competition and prey defences should have a strong influence on the community structure of animals such as insectivorous bats that have life histories characterized by low fecundity, low predation risk, long life expectancy, and stable populations. We investigated the relative influence of these two deterministic filters on the phenotypic structure of insectivorous bat ensembles in southern Africa. We used null models to simulate the random phenotypic patterns expected in the absence of competition or prey defences and analysed the deviations of the observed phenotypic pattern from these expected random patterns. The phenotypic structure at local scales exhibited non-random patterns consistent with both competition and prey defense hypotheses. There was evidence that competition influenced body size distribution across ensembles. Competition also influenced wing and echolocation patterns in ensembles and in functional foraging groups with high species richness or abundance. At the same time, prey defense filters influenced echolocation patterns in two species-poor ensembles. Non-random patterns remained evident even after we removed the influence of body size from wing morphology and echolocation parameters taking phylogeny into account. However, abiotic filters such as geographic distribution ranges of small and large-bodied species, extinction risk, and the physics of flight and sound probably also interacted with biotic filters at local and/or regional scales to influence the community structure of sympatric bats in southern Africa. Future studies should investigate alternative parameters that define bat community structure such as diet and abundance to better determine the influence of competition and prey defences on the structure of insectivorous bat ensembles in southern Africa. PMID:19005563

  4. The structure of the genotype-phenotype map strongly constrains the evolution of non-coding RNA.

    PubMed

    Dingle, Kamaludin; Schaper, Steffen; Louis, Ard A

    2015-12-01

    The prevalence of neutral mutations implies that biological systems typically have many more genotypes than phenotypes. But, can the way that genotypes are distributed over phenotypes determine evolutionary outcomes? Answering such questions is difficult, in part because the number of genotypes can be hyper-astronomically large. By solving the genotype-phenotype (GP) map for RNA secondary structure (SS) for systems up to length L = 126 nucleotides (where the set of all possible RNA strands would weigh more than the mass of the visible universe), we show that the GP map strongly constrains the evolution of non-coding RNA (ncRNA). Simple random sampling over genotypes predicts the distribution of properties such as the mutational robustness or the number of stems per SS found in naturally occurring ncRNA with surprising accuracy. Because we ignore natural selection, this strikingly close correspondence with the mapping suggests that structures allowing for functionality are easily discovered, despite the enormous size of the genetic spaces. The mapping is extremely biased: the majority of genotypes map to an exponentially small portion of the morphospace of all biophysically possible structures. Such strong constraints provide a non-adaptive explanation for the convergent evolution of structures such as the hammerhead ribozyme. These results present a particularly clear example of bias in the arrival of variation strongly shaping evolutionary outcomes and may be relevant to Mayr's distinction between proximate and ultimate causes in evolutionary biology. PMID:26640651

  5. Energetic stability, atomic and electronic structures of extended γ-graphyne: A density functional study.

    PubMed

    Chi, Baoqian; Liu, Yi; Li, Xiaowu; Xu, Jingcheng; Qin, Xuming; Sun, Chen; Bai, Chenghao; Zhao, Xinluo

    2015-06-01

    The energetic stability, atomic and electronic structures of γ-graphyne and its derivatives (γ-GYs) with extended carbon chains were investigated as a function of chain length by density functional calculations in this work. The studied γ-GYs consist of hexagon carbon rings connected by linear chains with C atoms n = 0-22. We predict that the even-numbered C chains of γ-GYs consist of alternating single and triple C-C bonds (polyyne), energetically more stable than the odd-numbered C chains made of continuous C-C double bonds (polycumulene). The calculated electronic structures indicate that γ-GYs can be either metallic (odd n) or semiconductive (even n) depending on the parity of the number of C chain atoms. The semiconducting γ-GYs are predicted to have ~1.2 eV direct band gaps and 0.1-0.2 effective electron masses independent of the chain length. Thus introducing sp carbon atoms into sp (2)-based graphene provides a novel way to open up band gaps without doping and defects while maintaining small electron masses critical to good transport properties. Graphical Abstract The typical atomic model of graphyne (middle) as well as their band gaps (left) and electron density (right).

  6. Electronic and structural properties of extended-chain compounds and polymers

    SciTech Connect

    Springborg, M.

    2000-04-20

    Results of density functional calculations on infinite, periodic chains are reported. The method that is applied is based on linearized muffin-tin orbitals as basis functions, although the full potential and not only its muffin-tin part is included in the calculations. Special emphasis is put on analyzing the interatomic interactions by means of crystal-orbital overlap or Hamilton populations (COOP and COHP, respectively). As examples of conjugated polymers, trans-polyacetylene and polycarbonitrile are studied. Here, in particular, the existence of a bond length alternation is discussed. Subsequently, PtS{sub 2} (both without and with K counterions) and NbSe{sub 3} chains are considered. For the former, the single-chain calculations are supplemented with calculations on the crystalline compounds, and it is shown how single-chain effects are responsible for the structural properties whereas interchain effects have to be included in order to account for all the electronic properties. Parts of the results are explained through an analysis of the COOP and COHP. For NbSe{sub 3} the three different structures occurring in the crystalline material are considered, and the implications of the results for the existence of charge density waves as well as the importance of spin-orbit couplings are discussed. Finally, HF as an example of an extended hydrogen-bonded system is examined, and it is demonstrated how the electronic interactions change when the covalent and hydrogen bonds are interchanged as it occurs in charge transport via solitons.

  7. Extended DLVO calculations expose the role of the structural nature of the adsorbent beads during chromatography.

    PubMed

    Aasim, Muhammad; Bibi, Noor Shad; Vennapusa, Rami Reddy; Fernandez-Lahore, Marcelo

    2012-05-01

    Protein adsorption onto hydrophobic interaction chromatography supports was studied by a surface-thermodynamics approach. To gather relevant experimental information, contact angle measurements and zeta potential determinations were performed on three different commercial adsorbent beads, Phenyl Sepharose 6 Fast Flow, Toyopearl Phenyl 650-C and Source 15 Phenyl, having soft to rigid backbone structure. Similar information was obtained for a collection of model proteins, lysozyme, bovine serum albumin (BSA), polygalacturonase, aminopeptidase, chymosin, aspartic protease, beta-galactosidase, human immunoglobulin G, and lactoferrin, were evaluated in the hydrated and in the dehydrated state. Based on the mentioned experimental data, calculations were performed to obtain the (interfacial) energy versus distance profiles of nine individual (model) proteins on (commercial) beads of three different types. All of these beads harbored the phenyl-ligand onto a matrix of differentiated chemical nature. Extended Derjaguin, Landau, Verwey, and Overbeek (DLVO) calculations were correlated with actual chromatographic behavior. Typical chromatography conditions were employed. The population of model proteins utilized in this study could be segregated into two groups, according to the minimum values observed for the resulting interaction energy pockets and the corresponding retention volumes (or times) during chromatography. Moreover, trends were also identified as a function of the type of adsorbent bead under consideration. This has revealed the influence of the physicochemical nature of the bead structure on the adsorption process and consequently, on the expected separation behavior.

  8. Free-energy landscape of mechanically unfolded model proteins: Extended Jarzinsky versus inherent structure reconstruction

    NASA Astrophysics Data System (ADS)

    Luccioli, Stefano; Imparato, Alberto; Torcini, Alessandro

    2008-09-01

    The equilibrium free-energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is accomplished via two independent methods: By employing an extended version of the Jarzynski equality and the inherent structure formalism. A comparison of the free energies estimated with these two schemes with equilibrium results obtained via the umbrella sampling technique reveals a good quantitative agreement among all the approaches in a range of temperatures around the “folding transition” for the two examined sequences. In particular, for the sequence with good foldability properties, the mechanically induced structural transitions can be related to thermodynamical aspects of folding. Moreover, for the same sequence the knowledge of the landscape profile allows for a good estimation of the lifetimes of the native configuration for temperatures ranging from the folding to the collapse temperature. For the random sequence, mechanical and thermal unfolding appear to follow different paths along the landscape.

  9. Extended X-ray Absorption Fine Structure (EXAFS) Analysis of Novel High Laser Media

    NASA Astrophysics Data System (ADS)

    Hemantha, Aranwela; Marasinghe, G. K.; Segre, Carlo; Brow, Richard

    2011-03-01

    Rare earth-doped phosphate glasses are useful for a variety of optical and optoelectronic applications including high energy/high power (~ 1015 watt) Lasers. Binary (R2 O3)x (P2 O5)1-x glasses can be prepared in the compositional range 0 <= x <= ~ 0.30 . Atomic-scale structure, especially the coordination environment of R3+ ions, play a major role in determining optical/physical characteristics. We have investigated the R3+ local environment of Praseodymium and Neodymium ultraphosphate and meta phosphate(REMP) glasses using extended X-ray absorption fine structure technique. For both Nd and Pr phosphate glasses, nearest neighbor (oxygen) coordination decreases with increasing RE concentration. For the first oxygen shell the RE-O distance ranges between 2.38-2.40 Å and 2.39-2.46 Å for Nd and Pr respectively. The second co-ordination shell around the RE ions consists of phosphorus ions, with RE-P distance about 3.4-3.5 Å and co-ordination numbers ranging from 1.5 to 3. There exists an Oxygen shell (third shell) about 4.1 Å from RE ion for both Nd and Pr phosphate glasses. Support was provided by the NSF (UND) and DoE (Argonne Natl. Lab).

  10. NMR studies of structure and dynamics of liquid molecules confined in extended nanospaces.

    PubMed

    Tsukahara, Takehiko; Mizutani, Wataru; Mawatari, Kazuma; Kitamori, Takehiko

    2009-08-01

    We fabricated an NMR cell equipped with 10-100 nm scale spaces on a glass substrate (called extended nanospaces), and investigated molecular structure and dynamics of water confined in the extended nanospaces by (1)H NMR chemical shift (delta(H)) and (1)H and (2)H NMR spin-lattice relaxation rate ((1)H- and (2)H-1/T(1)), (1)H NMR spin-spin relaxation rate ((1)H-1/T(2)), and (1)H NMR rotating-frame spin-lattice relaxation rate ((1)H-1/T(1rho)) measurements of H(2)O and (2)H(2)O. The delta(H) and (1)H- and (2)H-1/T(1) results showed that size-confinement produces slower translational motions and higher proton mobility of water, but does not affect the hydrogen-bonding structure and rotational motions. Such unique phenomena appeared in the space size of 40 to 800 nm. However, the (1)H-1/T(1) value at 40 nm was still different from that in 4 nm porous nanomaterial, because translational and rotational motions were inhibited for H(2)O molecules in the nanomaterial. By examining temperature- and deuterium-dependence of the (1)H-1/T(1) values, the molecular translational motions of the confined water were found to be controlled by protonic diffusion invoking a proton hopping pathway between adjacent water rather than hydrodynamic translational diffusion. Furthermore, we clarified that proton exchange between adjacent water molecules in extended nanospaces could be enhanced by the chemical exchange of protons between water and SiOH groups on glass surfaces, ( identical with SiO(-)...H(+)...H(2)O) + H(2)O --> triple bond SiO(-) + (H(3)O(+) + H(2)O) --> triple bond SiO(-) + (H(2)O + H(3)O(+)), based on (1)H-1/T(2) measurements. An enhancement of proton exchange rate of water due to the reduction of space sizes was verified from the results of (1)H-1/T(1rho) values, and the rate of water in the 100 nm sized spaces is larger by a factor of more than ten from that of bulk water. Such size-confinement effects were distinctly observed for hydrogen-bond solvents with strong proton

  11. Structural Analysis of Freshwater-Cultured Pearls with Different Lusters Using the Extended X-Ray Absorption Fine Structure Technique

    NASA Astrophysics Data System (ADS)

    Monarumit, N.; Noirawee, N.; Phlayrahan, A.; Promdee, K.; Won-in, K.; Satitkune, S.

    2016-05-01

    The quality of freshwater-cultured pearls (Chamberlainia hainesiana) is determined by their luster, which is related to the content of the two CaCO3 mineral phases: aragonite and vaterite. The atomic structures of pearl samples were analyzed by the extended X-ray absorption fine structure (EXAFS) technique using synchrotron radiation to compare the atomic environment and atomic bonding around Ca atoms of high- and low-luster pearls. The Ca K-edge EXAFS spectra of the pearl samples were determined and interpreted in terms of the photoelectron wave number and the distance between Ca atoms and neighboring atoms. From the results, the wave oscillation of high-luster pearls is less than that of low-luster pearls. This indicates the presence of the aragonite phase in high-luster pearls and a combination of aragonite and vaterite phases in low-luster pearls, especially in the fi rst and second shells of Ca atoms. It can be concluded that the different lusters of freshwater-cultured pearls are related to the different CaCO3 phases in their structures.

  12. Genetic structure is correlated with phenotypic divergence rather than geographic isolation in the highly polymorphic strawberry poison-dart frog.

    PubMed

    Wang, Ian J; Summers, Kyle

    2010-02-01

    Phenotypic and genetic divergence can be influenced by a variety of factors, including sexual and natural selection, genetic drift and geographic isolation. Investigating the roles of these factors in natural systems can provide insight into the relative influences of allopatric and ecological modes of biological diversification in nature. The strawberry poison frog, Dendrobates pumilio, presents an excellent opportunity for this kind of research, displaying a diverse array of colour morphs and inhabiting a heterogeneous landscape that includes oceanic islands, fragmented rainforest patches and wide expanses of suitable habitat. In this study, we use 15 highly polymorphic microsatellite loci to estimate population structure and gene flow among populations from across the range of D. pumilio and a causal modelling framework to statistically test 12 hypotheses regarding the geographic and phenotypic variables that explain genetic differentiation within this system. Our results demonstrate that the genetic distance between populations is most strongly associated with differences in dorsal coloration. Previous experimental studies have shown that phenotypic differences can result in sexual and natural selection against non-native phenotypes, and our results now show that these forces lead to genetic isolation between different colour morphs in the wild, presenting a potential case of incipient speciation through selection. PMID:20025652

  13. An extended structure-function model and its application to the analysis of solar wind intermittency

    NASA Technical Reports Server (NTRS)

    Tu, C.-Y.; Marsch, E.; Rosenbauer, H.

    1995-01-01

    An extended structure-function model is developed by including the new effect in the p-model of Meneveau and Sreenivasan (1987a), i.e., that the averaged energy cascade rate changes with scale, a situation which has been found to prevail in non-fully-developed turbulence in the inner solar wind. This model is useful for the small-scale fluctuations in the inner heliosphere, where the turbulence is not fully developed and cannot be explained quantitatively by any of the previous intermittency turbulence models. With two model parameters, the intrinsic index of the energy spectrum, alpha and the fragmentation fraction p, the model can fit, for the first time, all the observed scaling exponents of the structure functions, which are calculated for time lags ranging from 81 seconds to 0.7 hours from the Helios solar wind data. From the cases we studied we can establish for p neither a clear radial evolution trend, nor a solar-wind-speed, or stream-structure dependence, or a systematic anisotropy for both the flow velocity and magnetic field component fluctuations. Generally, p has values between 0. 7 and 0.8. However, in some cases in low-speed wind p has somewhat higher values for the magnetic components, especially for the radial component. In high-speed wind, the inferred intrinsic spectral indices (alpha) of the velocity and magnetic field components are about equal, while the experimental spectral indices derived from the observed power spectra differ. The magnetic index is somewhat larger than the index of the velocity spectrum. For magnetic fluctuations in both high- and low-speed winds, the intrinsic exponent alpha has values which are near 1.5, while the observed spectral exponent has much higher values.

  14. The local structure factor near an interface; beyond extended capillary-wave models

    NASA Astrophysics Data System (ADS)

    Parry, A. O.; Rascón, C.; Evans, R.

    2016-06-01

    We investigate the local structure factor S (zq) at a free liquid-gas interface in systems with short-ranged intermolecular forces and determine the corrections to the leading-order, capillary-wave-like, Goldstone mode divergence of S (zq) known to occur for parallel (i.e. measured along the interface) wavevectors q\\to 0 . We show from explicit solution of the inhomogeneous Ornstein-Zernike equation that for distances z far from the interface, where the profile decays exponentially, S (zq) splits unambiguously into bulk and interfacial contributions. On each side of the interface, the interfacial contributions can be characterised by distinct liquid and gas wavevector dependent surface tensions, {σ l}(q) and {σg}(q) , which are determined solely by the bulk two-body and three-body direct correlation functions. At high temperatures, the wavevector dependence simplifies and is determined almost entirely by the appropriate bulk structure factor, leading to positive rigidity coefficients. Our predictions are confirmed by explicit calculation of S (zq) within square-gradient theory and the Sullivan model. The results for the latter predict a striking temperature dependence for {σ l}(q) and {σg}(q) , and have implications for fluctuation effects. Our results account quantitatively for the findings of a recent very extensive simulation study by Höfling and Dietrich of the total structure factor in the interfacial region, in a system with a cut-off Lennard-Jones potential, in sharp contrast to extended capillary-wave models which failed completely to describe the simulation results.

  15. Structural characterization of alkaline hydrogen peroxide pretreated grasses exhibiting diverse lignin phenotypes

    PubMed Central

    2012-01-01

    Background For cellulosic biofuels processes, suitable characterization of the lignin remaining within the cell wall and correlation of quantified properties of lignin to cell wall polysaccharide enzymatic deconstruction is underrepresented in the literature. This is particularly true for grasses which represent a number of promising bioenergy feedstocks where quantification of grass lignins is particularly problematic due to the high fraction of p-hydroxycinnamates. The main focus of this work is to use grasses with a diverse range of lignin properties, and applying multiple lignin characterization platforms, attempt to correlate the differences in these lignin properties to the susceptibility to alkaline hydrogen peroxide (AHP) pretreatment and subsequent enzymatic deconstruction. Results We were able to determine that the enzymatic hydrolysis of cellulose to to glucose (i.e. digestibility) of four grasses with relatively diverse lignin phenotypes could be correlated to total lignin content and the content of p-hydroxycinnamates, while S/G ratios did not appear to contribute to the enzymatic digestibility or delignification. The lignins of the brown midrib corn stovers tested were significantly more condensed than a typical commercial corn stover and a significant finding was that pretreatment with alkaline hydrogen peroxide increases the fraction of lignins involved in condensed linkages from 88–95% to ~99% for all the corn stovers tested, which is much more than has been reported in the literature for other pretreatments. This indicates significant scission of β-O-4 bonds by pretreatment and/or induction of lignin condensation reactions. The S/G ratios in grasses determined by analytical pyrolysis are significantly lower than values obtained using either thioacidolysis or 2DHSQC NMR due to presumed interference by ferulates. Conclusions It was found that grass cell wall polysaccharide hydrolysis by cellulolytic enzymes for grasses exhibiting a diversity of

  16. Study of the Local Structure of II-Vi Ternary Alloys by Extended X-Ray Absorption Fine Structure

    NASA Astrophysics Data System (ADS)

    Pong, Way-Faung

    Bondlengths, Debye-Waller factors, and site occupancy in the diluted magnetic semiconductors Zn_ {rm 1 - x}Mn_{ rm x}Se and Hg_{ rm 1 - x}Mn_{rm x}Te, and the narrow-gap semiconductor Hg _{rm 1 - x}Cd _{rm x}Te have been measured using extended x-ray absorption fine structure (EXAFS). The nearest-neighbor bond lengths in all of these alloys are found to be constant as a function of alloy composition within the experimental uncertainty of 0.01A. Because the average cation-cation distance changes with Mn composition, these results necessarily imply distortion of the tetrahedral bond angles. In the case of Zn_{rm 1 - x}Mn_{rm x} Se, the anion sublattice is shown to suffer the largest distortion, but the cation sublattice also exhibits some relaxation. The repercussions of these results are discussed, in terms of the amount of cation and anion sublattice distortion at low temperature and its connection to the superexchange mechanism occurring between the Mn ^{+2} ions and mediated by the intervening anion in Zn_{rm 1 - x}Mn_{rm x} Se. From the NN bond length relaxation results shown in this study and those reported elsewhere for the III -V-based and II-VI-based ternary compounds and DMS alloys, it appears that substitution of Mn^{+2 } ions into II-VI-based compounds causes greater local distortion, in general, than otherwise observed when group II cations are substituted for one another. We believe that the tetrahedral bond weakening in DMS is due to MN 3d-orbital (t_2) and anion p-orbital hybridization in DMS, leaving fewer p-orbitals available for tetrahedral bonding. This leads to the weakening of the bond force constants alpha, beta, as well as the bond becoming more ionic as Mn^{+2} is substituted into the II-VI-based compounds. Finally, the experimentally extended electron energy loss fine structure (EXELFS) technique, with modulations in the differential inelastic electron scattering cross -section above an absorption core edge, has been used in recent years to

  17. New insights into the phenotypic covariance structure of the anthropoid cranium.

    PubMed

    Makedonska, Jana

    2014-12-01

    In complex organisms, suites of non-random, highly intercorrelated phenotypic traits, organized according to their developmental history and forming semi-autonomous units (i.e. modules), have the potential to impose constraints on morphological diversification or to improve evolvability. Because of its structural, developmental and functional complexity, the cranium is arguably one of the best models for studying the interplay between developmental history and the need for various parts of a structure to specialize in different functions. This study evaluated the significance of two specific types of developmental imprints in the adult anthropoid cranium, those imposed by ossification pattern (i.e. ossification with and without a pre-existing cartilaginous phase) and those imposed by tissue origin (i.e. tissues derived principally from neural-crest vs. those derived from paraxial mesoderm). Specifically, this study tests the hypothesis that the face and the basicranium form two distinct modules with higher within-unit trait integration magnitudes compared with the cranium as a whole. Data on 12 anthropoid primate species were collected in the form of 20 three-dimensional landmarks digitized on cranial surface models that sample the basicranium as well as regions of functional importance during feeding [corrected]. The presence of a significant modularity imprint in the adult cranium was assessed using a between-region within-species comparison of multivariate correlations (RV coefficients) obtained with partial least-squares, using within-module within-species eigenvalue variance (EV), and using cluster analyses and non-metric multidimensional scaling. In addition to addressing the validity of the cranial modularity hypothesis in anthropoids, this study addressed methodological aspects of the interspecific comparison of morphological integration, namely the effect of sample size and the effect of landmark number on integration magnitudes. Two methodological

  18. Item-Level Psychometrics of the Glasgow Outcome Scale: Extended Structured Interviews.

    PubMed

    Hong, Ickpyo; Li, Chih-Ying; Velozo, Craig A

    2016-04-01

    The Glasgow Outcome Scale-Extended (GOSE) structured interview captures critical components of activities and participation, including home, shopping, work, leisure, and family/friend relationships. Eighty-nine community dwelling adults with mild-moderate traumatic brain injury (TBI) were recruited (average = 2.7 year post injury). Nine items of the 19 items were used for the psychometrics analysis purpose. Factor analysis and item-level psychometrics were investigated using the Rasch partial-credit model. Although the principal components analysis of residuals suggests that a single measurement factor dominates the measure, the instrument did not meet the factor analysis criteria. Five items met the rating scale criteria. Eight items fit the Rasch model. The instrument demonstrated low person reliability (0.63), low person strata (2.07), and a slight ceiling effect. The GOSE demonstrated limitations in precisely measuring activities/participation for individuals after TBI. Future studies should examine the impact of the low precision of the GOSE on effect size. PMID:27504879

  19. Enhanced traveling wave amplification of co-planar slow wave structure by extended phase-matching

    SciTech Connect

    Palm, Andrew; Sirigiri, Jagadishwar; Shin, Young-Min

    2015-09-15

    The electron beam co-propagating with slow waves in a staggered double grating array (SDGA) efficiently amplifies millimeter and sub-millimeter waves over a wide spectrum. Our theoretical and numerical analyses show that the power amplification in the fundamental passband is enhanced by the extended beam-wave phase-matching. Particle-in-cell simulations on the SDGA slow wave structure, designed with 10.4 keV and 50–100 mA sheet beam, indicate that maintaining beam-wave synchronization along the entire length of the circuit improves the gain by 7.3% leading to a total gain of 28 dB, corresponding to 62 W saturated power at the middle of operating band, and a 3-dB bandwidth of 7 GHz with 10.5% at V-band (73.5 GHz center frequency) with saturated peak power reaching 80 W and 28 dB at 71 GHz. These results also show a reasonably good agreement with analytic calculations based on Pierce small signal gain theory.

  20. Computational extended magneto-hydrodynamical study of shock structure generated by flows past an obstacle

    SciTech Connect

    Zhao, Xuan; Seyler, C. E.

    2015-07-15

    The magnetized shock problem is studied in the context where supersonic plasma flows past a solid obstacle. This problem exhibits interesting and important phenomena such as a bow shock, magnetotail formation, reconnection, and plasmoid formation. This study is carried out using a discontinuous Galerkin method to solve an extended magneto-hydrodynamic model (XMHD). The main goals of this paper are to present a reasonably complete picture of the properties of this interaction using the MHD model and then to compare the results to the XMHD model. The inflow parameters, such as the magnetosonic Mach number M{sub f} and the ratio of thermal pressure to magnetic pressure β, can significantly affect the physical structures of the flow-obstacle interaction. The Hall effect can also significantly influence the results in the regime in which the ion inertial length is numerically resolved. Most of the results presented are for the two-dimensional case; however, two three-dimensional simulations are presented to make a connection to the important case in which the solar wind interacts with a solid body and to explore the possibility of performing scaled laboratory experiments.

  1. Structure and ligand binding of the extended Tudor domain of D. melanogaster Tudor-SN.

    PubMed

    Friberg, Anders; Corsini, Lorenzo; Mourão, André; Sattler, Michael

    2009-04-10

    The Tudor-SN protein (p100, SND1) has been implicated in a variety of cellular processes, such as transcription, processing of edited double-stranded RNA, and splicing regulation. Molecular details of these functions are not yet understood. Tudor domains have previously been shown to bind methylated ligands, such as methylated lysines and arginines. It has been suggested that the role of Tudor-SN in splicing may involve binding to such methylated ligands or to the methylated 5' cap of spliceosomal snRNAs. Here, we report the crystal structure of the extended Tudor domain of Tudor-SN from Drosophila melanogaster to a resolution of 2.1 A. NMR secondary chemical shifts, relaxation data, and residual dipolar couplings indicate that the solution and crystal structures are similar. Binding of various ligands was investigated by NMR. Binding sites and affinities were characterized by chemical shift perturbations. We show that the aromatic cage of the Tudor domain specifically binds a peptide containing symmetrically dimethylated arginines (sDMA) with micromolar affinity, while the same peptide comprising nonmethylated arginines does not show significant chemical shift perturbations. Tudor-SN preferentially recognizes sDMA over asymmetrically dimethylated arginine (aDMA). In contrast, two 5' cap analogues with different methylation patterns, as well as mono-, di-, and trimethyllysines, show no binding. Our data demonstrate that the Tudor domain of Tudor-SN specifically recognizes sDMA-containing ligands. The aromatic cage of Tudor-SN is very similar to the one in the Tudor domain of the survival of motor neuron protein, which also recognizes sDMA peptides, indicating a conserved binding motif for this methylation mark. Recognition of sDMA in the C-terminal tails of spliceosomal Sm proteins suggests how Tudor-SN may interact with small nuclear ribonucleoprotein particles during the regulation of splicing. PMID:19232356

  2. Characterization of basin concrete in support of structural integrity demonstration for extended storage

    SciTech Connect

    Duncan, A.

    2014-09-30

    Concrete core samples from C basin were characterized through material testing and analysis to verify the design inputs for structural analysis of the L Basin and to evaluate the type and extent of changes in the material condition of the concrete under extended service for fuel storage. To avoid the impact on operations, core samples were not collected from L area, but rather, several concrete core samples were taken from the C Basin prior to its closure. C basin was selected due to its similar environmental exposure and service history compared to L Basin. The microstructure and chemical composition of the concrete exposed to the water was profiled from the water surface into the wall to evaluate the impact and extent of exposure. No significant leaching of concrete components was observed. Ingress of carbonation or deleterious species was determined to be insignificant. No evidence of alkali-silica reactions (ASR) was observed. Ettringite was observed to form throughout the structure (in air voids or pores); however, the sulfur content was measured to be consistent with the initial concrete that was used to construct the facility. Similar ettringite trends were observed in the interior segments of the core samples. The compressive strength of the concrete at the mid-wall of the basin was measured, and similar microstructural analysis was conducted on these materials post compression testing. The microstructure was determined to be similar to near-surface segments of the core samples. The average strength was 4148 psi, which is well-above the design strength of 2500 psi. The analyses showed that phase alterations and minor cracking in a microstructure did not affect the design specification for the concrete.

  3. A surface extended X-ray absorption fine structure study of tellurium adsorbed onto Si(100)

    NASA Astrophysics Data System (ADS)

    Burgess, S. R.; Cowie, B. C. C.; Wilks, S. P.; Dunstan, P. R.; Dunscombe, C. J.; Williams, R. H.

    1996-09-01

    The adsorption of tellurium on Si(100) has been studied using surface extended X-ray adsorption fine structure (SEXAFS) and X-ray standing wave spectroscopy (XSW). This particular system is of interest due to its potential applicability in the surfactant aided growth of CdHgTeCdTeSi(100) based infra-red detectors. The Te/Si(100) structure was generated by depositing a thick layer (˜ 100 Å) of CdTe onto a clean Si (2 × 1) double domain surface, and annealing the sample to 350°C. This resulted is a ˜ 1 ML Te terminated surface where the (2 × 1) reconstruction was lost in favour of a (1 × 1) symmetry. X-ray absorption of the Te L 3 edge ( E = 4341 eV), with a photon energy range of 4440-4700 eV, was probed using a total yield detection scheme. The SEXAFS results indicated that the Te atoms sat in 2-fold bridge sites directly above a fourth layer Si atom. The corresponding bond length was measured to be 2.52 ± 0.05 Å. The XSW measurements of the (400) reflection gave a coherent position of 1.63 ± 0.03 Å and a coherent fraction of 0.65. This is consistent with the breaking of the SiSi dimers and thus could be an example of the phenomena of adsorbate-induced dereconstruction of the surface. These results are compared with those of Bennet et al. who examined a similar system using soft X-ray photoemission (SXPS) and the STM study of Yoshikawa et al.

  4. Spatial phenotypic and genetic structure of threespine stickleback (Gasterosteus aculeatus) in a heterogeneous natural system, Lake Mývatn, Iceland

    PubMed Central

    Millet, Antoine; Kristjánsson, Bjarni K; Einarsson, Árni; Räsänen, Katja

    2013-01-01

    Eco-evolutionary responses of natural populations to spatial environmental variation strongly depend on the relative strength of environmental differences/natural selection and dispersal/gene flow. In absence of geographic barriers, as often is the case in lake ecosystems, gene flow is expected to constrain adaptive divergence between environments – favoring phenotypic plasticity or high trait variability. However, if divergent natural selection is sufficiently strong, adaptive divergence can occur in face of gene flow. The extent of divergence is most often studied between two contrasting environments, whereas potential for multimodal divergence is little explored. We investigated phenotypic (body size, defensive structures, and feeding morphology) and genetic (microsatellites) structure in threespine stickleback (Gasterosteus aculeatus) across five habitat types and two basins (North and South) within the geologically young and highly heterogeneous Lake Mývatn, North East Iceland. We found that (1) North basin stickleback were, on average, larger and had relatively longer spines than South basin stickleback, whereas (2) feeding morphology (gill raker number and gill raker gap width) differed among three of five habitat types, and (3) there was only subtle genetic differentiation across the lake. Overall, our results indicate predator and prey mediated phenotypic divergence across multiple habitats in the lake, in face of gene flow. PMID:24223263

  5. Ovarian structures and uterine environment are associated with phenotypic and genetic merit for performance in lactating dairy cows.

    PubMed

    Fitzgerald, A M; Ryan, D P; Carthy, T R; Evans, R D; Berry, D P

    2014-12-01

    The objective of this study was to estimate the association between detailed reproductive phenotypes for cows categorized as divergent for phenotypic and genetic performance. The hypothesis was that higher yielding animals, either phenotypically or genetically, would have compromised ovarian and uterine reproductive performance. Detailed reproductive traits including multiple ovulations, cystic ovarian structures, corpus luteum (CL) presence, and uterine environment were available on 9675 ultrasound records from 8174 dairy lactating cows, calved between 10 and 70 days. Cows were categorized, within parity, into low, average, or high for each of the performance traits. There was a greater likelihood of multiple ovulations in cows with greater phenotypic yields (odds ratio: 1.53-1.81) and greater genetic merit for yield (odds ratio: 1.31-1.59) relative to lower performing contemporaries. After adjustment for genetic merit, a similar trend of increased odds (odds ratio: 1.29-1.87) of multiple ovulations in higher yielding cows was observed compared with the lowest yielding category. There was no association between either phenotypic milk composition or genetic merit for milk composition with the likelihood of multiple ovulations. The likelihood of cystic ovarian structures was highest in cows with greatest phenotypic milk yields (odds ratio: 2.75-3.24), greater genetic merit for milk yield (odds ratio: 1.30-1.51), and even after adjustment for genetic merit there was a greater likelihood of cystic ovarian structures in cows with the highest milk yields (odds ratio: 2.71-2.95), compared with cows in the lowest category for each of the milk traits. Cows with average phenotypic milk yields were more likely to have a CL, compared with the lowest yielding category (odds ratio: 1.20-1.23), and these associations remained after adjustment for genetic merit of the trait. The likelihood of CL presence was highest in cows with the lowest genetic merit for milk. Lower fat

  6. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    PubMed

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-09-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

  7. Research Resource: Correlating Human Cytochrome P450 21A2 Crystal Structure and Phenotypes of Mutations in Congenital Adrenal Hyperplasia

    PubMed Central

    Pallan, Pradeep S.; Lei, Li; Wang, Chunxue; Waterman, Michael R.; Guengerich, F. Peter

    2015-01-01

    Cytochrome P450 21A2 is a key player in steroid 21-hydroxylation and converts progesterone to 11-deoxycorticosterone and 17α-hydroxy progesterone to 11-deoxycortisol. More than 100 mutations in P450 21A2 have been established in patients thus far; these account for the vast majority of occurrences of congenital adrenal hyperplasia (CAH), which is among the most common heritable metabolic diseases in humans. CAH phenotypes range from the most severe, salt-wasting (SW), to the simple virilizing (SV), and nonclassical (NC) CAH forms. We recently determined the crystal structure of human P450 21A2 in complex with progesterone. To gain more insight into the structural and stability changes underlying the phenotypes of individual mutations, we analyzed 24 SW, SV, and NC mutants in the context of the crystal structure of the human enzyme. Our analysis reveals clear differences in the localization of SW, SV, and NC mutations, with many of the first type mapping to the active site and near the heme and/or substrate and mostly resulting in complete loss of enzyme activity. Conversely, NC mutations are often found near the periphery and close to the surface of the protein, and mutant enzymes retain partial activity. The main conclusion from the mutation-structure-activity study is that the severity of the CAH clinical manifestations can be directly correlated with the degree of mutation-induced damage in terms of protein fold stability and active site changes in the structural model. Thus, the NC phenotype is typically associated with mutations that have a compensatory effect, ie, H-bonding replacing hydrophobic interactions and vice versa. PMID:26172259

  8. Structure and development of old-growth, unmanaged second-growth, and extended rotation Pinus resinosa forests in Minnesota, USA

    USGS Publications Warehouse

    Silver, Emily J.; D'Amato, Anthony W.; Fraver, Shawn; Palik, Brian J.; Bradford, John B.

    2013-01-01

    The structure and developmental dynamics of old-growth forests often serve as important baselines for restoration prescriptions aimed at promoting more complex structural conditions in managed forest landscapes. Nonetheless, long-term information on natural patterns of development is rare for many commercially important and ecologically widespread forest types. Moreover, the effectiveness of approaches recommended for restoring old-growth structural conditions to managed forests, such as the application of extended rotation forestry, has been little studied. This study uses several long-term datasets from old growth, extended rotation, and unmanaged second growth Pinus resinosa (red pine) forests in northern Minnesota, USA, to quantify the range of variation in structural conditions for this forest type and to evaluate the effectiveness of extended rotation forestry at promoting the development of late-successional structural conditions. Long-term tree population data from permanent plots for one of the old-growth stands and the extended rotation stands (87 and 61 years, respectively) also allowed for an examination of the long-term structural dynamics of these systems. Old-growth forests were more structurally complex than unmanaged second-growth and extended rotation red pine stands, due in large part to the significantly higher volumes of coarse woody debris (70.7 vs. 11.5 and 4.7 m3/ha, respectively) and higher snag basal area (6.9 vs. 2.9 and 0.5 m2/ha, respectively). In addition, old-growth forests, although red pine-dominated, contained a greater abundance of other species, including Pinus strobus, Abies balsamea, and Picea glauca relative to the other stand types examined. These differences between stand types largely reflect historic gap-scale disturbances within the old-growth systems and their corresponding structural and compositional legacies. Nonetheless, extended rotation thinning treatments, by accelerating advancement to larger tree diameter

  9. Evaluation of the Clinical and Laboratory Standards Institute phenotypic confirmatory test to detect the presence of extended-spectrum β-lactamases from 4005 Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis isolates.

    PubMed

    Morrissey, Ian; Bouchillon, Samuel K; Hackel, Meredith; Biedenbach, Douglas J; Hawser, Stephen; Hoban, Daryl; Badal, Robert E

    2014-04-01

    A subset of Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis isolates collected for the Study for Monitoring Antimicrobial Resistance Trends that were positive for the Clinical and Laboratory Standards Institute (CLSI) extended-spectrum β-lactamase (ESBL) phenotypic confirmatory test (n = 3245) or had an ertapenem MIC of ≥0.5 µg ml(-1) (n = 293), or both (n = 467), were analysed for ESBL genes. Most ESBL phenotype E. coli or K. pneumoniae possessed an ESBL gene (95.8 and 88.4 %, respectively), and this was 93.1 % if carbapenem-non-susceptible K. pneumoniae were removed. This rate was lower for P. mirabilis (73.4 %) and K. oxytoca (62.5 %). Virtually all ESBL-positive isolates (99.5 %) were cefotaxime non-susceptible [CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints)]. Fewer isolates (82 %) were ceftazidime non-susceptible (CLSI breakpoints). In addition, 21.1 % of E. coli, 25 % of K. oxytoca and 78.7 % of P. mirabilis isolates were ceftazidime susceptible but ESBL positive. This suggests that CLSI breakpoints for ceftazidime are too high to detect ESBLs. The lower EUCAST breakpoints detected ESBLs in E. coli and K. oxytoca better, but 59.6 % of ESBL-positive isolates of P. mirabilis were ceftazidime susceptible. For isolates with ertapenem MICs ≥0.5 µg ml(-1), more accurate ESBL phenotype analysis was observed for E. coli and K. pneumoniae (sensitivity >95 % for both, specificity 94.4 and 54.1 %, respectively). If carbapenemase-positive K. pneumoniae were excluded, the specificity increased to 78 %. The positive predictive values for the ESBL phenotypic test with E. coli and K. pneumoniae were 97.6 and 81.8 %, respectively, and negative predictive values were 75.9 and 95.2 %, respectively. We therefore suggest that it would be prudent to confirm phenotypic ESBL-positive P. mirabilis, K. pneumoniae and K. oxytoca with molecular analysis.

  10. Structural and Theoretical Studies Indicate that the Cylindrical Protease ClpP Samples Extended and Compact Conformations

    SciTech Connect

    Kimber, Matthew S.; Yu, Angela Yeou Hsiung; Borg, Mikael; Leung, Elisa; Chan, Hue Sun; Houry, Walid A.

    2010-09-21

    The highly conserved ClpP protease consists of two heptameric rings that interact by the interdigitation of an {alpha}-helix {beta} strand handle domain motif to form a tetradecameric cylinder. We previously proposed that protease dynamics results in the temporary unstructuring of interacting pairs of handle domains, opening transient equatorial side pores that allow for peptide egress. Here, we report the structure of an Escherichia coli ClpP mutant in which each opposing pair of protomers is linked by a disulfide bond. This structure resembles the compact structures of Streptococcus pneumoniae, Mycobacterium tuberculosis, and Plasmodium falciparum ClpPs, rather than the active, extended structures that have previously been determined for E. coli ClpPs. The structural data, along with normal mode analysis, support a model whereby the ClpP cylinder switches dynamically between an active extended state required for substrate degradation and an inactive compact state allowing peptide product release.

  11. The Mud Hills, Mojave Desert, California: Structure, stratigraphy and sedimentology of a rapidly extended terrane

    SciTech Connect

    Ingersoll, R.V.; Devaney, K.A.; Geslin, J.K.; Cavazza, W.; Diamond, D.S.; Jagiello, K.J.; Marsaglia, K.M.; Paylor, E.D. II; Short, P.F. . Dept. of Earth and Space Sciences)

    1993-04-01

    The Mud Hills exposes synorogenic breccia (Mud Hills Fm.) deposited during the final stages of crustal extension of the upper plate above the Waterman Hills detachment (20--18 Ma). Previous workers have misinterpreted fault contacts as stratigraphic contacts, and have developed intricate pseudostratigraphy to explain their observations. The authors' detailed mapping, combined with stratigraphic and sedimentologic data, documents that the volcaniclastic Pickhandle Fm. is conformably overlain by the plutoniclastic Mud Hills Fm., with no interfingering. Repetition of these south-dipping lithologic units is due to imbricate, north-dipping listric faults. These relations are demonstrated by the systematic northward v''ing of fault contacts and southward v''ing of stratigraphic contacts. Stratigraphic dip decreases upsection, which is consistent with incremental rotation of basinal strata simultaneously with deposition. Most of the Mud Hills Fm. consists of rock-avalanche breccia and megabreccia derived from granodiorite, which is identical to basement exposed beneath the Pickhandle and Jackhammer Fms. to the north. The Mud Hills Fm. was derived from now-buried granodiorite of a stranded upper-plate block to the south, as demonstrated by northward paleocurrents, facies relations and the presence of fine-grained units close to the presumed master fault (as is typical of half-graben sedimentation). Unconformably overlying the Mud Hills Fm. is the Owl Conglomerate (Barstow Fm.), which has mixed provenance with southward paleocurrents; the Owl Conglomerate was derived from residual highlands after extension ceased. Integration of structural, stratigraphic and sedimentologic information is essential for correct reconstruction of highly extended terranes.

  12. RR Lyrae variables in the Small Magellanic Cloud - II. The extended area: chemical and structural analysis

    NASA Astrophysics Data System (ADS)

    Kapakos, E.; Hatzidimitriou, D.

    2012-11-01

    We have performed the Fourier decomposition analysis of 8- and 13-yr V-band light curves of a carefully selected sample of 454 fundamental-mode RR Lyrae variables (RRab type), detected in an ≃14 square degree area of the Small Magellanic Cloud (SMC) and listed in the Optical Gravitational Lensing Experiment, phase III, Catalogue of Variable Stars. The Fourier decomposition parameters were used to derive metal abundances and distance moduli, following the methodology described by Kapakos, Hatzidimitriou & Soszyński. The average metal abundance of the RRab stars on the new scale of Carretta et al. was found to be <[Fe/H]C09> = -1.69 ± 0.41 dex (std, with a standard error of 0.02 dex). A tentative metallicity gradient of -0.013 ± 0.007 dex kpc-1 was detected, with increasing metal abundance towards the dynamical centre of the SMC, but selection effects are also discussed. The distance modulus of the SMC was re-estimated and was found to be <μ> = 19.13 ± 0.19 (std) in a distance scale where the distance modulus of the Large Magellanic Cloud (LMC) is μLMC = 18.52 ± 0.06 (std). The average 1σ line-of-sight depth was found to be σ int =5.3±0.4 kpc (std), while spatial variations of the depth were detected. The SMC was found to be deeper in the north-eastern region, while metal-richer and metal-poorer objects in the sample seem to belong to different dynamical structures. The former have smaller scale height and may constitute a thick disc, its width being 10.40 ± 0.02 kpc, and a bulge whose size (radius) is estimated to be 2.09 ± 0.81 kpc. The latter seem to belong to a halo structure with a maximum depth along the line of sight extending over 16 kpc in the SMC central region and falling to ˜12 kpc in the outer regions.

  13. Detection of Healthcare-Related Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Transmission Events Using Combined Genetic and Phenotypic Epidemiology

    PubMed Central

    Boers, Stefan A.; Jansen, Ruud; Hays, John P.; Goessens, Wil H. F.; Vos, Margreet C.

    2016-01-01

    Background Since the year 2000 there has been a sharp increase in the prevalence of healthcare-related infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. However, the high community prevalence of ESBL-producing E. coli isolates means that many E. coli typing techniques may not be suitable for detecting E. coli transmission events. Therefore, we investigated if High-throughput MultiLocus Sequence Typing (HiMLST) and/or Raman spectroscopy were suitable techniques for detecting recent E. coli transmission events. Methods This study was conducted from January until December 2010 at Erasmus University Medical Center, Rotterdam, the Netherlands. Isolates were typed using HiMLST and Raman spectroscopy. A genetic cluster was defined as two or more patients carrying identical isolates. We used predefined definitions for epidemiological relatedness to assess healthcare-related transmission. Results We included 194 patients; strains of 112 patients were typed using HiMLST and strains of 194 patients were typed using Raman spectroscopy. Raman spectroscopy identified 16 clusters while HiMLST identified 10 clusters. However, no healthcare-related transmission events were detected. When combining data from both typing techniques, we identified eight clusters (n = 34 patients), as well as 78 patients with a non-cluster isolate. However, we could not detect any healthcare-related transmission in these 8 clusters. Conclusions Although clusters were genetically detected using HiMLST and Raman spectroscopy, no definite epidemiological relationships could be demonstrated which makes the possibility of healthcare-related transmission events highly unlikely. Our results suggest that typing of ESBL-producing E. coli using HiMLST and/or Raman spectroscopy is not helpful in detecting E. coli healthcare-related transmission events. PMID:27463231

  14. Phenotype and cell proliferation activity of duct-like structures in human sublingual glands: a histological and immunohistochemical study

    PubMed Central

    TOLENTINO, Elen de Souza; TEIXEIRA, Cleverson Soares; AZEVEDO-ALANIS, Luciana Reis; HONÓRIO, Heitor Marques; DAMANTE, José Humberto

    2015-01-01

    There are several age-related microscopic changes in the salivary glands, including the increase in the number of duct-like structures (DLS). However, the true origin and the phenotype of the DLS are not known. Objective To evaluate the phenotype and the cell proliferation index of the DLS of human sublingual glands. Material and Methods Sixty sublingual glands obtained from human cadavers were divided into two groups - 0-30 and 61-90 years old. The phenotype was estimated by immunostaining for cytokeratin 19 (CK 19) and the S-100 protein as well as by the presence of mucin and glycogen. The cell proliferation index was determined by the Ki-67 antibody. The histochemical techniques used periodic acid-Schiff (PAS) and Alcian Blue. In each captured microscopic field, the DLS were counted to establish a percentage for the staining profile. The statistical analysis was accomplished using Student’s t-test, the Mann-Whitney test and Pearson’s correlation coefficient (p<0.05). Results Comparing both groups, only CK 19 showed a statistically significant difference (p=0.033), with the strongest expression in the elderly group. There was no significant difference between PAS and Alcian Blue (p=0.270). In both groups, the immunostaining for CK 19 was stronger than that for S-100 (p=0.004;p<0.001), but there was no correlation between the two immunomarkers (ρ=-0.163; p=0.315). There was no immunostaining for Ki-67. Conclusions DLS demonstrate a ductal phenotypic profile and do not present cell proliferation activity. DLS may represent a regressive process arising from acini or represent the result of metaplasia. PMID:26221919

  15. Evolutionary dynamics of phenotype-structured populations: from individual-level mechanisms to population-level consequences

    NASA Astrophysics Data System (ADS)

    Chisholm, Rebecca H.; Lorenzi, Tommaso; Desvillettes, Laurent; Hughes, Barry D.

    2016-08-01

    Epigenetic mechanisms are increasingly recognised as integral to the adaptation of species that face environmental changes. In particular, empirical work has provided important insights into the contribution of epigenetic mechanisms to the persistence of clonal species, from which a number of verbal explanations have emerged that are suited to logical testing by proof-of-concept mathematical models. Here, we present a stochastic agent-based model and a related deterministic integrodifferential equation model for the evolution of a phenotype-structured population composed of asexually-reproducing and competing organisms which are exposed to novel environmental conditions. This setting has relevance to the study of biological systems where colonising asexual populations must survive and rapidly adapt to hostile environments, like pathogenesis, invasion and tumour metastasis. We explore how evolution might proceed when epigenetic variation in gene expression can change the reproductive capacity of individuals within the population in the new environment. Simulations and analyses of our models clarify the conditions under which certain evolutionary paths are possible and illustrate that while epigenetic mechanisms may facilitate adaptation in asexual species faced with environmental change, they can also lead to a type of "epigenetic load" and contribute to extinction. Moreover, our results offer a formal basis for the claim that constant environments favour individuals with low rates of stochastic phenotypic variation. Finally, our model provides a "proof of concept" of the verbal hypothesis that phenotypic stability is a key driver in rescuing the adaptive potential of an asexual lineage and supports the notion that intense selection pressure can, to an extent, offset the deleterious effects of high phenotypic instability and biased epimutations, and steer an asexual population back from the brink of an evolutionary dead end.

  16. Decentralized identification of nonlinear structure under strong ground motion using the extended Kalman filter and unscented Kalman filter

    NASA Astrophysics Data System (ADS)

    Tao, Dongwang; Li, Hui; Ma, Qiang

    2016-04-01

    Complete structure identification of complicate nonlinear system using extend Kalman filter (EKF) or unscented Kalman filter (UKF) may have the problems of divergence, huge computation and low estimation precision due to the large dimension of the extended state space for the system. In this article, a decentralized identification method of hysteretic system based on the joint EKF and UKF is proposed. The complete structure is divided into linear substructures and nonlinear substructures. The substructures are identified from the top to the bottom. For the linear substructure, EKF is used to identify the extended space including the displacements, velocities, stiffness and damping coefficients of the substructures, using the limited absolute accelerations and the identified interface force above the substructure. Similarly, for the nonlinear substructure, UKF is used to identify the extended space including the displacements, velocities, stiffness, damping coefficients and control parameters for the hysteretic Bouc-Wen model and the force at the interface of substructures. Finally a 10-story shear-type structure with multiple inter-story hysteresis is used for numerical simulation and is identified using the decentralized approach, and the identified results are compared with those using only EKF or UKF for the complete structure identification. The results show that the decentralized approach has the advantage of more stability, relative less computation and higher estimation precision.

  17. Structural and Functional Concepts in Current Mouse Phenotyping and Archiving Facilities

    PubMed Central

    Kollmus, Heike; Post, Rainer; Brielmeier, Markus; Fernández, Julia; Fuchs, Helmut; McKerlie, Colin; Montoliu, Lluis; Otaegui, Pedro J; Rebelo, Manuel; Riedesel, Hermann; Ruberte, Jesús; Sedlacek, Radislav; de Angelis, Martin Hrabě; Schughart, Klaus

    2012-01-01

    Collecting and analyzing available information on the building plans, concepts, and workflow from existing animal facilities is an essential prerequisite for most centers that are planning and designing the construction of a new animal experimental research unit. Here, we have collected and analyzed such information in the context of the European project Infrafrontier, which aims to develop a common European infrastructure for high-throughput systemic phenotyping, archiving, and dissemination of mouse models. A team of experts visited 9 research facilities and 3 commercial breeders in Europe, Canada, the United States, and Singapore. During the visits, detailed data of each facility were collected and subsequently represented in standardized floor plans and descriptive tables. These data showed that because the local needs of scientists and their projects, property issues, and national and regional laws require very specific solutions, a common strategy for the construction of such facilities does not exist. However, several basic concepts were apparent that can be described by standardized floor plans showing the principle functional units and their interconnection. Here, we provide detailed information of how individual facilities addressed their specific needs by using different concepts of connecting the principle units. Our analysis likely will be valuable to research centers that are planning to design new mouse phenotyping and archiving facilities. PMID:23043807

  18. Effects of Highly Conserved Major Histocompatibility Complex (MHC) Extended Haplotypes on Iron and Low CD8+ T Lymphocyte Phenotypes in HFE C282Y Homozygous Hemochromatosis Patients from Three Geographically Distant Areas

    PubMed Central

    Barton, James C.; Thorstensen, Ketil; Morais, Sandra; da Silva, Berta M.; Pinto, Jorge P.; Vieira, Cristina P.; Vieira, Jorge; Acton, Ronald T.; Porto, Graça

    2013-01-01

    Hereditary Hemochromatosis (HH) is a recessively inherited disorder of iron overload occurring commonly in subjects homozygous for the C282Y mutation in HFE gene localized on chromosome 6p21.3 in linkage disequilibrium with the human leukocyte antigen (HLA)-A locus. Although its genetic homogeneity, the phenotypic expression is variable suggesting the presence of modifying factors. One such genetic factor, a SNP microhaplotype named A-A-T, was recently found to be associated with a more severe phenotype and also with low CD8+T-lymphocyte numbers. The present study aimed to test whether the predictive value of the A-A-T microhaplotype remained in other population settings. In this study of 304 HH patients from 3 geographically distant populations (Porto, Portugal 65; Alabama, USA 57; Nord-Trøndelag, Norway 182), the extended haplotypes involving A-A-T were studied in 608 chromosomes and the CD8+ T-lymphocyte numbers were determined in all subjects. Patients from Porto had a more severe phenotype than those from other settings. Patients with A-A-T seemed on average to have greater iron stores (p = 0.021), but significant differences were not confirmed in the 3 separate populations. Low CD8+ T-lymphocytes were associated with HLA-A*03-A-A-T in Porto and Alabama patients but not in the greater series from Nord-Trøndelag. Although A-A-T may signal a more severe iron phenotype, this study was unable to prove such an association in all population settings, precluding its use as a universal predictive marker of iron overload in HH. Interestingly, the association between A-A-T and CD8+ T-lymphocytes, which was confirmed in Porto and Alabama patients, was not observed in Nord-Trøndelag patients, showing that common HLA haplotypes like A*01–B*08 or A*03–B*07 segregating with HFE/C282Y in the three populations may carry different messages. These findings further strengthen the relevance of HH as a good disease model to search for novel candidate loci associated with

  19. Devices with extended area structures for mass transfer processing of fluids

    DOEpatents

    TeGrotenhuis, Ward E.; Wegeng, Robert S.; Whyatt, Greg A.; King, David L.; Brooks, Kriston P.; Stenkamp, Victoria S.

    2009-04-21

    A microchannel device includes several mass transfer microchannels to receive a fluid media for processing at least one heat transfer microchannel in fluid communication with a heat transfer fluid defined by a thermally conductive wall, and at several thermally conductive fins each connected to the wall and extending therefrom to separate the mass transfer microchannels from one another. In one form, the device may optionally include another heat transfer microchannel and corresponding wall that is positioned opposite the first wall and has the fins and the mass transfer microchannels extending therebetween.

  20. The structure of the extended phase space of the Sitnikov problem

    NASA Astrophysics Data System (ADS)

    Kovács, T.; Érdi, B.

    2007-10-01

    The extended phase space of the Sitnikov problem is studied by using a stroboscopic map and computing escape times. Comparisons of phase portraits and plots of escape times reveal the intrinsic connection between the geometry of the phase space and the dynamical behaviour of the system. Properties of the phase space are analysed both in the central regular region and far from it.

  1. Effect of extended line defects on thermal conduction of carbon nanotubes: analyzing phonon structures by band unfolding

    NASA Astrophysics Data System (ADS)

    Huang, Huaqing

    2015-08-01

    We theoretically investigate the effect of extended line defects (ELDs) on thermal transport properties of carbon nanotubes (CNTs) using nonequilibrium Green’s function method. Our study shows that the thermal conductance of CNTs with ELDs can be 25% lower than that of pristine CNTs. By extending the application of the recently developed unfolding method for electronic structures to phonon spectra, we find that the unfolded phonon bands of defected CNTs are split with obvious gap opening, leading to lower phonon transmissions. Further phonon local density of states analysis reveals that the change of bonding configuration near the ELD in defected CNTs can tail the degree of phonon localization. Our results indicate that introducing ELDs might be an efficient way to control thermal conduction of CNTs. The extended unfolding method for phonon systems, found to be efficient in this work, is expected to be applicable to other systems with densely folded phonon bands.

  2. Photoluminescence and extended X-ray absorption fine structure studies on cadmium telluride material

    NASA Astrophysics Data System (ADS)

    Liu, Xiangxin

    The direct-band-gap semiconductor CdTe is an important material for fabricating high efficiency, polycrystalline thin-film solar cells in a heterojunction configuration. The outstanding physical properties of this material such as its good band-gap match to the solar spectrum, ease of fabrication of stoichiometric films, and easy grain boundary passivation make it an important candidate for large area, thin-film solar cells. However, there are several poorly understood processing steps that are commonly utilized in cell fabrication. One of these is a CdCl2 treatment near 400°C in the presence of oxygen, which can improve the cell efficiency a factor of two or more. Another factor is the role of copper in cell performance. In high performance CdS/CdTe thin-film solar cells, copper is usually included in the fabrication of low-resistance back contacts to obtain heavy p-type doping of the absorber CdTe at the contact. However, most of the copper is not electrically active. For example, secondary ion mass spectroscopy (SIMS) on typical CdTe cells has shown Cu concentrations of 1019 atoms/cm3 and even higher, although capacitance-voltage (C-V) measurements indicate typical ionized acceptor levels on the order of 1014/cm 3. Thus, there is great interest in the location and role of this inactive copper in CdTe photovoltaic (PV) devices. In this thesis, I will describe results obtained on magnetron-sputtered CdTe films that were diffused with copper following the procedure used for creating a cell back contact. Extended X-ray Absorption Fine Structure (EXAFS) measurements identified the chemical environment of the majority of the copper and show major differences depending on whether the CdTe film has been treated with chloride prior to the Cu diffusion. The EXAFS data indicate that the Cu chemistry is strongly affected by the chloride treatments---predominantly Cu2Te when Cu was diffused into the as-deposited CdTe film, but a Cu2O environment when Cu was diffused after

  3. Studying the local structures of novel materials using the Extended X-ray Absorption Fine Structure technique

    NASA Astrophysics Data System (ADS)

    Jiang, Yu

    2009-12-01

    In this dissertation, investigations on the local lattice structures for a variety of novel materials using Extended X-ray Absorption Fine Structure (EXAFS) technique are presented. Different experiment schemes were applied to obtain EXAFS data with high quality, and some interesting results were obtained by careful analysis. The power of the EXAFS technique was once again proved. In Chapter 1, I first briefly introduce the EXAFS theory and experiments, then give readers who are not familiar with this technique a short introduction on data reduction and analysis, and finally discuss some problems that are easily ignored in the interpretation of the experiment results. In Chapter 2, a temperature-dependent EXAFS investigation of La 1-xCaxMnO 3 is presented for the concentration range that spans the ferromagnetic-insulator (FMI) to ferromagnetic-metal (FMM) transition region, x = 0.16, 0.18, 0.20, and 0.22; the titrated hole concentrations are slightly higher y = 0.2, 0.22, 0.24, and 0.25 respectively. In Chapter 3, I report EXAFS studies of n- and p-type Ba8Ga 16Ge30 samples (type I clathrate) at the Ga, Ge, and Ba K-edges, to probe the local structure, particularly around the Ba atoms located inside 20- and 24-atom cages (Ba1 and Ba2 sites respectively) formed of Ga/Ge atoms. In agreement with diffraction analysis we find Ba2 is off-center, with a component in the bc plane (0.15 A) comparable to that found in diffraction; however, under the assumption of a stiff cage we also require a significant a component. This suggests a coupling or attraction between the Ba2 atoms and the hexagonal rings at the top or bottom of the cage that encloses the Ba2 site. In Chapter 4, I report detailed degradation and rejuvenation studies for AC electro-luminescence (EL) devices made using the phosphor ZnS:Cu,CI. We find that the AC EL emission spectra vary considerably with AC driving frequency but all spectra can be fit to a sum of four Gaussians. The combined experiments place

  4. Triplet excitons as sensitive spin probes for structure analysis of extended defects in microcrystalline silicon

    NASA Astrophysics Data System (ADS)

    Meier, Christoph; Teutloff, Christian; Behrends, Jan; Bittl, Robert; Astakhov, Oleksandr; Lips, Klaus

    2016-07-01

    Electrically detected magnetic resonance (EDMR) spectroscopy is employed to study the influence of triplet excitons on the photocurrent in state-of-the-art microcrystalline silicon thin-film solar cells. These triplet excitons are used as sensitive spin probes for the investigation of their electronic and nuclear environment in this mixed-phase material. According to low-temperature EDMR results obtained from solar cells with different extended defects in the crystallites of microcrystalline silicon that give rise to shallow states in the silicon band gap. The excitons possess a rather delocalized wave function, couple to electron spins in conduction band tail states nearby, and take part in a spin-dependent recombination process. Our study shows that extended defects such as grain boundaries or stacking faults in the crystalline part of the material act as charge carrier traps that can influence the material conductivity.

  5. The Matchmaker Exchange API: automating patient matching through the exchange of structured phenotypic and genotypic profiles.

    PubMed

    Buske, Orion J; Schiettecatte, François; Hutton, Benjamin; Dumitriu, Sergiu; Misyura, Andriy; Huang, Lijia; Hartley, Taila; Girdea, Marta; Sobreira, Nara; Mungall, Chris; Brudno, Michael

    2015-10-01

    Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis. PMID:26255989

  6. The Matchmaker Exchange API: automating patient matching through the exchange of structured phenotypic and genotypic profiles.

    PubMed

    Buske, Orion J; Schiettecatte, François; Hutton, Benjamin; Dumitriu, Sergiu; Misyura, Andriy; Huang, Lijia; Hartley, Taila; Girdea, Marta; Sobreira, Nara; Mungall, Chris; Brudno, Michael

    2015-10-01

    Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis.

  7. Viroids: from genotype to phenotype just relying on RNA sequence and structural motifs.

    PubMed

    Flores, Ricardo; Serra, Pedro; Minoia, Sofía; Di Serio, Francesco; Navarro, Beatriz

    2012-01-01

    As a consequence of two unique physical properties, small size and circularity, viroid RNAs do not code for proteins and thus depend on RNA sequence/structural motifs for interacting with host proteins that mediate their invasion, replication, spread, and circumvention of defensive barriers. Viroid genomes fold up on themselves adopting collapsed secondary structures wherein stretches of nucleotides stabilized by Watson-Crick pairs are flanked by apparently unstructured loops. However, compelling data show that they are instead stabilized by alternative non-canonical pairs and that specific loops in the rod-like secondary structure, characteristic of Potato spindle tuber viroid and most other members of the family Pospiviroidae, are critical for replication and systemic trafficking. In contrast, rather than folding into a rod-like secondary structure, most members of the family Avsunviroidae adopt multibranched conformations occasionally stabilized by kissing-loop interactions critical for viroid viability in vivo. Besides these most stable secondary structures, viroid RNAs alternatively adopt during replication transient metastable conformations containing elements of local higher-order structure, prominent among which are the hammerhead ribozymes catalyzing a key replicative step in the family Avsunviroidae, and certain conserved hairpins that also mediate replication steps in the family Pospiviroidae. Therefore, different RNA structures - either global or local - determine different functions, thus highlighting the need for in-depth structural studies on viroid RNAs.

  8. Pre-adsorbed type-I collagen structure-dependent changes in osteoblastic phenotype

    SciTech Connect

    Hanagata, Nobutaka . E-mail: HANAGATA.Nobutaka@nims.go.jp; Takemura, Taro; Monkawa, Akira; Ikoma, Toshiyuki; Tanaka, Junzo

    2006-06-16

    Type-I collagen is the most abundant extracellular matrix in bones and modulates various functions of osteoblasts. We prepared two different structures of type-I collagen on tissue culture grade polystylene (TCPS) surfaces, one is feltwork structure of filamentous molecules from acid solutions (ACs) and the other is network structure of fibrils from neutral solutions (NCs), to examine effects of the structures on the maturation process of osteoblast-like cells. No significant differences of cell proliferation were observed between TCPS and ACs, but NCs delayed the proliferation. In initial cell attachment, the cells on ACs had tense lamellipodia with sharp tips, while those on NCs had loose lamellipodia. No detectable differences in levels of expressed integrin {alpha}{sub 2}- and {alpha}{sub 5}-subunits were observed between the structures. Although the matrix mineralization in NCs was also delayed in comparison with TCPS and ACs, fully mineralized levels in NCs were the same as those of TCPS and ACs. In addition, although we examined the effects of densities of pre-adsorbed collagen molecules on osteoblast maturation, the effects were less serious than those of the structures. This study suggests that the structures of collagen affect proliferation and mineralization of osteoblast-like cells.

  9. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

    PubMed Central

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-01-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  10. SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype–Phenotype Correlations

    PubMed Central

    Lepri, Francesca; De Luca, Alessandro; Stella, Lorenzo; Rossi, Cesare; Baldassarre, Giuseppina; Pantaleoni, Francesca; Cordeddu, Viviana; Williams, Bradley J; Dentici, Maria L; Caputo, Viviana; Venanzi, Serenella; Bonaguro, Michela; Kavamura, Ines; Faienza, Maria F; Pilotta, Alba; Stanzial, Franco; Faravelli, Francesca; Gabrielli, Orazio; Marino, Bruno; Neri, Giovanni; Silengo, Margherita Cirillo; Ferrero, Giovanni B; Torrrente, Isabella; Selicorni, Angelo; Mazzanti, Laura; Digilio, Maria C; Zampino, Giuseppe; Dallapiccola, Bruno; Gelb, Bruce D; Tartaglia, Marco

    2011-01-01

    Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS is caused by aberrant RAS-MAPK signaling and is genetically heterogeneous, which explains, in part, the marked clinical variability documented for this Mendelian trait. Recently, we and others identified SOS1 as a major gene underlying NS. Here, we explored further the spectrum of SOS1 mutations and their associated phenotypic features. Mutation scanning of the entire SOS1 coding sequence allowed the identification of 33 different variants deemed to be of pathological significance, including 16 novel missense changes and in-frame indels. Various mutation clusters destabilizing or altering orientation of regions of the protein predicted to contribute structurally to the maintenance of autoinhibition were identified. Two previously unappreciated clusters predicted to enhance SOS1's recruitment to the plasma membrane, thus promoting a spatial reorientation of domains contributing to inhibition, were also recognized. Genotype–phenotype analysis confirmed our previous observations, establishing a high frequency of ectodermal anomalies and a low prevalence of cognitive impairment and reduced growth. Finally, mutation analysis performed on cohorts of individuals with nonsyndromic pulmonic stenosis, atrial septal defects, and ventricular septal defects excluded a major contribution of germline SOS1 lesions to the isolated occurrence of these cardiac anomalies. Hum Mutat 32:760–772, 2011. © 2011 Wiley-Liss, Inc. PMID:21387466

  11. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    PubMed

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-09-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  12. Exploring Optically Compact Dwarf Galaxies for Kinematic Structures and Extended HI Halos

    NASA Astrophysics Data System (ADS)

    Most, Hans; Cannon, J. M.; Salzer, J. J.; Rosenberg, J. L.

    2012-01-01

    We present Very Large Array H I spectral line and optical imaging of eight optically compact (optical radii <1 kpc), star-forming dwarf galaxies. These galaxies were chosen because of their optically compact stellar distributions, faint blue magnitudes, ongoing star formation, and relative proximity. The sample includes ADBS 113845+2008, which was found to have an HI halo that extends nearly 40 optical scale lengths from the stellar body (Cannon et al. 2009). Using this larger sample, we are working to discern if the "giant gas disk" dwarf galaxy is common or rare. We are also exploring the kinematics and dark matter contents of each of the sample galaxies.

  13. Extended line defects in BN, GaN, and AlN semiconductor materials: Graphene-like structures

    NASA Astrophysics Data System (ADS)

    Camacho-Mojica, Dulce C.; López-Urías, Florentino

    2016-05-01

    The extended line defect (ELD) mimicking grain boundaries in two-dimensional systems is theoretically investigated in BN, GaN, and AlN semiconductor materials with a single layer honeycomb structure. The ELD consists of octagonal-square membered rings. Density functional calculations of the electronic density of states, scanning tunneling microscopy and transmission electron microscopy image simulations are analyzed. Our results revealed that the ELDs are stable in all considered monolayers. In addition, electronic density of states calculations demonstrated that in gap states are emerged when ELD is incorporated into the honeycomb structures. Finally, results on armchair nanoribbons with bare-edges and hydrogenated edges are discussed.

  14. Displacive phase-transition of cuprite Ag2O revealed by extended x-ray absorption fine structure

    NASA Astrophysics Data System (ADS)

    Sanson, Andrea

    2016-08-01

    The low-temperature phase-transition of silver oxide (Ag2O) has been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy as a function of temperature. The thermal evolution of the local structure around Ag atoms has been determined. In particular, below the phase-transition temperature at ∼35 K, a progressive splitting of the Ag-Ag next-nearest-neighbor distances is observed. This definitely supports the idea that the phase-transition of Ag2O is due to displacive disorder of the Ag atoms.

  15. Traveling in the dark: the legibility of a regular and predictable structure of the environment extends beyond its borders.

    PubMed

    Yaski, Osnat; Portugali, Juval; Eilam, David

    2012-04-01

    The physical structure of the surrounding environment shapes the paths of progression, which in turn reflect the structure of the environment and the way that it shapes behavior. A regular and coherent physical structure results in paths that extend over the entire environment. In contrast, irregular structure results in traveling over a confined sector of the area. In this study, rats were tested in a dark arena in which half the area contained eight objects in a regular grid layout, and the other half contained eight objects in an irregular layout. In subsequent trials, a salient landmark was placed first within the irregular half, and then within the grid. We hypothesized that rats would favor travel in the area with regular order, but found that activity in the area with irregular object layout did not differ from activity in the area with grid layout, even when the irregular half included a salient landmark. Thus, the grid impact in one arena half extended to the other half and overshadowed the presumed impact of the salient landmark. This could be explained by mechanisms that control spatial behavior, such as grid cells and odometry. However, when objects were spaced irregularly over the entire arena, the salient landmark became dominant and the paths converged upon it, especially from objects with direct access to the salient landmark. Altogether, three environmental properties: (i) regular and predictable structure; (ii) salience of landmarks; and (iii) accessibility, hierarchically shape the paths of progression in a dark environment.

  16. OpenMx: An Open Source Extended Structural Equation Modeling Framework

    ERIC Educational Resources Information Center

    Boker, Steven; Neale, Michael; Maes, Hermine; Wilde, Michael; Spiegel, Michael; Brick, Timothy; Spies, Jeffrey; Estabrook, Ryne; Kenny, Sarah; Bates, Timothy; Mehta, Paras; Fox, John

    2011-01-01

    OpenMx is free, full-featured, open source, structural equation modeling (SEM) software. OpenMx runs within the "R" statistical programming environment on Windows, Mac OS-X, and Linux computers. The rationale for developing OpenMx is discussed along with the philosophy behind the user interface. The OpenMx data structures are introduced--these…

  17. Structurally Mapping the Diverse Phenotype of Adeno-Associated Virus Serotype 4▿

    PubMed Central

    Govindasamy, Lakshmanan; Padron, Eric; McKenna, Robert; Muzyczka, Nicholas; Kaludov, Nikola; Chiorini, John A.; Agbandje-McKenna, Mavis

    2006-01-01

    The adeno-associated viruses (AAVs) can package and deliver foreign DNA into cells for corrective gene delivery applications. The AAV serotypes have distinct cell binding, transduction, and antigenic characteristics that have been shown to be dictated by the capsid viral protein (VP) sequence. To understand the contribution of capsid structure to these properties, we have determined the crystal structure of AAV serotype 4 (AAV4), one of the most diverse serotypes with respect to capsid protein sequence and antigenic reactivity. Structural comparison of AAV4 to AAV2 shows conservation of the core β strands (βB to βI) and helical (αA) secondary structure elements, which also exist in all other known parvovirus structures. However, surface loop variations (I to IX), some containing compensating structural insertions and deletions in adjacent regions, result in local topological differences on the capsid surface. These include AAV4 having a deeper twofold depression, wider and rounder protrusions surrounding the threefold axes, and a different topology at the top of the fivefold channel from that of AAV2. Also, the previously observed “valleys” between the threefold protrusions, containing AAV2's heparin binding residues, are narrower in AAV4. The observed differences in loop topologies at subunit interfaces are consistent with the inability of AAV2 and AAV4 VPs to combine for mosaic capsid formation in efforts to engineer novel tropisms. Significantly, all of the surface loop variations are associated with amino acids reported to affect receptor recognition, transduction, and anticapsid antibody reactivity for AAV2. This observation suggests that these capsid regions may also play similar roles in the other AAV serotypes. PMID:16971437

  18. Extended Aging Theories for Predictions of Safe Operational Life of Critical Airborne Structural Components

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Chen, Tony

    2006-01-01

    The previously developed Ko closed-form aging theory has been reformulated into a more compact mathematical form for easier application. A new equivalent loading theory and empirical loading theories have also been developed and incorporated into the revised Ko aging theory for the prediction of a safe operational life of airborne failure-critical structural components. The new set of aging and loading theories were applied to predict the safe number of flights for the B-52B aircraft to carry a launch vehicle, the structural life of critical components consumed by load excursion to proof load value, and the ground-sitting life of B-52B pylon failure-critical structural components. A special life prediction method was developed for the preflight predictions of operational life of failure-critical structural components of the B-52H pylon system, for which no flight data are available.

  19. Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

    PubMed Central

    Rodriguez-Palacios, Alex; Kodani, Tomohiro; Kaydo, Lindsey; Pietropaoli, Davide; Corridoni, Daniele; Howell, Scott; Katz, Jeffry; Xin, Wei; Pizarro, Theresa T.; Cominelli, Fabio

    2015-01-01

    Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones' versus ‘villous mini-aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD. PMID:26154811

  20. Molecular fingerprinting of carbohydrate structure phenotypes of three porifera proteoglycan-like glyconectins.

    PubMed

    Guerardel, Yann; Czeszak, Xavier; Sumanovski, Lazar T; Karamanos, Yannis; Popescu, Octavian; Strecker, Gerard; Misevic, Gradimir N

    2004-04-01

    Glyconectins (GNs) represent a new class of proteoglycan-like cell adhesion and recognition molecules found in several Porifera species. Physico-chemical properties of GN carbohydrate moieties, such as size, composition, and resistance to most glycosaminoglycan-degrading enzymes, distinguish them from any other type of known glycoproteins. The molecular mechanism of GN-mediated self/non-self discrimination function is based on highly species-specific and Ca(2+)-dependent GN to GN associations that approach the selectivity of the evolutionarily advanced immunoglobulin superfamily. Carbohydrates of glyconectins 1, 2, and 3 are essential for species-specific auto-aggregation properties in three respective Porifera species. To obtain a structural insight into the molecular mechanisms, we performed carbohydrate structural analyses of glyconectins isolated from the three sponge model systems, Microciona prolifera (GN1), Halichondria panicea (GN2), and Cliona celata (GN3). The glycan content of all three GNs ranged between 40 and 60% of their total mass. Our approach using sequential and selective chemical degradation of GN glycans and subsequent mass spectrometric and NMR analyses revealed that each glyconectin presents novel and highly species-specific carbohydrate sequences. All three GNs include distinct acid-resistant and acid-labile carbohydrate domains, the latter composed of novel repetitive units. We have sequenced four short sulfated and one pyruvilated unit in GN1, eight larger and branched pyruvilated oligosaccharides in GN2, which represent a heterogeneous but related family of structures, and four sulfated units in GN3.

  1. Abnormalities in the basement membrane structure promote basal keratinocytes in the epidermis of hypertrophic scars to adopt a proliferative phenotype.

    PubMed

    Yang, Shaowei; Sun, Yexiao; Geng, Zhijun; Ma, Kui; Sun, Xiaoyan; Fu, Xiaobing

    2016-05-01

    The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a significant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro.

  2. Synthesis, structure, characterization and fluorescent properties of Ag+ complexes with extended π⋯π interactions

    NASA Astrophysics Data System (ADS)

    Huang, Ting-Hong; Yan, Jie; Yang, Hu; Qiang, Liu; Du, Huai-Ming

    2015-12-01

    Two mixed-ligand Ag (I) complexes, [Ag2(Phterpy)2(NO3)2(dppe)]·CH3CN (1) and [Ag4(Phterpy)2(NO3)2(dppp)2](NO3)2·6H2O (2) (dppe = 1, 2-bis (diphenylphosphino) ethane, dppp = 1, 3-bis (diphenylphosphino) propane, Phterpy = 4‧-phenyl-2, 2‧:6‧, 2″-terpyridine), have been synthesized and structurally characterized by IR, 1H-NMR, 31P-NMR, elemental analysis and X-ray crystal structure analysis. Structural analysis reveals that the change of bridging ligands from dppe to dppp lead to the formation of centrosymmetric cations [Ag2(Phterpy)2(NO3)2(dppe)] and [Ag4(Phterpy)2 (NO3)2(dppp)2]2+, especially complex 2 containing two independent centrosymmetric tetramers with the central (obligate) Ag2O2 planes. Complexes 1 and 2 consist of the 1D infinite chains, with different variations in π-stacking patterns. Crystal structure of 1 contains 1D infinite chains constructed by π⋯π interactions between Phterpy, while 2 is built by π⋯π interaction of phenylene rings from dppp. All these reveal that the change of phosphine ligands might be the key of construction of different types of polynuclear structures and 1D π-stacking chain. Moreover, the solid-state emission spectra of complexes 1 and 2 display broad emission bands at 420-600 nm.

  3. Damage Characterization Using the Extended Finite Element Method for Structural Health Management

    NASA Technical Reports Server (NTRS)

    Krishnamurthy, Thiagarajan; Gallegos, Adam M.

    2011-01-01

    The development of validated multidisciplinary Integrated Vehicle Health Management (IVHM) tools, technologies, and techniques to enable detection, diagnosis, prognosis, and mitigation in the presence of adverse conditions during flight will provide effective solutions to deal with safety related challenges facing next generation aircraft. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign impact that can reach a critical size during flight, resulting in loss of control of the aircraft. Hence, development of efficient methodologies to determine the presence, location, and severity of damage/cracks in critical structural components is highly important in developing efficient structural health management systems.

  4. Structural elucidation of lignin polymers of Eucalyptus chips during organosolv pretreatment and extended delignification.

    PubMed

    Wen, Jia-Long; Sun, Shao-Long; Yuan, Tong-Qi; Xu, Feng; Sun, Run-Cang

    2013-11-20

    Effective delignification of lignocelluloses is a very important to guarantee the economic feasibility of organosolv-based biorefinery. Eucalyptus chips were successively subjected to organosolv pretreatment (AEOP) and extended delignification (ED) process in the present study. The effects of delignification processes were scientifically evaluated by component analysis, SEM, and CP-MAS NMR techniques. It was found that the integrated process of organosolv pretreatment and subsequent delignification resulted in an effective delignification. The fundamental chemistry of the lignin obtained after these processes was thoroughly investigated by FT-IR, multidimensional NMR ((31)P-, (13)C-, and 2D-HSQC NMR), and GPC techniques. It was observed that an extensive cleavage of aryl ether linkages, ethoxylation, and some condensation reactions occurred in AEOP process, while α-oxidation mainly took place in alkaline hydrogen peroxide (AHP) process. It is believed that better understanding the fundamental chemistry of lignin facilitates the optimization of the delignification process. More importantly, well-defined of lignin polymers will facilitate their value-added applications in current and future biorefineries. PMID:24168231

  5. Anharmonicity in single-wall carbon nanotubes as evidenced by means of extended energy loss fine structure spectroscopy analysis

    SciTech Connect

    Castrucci, P.; Tombolini, F.; Scarselli, M.; Bini, S.; De Crescenzi, M.; Diociaiuti, M.; Casciardi, S.; El Khakani, M. A.; Rosei, F.

    2007-01-15

    A comparative study of the structure of free-standing parallel bundles of single-wall carbon nanotubes (SWCNTs), multiwalled carbon nanotubes (MWCNTs), and highly oriented pyrolytic graphite (HOPG) was achieved by means of transmission electron microscopy and electron energy loss spectroscopy analyses. In particular, the carbon K (1s) extended fine structure of SWCNTs is found to be characterized by an apparent contraction of the nearest neighbors distance. This contraction is interpreted here to originate from an asymmetric pair distribution function, mostly due to the high out-of-plane vibrational motion of the C atoms, as for the case of chemisorbed atoms on clean surfaces. In contrast, the MWCNTs did not exhibit any signature of such an anharmonic effect because of their more rigid structure. This indicates that the SWCNTs pair potential is significantly broader and its effect is much weaker than that experienced by the same C-C pair embedded in a multiwall nanotube.

  6. Expanding the SHOC2 Mutation Associated Phenotype of Noonan Syndrome with Loose Anagen Hair: Structural Brain Anomalies and Myelofibrosis

    PubMed Central

    Gripp, Karen W.; Zand, Dina J.; Demmer, Laurie; Anderson, Carol E.; Dobyns, William B.; Zackai, Elaine H.; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L.; Sol-Church, Katia

    2013-01-01

    Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4) (75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. PMID:23918763

  7. Genetic Structure and the Search for Genotype-Phenotype Relationships: An Example from Disequilibrium in the Apo B Gene Region

    PubMed Central

    Zerba, K. E.; Kessling, A. M.; Davignon, J.; Sing, C. F.

    1991-01-01

    We analyzed allelic associations (disequilibria) for four restriction fragment length polymorphisms (RFLPs) in the region of the 43-kb Apo B gene in a sample of 233 unrelated individuals from Montreal, Canada, sampled for health. This total sample (T) included 160 individuals of known French Canadian (FC) ancestry. We present a rigorous application of current methodology to these samples, including estimation of type II error probabilities and correlations between markers for estimates of disequilibria. We then consider the utility of these estimates of allelic disequilibria for the interpretation of genotype-phenotype relations. Significant deviations from Hardy-Weinberg equilibrium were not predicted by proximity to other markers in disequilibrium. We found significant quadri-allelic disequilibrium for two marker pairs despite absence of significant deviations from Hardy-Weinberg equilibrium for either marker or tri-allelic disequilibrium, respectively. Altogether these results underscore the complexity of the genotypic structure of the data. A combination of nonevolutionary factors, including sampling for health, small sample size and data exclusion due to methodological constraints of not successfully typing all members of the sample for every RFLP, is a likely explanation for this complexity. These types of factors are common to many RFLP studies. Patterns of composite di-allelic disequilibrium indicated that some RFLP allele pairs may have a longer shared evolutionary history than others and that disequilibrium is not predicted by distance between RFLPs. Type II error probabilities were generally much higher than those for type I errors. Correlations between marker pairs for disequilibria were generally not high. We show from a review of 14 published studies of association between the XbaI RFLP and variation in a total of 15 lipid traits that deviations from Hardy-Weinberg equilibrium can cause substantial differences in the estimation of variability

  8. Structural Equation Modelling of Multiple Facet Data: Extending Models for Multitrait-Multimethod Data

    ERIC Educational Resources Information Center

    Bechger, Timo M.; Maris, Gunter

    2004-01-01

    This paper is about the structural equation modelling of quantitative measures that are obtained from a multiple facet design. A facet is simply a set consisting of a finite number of elements. It is assumed that measures are obtained by combining each element of each facet. Methods and traits are two such facets, and a multitrait-multimethod…

  9. Multilevel Modeling of Two Cyclical Processes: Extending Differential Structural Equation Modeling to Nonlinear Coupled Systems

    ERIC Educational Resources Information Center

    Butner, Jonathan; Amazeen, Polemnia G.; Mulvey, Genna M.

    2005-01-01

    The authors present a dynamical multilevel model that captures changes over time in the bidirectional, potentially asymmetric influence of 2 cyclical processes. S. M. Boker and J. Graham's (1998) differential structural equation modeling approach was expanded to the case of a nonlinear coupled oscillator that is common in bimanual coordination…

  10. Evaluation of high temperature structural adhesives for extended service, phase 5

    NASA Technical Reports Server (NTRS)

    Hendricks, C. L.; Hill, S. G.; Hale, J. N.; Dumars, W. G.

    1987-01-01

    The evaluation of 3 experimental polymers from NASA-Langley and a commercially produced polymer from Mitsui Toatsu Chemicals as high temperature structural adhesives is presented. A polyphenylquinoxaline (PPQ), polyimide (STPI/LaRC-2), and a polyarylene ether (PAE-SO2) were evaluated as metal-to-metal adhesives. Lap shear, crack extension, and climbing drum peel specimens were fabricated from all three polymers and tested after thermal, combined thermal/humidity, and stressed hydraulic fluid (Skydrol) exposure. The fourth polymer, LARC-TPI was evaluated as an adhesive for titanium honeycomb sandwich structure. All three experimental polymers performed well as metal-to-metal adhesives from 219 K (-65 F) to 505 K (450 F), including humidity exposure. Structural adhesive strength was also maintained at 505 K for a minimum of 3000 hours. LaRC-TPI was evaluated as a high temperature (505 K) adhesive for titanium honeycomb sandwich structure. The LaRC-TPI bonding process development concentrated on improving the honeycomb core-to-skin bond. The most promising approach of those evaluated combined a LaRC-TPI polymer solution with a semi-crystalline LaRC-TPI powder for adhesive film fabrication and fillet formation.

  11. The CATH extended protein-family database: providing structural annotations for genome sequences.

    PubMed

    Pearl, Frances M G; Lee, David; Bray, James E; Buchan, Daniel W A; Shepherd, Adrian J; Orengo, Christine A

    2002-02-01

    An automatic sequence search and analysis protocol (DomainFinder) based on PSI-BLAST and IMPALA, and using conservative thresholds, has been developed for reliably integrating gene sequences from GenBank into their respective structural families within the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath_new). DomainFinder assigns a new gene sequence to a CATH homologous superfamily provided that PSI-BLAST identifies a clear relationship to at least one other Protein Data Bank sequence within that superfamily. This has resulted in an expansion of the CATH protein family database (CATH-PFDB v1.6) from 19,563 domain structures to 176,597 domain sequences. A further 50,000 putative homologous relationships can be identified using less stringent cut-offs and these relationships are maintained within neighbour tables in the CATH Oracle database, pending further evidence of their suggested evolutionary relationship. Analysis of the CATH-PFDB has shown that only 15% of the sequence families are close enough to a known structure for reliable homology modeling. IMPALA/PSI-BLAST profiles have been generated for each of the sequence families in the expanded CATH-PFDB and a web server has been provided so that new sequences may be scanned against the profile library and be assigned to a structure and homologous superfamily.

  12. Phenotypes in phylogeography: Species' traits, environmental variation, and vertebrate diversification.

    PubMed

    Zamudio, Kelly R; Bell, Rayna C; Mason, Nicholas A

    2016-07-19

    Almost 30 y ago, the field of intraspecific phylogeography laid the foundation for spatially explicit and genealogically informed studies of population divergence. With new methods and markers, the focus in phylogeography shifted to previously unrecognized geographic genetic variation, thus reducing the attention paid to phenotypic variation in those same diverging lineages. Although phenotypic differences among lineages once provided the main data for studies of evolutionary change, the mechanisms shaping phenotypic differentiation and their integration with intraspecific genetic structure have been underexplored in phylogeographic studies. However, phenotypes are targets of selection and play important roles in species performance, recognition, and diversification. Here, we focus on three questions. First, how can phenotypes elucidate mechanisms underlying concordant or idiosyncratic responses of vertebrate species evolving in shared landscapes? Second, what mechanisms underlie the concordance or discordance of phenotypic and phylogeographic differentiation? Third, how can phylogeography contribute to our understanding of functional phenotypic evolution? We demonstrate that the integration of phenotypic data extends the reach of phylogeography to explain the origin and maintenance of biodiversity. Finally, we stress the importance of natural history collections as sources of high-quality phenotypic data that span temporal and spatial axes. PMID:27432983

  13. Phenotypes in phylogeography: Species’ traits, environmental variation, and vertebrate diversification

    PubMed Central

    Bell, Rayna C.; Mason, Nicholas A.

    2016-01-01

    Almost 30 y ago, the field of intraspecific phylogeography laid the foundation for spatially explicit and genealogically informed studies of population divergence. With new methods and markers, the focus in phylogeography shifted to previously unrecognized geographic genetic variation, thus reducing the attention paid to phenotypic variation in those same diverging lineages. Although phenotypic differences among lineages once provided the main data for studies of evolutionary change, the mechanisms shaping phenotypic differentiation and their integration with intraspecific genetic structure have been underexplored in phylogeographic studies. However, phenotypes are targets of selection and play important roles in species performance, recognition, and diversification. Here, we focus on three questions. First, how can phenotypes elucidate mechanisms underlying concordant or idiosyncratic responses of vertebrate species evolving in shared landscapes? Second, what mechanisms underlie the concordance or discordance of phenotypic and phylogeographic differentiation? Third, how can phylogeography contribute to our understanding of functional phenotypic evolution? We demonstrate that the integration of phenotypic data extends the reach of phylogeography to explain the origin and maintenance of biodiversity. Finally, we stress the importance of natural history collections as sources of high-quality phenotypic data that span temporal and spatial axes. PMID:27432983

  14. EB1 regulates attachment of Ska1 with microtubules by forming extended structures on the microtubule lattice

    PubMed Central

    Thomas, Geethu E.; Bandopadhyay, K.; Sutradhar, Sabyasachi; Renjith, M. R.; Singh, Puja; Gireesh, K. K.; Simon, Steny; Badarudeen, Binshad; Gupta, Hindol; Banerjee, Manidipa; Paul, Raja; Mitra, J.; Manna, Tapas K.

    2016-01-01

    Kinetochore couples chromosome movement to dynamic microtubules, a process that is fundamental to mitosis in all eukaryotes but poorly understood. In vertebrates, spindle-kinetochore-associated (Ska1–3) protein complex plays an important role in this process. However, the proteins that stabilize Ska-mediated kinetochore-microtubule attachment remain unknown. Here we show that microtubule plus-end tracking protein EB1 facilitates Ska localization on microtubules in vertebrate cells. EB1 depletion results in a significant reduction of Ska1 recruitment onto microtubules and defects in mitotic chromosome alignment, which is also reflected in computational modelling. Biochemical experiments reveal that EB1 interacts with Ska1, facilitates Ska1-microtubule attachment and together stabilizes microtubules. Structural studies reveal that EB1 either with Ska1 or Ska complex forms extended structures on microtubule lattice. Results indicate that EB1 promotes Ska association with K-fibres and facilitates kinetochore-microtubule attachment. They also implicate that in vertebrates, chromosome coupling to dynamic microtubules could be mediated through EB1-Ska extended structures. PMID:27225956

  15. Nine new phosphorene polymorphs with non-honeycomb structures: a much extended family.

    PubMed

    Wu, Menghao; Fu, Huahua; Zhou, Ling; Yao, Kailun; Zeng, Xiao Cheng

    2015-05-13

    We predict a new class of monolayer phosphorus allotropes, namely, ε-P, ζ-P, η-P, and θ-P. Distinctly different from the monolayer α-P (black) and previously predicted β-P (Phys. Rev. Lett. 2014, 112, 176802), γ-P, and δ-P (Phys. Rev. Lett. 2014, 113, 046804) with buckled honeycomb lattice, the new allotropes are composed of P4 square or P5 pentagon units that favor tricoordination for P atoms. The new four polymorphs, together with five additional hybrid polymorphs, greatly enrich the phosphorene structures, and their stabilities are confirmed by first-principles calculations. In particular, the θ-P is shown to be equally stable as the α-P (black) and more stable than all previously reported phosphorene polymorphs. Prediction of nonvolatile ferroelastic switching and structural transformation among different polymorphs under strains points out their potential applications via strain engineering.

  16. Corrugated structure insertion for extending the SASE bandwidth up to 3% at the European XFEL

    NASA Astrophysics Data System (ADS)

    Zagorodnov, I.; Feng, G.; Limberg, T.

    2016-11-01

    The usage of x-ray free electron laser (XFEL) in femtosecond nanocrystallography involves sequential illumination of many small crystals of arbitrary orientation. Hence a wide radiation bandwidth will be useful in order to obtain and to index a larger number of Bragg peaks used for determination of the crystal orientation. Considering the baseline configuration of the European XFEL in Hamburg, and based on beam dynamics simulations, we demonstrate here that the usage of corrugated structures allows for a considerable increase in radiation bandwidth. Data collection with a 3% bandwidth, a few microjoule radiation pulse energy, a few femtosecond pulse duration, and a photon energy of 5.4 keV is possible. For this study we have developed an analytical modal representation of the short-range wake function of the flat corrugated structures for arbitrary offsets of the source and the witness particles.

  17. Nine new phosphorene polymorphs with non-honeycomb structures: a much extended family.

    PubMed

    Wu, Menghao; Fu, Huahua; Zhou, Ling; Yao, Kailun; Zeng, Xiao Cheng

    2015-05-13

    We predict a new class of monolayer phosphorus allotropes, namely, ε-P, ζ-P, η-P, and θ-P. Distinctly different from the monolayer α-P (black) and previously predicted β-P (Phys. Rev. Lett. 2014, 112, 176802), γ-P, and δ-P (Phys. Rev. Lett. 2014, 113, 046804) with buckled honeycomb lattice, the new allotropes are composed of P4 square or P5 pentagon units that favor tricoordination for P atoms. The new four polymorphs, together with five additional hybrid polymorphs, greatly enrich the phosphorene structures, and their stabilities are confirmed by first-principles calculations. In particular, the θ-P is shown to be equally stable as the α-P (black) and more stable than all previously reported phosphorene polymorphs. Prediction of nonvolatile ferroelastic switching and structural transformation among different polymorphs under strains points out their potential applications via strain engineering. PMID:25844524

  18. Extended surface for membrane association in Zika virus NS1 structure.

    PubMed

    Brown, W Clay; Akey, David L; Konwerski, Jamie R; Tarrasch, Jeffrey T; Skiniotis, Georgios; Kuhn, Richard J; Smith, Janet L

    2016-09-01

    The Zika virus, which has been implicated in an increase in neonatal microcephaly and Guillain-Barré syndrome, has spread rapidly through tropical regions of the world. The virulence protein NS1 functions in genome replication and host immune-system modulation. Here, we report the crystal structure of full-length Zika virus NS1, revealing an elongated hydrophobic surface for membrane association and a polar surface that varies substantially among flaviviruses. PMID:27455458

  19. An accurate, efficient algorithm for calculation of quantum transport in extended structures

    SciTech Connect

    Godin, T.J.; Haydock, R.

    1994-05-01

    In device structures with dimensions comparable to carrier inelastic scattering lengths, the quantum nature of carriers will cause interference effects that cannot be modeled by conventional techniques. The basic equations that govern these ``quantum`` circuit elements present significant numerical challenges. The authors describe the block recursion method, an accurate, efficient method for solving the quantum circuit problem. They demonstrate this method by modeling dirty inversion layers.

  20. Surface structure of an invariant manifold of a Halo Orbit (extended abstract)

    NASA Technical Reports Server (NTRS)

    Hirani, Anil N.; Lo, Martin W.

    2005-01-01

    We extract the surface structure of the unstable invariant manifold tube projected into position space, of a halo orbit near L2. We do this by using transversal planes to intersect trajectories that approximate the tube. From these intersection points we construct spline-interpolated cross section curves which give a good idea of the structure of the tube. For example, we show that, for the value of (mu) we use, the tube pinches, develops a self-intersection, develops loop-inside-tube structure, pinches some more, and so on. We also construct surfaces made of quadrilaterals and triangles from these cross-sections. The transversal planes are obtained by taking planes orthogonal to a curve that follows the general shape of the tube. One such curve we use, is the unstable invariant manifold of the equilibrium point L2 itself. In another example, we take a circle that follows the tube, as the curve for finding planes transversal to the tube. Our method is complementary to the method of taking cross-sections of constant time (the isochronous method), as used by some other researchers. The isochronous method is good at revealing the temporal structure of trajectories on a tube. However, due to the unequal speeds of different trajectories, it is harder to use for long length surface extraction. In contrast, using our method, we show cross-sections of the tube through an angular extent of nearly (pi) during which the tube becomes extremely convoluted. We also show that tubes of different energies, that start out in certain ordering, do not obey the ordering after a while. Our work is motivated by applications to space mission design.

  1. Extended surface for membrane association in Zika virus NS1 structure.

    PubMed

    Brown, W Clay; Akey, David L; Konwerski, Jamie R; Tarrasch, Jeffrey T; Skiniotis, Georgios; Kuhn, Richard J; Smith, Janet L

    2016-09-01

    The Zika virus, which has been implicated in an increase in neonatal microcephaly and Guillain-Barré syndrome, has spread rapidly through tropical regions of the world. The virulence protein NS1 functions in genome replication and host immune-system modulation. Here, we report the crystal structure of full-length Zika virus NS1, revealing an elongated hydrophobic surface for membrane association and a polar surface that varies substantially among flaviviruses.

  2. Extended Functional Groups (EFG): An Efficient Set for Chemical Characterization and Structure-Activity Relationship Studies of Chemical Compounds.

    PubMed

    Salmina, Elena S; Haider, Norbert; Tetko, Igor V

    2015-01-01

    The article describes a classification system termed "extended functional groups" (EFG), which are an extension of a set previously used by the CheckMol software, that covers in addition heterocyclic compound classes and periodic table groups. The functional groups are defined as SMARTS patterns and are available as part of the ToxAlerts tool (http://ochem.eu/alerts) of the On-line CHEmical database and Modeling (OCHEM) environment platform. The article describes the motivation and the main ideas behind this extension and demonstrates that EFG can be efficiently used to develop and interpret structure-activity relationship models. PMID:26703557

  3. Structural Studies of Amphiphilic 4-Helix Bundle Peptides Incorporating Designed Extended Chromophores for Nonlinear Optical Biomolecular Materials

    SciTech Connect

    Strzalka,J.; Xu, T.; Tronin, A.; Wu, S.; Miloradovic, I.; Kuzmenko, I.; Gog, T.; Therien, M.; Blasie, K.

    2006-01-01

    Extended conjugated chromophores containing (porphinato)zinc components that exhibit large optical polarizabilities and hyperpolarizabiliites are incorporated into amphiphilic 4-helix bundle peptides via specific axial histidyl ligation of the metal. The bundle's designed amphiphilicity enables vectorial orientation of the chromophore/peptide complex in macroscopic monolayer ensembles. The 4-helix bundle structure is maintained upon incorporation of two different chromophores at stoichiometries of 1-2 per bundle. The axial ligation site appears to effectively control the position of the chromophore along the length of the bundle.

  4. Correction method for the self-absorption effects in fluorescence extended X-ray absorption fine structure on multilayer samples.

    PubMed

    Li, Wen Bin; Yang, Xiao Yue; Zhu, Jing Tao; Tu, Yu Chun; Mu, Bao Zhong; Yu, Hai Sheng; Wei, Xiang Jun; Huang, Yu Ying; Wang, Zhan Shan

    2014-05-01

    A novel correction method for self-absorption effects is proposed for extended X-ray absorption fine structure (EXAFS) detected in the fluorescence mode on multilayer samples. The effects of refraction and multiple reflection at the interfaces are fully considered in this correction method. The correction is performed in k-space before any further data analysis, and it can be applied to single-layer or multilayer samples with flat surfaces and without thickness limit when the model parameters for the samples are known. The validity of this method is verified by the fluorescence EXAFS data collected for a Cr/C multilayer sample measured at different experimental geometries. PMID:24763646

  5. Exciton Localization in Extended π-Electron Systems: Comparison of Linear and Cyclic Structures.

    PubMed

    Thiessen, Alexander; Würsch, Dominik; Jester, Stefan-S; Aggarwal, A Vikas; Idelson, Alissa; Bange, Sebastian; Vogelsang, Jan; Höger, Sigurd; Lupton, John M

    2015-07-30

    We employ five π-conjugated model materials of different molecular shape-oligomers and cyclic structures-to investigate the extent of exciton self-trapping and torsional motion of the molecular framework following optical excitation. Our studies combine steady state and transient fluorescence spectroscopy in the ensemble with measurements of polarization anisotropy on single molecules, supported by Monte Carlo simulations. The dimer exhibits a significant spectral red shift within ∼100 ps after photoexcitation which is attributed to torsional relaxation. This relaxation mechanism is inhibited in the structurally rigid macrocyclic analogue. However, both systems show a high degree of exciton localization but with very different consequences: while, in the macrocycle, the exciton localizes randomly on different parts of the ring, scrambling polarization memory, in the dimer, localization leads to a deterministic exciton position with luminescence characteristics of a dipole. Monte Carlo simulations allow us to quantify the structural difference between the emitting and absorbing units of the π-conjugated system in terms of disorder parameters.

  6. Crystal Structures of Lys-63-linked tri- and di-ubiquitin Reveal a Highly Extended Chain Architecture

    SciTech Connect

    Weeks, S.; Grasty, K; Hernandez-Cuebas, L; Loll, P

    2009-01-01

    The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linked chains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 {angstrom}, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handed helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of {approx}110 {angstrom}. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.

  7. Quantifying seascape structure: Extending terrestrial spatial pattern metrics to the marine realm

    USGS Publications Warehouse

    Wedding, L.M.; Christopher, L.A.; Pittman, S.J.; Friedlander, A.M.; Jorgensen, S.

    2011-01-01

    Spatial pattern metrics have routinely been applied to characterize and quantify structural features of terrestrial landscapes and have demonstrated great utility in landscape ecology and conservation planning. The important role of spatial structure in ecology and management is now commonly recognized, and recent advances in marine remote sensing technology have facilitated the application of spatial pattern metrics to the marine environment. However, it is not yet clear whether concepts, metrics, and statistical techniques developed for terrestrial ecosystems are relevant for marine species and seascapes. To address this gap in our knowledge, we reviewed, synthesized, and evaluated the utility and application of spatial pattern metrics in the marine science literature over the past 30 yr (1980 to 2010). In total, 23 studies characterized seascape structure, of which 17 quantified spatial patterns using a 2-dimensional patch-mosaic model and 5 used a continuously varying 3-dimensional surface model. Most seascape studies followed terrestrial-based studies in their search for ecological patterns and applied or modified existing metrics. Only 1 truly unique metric was found (hydrodynamic aperture applied to Pacific atolls). While there are still relatively few studies using spatial pattern metrics in the marine environment, they have suffered from similar misuse as reported for terrestrial studies, such as the lack of a priori considerations or the problem of collinearity between metrics. Spatial pattern metrics offer great potential for ecological research and environmental management in marine systems, and future studies should focus on (1) the dynamic boundary between the land and sea; (2) quantifying 3-dimensional spatial patterns; and (3) assessing and monitoring seascape change. ?? Inter-Research 2011.

  8. ß-ureidopropionase deficiency: phenotype, genotype and protein structural consequences in 16 patients.

    PubMed

    van Kuilenburg, André B P; Dobritzsch, Doreen; Meijer, Judith; Krumpel, Michael; Selim, Laila A; Rashed, Mohamed S; Assmann, Birgit; Meinsma, Rutger; Lohkamp, Bernhard; Ito, Tetsuya; Abeling, Nico G G M; Saito, Kayoko; Eto, Kaoru; Smitka, Martin; Engvall, Martin; Zhang, Chunhua; Xu, Wang; Zoetekouw, Lida; Hennekam, Raoul C M

    2012-07-01

    ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyzes the conversion of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid, ammonia and CO(2). To date, only five genetically confirmed patients with a complete ß-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 11 newly identified ß-ureidopropionase deficient patients as well as the analysis of the mutations in a three-dimensional framework. Patients presented mainly with neurological abnormalities (intellectual disabilities, seizures, abnormal tonus regulation, microcephaly, and malformations on neuro-imaging) and markedly elevated levels of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid in urine and plasma. Analysis of UPB1, encoding ß-ureidopropionase, showed 6 novel missense mutations and one novel splice-site mutation. Heterologous expression of the 6 mutant enzymes in Escherichia coli showed that all mutations yielded mutant ß-ureidopropionase proteins with significantly decreased activity. Analysis of a homology model of human ß-ureidopropionase generated using the crystal structure of the enzyme from Drosophila melanogaster indicated that the point mutations p.G235R, p.R236W and p.S264R lead to amino acid exchanges in the active site and therefore affect substrate binding and catalysis. The mutations L13S, R326Q and T359M resulted most likely in folding defects and oligomer assembly impairment. Two mutations were identified in several unrelated ß-ureidopropionase patients, indicating that ß-ureidopropionase deficiency may be more common than anticipated.

  9. Ligand effects on the structures of extended networks of dicyanamide-containing transition-metal ions.

    PubMed

    Armentano, Donatella; De Munno, Giovanni; Guerra, Francesca; Julve, Miguel; Lloret, Francesc

    2006-06-12

    The structural characterization of a series of complexes of formula [M(dca)2L]n, where dca = dicyanamide, L = 1,10-phenanthroline (phen) [1-4] and 2,9-dimethylphenanthroline (2,9-dmphen) [9-12], and M = Mn (1 and 9), Fe (2 and 10), Co (3 and 11), and Ni (4 and 12), has revealed the effect of the presence of the methyl substituents of L on the resulting network. The structure of [Mn(dca)2(phen)]n (1), which is identical to those of 2-4, together with the investigation of its magnetic properties in the temperature range of 77-300 K were reported elsewhere. The use of the 4,7-dimethylphenanthroline (4,7-dmphen) as the co-ligand yielded a series of compounds of formula [M(dca)2(4,7-dmphen)]n [M = Mn (5), Fe (6), Co (7), and Ni (8)], which are isostructural with 1-4. Compounds containing phen (1-4) and 4,7-dmphen (5-8) are made of two-dimensional grids of metal atoms, each metal atom being linked to three other metal centers through single (three metal atoms involved) and double (two metal atoms involved) dca bridges exhibiting the mu-1,5 coordination mode. The isostructural complexes [M(dca)2(2,9-dmphen)]n (9-12) also have a sheetlike structure, the metal atoms in each layer being linked by two single and one double mu-1,5-dca units, as in 1-8. However, the topology of the network in 9-12 is different from that in 1-8 because of the different arrangement of the two single mu-1,5 dca bridges: cis in 1-8 versus trans in 9-12. The magnetic study of compounds 1-12 in the temperature range of 1.9-290 K has revealed the occurrence of weak ferromagnetic (M = Ni) and antiferromagnetic interactions (M = Mn, Fe, and Co). The different magnetic behavior in 1-12 was analyzed in the light of their structures, and the values of the magnetic interactions were compared to those of related systems.

  10. Phenotypic and molecular characterization of CTX-M-14 extended-spectrum β-lactamase and plasmid-mediated ACT-like AmpC β-lactamase produced by Klebsiella pneumoniae isolates from chickens in Henan Province, China.

    PubMed

    Wu, H; Liu, B-G; Liu, J-H; Pan, Y-S; Yuan, L; Hu, G-Z

    2012-01-01

    Extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases produced by a clinical isolate of Klebsiella pneumoniae from chickens were detected with confirmatory phenotypic tests of the Clinical and Laboratory Standards Institute. The minimum inhibitory concentrations of 18 antibacterial drugs against K. pneumoniae were determined by the 2-fold microdilution method. The genotype and subtype of the ESBL-producing and AmpC β-lactamase-producing K. pneumoniae isolate were identified by PCR amplification of the enzyme-encoding genes followed by DNA sequencing analysis. K. pneumoniae K(1) isolate was an ESBL-producing and AmpC β-lactamase-producing bacteria with high resistance to β-lactam antibiotics, such as penicillins, third-generation cephalosporins, fluoroquinolones, and aminoglycosides. The sequence analysis showed that K. pneumoniae K(1) harbored TEM-type, SHV-type, CTX-M-type, and ACT-type AmpC β-lactamase nucleotide sequences. The TEM-type sequence was designated as TEM-1; the SHV-type sequence was designated as SHV-11; the CTX-M-type sequence was designated as CTX-M-14. Compared with the ACT-like sequence (EF078894), the ACT-type sequence was characterized by 8 nucleotide mutations (A(75)G, C(84)G, T(90)C, A(105)G, G(213)A, G(246)A, C(309)T, and T(315)C). Only one mutation at position 75 led to an amino acid substitution (Asn28Lys). The bla(ACT) type was an ACT-like derivative. PMID:23079829

  11. An extended diffraction tomography method for quantifying structural damage using numerical Green's functions.

    PubMed

    Chan, Eugene; Rose, L R Francis; Wang, Chun H

    2015-05-01

    Existing damage imaging algorithms for detecting and quantifying structural defects, particularly those based on diffraction tomography, assume far-field conditions for the scattered field data. This paper presents a major extension of diffraction tomography that can overcome this limitation and utilises a near-field multi-static data matrix as the input data. This new algorithm, which employs numerical solutions of the dynamic Green's functions, makes it possible to quantitatively image laminar damage even in complex structures for which the dynamic Green's functions are not available analytically. To validate this new method, the numerical Green's functions and the multi-static data matrix for laminar damage in flat and stiffened isotropic plates are first determined using finite element models. Next, these results are time-gated to remove boundary reflections, followed by discrete Fourier transform to obtain the amplitude and phase information for both the baseline (damage-free) and the scattered wave fields. Using these computationally generated results and experimental verification, it is shown that the new imaging algorithm is capable of accurately determining the damage geometry, size and severity for a variety of damage sizes and shapes, including multi-site damage. Some aspects of minimal sensors requirement pertinent to image quality and practical implementation are also briefly discussed. PMID:25661053

  12. Structure and biosynthesis of the marine streptomycete ansamycin ansalactam A and its distinctive branched chain polyketide extender unit.

    PubMed

    Wilson, Micheal C; Nam, Sang-Jip; Gulder, Tobias A M; Kauffman, Christopher A; Jensen, Paul R; Fenical, William; Moore, Bradley S

    2011-02-16

    Reported is the structure and biosynthesis of ansalactam A, an ansamycin class polyketide produced by an unusual modification of the polyketide pathway. This new metabolite, produced by a marine sediment-derived bacterium of the genus Streptomyces , possesses a novel spiro γ-lactam moiety and a distinctive isobutyryl polyketide fragment observed for the first time in this class of natural products. The structure of ansalactam A was defined by spectroscopic methods including X-ray crystallographic analysis. Biosynthetic studies with stable isotopes further led to the discovery of a new, branched chain polyketide synthase extender unit derived from (E)-4-methyl-2-pentenoic acid for polyketide assembly observed for the first time in this class of natural products.

  13. OpenMx 2.0: Extended Structural Equation and Statistical Modeling.

    PubMed

    Neale, Michael C; Hunter, Michael D; Pritikin, Joshua N; Zahery, Mahsa; Brick, Timothy R; Kirkpatrick, Robert M; Estabrook, Ryne; Bates, Timothy C; Maes, Hermine H; Boker, Steven M

    2016-06-01

    The new software package OpenMx 2.0 for structural equation and other statistical modeling is introduced and its features are described. OpenMx is evolving in a modular direction and now allows a mix-and-match computational approach that separates model expectations from fit functions and optimizers. Major backend architectural improvements include a move to swappable open-source optimizers such as the newly written CSOLNP. Entire new methodologies such as item factor analysis and state space modeling have been implemented. New model expectation functions including support for the expression of models in LISREL syntax and a simplified multigroup expectation function are available. Ease-of-use improvements include helper functions to standardize model parameters and compute their Jacobian-based standard errors, access to model components through standard R $ mechanisms, and improved tab completion from within the R Graphical User Interface. PMID:25622929

  14. A framework for performance measurement in university using extended network data envelopment analysis (DEA) structures

    NASA Astrophysics Data System (ADS)

    Kashim, Rosmaini; Kasim, Maznah Mat; Rahman, Rosshairy Abd

    2015-12-01

    Measuring university performance is essential for efficient allocation and utilization of educational resources. In most of the previous studies, performance measurement in universities emphasized the operational efficiency and resource utilization without investigating the university's ability to fulfill the needs of its stakeholders and society. Therefore, assessment of the performance of university should be separated into two stages namely efficiency and effectiveness. In conventional DEA analysis, a decision making unit (DMU) or in this context, a university is generally treated as a black-box which ignores the operation and interdependence of the internal processes. When this happens, the results obtained would be misleading. Thus, this paper suggest an alternative framework for measuring the overall performance of a university by incorporating both efficiency and effectiveness and applies network DEA model. The network DEA models are recommended because this approach takes into account the interrelationship between the processes of efficiency and effectiveness in the system. This framework also focuses on the university structure which is expanded from the hierarchical to form a series of horizontal relationship between subordinate units by assuming both intermediate unit and its subordinate units can generate output(s). Three conceptual models are proposed to evaluate the performance of a university. An efficiency model is developed at the first stage by using hierarchical network model. It is followed by an effectiveness model which take output(s) from the hierarchical structure at the first stage as a input(s) at the second stage. As a result, a new overall performance model is proposed by combining both efficiency and effectiveness models. Thus, once this overall model is realized and utilized, the university's top management can determine the overall performance of each unit more accurately and systematically. Besides that, the result from the network

  15. Refinement of the nickel site structure in Desulfovibrio gigas hydrogenase using range-extended EXAFS spectroscopy.

    PubMed

    Gu, Weiwei; Jacquamet, L; Patil, D S; Wang, H X; Evans, D J; Smith, M C; Millar, M; Koch, S; Eichhorn, D M; Latimer, M; Cramer, S P

    2003-01-01

    We have reexamined the Ni EXAFS of oxidized, inactive (as-isolated) and H(2) reduced Desulfovibrio gigas hydrogenase. Better spatial resolution was achieved by analyzing the data over a 50% wider k-range than was previously available. A lower k(min) was obtained using the FEFF code for phase shifts and amplitudes. A higher k(max) was obtained by removing an interfering Cu signal from the raw spectra using multiple energy fluorescence detection. The larger k-range allowed us to better resolve the Ni-S bond lengths and to define more accurately the Ni-O and Ni-Fe bond lengths. We find that as-isolated, hydrogenase has two Ni-S bonds at approximately 2.2 A, but also 1-2 Ni-S bonds in the 2.35+/-0.05 A range. A Ni-O interaction is evident at 1.91 A. The as-isolated Ni-Fe distance cannot be unambiguously determined. Upon H(2) reduction, two short Ni-S bonds persist at approximately 2.2 A, but the remaining Ni-S bonds lengthen to 2.47+/-0.05 A. Good simulations are obtained with a Ni-Fe distance at 2.52 A, in agreement with crystal structures of the reduced enzyme. Although not evident in the crystal structures, an improvement in the fit is obtained by inclusion of one Ni-O interaction at 2.03 A. Implications of these distances for the spin-state of H(2) reduced H(2)ase are discussed. PMID:12538051

  16. Phenotype characterization of embryoid body structures generated by a crystal comet effect tail in an intercellular cancer collision scenario

    PubMed Central

    Diaz, Jairo A; Murillo, Mauricio F

    2012-01-01

    Cancer is, by definition, the uncontrolled growth of autonomous cells that eventually destroy adjacent tissues and generate architectural disorder. However, this concept cannot be totally true. In three well documented studies, we have demonstrated that cancer tissues produce order zones that evolve over time and generate embryoid body structures in a space-time interval. The authors decided to revise the macroscopic and microscopic material in well-developed malignant tumors in which embryoid bodies were identified to determine the phenotype characterization that serves as a guideline for easy recognition. The factors responsible for this morphogenesis are physical, bioelectric, and magnetic susceptibilities produced by crystals that act as molecular designers for the topographic gradients that guide the surrounding silhouette and establish tissue head-tail positional identities. The structures are located in amniotic-like cavities and show characteristic somite-like embryologic segmentation. Immunophenotypic study has demonstrated exclusion factor positional identity in relation to enolase-immunopositive expression of embryoid body and human chorionic gonadotropin immunopositivity exclusion factor expression in the surrounding tissues. The significance of these observations is that they can also be predicted by experimental image data collected by the Large Hadron Collider (LHC) accelerator at the European Organization for Nuclear Research, in which two-beam subatomic collision particles in the resulting debris show hyperorder domains similar to those identified by us in intercellular cancer collisions. Our findings suggest that we are dealing with true reverse biologic system information in an activated collective cancer stem cell memory, in which physics participates in the elaboration of geometric complexes and chiral biomolecules that serve to build bodies with embryoid print as it develops during gestation. Reversal mechanisms in biology are intimately

  17. Sub-ångstrom experimental validation of molecular dynamics for predictive modeling of extended defect structures in Si.

    PubMed

    Dudeck, K J; Marqués, L A; Knights, A P; Gwilliam, R M; Botton, G A

    2013-04-19

    In this Letter we present the detailed, quantitative comparison between experimentally and theoretically derived structures of the extended {311} defect in silicon. Agreement between experimental and theoretical column positions of better than ±0.05 nm has been achieved for all 100 atomic columns in the defect structure. This represents a calculated density of 5.5×10(14) silicon interstitials per cm(2) on {311} planes, in agreement with previous work [S. Takeda, Jpn. J. Appl. Phys., Part 2, 30, L639 (1991)]. We show that although the {311} defect is made up of five-, six-, seven-, and eight-member rings, the shape of these rings varies as a function of position along the defect, and these variations can be determined experimentally with high precision and accuracy. The excellent agreement between the calculated and experimentally derived structure, including the position of atomic columns and the shape of the distinct structural units of the defect, provides strong evidence for the quality and robustness of the molecular dynamics simulation approach for structural studies of defects. The experimental approach is straightforward, without the need for complicated image processing methods, and is therefore widely applicable.

  18. Peculiarities of extended defect system in III-nitrides with different degrees of order of mosaic structure

    NASA Astrophysics Data System (ADS)

    Ankudinov, A. V.; Besyulkin, A. I.; Kolmakov, A. G.; Lundin, W. V.; Ratnikov, V. V.; Shmidt, N. M.; Sitnikova, A. A.; Titkov, A. N.; Usikov, A. S.; Yakimov, E. B.; Zavarin, E. E.; Zolotareva, R. V.

    2003-12-01

    Extended defect system (EDS), which included the threading dislocations and the mosaic structure in GaN epilayers grown on (0 0 0 1) sapphire substrates by MOCVD, has been investigated by transmission electron microscopy and atomic force microscopy. Strain relaxation of EDS with different degrees of order of mosaic structure (DOMS, Δ) has been found to distinguish noticeably. For EDS with poor DOMS (Δ⩾0.34), a 3D-growth with a formation of large agglomerates of the mosaic structure domains in the regions near the threading (screw) dislocations has occurred. Numerous domain dislocation boundaries in these structures have been observed. Coherent concordance of domains with the formation of the dilatation boundaries was more typical of EDS with the better DOMS (Δ<0.34). Moreover, 2D-growth with the formation of additional growth steps with participation of screw dislocations has been observed. The optical and electrical properties of GaN epilayers correlate well with these structural peculiarities.

  19. The Star Formation History and Extended Structure of the Hercules Milky Way Satellite

    NASA Astrophysics Data System (ADS)

    Sand, David J.; Olszewski, Edward W.; Willman, Beth; Zaritsky, Dennis; Seth, Anil; Harris, Jason; Piatek, Slawomir; Saha, Abi

    2009-10-01

    We present imaging of the recently discovered Hercules Milky Way satellite and its surrounding regions to study its structure, star formation history and to thoroughly search for signs of disruption. We robustly determine the distance, luminosity, size, and morphology of Hercules utilizing a bootstrap approach to characterize our uncertainties. We derive a distance to Hercules via a comparison to empirical and theoretical isochrones, finding a best match with the isochrone of M92, which yields a distance of 133 ± 6 kpc. As previous studies have found, Hercules is very elongated, with epsilon = 0.67 ± 0.03 and a half-light radius of rh sime 230 pc. Using the color-magnitude-fitting package StarFISH, we determine that Hercules is old (>12 Gyr) and metal-poor ([Fe/H] ~ -2.0), with a spread in metallicity, in agreement with previous spectroscopic work. This result is robust with respect to slight variations in the distance to Hercules and mismatches between the observed Hercules color-magnitude diagram and theoretical isochrones. We infer a total absolute magnitude of MV = -6.2 ± 0.4. Our innovative search for external Hercules structure both in the plane of the sky and along the line of sight yields some evidence that Hercules is embedded in a larger stream of stars. A clear stellar extension is seen to the northwest with several additional candidate stellar overdensities along the position angle of Hercules out to ~35' (~1.3 kpc). While the association of any of the individual stellar overdensities with Hercules is difficult to determine, we do show that the summed color-magnitude diagram of all three is consistent with Hercules' stellar population. Finally, we estimate that any change in the distance to Hercules across its face is at most ~6 kpc, and the data are consistent with Hercules being at the same distance throughout. Based on data acquired using the Large Binocular Telescope (LBT). The LBT is an international collaboration among institutions in the US

  20. Extended tracking of the microbial community structure and dynamics in an industrial synthetic metalworking fluid system.

    PubMed

    Kapoor, Renuka; Selvaraju, Suresh B; Yadav, Jagjit S

    2014-03-01

    Understanding of the occupational exposure risk scenario and disease etiology associated with industrial metalworking fluids (MWFs) requires knowledge of the development and composition of their microbial diversity in relation to the underlying fluid management factors. In this study, a managed synthetic MWF operation freshly recharged following the dumping, cleaning, and recharge (DCR) process was tracked in real time for microbial community changes over a period of 1.25 years (65 weeks). The recharged fluid developed very high bacterial counts (viable and nonviable) fairly quickly after the DCR process, indicating its inadequacy. Genus-/group-specific real-time qPCR confirmed the prevalence of six potentially pathogenic/immunogenic microbial genera/groups, viz. pseudomonads, enterics, mycobacteria, legionellae, actinomycetes, and fungi. Selective culturing revealed Acinetobacter and Bacillus as the most frequently isolated Gram-negative and Gram-positive genera, respectively, in addition to the presence of fungi and actinomycetes. Endotoxin perturbations (< 1000 to > 100000 EU mL⁻¹) coincided with temporal increases in Gram-negative bacteria and/or periodic biocide additions. PCR-DGGE-sequencing revealed an expanded estimated bacterial richness (up to 23 bands per sample). Of the 16 dominant bacterial phylotypes identified, the majority were detected for the first time in MWF. Interestingly, the study revealed a crucial role for MWF brand, among other fluid factors, in modulating the community structure and dynamics. PMID:24256434

  1. Associative Account of Self-Cognition: Extended Forward Model and Multi-Layer Structure

    PubMed Central

    Sugiura, Motoaki

    2013-01-01

    The neural correlates of “self” identified by neuroimaging studies differ depending on which aspects of self are addressed. Here, three categories of self are proposed based on neuroimaging findings and an evaluation of the likely underlying cognitive processes. The physical self, representing self-agency of action, body-ownership, and bodily self-recognition, is supported by the sensory and motor association cortices located primarily in the right hemisphere. The interpersonal self, representing the attention or intentions of others directed at the self, is supported by several amodal association cortices in the dorsomedial frontal and lateral posterior cortices. The social self, representing the self as a collection of context-dependent social-values, is supported by the ventral aspect of the medial prefrontal cortex and the posterior cingulate cortex. Despite differences in the underlying cognitive processes and neural substrates, all three categories of self are likely to share the computational characteristics of the forward model, which is underpinned by internal schema or learned associations between one’s behavioral output and the consequential input. Additionally, these three categories exist within a hierarchical layer structure based on developmental processes that updates the schema through the attribution of prediction error. In this account, most of the association cortices critically contribute to some aspect of the self through associative learning while the primary regions involved shift from the lateral to the medial cortices in a sequence from the physical to the interpersonal to the social self. PMID:24009578

  2. Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed "in vivo".

    PubMed

    Hirt, Christian; Papadimitropoulos, Adam; Muraro, Manuele G; Mele, Valentina; Panopoulos, Evangelos; Cremonesi, Eleonora; Ivanek, Robert; Schultz-Thater, Elke; Droeser, Raoul A; Mengus, Chantal; Heberer, Michael; Oertli, Daniel; Iezzi, Giandomenica; Zajac, Paul; Eppenberger-Castori, Serenella; Tornillo, Luigi; Terracciano, Luigi; Martin, Ivan; Spagnoli, Giulio C

    2015-09-01

    Anticancer compound screening on 2D cell cultures poorly predicts "in vivo" performance, while conventional 3D culture systems are usually characterized by limited cell proliferation, failing to produce tissue-like-structures (TLS) suitable for drug testing. We addressed engineering of TLS by culturing cancer cells in porous scaffolds under perfusion flow. Colorectal cancer (CRC) HT-29 cells were cultured in 2D, on collagen sponges in static conditions or in perfused bioreactors, or injected subcutaneously in immunodeficient mice. Perfused 3D (p3D) cultures resulted in significantly higher (p < 0.0001) cell proliferation than static 3D (s3D) cultures and yielded more homogeneous TLS, with morphology and phenotypes similar to xenografts. Transcriptome analysis revealed a high correlation between xenografts and p3D cultures, particularly for gene clusters regulating apoptotic processes and response to hypoxia. Treatment with 5-Fluorouracil (5-FU), a frequently used but often clinically ineffective chemotherapy drug, induced apoptosis, down-regulation of anti-apoptotic genes (BCL-2, TRAF1, and c-FLIP) and decreased cell numbers in 2D, but only "nucleolar stress" in p3D and xenografts. Conversely, BCL-2 inhibitor ABT-199 induced cytotoxic effects in p3D but not in 2D cultures. Our findings advocate the importance of perfusion flow in 3D cultures of tumor cells to efficiently mimic functional features observed "in vivo" and to test anticancer compounds. PMID:26051518

  3. Amine-containing molecules and the induction of an expanded lysosomal volume phenotype: a structure-activity relationship study.

    PubMed

    Logan, Randall; Kong, Alex C; Axcell, Erick; Krise, Jeffrey P

    2014-05-01

    Many weakly basic amine-containing compounds have a strong propensity to become highly concentrated in lysosomes by virtue of an ion-trapping-type mechanism; the substrates for this are referred to as lysosomotropic. We have previously shown that many lysosomotropic drugs can produce a significant expansion in the apparent volume of lysosomes, which can ultimately result in an intracellular distribution-based drug-drug interaction. In this study, we have systematically evaluated the physicochemical and structural features of weakly basic molecules that correlate with their ability to induce an expanded lysosomal volume phenotype (ELVP) in cultured human fibroblasts. By quantitatively evaluating the cellular accumulation of Lysotracker Red, a fluorescent lysosomotropic probe, the volume of the lysosomal compartment was determined. We specifically explored the influence that lysosomotropism, molecular size, and amphiphilicity had on a molecule's ability to induce an ELVP. The capacity of these molecules to intercalation into biological membranes was also evaluated using a red blood cell hemolysis assay. The present results suggest that a molecule's potency in eliciting an ELVP is influenced by lysosomotropism, amphiphilicity, and its ability to intercalate into biological membranes. Despite being highly lysosomotropic, low-molecular-weight, nonaromatic amines failed to cause an ELVP at all concentrations evaluated.

  4. High structural resolution hydroxyl radical protein footprinting reveals an extended Robo1-heparin binding interface.

    PubMed

    Li, Zixuan; Moniz, Heather; Wang, Shuo; Ramiah, Annapoorani; Zhang, Fuming; Moremen, Kelley W; Linhardt, Robert J; Sharp, Joshua S

    2015-04-24

    Interaction of transmembrane receptors of the Robo family and the secreted protein Slit provides important signals in the development of the central nervous system and regulation of axonal midline crossing. Heparan sulfate, a sulfated linear polysaccharide modified in a complex variety of ways, serves as an essential co-receptor in Slit-Robo signaling. Previous studies have shown that closely related heparin octasaccharides bind to Drosophila Robo directly, and surface plasmon resonance analysis revealed that Robo1 binds more tightly to full-length unfractionated heparin. For the first time, we utilized electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting to identify two separate binding sites for heparin interaction with Robo1: one binding site at the previously identified site for heparin dp8 and a second binding site at the N terminus of Robo1 that is disordered in the x-ray crystal structure. Mutagenesis of the identified N-terminal binding site exhibited a decrease in binding affinity as measured by surface plasmon resonance and heparin affinity chromatography. Footprinting also indicated that heparin binding induces a minor change in the conformation and/or dynamics of the Ig2 domain, but no major conformational changes were detected. These results indicate a second low affinity binding site in the Robo-Slit complex as well as suggesting the role of the Ig2 domain of Robo1 in heparin-mediated signal transduction. This study also marks the first use of electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting, which shows great utility for the characterization of protein-carbohydrate complexes. PMID:25752613

  5. High Structural Resolution Hydroxyl Radical Protein Footprinting Reveals an Extended Robo1-Heparin Binding Interface*

    PubMed Central

    Li, Zixuan; Moniz, Heather; Wang, Shuo; Ramiah, Annapoorani; Zhang, Fuming; Moremen, Kelley W.; Linhardt, Robert J.; Sharp, Joshua S.

    2015-01-01

    Interaction of transmembrane receptors of the Robo family and the secreted protein Slit provides important signals in the development of the central nervous system and regulation of axonal midline crossing. Heparan sulfate, a sulfated linear polysaccharide modified in a complex variety of ways, serves as an essential co-receptor in Slit-Robo signaling. Previous studies have shown that closely related heparin octasaccharides bind to Drosophila Robo directly, and surface plasmon resonance analysis revealed that Robo1 binds more tightly to full-length unfractionated heparin. For the first time, we utilized electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting to identify two separate binding sites for heparin interaction with Robo1: one binding site at the previously identified site for heparin dp8 and a second binding site at the N terminus of Robo1 that is disordered in the x-ray crystal structure. Mutagenesis of the identified N-terminal binding site exhibited a decrease in binding affinity as measured by surface plasmon resonance and heparin affinity chromatography. Footprinting also indicated that heparin binding induces a minor change in the conformation and/or dynamics of the Ig2 domain, but no major conformational changes were detected. These results indicate a second low affinity binding site in the Robo-Slit complex as well as suggesting the role of the Ig2 domain of Robo1 in heparin-mediated signal transduction. This study also marks the first use of electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting, which shows great utility for the characterization of protein-carbohydrate complexes. PMID:25752613

  6. High structural resolution hydroxyl radical protein footprinting reveals an extended Robo1-heparin binding interface.

    PubMed

    Li, Zixuan; Moniz, Heather; Wang, Shuo; Ramiah, Annapoorani; Zhang, Fuming; Moremen, Kelley W; Linhardt, Robert J; Sharp, Joshua S

    2015-04-24

    Interaction of transmembrane receptors of the Robo family and the secreted protein Slit provides important signals in the development of the central nervous system and regulation of axonal midline crossing. Heparan sulfate, a sulfated linear polysaccharide modified in a complex variety of ways, serves as an essential co-receptor in Slit-Robo signaling. Previous studies have shown that closely related heparin octasaccharides bind to Drosophila Robo directly, and surface plasmon resonance analysis revealed that Robo1 binds more tightly to full-length unfractionated heparin. For the first time, we utilized electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting to identify two separate binding sites for heparin interaction with Robo1: one binding site at the previously identified site for heparin dp8 and a second binding site at the N terminus of Robo1 that is disordered in the x-ray crystal structure. Mutagenesis of the identified N-terminal binding site exhibited a decrease in binding affinity as measured by surface plasmon resonance and heparin affinity chromatography. Footprinting also indicated that heparin binding induces a minor change in the conformation and/or dynamics of the Ig2 domain, but no major conformational changes were detected. These results indicate a second low affinity binding site in the Robo-Slit complex as well as suggesting the role of the Ig2 domain of Robo1 in heparin-mediated signal transduction. This study also marks the first use of electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting, which shows great utility for the characterization of protein-carbohydrate complexes.

  7. Extended structure and fate of the nucleus in Henize 2-10

    SciTech Connect

    Nguyen, Dieu D.; Seth, Anil C.; Den Brok, Mark; Reines, Amy E.; Sand, David; McLeod, Brian E-mail: aseth@astro.utah.edu E-mail: areines@nrao.edu E-mail: bmcleod@cfa.harvard.edu

    2014-10-10

    We investigate the structure and nuclear region of the black hole (BH) hosting galaxy Henize 2-10. Surface brightness profiles are analyzed using Magellan/Megacam g- and r-band images. Excluding the central starburst, we find a best-fit two-component Sérsic profile with n {sub in} ∼ 0.6, r {sub eff,} {sub in} ∼ 260 pc and n {sub out} ∼ 1.8, r ∼ 1 kpc. Integrating out to our outermost data point (100'' ∼ 4.3 kpc), we calculate M{sub g} = –19.2 and M{sub r} = –19.8. The corresponding enclosed stellar mass is M {sub *} ∼ (10 ± 3) × 10{sup 9} M {sub ☉}, ∼3 × larger than previous estimates. Apart from the central ≲500 pc, with blue colors and an irregular morphology, the galaxy appears to be an early-type system. The outer color is quite red, (g – r){sub 0} = 0.75, suggesting a dominant old population. We study the nuclear region of the galaxy using archival Gemini/NIFS K-band adaptive optics spectroscopy and Hubble Space Telescope imaging. We place an upper limit on the BH mass of ∼10{sup 7} M {sub ☉} from the NIFS data, consistent with that from the M {sub BH}-radio-X-ray fundamental plane. No coronal lines are seen, but a Brγ source is located at the position of the BH with a luminosity consistent with the X-ray emission. The starburst at the center of Henize 2-10 has led to the formation of several super star clusters, which are within ∼100 pc of the BH. We examine the fate of the nucleus by estimating the dynamical masses and dynamical friction timescales of the clusters. The most massive clusters (∼10{sup 6} M {sub ☉}) have τ{sub dyn} ≲ 200 Myr, and thus Henize 2-10 may represent a rare snapshot of nuclear star cluster formation around a preexisting massive BH.

  8. Comparison of Muscle Transcriptome between Pigs with Divergent Meat Quality Phenotypes Identifies Genes Related to Muscle Metabolism and Structure

    PubMed Central

    Damon, Marie; Wyszynska-Koko, Joanna; Vincent, Annie; Hérault, Frédéric; Lebret, Bénédicte

    2012-01-01

    Background Meat quality depends on physiological processes taking place in muscle tissue, which could involve a large pattern of genes associated with both muscle structural and metabolic features. Understanding the biological phenomena underlying muscle phenotype at slaughter is necessary to uncover meat quality development. Therefore, a muscle transcriptome analysis was undertaken to compare gene expression profiles between two highly contrasted pig breeds, Large White (LW) and Basque (B), reared in two different housing systems themselves influencing meat quality. LW is the most predominant breed used in pig industry, which exhibits standard meat quality attributes. B is an indigenous breed with low lean meat and high fat contents, high meat quality characteristics, and is genetically distant from other European pig breeds. Methodology/Principal Findings Transcriptome analysis undertaken using a custom 15 K microarray, highlighted 1233 genes differentially expressed between breeds (multiple-test adjusted P-value<0.05), out of which 635 were highly expressed in the B and 598 highly expressed in the LW pigs. No difference in gene expression was found between housing systems. Besides, expression level of 12 differentially expressed genes quantified by real-time RT-PCR validated microarray data. Functional annotation clustering emphasized four main clusters associated to transcriptome breed differences: metabolic processes, skeletal muscle structure and organization, extracellular matrix, lysosome, and proteolysis, thereby highlighting many genes involved in muscle physiology and meat quality development. Conclusions/Significance Altogether, these results will contribute to a better understanding of muscle physiology and of the biological and molecular processes underlying meat quality. Besides, this study is a first step towards the identification of molecular markers of pork quality and the subsequent development of control tools. PMID:22470472

  9. Nectar robbery by a hermit hummingbird: association to floral phenotype and its influence on flowers and network structure.

    PubMed

    Maruyama, Pietro Kiyoshi; Vizentin-Bugoni, Jeferson; Dalsgaard, Bo; Sazima, Ivan; Sazima, Marlies

    2015-07-01

    Interactions between flowers and their visitors span the spectrum from mutualism to antagonism. The literature is rich in studies focusing on mutualism, but nectar robbery has mostly been investigated using phytocentric approaches focused on only a few plant species. To fill this gap, we studied the interactions between a nectar-robbing hermit hummingbird, Phaethornis ruber, and the array of flowers it visits. First, based on a literature review of the interactions involving P. ruber, we characterized the association of floral larceny to floral phenotype. We then experimentally examined the effects of nectar robbing on nectar standing crop and number of visits of the pollinators to the flowers of Canna paniculata. Finally, we asked whether the incorporation of illegitimate interactions into the analysis affects plant-hummingbird network structure. We identified 97 plant species visited by P. ruber and found that P. ruber engaged in floral larceny in almost 30% of these species. Nectar robbery was especially common in flowers with longer corolla. In terms of the effect on C. paniculata, the depletion of nectar due to robbery by P. ruber was associated with decreased visitation rates of legitimate pollinators. At the community level, the inclusion of the illegitimate visits of P. ruber resulted in modifications of how modules within the network were organized, notably giving rise to a new module consisting of P. ruber and mostly robbed flowers. However, although illegitimate visits constituted approximately 9% of all interactions in the network, changes in nestedness, modularity, and network-level specialization were minor. Our results indicate that although a flower robber may have a strong effect on the pollination of a particular plant species, the inclusion of its illegitimate interactions has limited capacity to change overall network structure.

  10. Nectar robbery by a hermit hummingbird: association to floral phenotype and its influence on flowers and network structure.

    PubMed

    Maruyama, Pietro Kiyoshi; Vizentin-Bugoni, Jeferson; Dalsgaard, Bo; Sazima, Ivan; Sazima, Marlies

    2015-07-01

    Interactions between flowers and their visitors span the spectrum from mutualism to antagonism. The literature is rich in studies focusing on mutualism, but nectar robbery has mostly been investigated using phytocentric approaches focused on only a few plant species. To fill this gap, we studied the interactions between a nectar-robbing hermit hummingbird, Phaethornis ruber, and the array of flowers it visits. First, based on a literature review of the interactions involving P. ruber, we characterized the association of floral larceny to floral phenotype. We then experimentally examined the effects of nectar robbing on nectar standing crop and number of visits of the pollinators to the flowers of Canna paniculata. Finally, we asked whether the incorporation of illegitimate interactions into the analysis affects plant-hummingbird network structure. We identified 97 plant species visited by P. ruber and found that P. ruber engaged in floral larceny in almost 30% of these species. Nectar robbery was especially common in flowers with longer corolla. In terms of the effect on C. paniculata, the depletion of nectar due to robbery by P. ruber was associated with decreased visitation rates of legitimate pollinators. At the community level, the inclusion of the illegitimate visits of P. ruber resulted in modifications of how modules within the network were organized, notably giving rise to a new module consisting of P. ruber and mostly robbed flowers. However, although illegitimate visits constituted approximately 9% of all interactions in the network, changes in nestedness, modularity, and network-level specialization were minor. Our results indicate that although a flower robber may have a strong effect on the pollination of a particular plant species, the inclusion of its illegitimate interactions has limited capacity to change overall network structure. PMID:25740333

  11. Growth in Turface® clay permits root hair phenotyping along the entire crown root in cereal crops and demonstrates that root hair growth can extend well beyond the root hair zone.

    PubMed

    Goron, Travis L; Watts, Sophia; Shearer, Charles; Raizada, Manish N

    2015-04-12

    In cereal crops, root hairs are reported to function within the root hair zone to carry out important roles in nutrient and water absorption. Nevertheless, these single cells remain understudied due to the practical challenges of phenotyping these delicate structures in large cereal crops growing on soil or other growth systems. Here we present an alternative growth system for examining the root hairs of cereal crops: the use of coarse Turface® clay alongside fertigation. This system allowed for root hairs to be easily visualized along the entire lengths of crown roots in three different cereal crops (maize, wheat, and finger millet). Surprisingly, we observed that the root hairs in these crops continued to grow beyond the canonical root hair zone, with the most root hair growth occurring on older crown root segments. We suggest that the Turface® fertigation system may permit a better understanding of the changing dynamics of root hairs as they age in large plants, and may facilitate new avenues for crop improvement below ground. However, the relevance of this system to field conditions must be further evaluated in other crops.

  12. 21 centimeter HI absorption at z = 0. 437 against the extended radio structure of 3c 196

    SciTech Connect

    Brown, R.L.; Mitchell, K.J.

    1983-01-01

    We report the detection of an absorption line at 988.7. MHz toward the quasar 3C 196. We identify this line as the lambda21 cm line of neutral atomic hydrogen seen at a redshift of z/sub abs/ = 0.4366. No optical absorption lines have been noted in the z/sub em/ = 0.871 quasar 3C 196 heretofore. All the radio emission of 3C 196 is contained in two thetaroughly-equal3'' extended lobes symmetrically placed (position angle approx.26/sup 0/) about the optical object. The optical QSO itself is an extremely weak, <1 mJy, radio source. Thus to account for the approx.0.5 Jy seen in the absorption line we infer that the diameter of the absorbing region must be at least as large as 750 pc and perhaps as large as, or larger than, 30 kpc. We note further than an optical wisp is seen extending approx.3'' x 1'' from the QSO at position angle approx.120/sup 0/, that is in a direction perpendicular to the separation of the radio lobes. If this wisp is the disk of an intervening galaxy, then the H i absorption is direct evidence for absorption in a galactic halo. Puzzles abound; (1) If the optical wisp seen superposed on the QSO is an intervening galaxy then what aspects, if any, of the emission from 3C 196 are gravitational lens effects. (2) If the wisp is associated with the QSO, why is it radio quiet and why is it orthogonal to the extended radio structure of 3C 196. (3) Is it significant that z/sub abs/ is one-half z/sub em/ within the errors.

  13. Profiling functions of ectomycorrhizal diversity and root structuring in seedlings of Norway spruce (Picea abies) with fast- and slow-growing phenotypes.

    PubMed

    Velmala, Sannakajsa M; Rajala, Tiina; Heinonsalo, Jussi; Taylor, Andy F S; Pennanen, Taina

    2014-01-01

    We studied the role of taxonomical and functional ectomycorrhizal (ECM) fungal diversity in root formation and nutrient uptake by Norway spruce (Picea abies) seedlings with fast- and slow-growing phenotypes. Seedlings were grown with an increasing ECM fungal diversity gradient from one to four species and sampled before aboveground growth differences between the two phenotypes were apparent. ECM fungal colonization patterns were determined and functional diversity was assayed via measurements of potential enzyme activities of eight exoenzymes probably involved in nutrient mobilization. Phenotypes did not vary in their receptiveness to different ECM fungal species. However, seedlings of slow-growing phenotypes had higher fine-root density and thus more condensed root systems than fast-growing seedlings, but the potential enzyme activities of ectomycorrhizas did not differ qualitatively or quantitatively. ECM species richness increased host nutrient acquisition potential by diversifying the exoenzyme palette. Needle nitrogen content correlated positively with high chitinase activity of ectomycorrhizas. Rather than fast- and slow-growing phenotypes exhibiting differing receptiveness to ECM fungi, our results suggest that distinctions in fine-root structuring and in the belowground growth strategy already apparent at early stages of seedling development may explain later growth differences between fast- and slow-growing families.

  14. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

    PubMed Central

    Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P. M. A.; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-01-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation. PMID:27253709

  15. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens.

    PubMed

    Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P M A; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-06-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation. PMID:27253709

  16. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens.

    PubMed

    Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P M A; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-06-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation.

  17. Evidence of the nature of core-level photoemission satellites using angle-resolved photoemission extended fine structure

    SciTech Connect

    Moler, E.J.; Kellar, S.A.; Huff, W.R.A.

    1997-04-01

    The authors present a unique method of experimentally determining the angular momentum and intrinsic/extrinsic origin of core-level photoemission satellites by examining the satellite diffraction pattern in the Angle Resolved Photoemission Extended Fine Structure (ARPEFS) mode. They show for the first time that satellite peaks not associated with chemically differentiated atomic species display an ARPEFS intensity oscillation. They present ARPEFS data for the carbon 1s from ({radical}3x{radical}3)R30 CO/Cu(111) and p2mg(2xl)CO/Ni(110), nitrogen 1s from c(2x2) N{sub 2}/Ni(100), cobalt 1s from p(1x1)Co/Cu(100), and nickel 3p from clean nickel (111). The satellite peaks and tails of the Doniach-Sunjic line shapes in all cases exhibit ARPEFS curves which indicate an angular momentum identical to the main peak and are of an intrinsic nature.

  18. Multiresistant Uropathogenic Escherichia coli from a Region in India Where Urinary Tract Infections Are Endemic: Genotypic and Phenotypic Characteristics of Sequence Type 131 Isolates of the CTX-M-15 Extended-Spectrum-β-Lactamase-Producing Lineage

    PubMed Central

    Hussain, Arif; Ewers, Christa; Nandanwar, Nishant; Guenther, Sebastian; Jadhav, Savita; Wieler, Lothar H.

    2012-01-01

    Escherichia coli sequence type 131 (O25b:H4), associated with the CTX-M-15 extended-spectrum beta-lactamases (ESBLs) and linked predominantly to the community-onset antimicrobial-resistant infections, has globally emerged as a public health concern. However, scant attention is given to the understanding of the molecular epidemiology of these strains in high-burden countries such as India. Of the 100 clinical E. coli isolates obtained by us from a setting where urinary tract infections are endemic, 16 ST131 E. coli isolates were identified by multilocus sequence typing (MLST). Further, genotyping and phenotyping methods were employed to characterize their virulence and drug resistance patterns. All the 16 ST131 isolates harbored the CTX-M-15 gene, and half of them also carried TEM-1; 11 of these were positive for blaOXA groups 1 and 12 for aac(6′)-Ib-cr. At least 12 isolates were refractory to four non-beta-lactam antibiotics: ciprofloxacin, gentamicin, sulfamethoxazole-trimethoprim, and tetracycline. Nine isolates carried the class 1 integron. Plasmid analysis indicated a large pool of up to six plasmids per strain with a mean of approximately three plasmids. Conjugation and PCR-based replicon typing (PBRT) revealed that the spread of resistance was associated with the FIA incompatibility group of plasmids. Pulsed-field gel electrophoresis (PFGE) and genotyping of the virulence genes showed a low level of diversity among these strains. The association of ESBL-encoding plasmid with virulence was demonstrated in transconjugants by serum assay. None of the 16 ST131 ESBL-producing E. coli strains were known to synthesize carbapenemase enzymes. In conclusion, our study reports a snapshot of the highly virulent/multiresistant clone ST131 of uropathogenic E. coli from India. This study suggests that the ST131 genotypes from this region are clonally evolved and are strongly associated with the CTX-M-15 enzyme, carry a high antibiotic resistance background, and have

  19. Structures of Liquid GaSb and InSb Studied with the Extended X-Ray-Absorption Fine-Structure Method

    NASA Astrophysics Data System (ADS)

    Wang, Yuren; Lu, Kunquan; Li, Chenxi

    1997-11-01

    The extended x-ray-absorption fine-structure technique is applied to study the local atomic structures of liquid GaSb and InSb using an improved sample holding method. The partial pair distribution functions and coordination distributions of the two liquids are given by using reverse Monte Carlo simulation. The coordination numbers in liquid GaSb are mostly 5 and 6, in addition to which there are about 15% of 4 coordination and about 10% of 7 coordination. On average, the coordination number is 5.4. The results are similar in liquid InSb. This structural study provides some hints of the metallic behavior and density increase in the liquid.

  20. Quick extended x-ray absorption fine structure instrument with millisecond time scale, optimized for in situ applications.

    PubMed

    Khalid, S; Caliebe, W; Siddons, P; So, I; Clay, B; Lenhard, T; Hanson, J; Wang, Q; Frenkel, A I; Marinkovic, N; Hould, N; Ginder-Vogel, M; Landrot, G L; Sparks, D L; Ganjoo, A

    2010-01-01

    In order to learn about in situ structural changes in materials at subseconds time scale, we have further refined the techniques of quick extended x-ray absorption fine structure (QEXAFS) and quick x-ray absorption near edge structure (XANES) spectroscopies at beamline X18B at the National Synchrotron Light Source. The channel cut Si (111) monochromator oscillation is driven through a tangential arm at 5 Hz, using a cam, dc motor, pulley, and belt system. The rubber belt between the motor and the cam damps the mechanical noise. EXAFS scan taken in 100 ms is comparable to standard data. The angle and the angular range of the monochromator can be changed to collect a full EXAFS or XANES spectrum in the energy range 4.7-40.0 KeV. The data are recorded in ascending and descending order of energy, on the fly, without any loss of beam time. The QEXAFS mechanical system is outside the vacuum system, and therefore changing the mode of operation from conventional to QEXAFS takes only a few minutes. This instrument allows the acquisition of time resolved data in a variety of systems relevant to electrochemical, photochemical, catalytic, materials, and environmental sciences.

  1. Topolology-symmetry law of structure of natural titanosilicate micas and related heterophyllosilicates based on the extended OD theory: Structure prediction

    NASA Astrophysics Data System (ADS)

    Belokoneva, E. L.; Topnikova, A. P.; Aksenov, S. M.

    2015-01-01

    A topology-symmetry analysis of the structures in the family of titanosilicate micas and related heterophyllosilicates based on the extended OD theory reveals their kinship with the family of rhodezite, delhayelite, and other minerals that had been analyzed earlier by distinguishing sheets common for all the structures. Like in the family studied earlier, the structural variety of a more complex titanosilicate family is determined by different local symmetries of sheets. Sheets consist of central O layers of edge-sharing octahedra and H layers formed by tetrahedra connected into diortho groups and Ti(Nb,Fe) semioctahedra (octahedra). Three patterns of connection of O and H layers correspond to sheet symmetry P2/ m, P21/ m, and . Various symmetry modes of sheet connection in the structures are analyzed. Hypothetical structures, including structures with a higher degree of disorder, which can be found in nature or obtained by crystal synthesis, are deduced. Factors responsible for structural variety, including the existence of two main sheet varieties (with P2/ m and P21/ m symmetry) are considered a consequence of the difference in the chemism of the mineral formation medium.

  2. Phenotypic and Molecular Characterization of Antimicrobial Resistance in Klebsiella spp. Isolates from Companion Animals in Japan: Clonal Dissemination of Multidrug-Resistant Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae.

    PubMed

    Harada, Kazuki; Shimizu, Takae; Mukai, Yujiro; Kuwajima, Ken; Sato, Tomomi; Usui, Masaru; Tamura, Yutaka; Kimura, Yui; Miyamoto, Tadashi; Tsuyuki, Yuzo; Ohki, Asami; Kataoka, Yasushi

    2016-01-01

    The emergence of antimicrobial resistance in Klebsiella spp., including resistance to extended-spectrum cephalosporins (ESC) and fluoroquinolones, is of great concern in both human and veterinary medicine. In this study, we investigated the prevalence of antimicrobial resistance in a total of 103 Klebsiella spp. isolates, consisting of Klebsiella pneumoniae complex (KP, n = 89) and K. oxytoca (KO, n = 14) from clinical specimens of dogs and cats in Japan. Furthermore, we characterized the resistance mechanisms, including extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC β-lactamase (PABL), and plasmid-mediated quinolone resistance (PMQR); and assessed genetic relatedness of ESC-resistant Klebsiella spp. strains by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility testing demonstrated that resistance rates to ampicillin, cephalothin, enrofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, cefotaxime, gentamicin, tetracycline, chloramphenicol, amoxicillin-clavulanic acid, and cefmetazole were 98.1, 37.9, 37.9, 35.9, 35.0, 34.0, 31.1, 30.1, 28.2, 14.6, and 6.8%, respectively. Phenotypic testing detected ESBLs and/or AmpC β-lactamases in 31 of 89 (34.8%) KP isolates, but not in KO isolates. Resistances to 5 of the 12 antimicrobials tested, as well as the three PMQRs [qnrB, qnrS, and aac(6')-Ib-cr], were detected significantly more frequently in ESBL-producing KP, than in non-ESBL-producing KP and KO. The most frequent ESBL was CTX-M-15 (n = 13), followed by CTX-M-14 (n = 7), CTX-M-55 (n = 6), SHV-2 (n = 5), CTX-M-2 (n = 2), and CTX-M-3 (n = 2). Based on the rpoB phylogeny, all ESBL-producing strains were identified as K. pneumoniae, except for one CTX-M-14-producing strain, which was identified as K. quasipneumoniae. All of AmpC β-lactamase positive isolates (n = 6) harbored DHA-1, one of the PABLs. Based on MLST and PFGE analysis, ST15 KP clones producing CTX-M-2, CTX-M-15, CTX-M-55, and

  3. Phenotypic and Molecular Characterization of Antimicrobial Resistance in Klebsiella spp. Isolates from Companion Animals in Japan: Clonal Dissemination of Multidrug-Resistant Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae

    PubMed Central

    Harada, Kazuki; Shimizu, Takae; Mukai, Yujiro; Kuwajima, Ken; Sato, Tomomi; Usui, Masaru; Tamura, Yutaka; Kimura, Yui; Miyamoto, Tadashi; Tsuyuki, Yuzo; Ohki, Asami; Kataoka, Yasushi

    2016-01-01

    The emergence of antimicrobial resistance in Klebsiella spp., including resistance to extended-spectrum cephalosporins (ESC) and fluoroquinolones, is of great concern in both human and veterinary medicine. In this study, we investigated the prevalence of antimicrobial resistance in a total of 103 Klebsiella spp. isolates, consisting of Klebsiella pneumoniae complex (KP, n = 89) and K. oxytoca (KO, n = 14) from clinical specimens of dogs and cats in Japan. Furthermore, we characterized the resistance mechanisms, including extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC β-lactamase (PABL), and plasmid-mediated quinolone resistance (PMQR); and assessed genetic relatedness of ESC-resistant Klebsiella spp. strains by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility testing demonstrated that resistance rates to ampicillin, cephalothin, enrofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, cefotaxime, gentamicin, tetracycline, chloramphenicol, amoxicillin-clavulanic acid, and cefmetazole were 98.1, 37.9, 37.9, 35.9, 35.0, 34.0, 31.1, 30.1, 28.2, 14.6, and 6.8%, respectively. Phenotypic testing detected ESBLs and/or AmpC β-lactamases in 31 of 89 (34.8%) KP isolates, but not in KO isolates. Resistances to 5 of the 12 antimicrobials tested, as well as the three PMQRs [qnrB, qnrS, and aac(6′)-Ib-cr], were detected significantly more frequently in ESBL-producing KP, than in non-ESBL-producing KP and KO. The most frequent ESBL was CTX-M-15 (n = 13), followed by CTX-M-14 (n = 7), CTX-M-55 (n = 6), SHV-2 (n = 5), CTX-M-2 (n = 2), and CTX-M-3 (n = 2). Based on the rpoB phylogeny, all ESBL-producing strains were identified as K. pneumoniae, except for one CTX-M-14-producing strain, which was identified as K. quasipneumoniae. All of AmpC β-lactamase positive isolates (n = 6) harbored DHA-1, one of the PABLs. Based on MLST and PFGE analysis, ST15 KP clones producing CTX-M-2, CTX-M-15, CTX-M-55, and

  4. Synthesis, Structures, and Properties of π-Extended Double Helicene: A Combination of Planar and Nonplanar π-Systems.

    PubMed

    Fujikawa, Takao; Segawa, Yasutomo; Itami, Kenichiro

    2015-06-24

    The synthesis, structures, and properties of a π-extended double helicene 1 are described. This double helicene 1 was synthesized by a four-fold oxidative C-H biphenylation of naphthalene followed by the Scholl reaction or via five steps including the Suzuki-Miyaura cross-coupling reaction and the Scholl reaction. Due to the two helical substructures, 1 has three isomers, i.e., two enantiomers in a twisted form [(P,P) and (M,M)] and one diastereoisomer in a meso form. X-ray crystallographic analysis of the twisted isomers (twisted-1) revealed a tightly offset packing pattern of (P,P)- and (M,M)-twisted isomers, affording a three-dimensional lamellar stacking structure. A high isomerization barrier (43.5 kcal mol(-1)) and the relative thermal stability of twisted-1 isomer over meso-1 by 0.9 kcal mol(-1) were estimated by DFT calculations. The three isomers were successfully separated by chiral HPLC and characterized by circular dichroism spectroscopy as well as by TD-DFT studies. Electronic state variation resulting from the molecular geometry difference between the two diastereoisomers (twisted-1 and meso-1) was observed by UV-vis absorption and fluorescence spectra. PMID:26028308

  5. Crystal chemistry and application development of uranyl extended structure and nanoscale materials and actinyl ion-substituted mineral phases

    NASA Astrophysics Data System (ADS)

    Wylie, Ernest M.

    The worldwide use of nuclear energy presents both significant advantages and challenges for society. Actinide research seeks to address these challenges and drive advancement in the fields of nuclear science and engineering. Here, key aspects of the fuel cycle are examined from both a fundamental and an applications-based perspective. Hydrothermal, ionothermal, room-temperature evaporation, and liquid diffusion synthesis techniques and single-crystal X-ray diffraction were used to study the structures of 18 uranyl compounds and six actinyl-doped mineral phases. These compounds represent a diverse group ranging from unique molecular clusters to novel and known extended structures isolated from aqueous and ionic liquid media. Ultrafiltration techniques were utilized to separate uranyl peroxide nanoclusters from complex aqueous solutions. Inductively coupled plasma optical emission spectroscopy and mass spectrometry were used to quantify elemental distributions in the feed and permeate solutions while Raman spectroscopy, small-angle X-ray scattering, and electrospray ionization mass spectrometry were used to define the characteristics of the cluster species across a range different solution conditions.

  6. Amyloid-β-Anti-Amyloid-β Complex Structure Reveals an Extended Conformation in the Immunodominant B-Cell Epitope

    SciTech Connect

    Miles, Luke A; Wun, Kwok S; Crespi, Gabriela A.N.; Fodero-Tavoletti, Michelle T; Galatis, Denise; Bagley, Christopher J; Beyreuther, Konrad; Masters, Colin L; Cappai, Roberto; McKinstry, William J; Barnham, Kevin J; Parker, Michael W

    2008-04-29

    Alzheimer's disease (AD) is the most common form of dementia. Amyloid-β (Aβ) peptide, generated by proteolytic cleavage of the amyloid precursor protein, is central to AD pathogenesis. Most pharmaceutical activity in AD research has focused on Aβ, its generation and clearance from the brain. In particular, there is much interest in immunotherapy approaches with a number of anti-Aβ antibodies in clinical trials. We have developed a monoclonal antibody, called WO2, which recognises the Aβ peptide. To this end, we have determined the three-dimensional structure, to near atomic resolution, of both the antibody and the complex with its antigen, the Aβ peptide. The structures reveal the molecular basis for WO2 recognition and binding of Aβ. The Aβ peptide adopts an extended, coil-like conformation across its major immunodominant B-cell epitope between residues 2 and 8. We have also studied the antibody-bound Aβ peptide in the presence of metals known to affect its aggregation state and show that WO2 inhibits these interactions. Thus, antibodies that target the N-terminal region of Aβ, such as WO2, hold promise for therapeutic development.

  7. Amyloid-β-Anti-Amyloid-β Complex Structure Reveals an Extended Conformation in the Immunodominant B-Cell Epitope

    SciTech Connect

    Miles, Luke A; Wun, Kwok S; Crespi, Gabriela A.N.; Fodero-Tavoletti, Michelle T; Galatis, Denise; Bagley, Christopher J; Beyreuther, Konrad; Masters, Colin L; Cappai, Roberto; McKinstry, William J; Barnham, Kevin J; Parker, Michael W

    2012-04-17

    Alzheimer's disease (AD) is the most common form of dementia. Amyloid-β (Aβ) peptide, generated by proteolytic cleavage of the amyloid precursor protein, is central to AD pathogenesis. Most pharmaceutical activity in AD research has focused on Aβ, its generation and clearance from the brain. In particular, there is much interest in immunotherapy approaches with a number of anti-Aβ antibodies in clinical trials. We have developed a monoclonal antibody, called WO2, which recognises the Aβ peptide. To this end, we have determined the three-dimensional structure, to near atomic resolution, of both the antibody and the complex with its antigen, the Aβ peptide. The structures reveal the molecular basis for WO2 recognition and binding of Aβ. The Aβ peptide adopts an extended, coil-like conformation across its major immunodominant B-cell epitope between residues 2 and 8. We have also studied the antibody-bound Aβ peptide in the presence of metals known to affect its aggregation state and show that WO2 inhibits these interactions. Thus, antibodies that target the N-terminal region of Aβ, such as WO2, hold promise for therapeutic development.

  8. Extended x-ray absorption fine structure measurements of quasi-isentropically compressed vanadium targets on the OMEGA laser

    SciTech Connect

    Yaakobi, B.; Boehly, T. R.; Sangster, T. C.; Meyerhofer, D. D.; Remington, B. A.; Allen, P. G.; Pollaine, S. M.; Lorenzana, H. E.; Lorenz, K. T.; Hawreliak, J. A.

    2008-06-15

    The use of in situ extended x-ray absorption fine structure (EXAFS) for characterizing nanosecond laser-shocked vanadium, titanium, and iron has recently been demonstrated. These measurements are extended to laser-driven, quasi-isentropic compression experiments (ICE). The radiation source (backlighter) for EXAFS in all of these experiments is obtained by imploding a spherical target on the OMEGA laser [T. R. Boehly et al., Rev. Sci. Instrum. 66, 508 (1995)]. Isentropic compression (where the entropy is kept constant) enables to reach high compressions at relatively low temperatures. The absorption spectra are used to determine the temperature and compression in a vanadium sample quasi-isentropically compressed to pressures of up to {approx}0.75 Mbar. The ability to measure the temperature and compression directly is unique to EXAFS. The drive pressure is calibrated by substituting aluminum for the vanadium and interferometrically measuring the velocity of the back target surface by the velocity interferometer system for any reflector (VISAR). The experimental results obtained by EXAFS and VISAR agree with each other and with the simulations of a hydrodynamic code. The role of a shield to protect the sample from impact heating is studied. It is shown that the shield produces an initial weak shock that is followed by a quasi-isentropic compression at a relatively low temperature. The role of radiation heating from the imploding target as well as from the laser-absorption region is studied. The results show that in laser-driven ICE, as compared with laser-driven shocks, comparable compressions can be achieved at lower temperatures. The EXAFS results show important details not seen in the VISAR results.

  9. Extended X-Ray Absorption Fine Structure Measurements of Quasi-Isentropically Compressed Vanadium Targets on the OMEGA Laser

    SciTech Connect

    Yaakobi, B.; Boehly, T.R.; Sangster, T.C.; Meyerhofer, D.D.; Remington, B.A.; Allen, P.G.; Pollaine, S.M.; Lorenzana, H.E.; Lorenz, K.T.; Hawreliak, J.A.

    2008-07-21

    The use of in situ extended x-ray absorption fine structure (EXAFS) for characterizing nanosecond laser-shocked vanadium, titanium, and iron has recently been demonstrated. These measurements are extended to laser-driven, quasi-isentropic compression experiments (ICE). The radiation source (backlighter) for EXAFS in all of these experiments is obtained by imploding a spherical target on the OMEGA laser [T. R. Boehly et al., Rev. Sci. Instrum. 66, 508 (1995)]. Isentropic compression (where the entropy is kept constant) enables to reach high compressions at relatively low temperatures. The absorption spectra are used to determine the temperature and compression in a vanadium sample quasi-isentropically compressed to pressures of up to ~0.75 Mbar. The ability to measure the temperature and compression directly is unique to EXAFS. The drive pressure is calibrated by substituting aluminum for the vanadium and interferometrically measuring the velocity of the back target surface by the velocity interferometer system for any reflector (VISAR). The experimental results obtained by EXAFS and VISAR agree with each other and with the simulations of a hydrodynamic code. The role of a shield to protect the sample from impact heating is studied. It is shown that the shield produces an initial weak shock that is followed by a quasi-isentropic compression at a relatively low temperature. The role of radiation heating from the imploding target as well as from the laser-absorption region is studied. The results show that in laser-driven ICE, as compared with laser-driven shocks, comparable compressions can be achieved at lower temperatures. The EXAFS results show important details not seen in the VISAR results.

  10. Genetic Structure Associated with blaOXA-18, Encoding a Clavulanic Acid-Inhibited Extended-Spectrum Oxacillinase▿

    PubMed Central

    Naas, Thierry; Namdari, Fatemeh; Bogaerts, Pierre; Huang, Te-Din; Glupczynski, Youri; Nordmann, Patrice

    2008-01-01

    The genetic environment of the blaOXA-18 gene encoding a peculiar clavulanic acid-inhibitable Ambler class D extended-spectrum β-lactamase was determined from the prototype OXA-18-producing Pseudomonas aeruginosa MUS clinical isolate. An 8.2-kb genomic DNA fragment containing blaOXA-18 was cloned from P. aeruginosa MUS. Although most oxacillinases are located in integrons, blaOXA-18 lacked gene cassette-specific features. It was bracketed by two duplicated sequences containing ISCR19, a novel insertion sequence of the ISCR family of mobile elements; ΔintI1, a truncated integrase gene; and a truncated Δaac6′-Ib gene cassette. It is likely that ISCR19 was at the origin of the blaOXA-18 gene mobilization by a rolling-circle transposition event followed by homologous recombination. Furthermore, analysis of the cloned genomic DNA fragment revealed the presence of the integron-containing blaOXA-20 gene. Concomitantly, three P. aeruginosa clinical isolates, displaying a synergy image as determined by double-disk diffusion tests on cloxacillin-containing plates, were isolated from three patients hospitalized in different wards over a 9-month period at the Saint-Luc University hospital (Brussels, Belgium). These isolates were positive by PCR for blaOXA-18 and blaOXA-20 genes, genetically related to P. aeruginosa MUS as determined by pulsed-field gel electrophoresis, and carried the same blaOXA-18/blaOXA-20-associated genetic structures. This report characterized the genetic elements likely at the origin of blaOXA-18 gene mobilization in P. aeruginosa and suggests the spread of oxacillin-type extended-spectrum β-lactamases in P. aeruginosa at the Saint-Luc University hospital of Brussels, Belgium. PMID:18663027

  11. Orientation-dependent local structural properties of Zn(1-x)Mg(x)O nanorods studied by extended X-ray absorption fine structure.

    PubMed

    Jeong, E S; Park, Changin; Jin, Zhenlan; Yoo, Jinkyoung; Yi, Gyu-Chul; Han, S W

    2013-03-01

    The orientation-dependent structural properties of Zn(1-x)Mg(x)O nanorods with different Mg concentrations were investigated quantitatively using polarization-dependent extended X-ray absorption fine structure (EXAFS) measurements at the Zn K edge. Vertically-aligned Zn(1-x)Mg(x)O nanorods were synthesized on Si substrates using catalyst free metal organic chemical vapor deposition. Polarization-dependent EXAFS measurements showed that Mg ions mainly occupied the Zn sites of the nanorods. EXAFS revealed that the distance between Zn-Mg pairs in all directions is - 0.2 angstroms shorter than that of Zn-Zn pairs and that there is a substantial amount of disorder in the Mg sites of the nanorods, independent of Mg concentrations.

  12. Structural analysis of polymer-protected Pd/Pt bimetallic clusters as dispersed catalysts by using extended x-ray absorption fine structure spectroscopy

    SciTech Connect

    Toshima, Naoki; Harada, Masafumi; Yonezawa, Tetsu; Kushihashi, Kakuta; Asakura, Kiyotaka )

    1991-09-19

    Extended X-ray absorption fine structure (EXAFS) was applied to the determination of the structure of colloidal dispersions of the poly (N-vinyl-2-pyrrolidone)-protected palladium/platinum bimetallic clusters, which work as the catalysts for selective partial hydrogenation of 1,3-cyclooctadiene to cyclooctene. The catalytic activity was found to depend on the structure of the bimetallic clusters. The EXAFS data on the Pd/Pt (4/1) bimetallic clusters, which are the most active catalysts, indicate a Pt core structure, in which the 42 Pd atoms are on the surface of the cluster particle and 13 Pt atoms are at the center of the particle, forming a core. In contrast, the Pd/Pt (1/1) bimetallic clusters are suggested to have a modified Pt core structure, in which 28 Pt atoms connect directly with each other, being located both in the core and on the surface, and 27 Pd atoms form three islands on the surface of the cluster particle. These bimetallic clusters work as active catalysts for selective hydrogenation of olefins, selective partial hydrogenation of diene to monoene, and visible light-induced hydrogen generation from water.

  13. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila.

    PubMed

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K

    2015-12-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context.

  14. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila.

    PubMed

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K

    2015-12-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context. PMID:26530416

  15. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila

    PubMed Central

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K.

    2015-01-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual’s genetic and environmental context. PMID:26530416

  16. Local structure and polarization resistance of Ce doped SrMnO{sub 3} using extended x-ray fine structure analysis

    SciTech Connect

    Ryu, Jiseung; Lee, Heesoo

    2014-09-15

    Changes to the local structure of Sr and Mn atoms in Sr{sub 1−x}Ce{sub x}MnO{sub 3} (SCM) according to increasing Ce content and the effect of the structural change on the polarization resistance of SCM were investigated. The reduction of manganese was confirmed by the absorption edge shift of the Mn K-edge toward lower energies. The noise of oscillation in extended X-ray absorption fine structure k{sup 3}χ data at Mn K-edge reveals the distortion of the local structure of Mn atoms, and the peak that indicates the bonding length of Mn-O, Sr/Ce, and -Mn decreased with the addition of Ce content in Fourier transformations of the Mn K-edge. The distortion of the local structure at Mn atoms was affected by the reduced manganese ions having larger ionic radii than Mn{sup 4+}. Meanwhile, few distortions of local atomic structures of Sr atoms occurred, and the average nearest neighboring distances of Sr-O and Sr-Mn are ∼2.13 Å and ∼2.95 Å, respectively. The average bonding lengths of the Ce-O and Ce-Mn increased because the ionic radius of substituted Ce ion with 12 coordination number is smaller than that of Sr ion, which leads the reduction of Mn ions and the distortion of local structure at the substituted A-site. Therefore, we reasoned that the distortion of the local atomic structure at Mn atoms in MnO{sub 6} and Ce atoms in A-site is one of the causes for interrupting oxygen ion transfers as a geometric factor, which results in an increase in the polarization resistance of SCM within the Ce composition range from 10 mol. % to 30 mol. %.

  17. The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease.

    PubMed

    Hui, Gar Kay; Wright, David W; Vennard, Owen L; Rayner, Lucy E; Pang, Melisa; Yeo, See Cheng; Gor, Jayesh; Molyneux, Karen; Barratt, Jonathan; Perkins, Stephen J

    2015-10-15

    Native IgA1, for which no crystal structure is known, contains an O-galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s(0)20,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self-association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn(263) were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcαR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN.

  18. The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease

    PubMed Central

    Hui, Gar Kay; Wright, David W.; Vennard, Owen L.; Rayner, Lucy E.; Pang, Melisa; Yeo, See Cheng; Gor, Jayesh; Molyneux, Karen; Barratt, Jonathan; Perkins, Stephen J.

    2015-01-01

    Native IgA1, for which no crystal structure is known, contains an O-galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s020,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self-association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn263 were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcαR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN. PMID:26268558

  19. Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes.

    PubMed

    Omosa, Leonidah K; Midiwo, Jacob O; Mbaveng, Armelle T; Tankeo, Simplice B; Seukep, Jackson A; Voukeng, Igor K; Dzotam, Joachim K; Isemeki, John; Derese, Solomon; Omolle, Ruth A; Efferth, Thomas; Kuete, Victor

    2016-01-01

    In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3' together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are

  20. Extended x-ray-absorption fine-structure measurements of copper: Local dynamics, anharmonicity, and thermal expansion

    SciTech Connect

    Fornasini, P.; Beccara, S.; Dalba, G.; Grisenti, R.; Sanson, A.; Vaccari, M.; Rocca, F.

    2004-11-01

    Extended x-ray-absorption fine-structure (EXAFS) of copper has been measured from 4 to 500 K and analyzed by the cumulant method, to check the effectiveness of EXAFS as a probe of local dynamics and thermal expansion. The comparison between parallel mean square relative displacements (MSRD) of the first four coordination shells has allowed detecting a significant deviation from a pure Debye behavior. The first-shell EXAFS thermal expansion is larger than the crystallographic one: the difference has allowed evaluating the perpendicular MSRD, whose Debye temperature is slightly larger than the one of the parallel MSRD, due to anisotropy effects. High-order first-shell cumulants are in good agreement with quantum perturbative models. The anharmonic contribution to the first-shell parallel MSRD amounts to less than 1.5 percent. The third cumulant cannot be neglected in the analysis, if accurate values of the first cumulant are sought; it cannot however be used to directly estimate the thermal expansion. The shape of the effective pair potential is independent of temperature; a rigid shift, partially due to the relative motion perpendicular to the bond direction, is however observed.

  1. Structural and Dynamic Characterization of the C313Y Mutation in Myostatin Dimeric Protein, Responsible for the “Double Muscle” Phenotype in Piedmontese Cattle

    PubMed Central

    Bongiorni, Silvia; Valentini, Alessio; Chillemi, Giovanni

    2016-01-01

    The knowledge of the molecular effects of the C313Y mutation, responsible for the “double muscle” phenotype in Piedmontese cattle, can help understanding the actual mechanism of phenotype determination and paves the route for a better modulation of the positive effects of this economic important phenotype in the beef industry, while minimizing the negative side effects, now inevitably intersected. The structure and dynamic behavior of the active dimeric form of Myostatin in cattle was analyzed by means of three state-of-the-art Molecular Dynamics simulations, 200-ns long, of wild-type and C313Y mutants. Our results highlight a role for the conserved Arg333 in establishing a network of short and long range interactions between the two monomers in the wild-type protein that is destroyed upon the C313Y mutation even in a single monomer. Furthermore, the native protein shows an asymmetry in residue fluctuation that is absent in the double monomer mutant. Time window analysis on further 200-ns of simulation demonstrates that this is a characteristic behavior of the protein, likely dependent on long range communications between monomers. The same behavior, in fact, has already been observed in other mutated dimers. Finally, the mutation does not produce alterations in the secondary structure elements that compose the characteristic TGF-β cystine-knot motif. PMID:26904102

  2. Microbial structural diversity estimated by dilution-extinction of phenotypic traits and T-RFLP analysis along a land-use intensification gradient.

    PubMed

    Gomez, Elena; Garland, Jay L; Roberts, Michael S

    2004-08-01

    The present work tested whether the relationship between functional traits and inoculum density reflected structural diversity in bacterial communities from a land-use intensification gradient applying a mathematical model. Terminal restriction fragment length polymorphism (T-RFLP) analysis was also performed to provide an independent assessment of species richness. Successive 10-fold dilutions of a soil suspension were inoculated onto Biolog GN(R) microplates. Soil bacterial density was determined by total cell and plate counts. The relationship between phenotypic traits and inoculum density fit the model, allowing the estimation of maximal phenotypic potential (Rmax) and inoculum density (KI) at which Rmax will be half-reduced. Though Rmax decreased with time elapsed since clearing of native vegetation, KI remained high in two of the disturbed sites. The genetic pool of bacterial community did not experience a significant reduction, but the active fraction responding in the Biolog assay was adversely affected, suggesting a reduction in the functional potential.

  3. Adsorption site and structure determination of c(2x2) N{sub 2}/Ni(100) using angle-resolved photoemission extended fine structure

    SciTech Connect

    Moler, E.J.; Kellar, S.A.; Huff, W.R.A.

    1997-04-01

    The authors have determined the atomic spatial structure of c(2x2) N2Ni(100) with Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) from the nitrogen 1s core level using monochromatized x-rays from beamline 6.1 at SSRL and beamline 9.3.2 at the ALS. The chemically shifted N 1s peak intensities were summed together to obtain ARPEFS curves for both nitrogen atoms in the molecule. They used a new, highly-optimized program based on the Rehr-Albers scattering matrix formalism to find the adsorption site and to quantitatively determine the bond-lengths. The nitrogen molecule stands upright at an atop site, with a N-Ni bond length of 2.25(1) {angstrom}, a N-N bond length of 1.10(7) {angstrom}, and a first layer Ni-Ni spacing of 1.76(4) {angstrom}. The shake-up peak shows an identical ARPEFS diffraction pattern, confirming its intrinsic nature and supporting a previous use of this feature to decompose the peak into contributions from the chemically inequivalent nitrogen atoms. Comparison to a previously published theoretical treatment of N-N-Ni and experimental structures of analogous adsorbate systems demonstrates the importance of adsorbate-adsorbate interactions in weakly chemisorbed systems.

  4. Geometric Structure Determination of N694C Lipoxygenase: a Comparative Near-Edge X-Ray Absorption Spectroscopy And Extended X-Ray Absorption Fine Structure Study

    SciTech Connect

    Sarangi, R.; Hocking, R.K.; Neidig, M.L.; Benfatto, M.; Holman, T.R.; Solomon, E.I.; Hodgson, K.O.; Hedman, B.

    2009-05-27

    The mononuclear nonheme iron active site of N694C soybean lipoxygenase (sLO1) has been investigated in the resting ferrous form using a combination of Fe-K-pre-edge, near-edge (using the minuit X-ray absorption near-edge full multiple-scattering approach), and extended X-ray absorption fine structure (EXAFS) methods. The results indicate that the active site is six-coordinate (6C) with a large perturbation in the first-shell bond distances in comparison to the more ordered octahedral site in wild-type sLO1. Upon mutation of the asparigine to cystiene, the short Fe-O interaction with asparigine is replaced by a weak Fe-(H{sub 2}O), which leads to a distorted 6C site with an effective 5C ligand field. In addition, it is shown that near-edge multiple scattering analysis can give important three-dimensional structural information, which usually cannot be accessed using EXAFS analysis. It is further shown that, relative to EXAFS, near-edge analysis is more sensitive to partial coordination numbers and can be potentially used as a tool for structure determination in a mixture of chemical species.

  5. The determination of interfacial structure and phase transitions in Al/Cu and Al/Ni interfaces by means of surface extended x-ray absorption fine structure

    SciTech Connect

    Barrera, E.V. . Dept. of Mechanical Engineering and Materials Science); Heald, S.M. )

    1991-01-01

    Surface extended x-ray absorption fine structure (SEXAFS) was used to investigate the interfacial conditions of Al/Cu and Al/Ni shallow buried interfaces. Previous studies using glancing angle extended x-ray absorption fine structure, x-ray reflectivity, photoemission, and SEXAFS produced conflicting results as to whether or not the interfaces between Al and Cu and Al and Ni were reacted upon room temperature deposition. In this study polycrystalline bilayers of Al/Cu and Al/Ni and trilayers of Al/Cu/Al and Al/Ni/Al were deposited on tantalum foil at room temperature in ultra high vacuum and analyzed to evaluate the reactivity of these systems on a nanometer scale. It become overwhelming apparent that the interfacial phase reactions were a function of the vacuum conditions. Samples deposited with the optimum vacuum conditions showed reaction products upon deposition at room temperature which were characterized by comparisons to standards and by least squares fitting the be CuAl{sub 2} and NiAl{sub 3} respectively. The results of this study that the reacted zone thicknesses were readily dependent on the deposition parameters. For both Al on Cu and Al on Ni as well as the metal on Al conditions 10{Angstrom} reaction zones were observed. These reaction zones were smaller than that observed for bilayers of Al on Cu (30{Angstrom}) and Al on Ni (60{Angstrom}) where deposition rates were much higher and samples were much thicker. The reaction species are evident by SEXAFS, where the previous photoemission studies only indicated that changes had occurred. Improved vacuum conditions as compared to the earlier experiments is primarily the reason reactions on deposition were seen in this study as compared to the earlier SEXAFS studies.

  6. The determination of interfacial structure and phase transitions in Al/Cu and Al/Ni interfaces by means of surface extended x-ray absorption fine structure

    SciTech Connect

    Barrera, E.V.; Heald, S.M.

    1991-12-31

    Surface extended x-ray absorption fine structure (SEXAFS) was used to investigate the interfacial conditions of Al/Cu and Al/Ni shallow buried interfaces. Previous studies using glancing angle extended x-ray absorption fine structure, x-ray reflectivity, photoemission, and SEXAFS produced conflicting results as to whether or not the interfaces between Al and Cu and Al and Ni were reacted upon room temperature deposition. In this study polycrystalline bilayers of Al/Cu and Al/Ni and trilayers of Al/Cu/Al and Al/Ni/Al were deposited on tantalum foil at room temperature in ultra high vacuum and analyzed to evaluate the reactivity of these systems on a nanometer scale. It become overwhelming apparent that the interfacial phase reactions were a function of the vacuum conditions. Samples deposited with the optimum vacuum conditions showed reaction products upon deposition at room temperature which were characterized by comparisons to standards and by least squares fitting the be CuAl{sub 2} and NiAl{sub 3} respectively. The results of this study that the reacted zone thicknesses were readily dependent on the deposition parameters. For both Al on Cu and Al on Ni as well as the metal on Al conditions 10{Angstrom} reaction zones were observed. These reaction zones were smaller than that observed for bilayers of Al on Cu (30{Angstrom}) and Al on Ni (60{Angstrom}) where deposition rates were much higher and samples were much thicker. The reaction species are evident by SEXAFS, where the previous photoemission studies only indicated that changes had occurred. Improved vacuum conditions as compared to the earlier experiments is primarily the reason reactions on deposition were seen in this study as compared to the earlier SEXAFS studies.

  7. A combined fit of total scattering and extended x-ray absorption fine structure data for local-structure determination in crystalline materials

    SciTech Connect

    Proffen, Thomas E; Krayzman, Victor; Levin, Igor; Tucker, Matt

    2009-01-01

    Reverse Monte Carlo (RMC) refinements of local structure using a simultaneous fit of X-ray/neutron total scattering and extended X-ray absorption fine structure (EXAFS) data were developed to incorporate an explicit treatment of both single- and multiple-scattering contributions to EXAFS. The refinement algorithm, implemented as an extension to the public domain computer software RMCProfile, enables accurate modeling of EXAFS over distances encompassing several coordination shells around the absorbing species. The approach was first tested on Ni, which exhibits extensive multiple scattering in EXAFS, and then applied to perovskite-like SrAl{sub 1/2}Nb{sub 1/2}O{sub 3}. This compound crystal1izes with a cubic double-perovskite structure but presents a challenge for local-structure determination using a total pair-distribution function (PDF) alone because of overlapping peaks of the constituent partial PDFs (e.g. Al-O and Nb-O or Sr-O and O-O). The results obtained here suggest that the combined use of the total scattering and EXAFS data provides sufficient constraints for RMC refinements to recover fine details of local structure in complex perovskites. Among other results, it was found that the probability density distribution for Sr in SrAl{sub 1/2}Nb{sub 1/2}O{sub 3} adopts T{sub d} point-group symmetry for the Sr sites, determined by the ordered arrangement of Al and Nb, as opposed to a spherical distribution commonly assumed in traditional Rietveld refinements.

  8. A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations

    PubMed Central

    Chen, Dong-Hui; Raskind, Wendy H.; Parson, William W.; Sonnen, Joshua A.; Vu, Tiffany; Zheng, YunLin; Matsushita, Mark; Wolff, John; Lipe, Hillary; Bird, Thomas D.

    2010-01-01

    An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and X-linked inheritance pattern will help clinicians arrive at the correct diagnosis. PMID:20633900

  9. The Fras1/Frem family of extracellular matrix proteins: structure, function, and association with Fraser syndrome and the mouse bleb phenotype.

    PubMed

    Petrou, Petros; Makrygiannis, Apostolos K; Chalepakis, Georges

    2008-01-01

    Fras1 and the structurally related proteins Frem1, Frem2, and Frem3, comprise a novel family of extracellular matrix proteins, which localize in a similar fashion underneath the lamina densa of epithelial basement membranes. They are involved in the structural adhesion of the skin epithelium to its underlying mesenchyme. Deficiency in the individual murine Fras1/Frem genes gives rise to the bleb phenotype, which is equivalent to the human hereditary disorder Fraser syndrome, characterized by cryptophthalmos (hidden eyes), embryonic skin blistering, renal agenesis, and syndactyly. Recent studies revealed a functional cooperation between the Fras1/Frem gene products, in which Fras1, Frem1 and Frem2 are simultaneously stabilized at the lowermost region of the basement membrane by forming a macromolecular ternary complex. Loss of any of these proteins results in the collapse of the protein assembly, thus providing a molecular explanation for the highly similar phenotypic defects displayed by the respective mutant mice. Here, we summarize the current knowledge regarding the structure, function, and interplay between the proteins of the Fras1/Frem family and further propose a possible scenario for the evolution of the corresponding genes.

  10. Belief propagation in genotype-phenotype networks.

    PubMed

    Moharil, Janhavi; May, Paul; Gaile, Daniel P; Blair, Rachael Hageman

    2016-03-01

    Graphical models have proven to be a valuable tool for connecting genotypes and phenotypes. Structural learning of phenotype-genotype networks has received considerable attention in the post-genome era. In recent years, a dozen different methods have emerged for network inference, which leverage natural variation that arises in certain genetic populations. The structure of the network itself can be used to form hypotheses based on the inferred direct and indirect network relationships, but represents a premature endpoint to the graphical analyses. In this work, we extend this endpoint. We examine the unexplored problem of perturbing a given network structure, and quantifying the system-wide effects on the network in a node-wise manner. The perturbation is achieved through the setting of values of phenotype node(s), which may reflect an inhibition or activation, and propagating this information through the entire network. We leverage belief propagation methods in Conditional Gaussian Bayesian Networks (CG-BNs), in order to absorb and propagate phenotypic evidence through the network. We show that the modeling assumptions adopted for genotype-phenotype networks represent an important sub-class of CG-BNs, which possess properties that ensure exact inference in the propagation scheme. The system-wide effects of the perturbation are quantified in a node-wise manner through the comparison of perturbed and unperturbed marginal distributions using a symmetric Kullback-Leibler divergence. Applications to kidney and skin cancer expression quantitative trait loci (eQTL) data from different mus musculus populations are presented. System-wide effects in the network were predicted and visualized across a spectrum of evidence. Sub-pathways and regions of the network responded in concert, suggesting co-regulation and coordination throughout the network in response to phenotypic changes. We demonstrate how these predicted system-wide effects can be examined in connection with

  11. New dicyano cyclometalated compounds containing Pd(II)-Tl(I) bonds as building blocks in 2D extended structures: synthesis, structure, and luminescence studies.

    PubMed

    Sicilia, Violeta; Forniés, Juan; Fuertes, Sara; Martín, Antonio

    2012-10-15

    New mixed metal complexes [PdTl(C^N)(CN)(2)] [C^N = 7,8-benzoquinolinate (bzq, 3); 2-phenylpyridinate (ppy, 4)] have been synthesized by reaction of their corresponding precursors (NBu(4))[Pd(C^N)(CN)(2)] [C^N = bzq (1), ppy (2)] with TlPF(6). Compounds 3 and 4 were studied by X-ray diffraction, showing the not-so-common Pd(II)-Tl(I) bonds. Both crystal structures exhibit 2-D extended networks fashioned by organometallic "PdTl(C^N)(CN)(2)" units, each one containing a donor-acceptor Pd(II)-Tl(I) bond, which are connected through additional Tl···N≡C contacts and weak Tl···π (bzq) contacts in the case of 3. Solid state emissions are red-shifted compared with those of the precursors and have been assigned to metal-metal'-to-ligand charge transfer (MM'LCT [d/s σ*(Pd,Tl) → π*(C^N)]) mixed with some intraligand ((3)IL[π(C^N) → π*(C^N)]) character. In diluted solution either at room temperature or 77 K, the Pd-Tl bond is no longer retained as confirmed by mass spectrometry, NMR, and UV-vis spectroscopic techniques.

  12. New dicyano cyclometalated compounds containing Pd(II)-Tl(I) bonds as building blocks in 2D extended structures: synthesis, structure, and luminescence studies.

    PubMed

    Sicilia, Violeta; Forniés, Juan; Fuertes, Sara; Martín, Antonio

    2012-10-15

    New mixed metal complexes [PdTl(C^N)(CN)(2)] [C^N = 7,8-benzoquinolinate (bzq, 3); 2-phenylpyridinate (ppy, 4)] have been synthesized by reaction of their corresponding precursors (NBu(4))[Pd(C^N)(CN)(2)] [C^N = bzq (1), ppy (2)] with TlPF(6). Compounds 3 and 4 were studied by X-ray diffraction, showing the not-so-common Pd(II)-Tl(I) bonds. Both crystal structures exhibit 2-D extended networks fashioned by organometallic "PdTl(C^N)(CN)(2)" units, each one containing a donor-acceptor Pd(II)-Tl(I) bond, which are connected through additional Tl···N≡C contacts and weak Tl···π (bzq) contacts in the case of 3. Solid state emissions are red-shifted compared with those of the precursors and have been assigned to metal-metal'-to-ligand charge transfer (MM'LCT [d/s σ*(Pd,Tl) → π*(C^N)]) mixed with some intraligand ((3)IL[π(C^N) → π*(C^N)]) character. In diluted solution either at room temperature or 77 K, the Pd-Tl bond is no longer retained as confirmed by mass spectrometry, NMR, and UV-vis spectroscopic techniques. PMID:22998590

  13. Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domain-specific structural phenotypes in the tectorial membrane

    PubMed Central

    Legan, P. Kevin; Goodyear, Richard J.; Morín, Matías; Mencia, Angeles; Pollard, Hilary; Olavarrieta, Leticia; Korchagina, Julia; Modamio-Hoybjor, Silvia; Mayo, Fernando; Moreno, Felipe; Moreno-Pelayo, Miguel-Angel; Richardson, Guy P.

    2014-01-01

    Tecta is a modular, non-collagenous protein of the tectorial membrane (TM), an extracellular matrix of the cochlea essential for normal hearing. Missense mutations in Tecta cause dominant forms of non-syndromic deafness and a genotype–phenotype correlation has been reported in humans, with mutations in different Tecta domains causing mid- or high-frequency hearing impairments that are either stable or progressive. Three mutant mice were created as models for human Tecta mutations; the TectaL1820F,G1824D/+ mouse for zona pellucida (ZP) domain mutations causing stable mid-frequency hearing loss in a Belgian family, the TectaC1837G/+ mouse for a ZP-domain mutation underlying progressive mid-frequency hearing loss in a Spanish family and the TectaC1619S/+ mouse for a zonadhesin-like (ZA) domain mutation responsible for progressive, high-frequency hearing loss in a French family. Mutations in the ZP and ZA domains generate distinctly different changes in the structure of the TM. Auditory brainstem response thresholds in the 8–40 kHz range are elevated by 30–40 dB in the ZP-domain mutants, whilst those in the ZA-domain mutant are elevated by 20–30 dB. The phenotypes are stable and no evidence has been found for a progressive deterioration in TM structure or auditory function. Despite elevated auditory thresholds, the Tecta mutant mice all exhibit an enhanced tendency to have audiogenic seizures in response to white noise stimuli at low sound pressure levels (≤84 dB SPL), revealing a previously unrecognised consequence of Tecta mutations. These results, together with those from previous studies, establish an allelic series for Tecta unequivocally demonstrating an association between genotype and phenotype. PMID:24363064

  14. Characterization of Maize Amylose-Extender (ae) Mutant Starches. Part I: Relationship Between Resistant Starch Contents and Molecular Structures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endosperm starches were isolated from kernels of seven maize amylose-extender (ae) lines. The resistant starch (RS) contents, measured using AOAC method 991.43, showed that three new ae-mutant starch lines developed by the USDA-ARS Germplasm Enhancement (GEM) and Truman State University had larger R...

  15. Using an Advanced Computational Laboratory Experiment to Extend and Deepen Physical Chemistry Students' Understanding of Atomic Structure

    ERIC Educational Resources Information Center

    Hoffman, Gary G.

    2015-01-01

    A computational laboratory experiment is described, which involves the advanced study of an atomic system. The students use concepts and techniques typically covered in a physical chemistry course but extend those concepts and techniques to more complex situations. The students get a chance to explore the study of atomic states and perform…

  16. The stay-green phenotype of TaNAM-RNAi wheat plants is associated with maintenance of chloroplast structure and high enzymatic antioxidant activity.

    PubMed

    Checovich, Mariana L; Galatro, Andrea; Moriconi, Jorge I; Simontacchi, Marcela; Dubcovsky, Jorge; Santa-María, Guillermo E

    2016-07-01

    TaNAM transcription factors play an important role in controlling senescence, which in turn, influences the delivery of nitrogen, iron and other elements to the grain of wheat (Triticum aestivum) plants, thus contributing to grain nutritional value. While lack or diminished expression of TaNAMs determines a stay-green phenotype, the precise effect of these factors on chloroplast structure has not been studied. In this work we focused on the events undergone by chloroplasts in two wheat lines having either control or diminished TaNAM expression due to RNA interference (RNAi). It was found that in RNAi plants maintenance of chlorophyll levels and maximal photochemical efficiency of photosystem II were associated with lack of chloroplast dismantling. Flow cytometer studies and electron microscope analysis showed that RNAi plants conserved organelle ultrastructure and complexity. It was also found that senescence in control plants was accompanied by a low leaf enzymatic antioxidant activity. Lack of chloroplast dismantling in RNAi plants was associated with maintenance of protein and iron concentration in the flag leaf, the opposite being observed in control plants. These data provide a structural basis for the observation that down regulation of TaNAMs confers a functional stay-green phenotype and indicate that the low export of iron and nitrogen from the flag leaf of these plants is concomitant, within the developmental window studied, with lack of chloroplast degradation and high enzymatic antioxidant activity.

  17. Genetic Structure Is Associated with Phenotypic Divergence in Floral Traits and Reproductive Investment in a High-Altitude Orchid from the Iron Quadrangle, Southeastern Brazil

    PubMed Central

    Leles, Bruno; Chaves, Anderson V.; Russo, Philip; Batista, João A. N.; Lovato, Maria Bernadete

    2015-01-01

    Knowledge of the role of Neotropical montane landscapes in shaping genetic connectivity and local adaptation is essential for understanding the evolutionary processes that have shaped the extraordinary species diversity in these regions. In the present study, we examined the landscape genetics, estimated genetic diversity, and explored genetic relationships with morphological variability and reproductive strategies in seven natural populations of Cattleya liliputana (Orchidaceae). Nuclear microsatellite markers were used for genetic analyses. Spatial Bayesian clustering and population-based analyses revealed significant genetic structuring and high genetic diversity (He = 0.733 ± 0.03). Strong differentiation was found between populations over short spatial scales (FST = 0.138, p < 0.001), reflecting the landscape discontinuity and isolation. Monmonier´s maximum difference algorithm, Bayesian analysis on STRUCTURE and principal component analysis identified one major genetic discontinuity between populations. Divergent genetic groups showed phenotypic divergence in flower traits and reproductive strategies. Increased sexual reproductive effort was associated with rock outcrop type and may be a response to adverse conditions for growth and vegetative reproduction. Here we discuss the effect of restricted gene flow, local adaptation and phenotypic plasticity as drivers of population differentiation in Neotropical montane rock outcrops. PMID:25756994

  18. Structural in silico dissection of the collagen V interactome to identify genotype-phenotype correlations in classic Ehlers-Danlos Syndrome (EDS).

    PubMed

    Paladin, Lisanna; Tosatto, Silvio C E; Minervini, Giovanni

    2015-12-21

    Collagen V mutations are associated with Elhers-Danlos syndrome (EDS), a group of heritable collagenopathies. Collagen V structure is not available and the disease-causing mechanism is unclear. To address this issue, we manually curated missense mutations suspected to promote classic type EDS (cEDS) insurgence from the literature and performed a genotype-phenotype correlation study. Further, we generated a homology model of the collagen V triple helix to evaluate the pathogenic effects. The resulting structure was used to map known protein-protein interactions enriched with in silico predictions. An interaction network model for collagen V was created. We found that cEDS heterogeneous manifestations may be explained by the involvement in two different extracellular matrix pathways, related to cell adhesion and tissue repair or cell differentiation, growth and apoptosis.

  19. Structural in silico dissection of the collagen V interactome to identify genotype-phenotype correlations in classic Ehlers-Danlos Syndrome (EDS).

    PubMed

    Paladin, Lisanna; Tosatto, Silvio C E; Minervini, Giovanni

    2015-12-21

    Collagen V mutations are associated with Elhers-Danlos syndrome (EDS), a group of heritable collagenopathies. Collagen V structure is not available and the disease-causing mechanism is unclear. To address this issue, we manually curated missense mutations suspected to promote classic type EDS (cEDS) insurgence from the literature and performed a genotype-phenotype correlation study. Further, we generated a homology model of the collagen V triple helix to evaluate the pathogenic effects. The resulting structure was used to map known protein-protein interactions enriched with in silico predictions. An interaction network model for collagen V was created. We found that cEDS heterogeneous manifestations may be explained by the involvement in two different extracellular matrix pathways, related to cell adhesion and tissue repair or cell differentiation, growth and apoptosis. PMID:26608033

  20. High resolution spectrometer for extended x-ray absorption fine structure measurements in the 6 keV to 15 keV energy range

    NASA Astrophysics Data System (ADS)

    Seely, J. F.; Hudson, L. T.; Henins, Albert; Feldman, U.

    2016-11-01

    A Cauchois transmission-crystal spectrometer has been developed with high crystal resolving power in the 6 keV-15 keV energy range and sufficient sensitivity to record single-shot spectra from the Lawrence Livermore National Laboratory (LLNL) Titan laser and other comparable or more energetic lasers. The spectrometer capabilities were tested by recording the W L transitions from a laboratory source and the extended x-ray absorption fine structure (EXAFS) spectrum through a Cu foil.

  1. The Effects of X Chromosome Loss on Neuroanatomical and Cognitive Phenotypes During Adolescence: a Multi-modal Structural MRI and Diffusion Tensor Imaging Study.

    PubMed

    Xie, Sheng; Zhang, Zhixin; Zhao, Qiuling; Zhang, Jiaying; Zhong, Suyu; Bi, Yanchao; He, Yong; Pan, Hui; Gong, Gaolang

    2015-09-01

    The absence of all or part of one X chromosome in female humans causes Turner's syndrome (TS), providing a unique "knockout model" to investigate the role of the X chromosome in neuroanatomy and cognition. Previous studies have demonstrated TS-associated brain differences; however, it remains largely unknown 1) how the brain structures are affected by the type of X chromosome loss and 2) how X chromosome loss influences the brain-cognition relationship. Here, we addressed these by investigating gray matter morphology and white matter connectivity using a multimodal MRI dataset from 34 adolescent TS patients (13 mosaic and 21 nonmosaic) and 21 controls. Intriguingly, the 2 TS groups exhibited significant differences in surface area in the right angular gyrus and in white matter integrity of the left tapetum of corpus callosum; these data support a link between these brain phenotypes and the type of X chromosome loss in TS. We further showed that the X chromosome modulates specific brain-cognition relationships: thickness and surface area in multiple cortical regions are positively correlated with working-memory performance in controls but negatively in TS. These findings provide novel insights into the X chromosome effect on neuroanatomical and cognitive phenotypes and highlight the role of genetic factors in brain-cognition relationships.

  2. Microbial structural diversity estimated by dilution-extinction of phenotypic traits and T-RFLP analysis along a land-use intensification gradient

    NASA Technical Reports Server (NTRS)

    Gomez, Elena del V.; Garland, Jay L.; Roberts, Michael S.

    2004-01-01

    The present work tested whether the relationship between functional traits and inoculum density reflected structural diversity in bacterial communities from a land-use intensification gradient applying a mathematical model. Terminal restriction fragment length polymorphism (T-RFLP) analysis was also performed to provide an independent assessment of species richness. Successive 10-fold dilutions of a soil suspension were inoculated onto Biolog GN(R) microplates. Soil bacterial density was determined by total cell and plate counts. The relationship between phenotypic traits and inoculum density fit the model, allowing the estimation of maximal phenotypic potential (Rmax) and inoculum density (KI) at which Rmax will be half-reduced. Though Rmax decreased with time elapsed since clearing of native vegetation, KI remained high in two of the disturbed sites. The genetic pool of bacterial community did not experience a significant reduction, but the active fraction responding in the Biolog assay was adversely affected, suggesting a reduction in the functional potential. c2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

  3. The Effects of X Chromosome Loss on Neuroanatomical and Cognitive Phenotypes During Adolescence: a Multi-modal Structural MRI and Diffusion Tensor Imaging Study.

    PubMed

    Xie, Sheng; Zhang, Zhixin; Zhao, Qiuling; Zhang, Jiaying; Zhong, Suyu; Bi, Yanchao; He, Yong; Pan, Hui; Gong, Gaolang

    2015-09-01

    The absence of all or part of one X chromosome in female humans causes Turner's syndrome (TS), providing a unique "knockout model" to investigate the role of the X chromosome in neuroanatomy and cognition. Previous studies have demonstrated TS-associated brain differences; however, it remains largely unknown 1) how the brain structures are affected by the type of X chromosome loss and 2) how X chromosome loss influences the brain-cognition relationship. Here, we addressed these by investigating gray matter morphology and white matter connectivity using a multimodal MRI dataset from 34 adolescent TS patients (13 mosaic and 21 nonmosaic) and 21 controls. Intriguingly, the 2 TS groups exhibited significant differences in surface area in the right angular gyrus and in white matter integrity of the left tapetum of corpus callosum; these data support a link between these brain phenotypes and the type of X chromosome loss in TS. We further showed that the X chromosome modulates specific brain-cognition relationships: thickness and surface area in multiple cortical regions are positively correlated with working-memory performance in controls but negatively in TS. These findings provide novel insights into the X chromosome effect on neuroanatomical and cognitive phenotypes and highlight the role of genetic factors in brain-cognition relationships. PMID:24770708

  4. Integration of genome and phenotypic scanning gives evidence of genetic structure in Mesoamerican common bean (Phaseolus vulgaris L.) landraces from the southwest of Europe.

    PubMed

    Santalla, M; De Ron, A M; De La Fuente, M

    2010-05-01

    Southwestern Europe has been considered as a secondary centre of genetic diversity for the common bean. The dispersal of domesticated materials from their centres of origin provides an experimental system that reveals how human selection during cultivation and adaptation to novel environments affects the genetic composition. In this paper, our goal was to elucidate how distinct events could modify the structure and level of genetic diversity in the common bean. The genome-wide genetic composition was analysed at 42 microsatellite loci in individuals of 22 landraces of domesticated common bean from the Mesoamerican gene pool. The accessions were also characterised for phaseolin seed protein and for nine allozyme polymorphisms and phenotypic traits. One of this study's important findings was the complementary information obtained from all the polymorphisms examined. Most of the markers found to be potentially under the influence of selection were located in the proximity of previously mapped genes and quantitative trait loci (QTLs) related to important agronomic traits, which indicates that population genomics approaches are very efficient in detecting QTLs. As it was revealed by outlier simple sequence repeats, loci analysis with STRUCTURE software and multivariate analysis of phenotypic data, the landraces were grouped into three clusters according to seed size and shape, vegetative growth habit and genetic resistance. A total of 151 alleles were detected with an average of 4 alleles per locus and an average polymorphism information content of 0.31. Using a model-based approach, on the basis of neutral markers implemented in the software STRUCTURE, three clusters were inferred, which were in good agreement with multivariate analysis. Geographic and genetic distances were congruent with the exception of a few putative hybrids identified in this study, suggesting a predominant effect of isolation by distance. Genomic scans using both markers linked to genes affected

  5. Trust-region based instantaneous optimal semi-active control of long-span spatially extended structures with MRF-04K damper

    NASA Astrophysics Data System (ADS)

    Lin, Wei; Li, Zhongxian; Ding, Yang

    2008-12-01

    In the field of civil engineering, magneto rheological fluid (MRF) damper-based semi-active control systems have received considerable attention for use in protecting structures from natural hazards such as strong earthquakes and high winds. In this paper, the MRF damper-based semi-active control system is applied to a long-span spatially extended structure and its feasibility is discussed. Meanwhile, a trust-region method based instantaneous optimal semi-active control algorithm (TIOC) is proposed to improve the performance of the semi-active control system in a multiple damper situation. The proposed TIOC describes the control process as a bounded constraint optimization problem, in which an optimal semiactive control force vector is solved by the trust-region method in every control step to minimize the structural responses. A numerical example of a railway station roof structure installed with MRF-04K dampers is presented. First, a modified Bouc-Wen model is utilized to describe the behavior of the selected MRF-04K damper. Then, two semi-active control systems, including the well-known clipped-optimal controller and the proposed TIOC controller, are considered. Based on the characteristics of the long-span spatially extended structure, the performance of the control system is evaluated under uniform earthquake excitation and travelling-wave excitation with different apparent velocities. The simulation results indicate that the MR fluid damper-based semi-active control systems have the potential to mitigate the responses of full-scale long-span spatially extended structures under earthquake hazards. The superiority of the proposed TIOC controller is demonstrated by comparing its control effectiveness with the clipped-optimal controller for several different cases.

  6. High temperature extended x-ray absorption fine structure study of multiferroic BiFeO3

    NASA Astrophysics Data System (ADS)

    Raghavendra Reddy, V.; Meneghini, Carlo; Kothari, Deepti; Gupta, Ajay; Aquilanti, Giuliana

    2012-08-01

    Local atomic structure modifications around Fe atoms in polycrystalline multiferroic BiFeO3 are studied by Fe K edge x-ray absorption spectroscopy as a function of temperature across the Néel temperature (TN = 643 K) in order to reveal local structure modifications related to the magnetic transition. This work demonstrates that on crossing TN the local structure around Fe shows peculiar changes: the Fe-O bond lengths get shorter, the ligand symmetry increases and the Fe-O bond length disorder (σ2) deviates from Debye behaviour. These results suggest that the structural transition at the ferroelectric Curie temperature (TC = 1103 K) is anticipated by early local rearrangement of the structure starting already at TN.

  7. The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships.

    PubMed

    Shaghafi, Michael B; Barrett, David G; Willard, Francis S; Overman, Larry E

    2014-02-15

    We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner.

  8. Extended X-ray absorption fine structure studies of Zn2Fe2 hybrid hemoglobins: absence of heme bond length changes in half-ligated species.

    PubMed

    Simolo, K; Korszun, Z R; Stucky, G; Moffat, K; McLendon, G; Bunker, G

    1986-07-01

    Metal hybrid hemoglobins, in which Zn(II) replaces Fe(II), have been structurally characterized by extended X-ray absorption structure (EXAFS) studies. Since Zn and Fe have very different K absorption edge energies, the structures of the ligated (Fe) and unligated (Zn) sites could be examined independently within a single molecule that mimics an intermediate ligation state. The observed EXAFS spectra and associated structural parameters are compared among the ligand free (alpha Zn)2(beta Zn)2, half-ligated (alpha FeCO)2(beta Zn)2 and (alpha Zn)2(beta FeCO)2, and fully ligated (alpha FeCO)2(beta FeCO)2 systems.

  9. Extended BCDM

    NASA Astrophysics Data System (ADS)

    Occhionero, Franco; Baccigalupi, Carlo; Amendola, Luca

    1999-05-01

    We propose a new inflationary toy model that produces two episodes of phase transitions. With the first one, super-horizon-sized bubbles are nucleated, which are seen from inside as open universes, thereby reconciling inflation with the recent observations of a low Ω0. With the second transition, a distribution of sub-horizon voids, of sizes typically around 10-100 Mpc/h are generated inside the open universes. These primordial voids can be the seeds of the present large scale voids that are detected in redshift surveys, and provide a non-Gaussian signal on the microwave background. The model realizes this sequence along the same slow-rolling path, by modulating the energy difference between the vacuum states. In this model, that we call extended Bubbly CDM, openness and bubblyness, rather than flatness and homogeneity, are the main products of inflation.

  10. The structural basis of the dominant negative phenotype of the Gαi1β1γ2 G203A/A326S heterotrimer

    PubMed Central

    Liu, Ping; Jia, Ming-zhu; Zhou, X Edward; De Waal, Parker W; Dickson, Bradley M; Liu, Bo; Hou, Li; Yin, Yan-ting; Kang, Yan-yong; Shi, Yi; Melcher, Karsten; Xu, H Eric; Jiang, Yi

    2016-01-01

    Aim: Dominant negative mutant G proteins have provided critical insight into the mechanisms of G protein-coupled receptor (GPCR) signaling, but the mechanisms underlying the dominant negative characteristics are not completely understood. The aim of this study was to determine the structure of the dominant negative Gαi1β1γ2 G203A/A326S complex (Gi-DN) and to reveal the structural basis of the mutation-induced phenotype of Gαi1β1γ2. Methods: The three subunits of the Gi-DN complex were co-expressed with a baculovirus expression system. The Gi-DN heterotrimer was purified, and the structure of its complex with GDP was determined through X-ray crystallography. Results: The Gi-DN heterotrimer structure revealed a dual mechanism underlying the dominant negative characteristics. The mutations weakened the hydrogen bonding network between GDP/GTP and the binding pocket residues, and increased the interactions in the Gα-Gβγ interface. Concomitantly, the Gi-DN heterotrimer adopted a conformation, in which the C-terminus of Gαi and the N-termini of both the Gβ and Gγ subunits were more similar to the GPCR-bound state compared with the wild type complex. From these structural observations, two additional mutations (T48F and D272F) were designed that completely abolish the GDP binding of the Gi-DN heterotrimer. Conclusion: Overall, the results suggest that the mutations impede guanine nucleotide binding and Gα-Gβγ protein dissociation and favor the formation of the G protein/GPCR complex, thus blocking signal propagation. In addition, the structure provides a rationale for the design of other mutations that cause dominant negative effects in the G protein, as exemplified by the T48F and D272F mutations. PMID:27498775

  11. Structure and orientation of the Mn4Ca cluster in plant photosystem II membranes studied by polarized range-extended x-ray absorption spectroscopy.

    PubMed

    Pushkar, Yulia; Yano, Junko; Glatzel, Pieter; Messinger, Johannes; Lewis, Azul; Sauer, Kenneth; Bergmann, Uwe; Yachandra, Vittal

    2007-03-01

    X-ray absorption spectroscopy has provided important insights into the structure and function of the Mn(4)Ca cluster in the oxygen-evolving complex of Photosystem II (PS II). The range of manganese extended x-ray absorption fine structure data collected from PS II until now has been, however, limited by the presence of iron in PS II. Using a crystal spectrometer with high energy resolution to detect solely the manganese Kalpha fluorescence, we are able to extend the extended x-ray absorption fine structure range beyond the onset of the iron absorption edge. This results in improvement in resolution of the manganese-backscatterer distances in PS II from 0.14 to 0.09A(.) The high resolution data obtained from oriented spinach PS II membranes in the S(1) state show that there are three di-mu-oxo-bridged manganese-manganese distances of approximately 2.7 and approximately 2.8A in a 2:1 ratio and that these three manganese-manganese vectors are aligned at an average orientation of approximately 60 degrees relative to the membrane normal. Furthermore, we are able to observe the separation of the Fourier peaks corresponding to the approximately 3.2A manganese-manganese and the approximately 3.4A manganese-calcium interactions in oriented PS II samples and determine their orientation relative to the membrane normal. The average of the manganese-calcium vectors at approximately 3.4A is aligned along the membrane normal, while the approximately 3.2A manganese-manganese vector is oriented near the membrane plane. A comparison of this structural information with the proposed Mn(4)Ca cluster models based on spectroscopic and diffraction data provides input for refining and selecting among these models.

  12. Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity

    PubMed Central

    Wang, Juexin; Shen, Dingding; Xia, Geqing; Shen, Wangzhen; Macdonald, Robert L.; Xu, Dong; Kang, Jing-Qiong

    2016-01-01

    Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities. Structural modeling and structure-based analysis indicated that the surface of the wild-type γ2 subunit was naturally hydrophobic, which is suitable to be buried in the cell membrane. Different mutant γ2 subunits had different stabilities and different interactions with their wild-type subunit binding partners because they adopted different conformations and had different surface hydrophobicities and different tendency to dimerize. We utilized flow cytometry and biochemical approaches in combination with lifted whole cell patch-clamp recordings. We demonstrated that the truncated subunits had no to minimal surface expression and unchanged or reduced surface expression of wild-type partnering subunits. The amplitudes of GABA-evoked currents from the mutant α1β2γ2(R136*), α1β2γ2(Q390*) and α1β2γ2(W429*) receptors were reduced compared to the currents from α1β2γ2 receptors but with differentially reduced levels. This thus suggests differential protein structure disturbances are correlated with disease severity. PMID:27762395

  13. Exploration of Heterogeneous Chemistry in Model Atmospheric Particles Using Extended X-ray Absorption Fine Structure Analysis

    SciTech Connect

    Bramante,J.; Hinrichs, R.; Brown, E.; Calvin, S.

    2007-01-01

    As models of the composition and heterogeneous chemical reactions of the troposphere undergo refinement, novel application of state-of-the-art analytical techniques will be necessary to propound realistic characterizations of mineral dust chemistry. In this study, strontium carbonate particles treated with gaseous nitric acid and nitrogen dioxide were examined with X-ray absorption fine structure analysis (EXAFS). The X-ray spectra of carbonate and nitrate standards were fitted to ab initio calculations, which were used to determine the structure and consistency of strontium nitrate formed on strontium carbonate. By examining differences in mean square radial displacement and lattice spacing values obtained for bulk Sr(NO3)2 as compared to Sr(NO3)2 formed on SrCO3, EXAFS proves effective as a tool for investigating the local structure and composition of heterogeneous aerosol particles. The implications of findings on reacted strontium carbonate for atmospheric models of calcium carbonate aerosol are discussed.

  14. [Plasticity of the cellular phenotype].

    PubMed

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours. PMID:21501574

  15. [Plasticity of the cellular phenotype].

    PubMed

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours.

  16. Structured three-dimensional co-culture of mesenchymal stem cells with meniscus cells promotes meniscal phenotype without hypertrophy

    PubMed Central

    Cui, Xiaofeng; Hasegawa, Akihiko; Lotz, Martin; D’Lima, Darryl

    2012-01-01

    Menisci play a crucial role in weight distribution, load bearing, shock absorption, lubrication, and nutrition of articular cartilage within the knee joint. Damage to the meniscus typically does not heal spontaneously due to its partial avascular nature. Partial or complete meniscectomy is a common clinical treatment of the defective meniscus. However, this procedure ultimately leads to osteoarthritis due to increased mechanical stress to the articular cartilage. Meniscus tissue engineering offers a promising solution for partial or complete meniscus deficiency. Mesenchymal stem cells (MSC) have the potential to differentiate into meniscal fibrochondrocyte as well as deliver trophic effects to the differentiated cells. This study tested the feasibility of using MSC co-cultured with mature meniscal cells (MC) for meniscus tissue engineering. Structured cell pellets were created using MC and MSC at varying ratios (100:0, 75:25, 50:50, 25:75, and 0:100) and cultured with or without transforming growth factor-beta 3 supplemented chondrogenic media for 21 days. The meniscal and hypertrophic gene expression, gross appearance and structure of the pellets, meniscus extracellular matrix (ECM), histology and immunohistochemistry of proteoglycan and collagen were evaluated. Co-culture of MC with MSC at 75:25 demonstrated highest levels of collagen type I and glycosaminoglycans (GAG) production, as well as the lowest levels of hypertrophic genes, such as COL10A1 and MMP13. All co-culture conditions showed better meniscus ECM production and hypertrophic inhibition as compared to MSC culture alone. The collagen fiber bundles observed in the co-cultures are important to produce heterogenic ECM structure of meniscus. In conclusion, co-culturing MC and MSC is a feasible and efficient approach to engineer meniscus tissue with enhanced ECM production without hypertrophy. PMID:22422555

  17. Conceptual and Data-based Investigation of Genetic Influences and Brain Asymmetry: A Twin Study of Multiple Structural Phenotypes

    PubMed Central

    Eyler, Lisa T.; Vuoksimaa, Eero; Panizzon, Matthew S.; Fennema-Notestine, Christine; Neale, Michael C.; Chen, Chi-Hua; Jak, Amy; Franz, Carol E.; Lyons, Michael J.; Thompson, Wesley K.; Spoon, Kelly M.; Fischl, Bruce; Dale, Anders M.; Kremen, William S.

    2014-01-01

    Right–left regional cerebral differences are a feature of the human brain linked to functional abilities, aging, and neuro-developmental and mental disorders. The role of genetic factors in structural asymmetry has been incompletely studied. We analyzed data from 515 individuals (130 monozygotic twin pairs, 97 dizygotic pairs, and 61 unpaired twins) from the Vietnam Era Twin Study of Aging to answer three questions about genetic determinants of brain structural asymmetry: First, does the magnitude of heritability differ for homologous regions in each hemisphere? Despite adequate power to detect regional differences, heritability estimates were not significantly larger in one hemisphere versus the other, except left > right inferior lateral ventricle heritability. Second, do different genetic factors influence left and right hemisphere size in homologous regions? Inter-hemispheric genetic correlations were high and significant; in only two subcortical regions (pallidum and accumbens) did the estimate statistically differ from 1.0. Thus, there was little evidence for different genetic influences on left and right hemisphere regions. Third, to what extent do genetic factors influence variability in left–right size differences? There was no evidence that variation in asymmetry (i.e., the size difference) of left and right homologous regions was genetically determined, except in pallidum and accumbens. Our findings suggest that genetic factors do not play a significant role in determining individual variation in the degree of regional cortical size asymmetries measured with MRI, although they may do so for volume of some subcortical structures. Despite varying interpretations of existing left–right, we view the present results as consistent with previous findings. PMID:24283492

  18. Crystal structure of the infectious phenotype-associated outer surface protein BBA66 from the Lyme disease agent Borrelia burgdorferi.

    PubMed

    Brangulis, Kalvis; Petrovskis, Ivars; Kazaks, Andris; Tars, Kaspars; Ranka, Renate

    2014-02-01

    Borrelia burgdorferi, the causative agent of Lyme disease is transmitted to the mammalian host organisms by infected Ixodes ticks. Transfer of the spirochaetal bacteria from Ixodes ticks to the warm-blooded mammalian organism provides a challenge for the bacteria to adapt and survive in the different environmental conditions. B. burgdorferi has managed to differentially express genes in response to the encountered changes such as temperature and pH variance or metabolic rate to survive in both environments. In recent years, much interest has been turned on genes that are upregulated during the borrelial transfer to mammalian organisms as this could reveal the proteins important in the pathogenesis of Lyme disease. BBA66 is one of the upregulated outer surface proteins thought to be important in the pathogenesis of B. burgdorferi as it has been found out that BBA66 is necessary during the transmission and propagation phase to initiate Lyme disease. As there is still little known about the pathogenesis of B. burgdorferi, we have solved the crystal structure of the outer surface protein BBA66 at 2.25Å resolution. A monomer of BBA66 consists of 6 α-helices packed in a globular domain, and the overall folding is similar to the homologous proteins BBA64, BBA73, and CspA. Structure-based sequence alignment with the homologous protein BBA64 revealed that the conserved residues are mainly located inwards the core region of the protein and thus may be required to maintain the overall fold of the protein. Unlike the other homologous proteins, BBA66 has an atypically long disordered region at the N terminus thought to act as a "tether" between the structural domain and the cell surface.

  19. Rats subjected to extended L-tryptophan restriction during early postnatal stage exhibit anxious-depressive features and structural changes.

    PubMed

    Zhang, Limei; Guadarrama, Leyla; Corona-Morales, Aleph A; Vega-Gonzalez, Arturo; Rocha, Luisa; Escobar, Alfonso

    2006-06-01

    Serotonin transmission dysfunction has been suggested to play an important role in depression and anxiety. This study reports the results of a series of experiments in which rats were subjected to extended maize-based tortilla diets during early postnatal stages. This diet contains only approximately 20% of the L-tryptophan in normal diets of laboratory rodents. Compared with controls, experimental rats displayed a significant increase of immobility counts in the forced swimming test and exhibited anxiety-like behavior in the elevated plus maze test after 1 month of diet treatment. Low levels of serotonin contents were found in prefrontal cortex, striatum, hippocampus, and brainstem using high-performance liquid chromatography. Immunocytochemical reactions against 5-Bromo-2'-deoxyuridine revealed a significant decrease in the proliferation rate for the subgranular zone of dentate gyrus. c-Fos expression after the forced swimming test was found reduced in prefrontal cortex, dentate gyrus, CA1, and hilus of hippocampus and amygdala. Moreover, dendrite arbor atrophy and decreased spine density were evident in Golgi-Cox-impregnated CA1 pyramidal neurons. Abnormal dendrite swelling in dentate gyrus granule cells was also observed. These findings indicate an involvement of hyposerotoninergia in emotional disturbance produced by L-tryptophan restriction during critical developmental stages and suggest that neuroplasticity changes might underlie these changes.

  20. Infrared quasi-fixed-point structure in extended Yukawa sectors and application to R-parity violation

    NASA Astrophysics Data System (ADS)

    Mambrini, Y.; Moultaka, G.

    2002-06-01

    We investigate the one-loop renormalization-group evolution of extended sectors of Yukawa-type couplings. It is shown that Landau poles, which usually provide the necessary low-energy upper bounds that saturate quickly with increasing initial value conditions, lead in some cases to the opposite behavior: some of the low-energy couplings decrease and become vanishingly small for increasingly large initial conditions. We write down the general criteria for this to happen in typical situations, highlighting a concept of repulsive quasifixed points, and illustrate the case both within a two-Yukawa toy model as well as in the minimal supersymmetric standard model with R-parity violation. In the latter case, we consider the theoretical upper bounds on the various couplings, identifying regimes where λkl3,λ'kkk,λ″3kl are dynamically suppressed due to the Landau pole. We stress the importance of considering a large number of couplings simultaneously. This leads altogether to a phenomenologically interesting seesaw effect in the magnitudes of the various R-parity violating couplings, complementing and in some cases improving the existing limits.

  1. Relativistically parameterized extended Hueckel calculations. 3. Structure and bonding for some compounds of uranium and other heavy elements

    SciTech Connect

    Pyykkoe, P.; Lohr, L.L. Jr.

    1981-07-01

    The relativistically parameterized extended Hueckel molecular orbital method REX is used to explore the effects of relativity upon molecular orbital energies and compositions. The uranium compounds studied are UO/sub 2//sup 2 +/, UO/sub 2/Cl/sub 4//sup 2 -/, UF/sub 6/, UCl/sub 6/, UCl/sub 4/, U(BH/sub 4/)/sub 4/, and U(C/sub 8/H/sub 8/)/sub 2/. Other heavy element compounds studied are MI/sub 3/ (M = La, Gd, Lu), PoH/sub 2/, (eka)PoH/sub 2/, I/sub 3//sup -/, AtI/sub 2//sup -/, and RnF/sub 2/. Relativistic orbital energy parameters and atomic orbital exponents are presented as supplementary material for all elements with Z = 1 to 120 together with corresponding nonrelativistic values for all elements with Z = 1 to 100. It is concluded that the REX method provides semiquantitative estimates of spin-orbit splittings and relativistic bonding effects for compounds of heavy elements.

  2. Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation and CNS structural anomalies: defining the phenotype.

    PubMed

    Guion-Almeida, M L; Richieri-Costa, A

    2001-04-01

    We report a Brazilian boy, born to normal and nonconsanguineous parents showing, among other signs, brachycephaly, a wide forehead, a widow's peak, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, a broad nasal root, a long philtrum, macrostomia, prominent lips, a high arched palate, a midline alveolar cleft, a small and grooved chin, ear anomalies, structural anomaly of the corpus callosum, and mental retardation. To our knowledge this additional patient defines a particular clinical condition previously reported [Guion-Almeida M.L. Richieri-Costa A. (1999) Clinical Dysmorphol 8;1-4; Masuno M. et al. (2000) Clin Dysmorphol 9:59-60].

  3. Thermal and magnetic anomalies of α-iron: an exploration by extended x-ray absorption fine structure spectroscopy and synchrotron x-ray diffraction

    NASA Astrophysics Data System (ADS)

    Boccato, Silvia; Sanson, Andrea; Kantor, Innokenty; Mathon, Olivier; Dyadkin, Vadim; Chernyshov, Dmitry; Carnera, Alberto; Pascarelli, Sakura

    2016-09-01

    The local structure and dynamics of α-iron have been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy and x-ray diffraction (XRD) in order to shed light on some thermal and magnetic anomalies observed in the last decades. The quantitative EXAFS analysis of the first two coordination shells reveals a peculiar local vibrational dynamics of α-iron: the second neighbor distance exhibits anharmonicity and vibrational anisotropy larger than the first neighbor distance. We search for possible distortions of the bcc structure to justify the unexplained magnetostriction anomalies of α-iron and provide a value for the maximum dislocation of the central Fe atom. No thermal anomalies have been detected from the current XRD data. On the contrary, an intriguing thermal anomaly at about 150 K, ascribed to a stiffening of the Fe–Fe bonds, was found by EXAFS.

  4. Thermal and magnetic anomalies of α-iron: an exploration by extended x-ray absorption fine structure spectroscopy and synchrotron x-ray diffraction

    NASA Astrophysics Data System (ADS)

    Boccato, Silvia; Sanson, Andrea; Kantor, Innokenty; Mathon, Olivier; Dyadkin, Vadim; Chernyshov, Dmitry; Carnera, Alberto; Pascarelli, Sakura

    2016-09-01

    The local structure and dynamics of α-iron have been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy and x-ray diffraction (XRD) in order to shed light on some thermal and magnetic anomalies observed in the last decades. The quantitative EXAFS analysis of the first two coordination shells reveals a peculiar local vibrational dynamics of α-iron: the second neighbor distance exhibits anharmonicity and vibrational anisotropy larger than the first neighbor distance. We search for possible distortions of the bcc structure to justify the unexplained magnetostriction anomalies of α-iron and provide a value for the maximum dislocation of the central Fe atom. No thermal anomalies have been detected from the current XRD data. On the contrary, an intriguing thermal anomaly at about 150 K, ascribed to a stiffening of the Fe-Fe bonds, was found by EXAFS.

  5. Thermal and magnetic anomalies of α-iron: an exploration by extended x-ray absorption fine structure spectroscopy and synchrotron x-ray diffraction.

    PubMed

    Boccato, Silvia; Sanson, Andrea; Kantor, Innokenty; Mathon, Olivier; Dyadkin, Vadim; Chernyshov, Dmitry; Carnera, Alberto; Pascarelli, Sakura

    2016-09-01

    The local structure and dynamics of α-iron have been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy and x-ray diffraction (XRD) in order to shed light on some thermal and magnetic anomalies observed in the last decades. The quantitative EXAFS analysis of the first two coordination shells reveals a peculiar local vibrational dynamics of α-iron: the second neighbor distance exhibits anharmonicity and vibrational anisotropy larger than the first neighbor distance. We search for possible distortions of the bcc structure to justify the unexplained magnetostriction anomalies of α-iron and provide a value for the maximum dislocation of the central Fe atom. No thermal anomalies have been detected from the current XRD data. On the contrary, an intriguing thermal anomaly at about 150 K, ascribed to a stiffening of the Fe-Fe bonds, was found by EXAFS.

  6. Extending the molecular size in accurate quantum-chemical calculations: the equilibrium structure and spectroscopic properties of uracil.

    PubMed

    Puzzarini, Cristina; Barone, Vincenzo

    2011-04-21

    The equilibrium structure of uracil has been investigated using both theoretical and experimental data. With respect to the former, quantum-chemical calculations at the coupled-cluster level in conjunction with a triple-zeta basis set have been carried out. Extrapolation to the basis set limit, performed employing the second-order Møller-Plesset perturbation theory, and inclusion of core-correlation and diffuse-function corrections have also been considered. Based on the available rotational constants for various isotopic species together with corresponding computed vibrational corrections, the semi-experimental equilibrium structure of uracil has been determined for the first time. Theoretical and semi-experimental structures have been found in remarkably good agreement, thus pointing out the limitations of previous experimental determinations. Molecular and spectroscopic properties of uracil have then been studied by means of the composite computational approach introduced for the molecular structure evaluation. Among the results achieved, we mention the revision of the dipole moment. On the whole, it has been proved that the computational procedure presented is able to provide parameters with the proper accuracy to support experimental investigations of large molecules of biological interest.

  7. Structure of a novel dodecaheme cytochrome c from Geobacter sulfurreducens reveals an extended 12 nm protein with interacting hemes.

    SciTech Connect

    Pokkuluri, P. R.; Londer, Y. Y.; Duke, N. E. C.; Pessanha, M.; Yang, X.; Orshonsky, V.; Orshonsky, L.; Erickson, J.; Zagyansky, Y.; Salgueiro, C. A.; Schiffer, M.

    2011-04-01

    Multiheme cytochromes c are important in electron transfer pathways in reduction of both soluble and insoluble Fe(III) by Geobacter sulfurreducens. We determined the crystal structure at 3.2 {angstrom} resolution of the first dodecaheme cytochrome c (GSU1996) along with its N-terminal and C-terminal hexaheme fragments at 2.6 and 2.15 {angstrom} resolution, respectively. The macroscopic reduction potentials of the full-length protein and its fragments were measured. The sequence of GSU1996 can be divided into four c{sub 7}-type domains (A, B, C and D) with homology to triheme cytochromes c{sub 7}. In cytochromes c{sub 7} all three hemes are bis-His coordinated, whereas in c{sub 7}-type domains the last heme is His-Met coordinated. The full-length GSU1996 has a 12 nm long crescent shaped structure with the 12 hemes arranged along a polypeptide to form a 'nanowire' of hemes; it has a modular structure. Surprisingly, while the C-terminal half of the protein consists of two separate c{sub 7}-type domains (C and D) connected by a small linker, the N-terminal half of the protein has two c{sub 7}-type domains (A and B) that form one structural unit. This is also observed in the AB fragment. There is an unexpected interaction between the hemes at the interface of domains A and B, which form a heme-pair with nearly parallel stacking of their porphyrin rings. The hemes adjacent to each other throughout the protein are within van der Waals distance which enables efficient electron exchange between them. For the first time, the structural details of c{sub 7}-type domains from one multiheme protein were compared.

  8. Epitaxy of CoSix (1extended x-ray-absorption fine-structure techniques

    NASA Astrophysics Data System (ADS)

    Pirri, C.; Hong, S.; Tuilier, M. H.; Wetzel, P.; Gewinner, G.; Cortès, R.

    1996-01-01

    Electronic and structural properties of epitaxial CoSix layers have been investigated by means of core-level and valence-band photoemission, x-ray photoelectron diffraction, and extended x-ray-absorption fine-structure (EXAFS) experiments. CoSix layers of various x compositions have been grown on silicon by low rate Co and Si co-deposition onto room-temperature Si(111) substrates, with film thicknesses ranging from 30 to 100 Å. Photoemission shows substantial differences in valence and core-level spectra with respect to those of stable fluorite-type CoSi2 and ɛ-CoSi and indicate that well-defined metastable phases are formed. In particular, core-level photoemission experiments performed with a monochromatized x-ray source show large Si 2p binding-energy shifts (~0.4 eV) in the room-temperature deposited CoSix (1extended x-ray-absorption fine-structure measurements suggest that these pseudomorphic phases have a cubic structure, over a wide composition range. EXAFS measurements reveal that Co atoms are coordinated with eight Si atoms with a bond length of ~2.33 Å and with Co atoms with bond lengths in the 2.67-2.68 Å range. Such short Co-Co bond lengths show that the structure is definitively different from the stable CaF2-type CoSi2, even at the CoSi2 composition. All experimental data indicate that CoSix silicides crystallize in a cubic lattice close to that of pseudomorphic FeSix silicides, namely, a CsCl-type derived structure.

  9. Structure of the Brachydanio Rerio Polo-Like Kinase 1 (Plk1) Catalytic Domain in Complex With An Extended Inhibitor Targeting the Adaptive Pocket of the Enzyme

    SciTech Connect

    Elling, R.A.; Fucini, R.V.; Hanan, E.J.; Barr, K.J.; Zhu, J.; Paulvannan, K.; Yang, W.; Romanowski, M.J.

    2009-05-18

    Polo-like kinase 1 (Plk1) is a member of the Polo-like kinase family of serine/threonine kinases involved in the regulation of cell-cycle progression and cytokinesis and is an attractive target for the development of anticancer therapeutics. The catalytic domain of this enzyme shares significant primary amino-acid homology and structural similarity with another mitotic kinase, Aurora A. While screening an Aurora A library of ATP-competitive compounds, a urea-containing inhibitor with low affinity for mouse Aurora A but with submicromolar potency for human and zebrafish Plk1 (hPlk1 and zPlk1, respectively) was identified. A crystal structure of the zebrafish Plk1 kinase domain-inhibitor complex reveals that the small molecule occupies the purine pocket and extends past the catalytic lysine into the adaptive region of the active site. Analysis of the structures of this protein-inhibitor complex and of similar small molecules cocrystallized with other kinases facilitates understanding of the specificity of the inhibitor for Plk1 and documents for the first time that Plk1 can accommodate extended ATP-competitive compounds that project toward the adaptive pocket and help the enzyme order its activation segment.

  10. Photophysical properties and electronic structure of stable, tunable synthetic bacteriochlorins: extending the features of native photosynthetic pigments.

    PubMed

    Yang, Eunkyung; Kirmaier, Christine; Krayer, Michael; Taniguchi, Masahiko; Kim, Han-Je; Diers, James R; Bocian, David F; Lindsey, Jonathan S; Holten, Dewey

    2011-09-22

    Bacteriochlorins, which are tetrapyrrole macrocycles with two reduced pyrrole rings, are Nature's near-infrared (NIR) absorbers (700-900 nm). The strong absorption in the NIR region renders bacteriochlorins excellent candidates for a variety of applications including solar light harvesting, flow cytometry, molecular imaging, and photodynamic therapy. Natural bacteriochlorins are inherently unstable due to oxidative conversion to the chlorin (one reduced pyrrole ring) or the porphyrin. The natural pigments are also only modestly amenable to synthetic manipulation, owing to a nearly full complement of substituents on the macrocycle. Recently, a new synthetic methodology has afforded access to stable synthetic bacteriochlorins wherein a wide variety of substituents can be appended to the macrocycle at preselected locations. Herein, the spectroscopic and photophysical properties of 33 synthetic bacteriochlorins are investigated. The NIR absorption bands of the chromophores range from ∼700 to ∼820 nm; the lifetimes of the lowest excited singlet state range from ∼2 to ∼6 ns; the fluorescence quantum yields range from ∼0.05 to ∼0.25; and the yield of the lowest triplet excited state is ∼0.5. The spectroscopic/photophysical studies of the bacteriochlorins are accompanied by density functional theory (DFT) calculations that probe the characteristics of the frontier molecular orbitals. The DFT calculations indicate that the impact of substituents on the spectral properties of the molecules derives primarily from effects on the lowest unoccupied molecular orbital. Collectively, the studies show how the palette of synthetic bacteriochlorins extends the properties of the native photosynthetic pigments (bacteriochlorophylls). The studies have also elucidated design principles for tuning the spectral and photophysical characteristics as required for a wide variety of photochemical applications.

  11. An extended inner-outer factorisation algorithm based on the structure of a transfer function matrix inverse

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Zhao, Chunhui; He, Xing; Zhang, Weidong

    2016-05-01

    In this paper, the structure feature of the inverse of a multi-input/multi-output square transfer function matrix is explored. Instead of complicated advanced mathematical tools, we only use basic results of complex analysis in the analysing procedure. By employing the Laurent expression, an elegant structure form of the expansion is obtained for the transfer function matrix inverse. This expansion form is the key of deriving an analytical solution to the inner-outer factorisation for both stable plants and unstable plants. Different from other computation algorithm, the obtained inner-outer factorisation is given in an analytical form. The solution is exact and without approximation. Numerical examples are provided to verify the correctness of the obtained results.

  12. Structural prototypes for an extended family of flavoprotein reductases: comparison of phthalate dioxygenase reductase with ferredoxin reductase and ferredoxin.

    PubMed Central

    Correll, C. C.; Ludwig, M. L.; Bruns, C. M.; Karplus, P. A.

    1993-01-01

    The structure of phthalate dioxygenase reductase (PDR), a monomeric iron-sulfur flavoprotein that delivers electrons from NADH to phthalate dioxygenase, is compared to ferredoxin-NADP+ reductase (FNR) and ferredoxin, the proteins that reduce NADP+ in the final reaction of photosystem I. The folding patterns of the domains that bind flavin, NAD(P), and [2Fe-2S] are very similar in the two systems. Alignment of the X-ray structures of PDR and FNR substantiates the assignment of features that characterize a family of flavoprotein reductases whose members include cytochrome P-450 reductase, sulfite and nitrate reductases, and nitric oxide synthase. Hallmarks of this subfamily of flavoproteins, here termed the FNR family, are an antiparallel beta-barrel that binds the flavin prosthetic group, and a characteristic variant of the classic pyridine nucleotide-binding fold. Despite the similarities between FNR and PDR, attempts to model the structure of a dissociable FNR:ferredoxin complex by analogy with PDR reveal features that are at odds with chemical crosslinking studies (Zanetti, G., Morelli, D., Ronchi, S., Negri, A., Aliverti, A., & Curti, B., 1988, Biochemistry 27, 3753-3759). Differences in the binding sites for flavin and pyridine nucleotides determine the nucleotide specificities of FNR and PDR. The specificity of FNR for NADP+ arises primarily from substitutions in FNR that favor interactions with the 2' phosphate of NADP+. Variations in the conformation and sequences of the loop adjoining the flavin phosphate affect the selectivity for FAD versus FMN. The midpoint potentials for reduction of the flavin and [2Fe-2S] groups in PDR are higher than their counterparts in FNR and spinach ferredoxin, by about 120 mV and 260 mV, respectively. Comparisons of the structure of PDR with spinach FNR and with ferredoxin from Anabaena 7120, along with calculations of electrostatic potentials, suggest that local interactions, including hydrogen bonds, are the dominant

  13. Research Investigation Directed Toward Extending the Useful Range of the Electromagnetic Spectrum. [atomic spectra and electronic structure of alkali metals

    NASA Technical Reports Server (NTRS)

    Hartmann, S. R.; Happer, W.

    1974-01-01

    The report discusses completed and proposed research in atomic and molecular physics conducted at the Columbia Radiation Laboratory from July 1972 to June 1973. Central topics described include the atomic spectra and electronic structure of alkali metals and helium, molecular microwave spectroscopy, the resonance physics of photon echoes in some solid state systems (including Raman echoes, superradiance, and two photon absorption), and liquid helium superfluidity.

  14. State of manganese in the photosynthetic apparatus. 1. Extended x-ray absorption fine structure studies on chloroplasts and di-.mu.-oxo-bridged dimanganese model compounds

    SciTech Connect

    Kirby, J. A.; Robertson, A. S.; Smith, J. P.; Thompson, A. C.; Cooper, S. R.; Klein, M. P.

    1981-09-01

    In this paper, extended X-ray absorption fine structure studies on the manganese contained in spinach chloroplasts and on certain di-p-oxo-bridged manganese dimers of the form (X2Mn)O2(MnX2) (X = 2,2'-bipyridine and 1 ,10-phenanthroline) are reported. From these studies, the manganese associated with photosynthetic oxygen evolution is suggested to occur as a bridged transition-metal dimer with most likely another manganese. Finally, extensive details on the analysis are included.

  15. Structure-Property Characterization of the Crinkle-Leaf Peach Wood Phenotype: A Future Model System for Wood Properties Research?

    NASA Astrophysics Data System (ADS)

    Wiedenhoeft, Alex C.; Arévalo, Rafael; Ledbetter, Craig; Jakes, Joseph E.

    2016-09-01

    Nearly 400 million years of evolution and field-testing by the natural world has given humans thousands of wood types, each with unique structure-property relationships to study, exploit, and ideally, to manipulate, but the slow growth of trees makes them a recalcitrant experimental system. Variations in wood features of two genotypes of peach ( Prunus persica L.) trees, wild-type and crinkle-leaf, were examined to elucidate the nature of weak wood in crinkle-leaf trees. Crinkle-leaf is a naturally-occurring mutation in which wood strength is altered in conjunction with an easily observed `crinkling' of the leaves' surface. Trees from three vigor classes (low growth rate, average growth rate, and high growth rate) of each genotype were sampled. No meaningful tendency of dissimilarities among the different vigor classes was found, nor any pattern in features in a genotype-by-vigor analysis. Wild-type trees exhibited longer vessels and fibers, wider rays, and slightly higher specific gravity. Neither cell wall mechanical properties measured with nanoindentation nor cell wall histochemical properties were statistically or observably different between crinkle-leaf and wild-type wood. The crinkle-leaf mutant has the potential to be a useful model system for wood properties investigation and manipulation if it can serve as a field-observable vegetative marker for altered wood properties.

  16. Structure-Property Characterization of the Crinkle-Leaf Peach Wood Phenotype: A Future Model System for Wood Properties Research?

    NASA Astrophysics Data System (ADS)

    Wiedenhoeft, Alex C.; Arévalo, Rafael; Ledbetter, Craig; Jakes, Joseph E.

    2016-08-01

    Nearly 400 million years of evolution and field-testing by the natural world has given humans thousands of wood types, each with unique structure-property relationships to study, exploit, and ideally, to manipulate, but the slow growth of trees makes them a recalcitrant experimental system. Variations in wood features of two genotypes of peach (Prunus persica L.) trees, wild-type and crinkle-leaf, were examined to elucidate the nature of weak wood in crinkle-leaf trees. Crinkle-leaf is a naturally-occurring mutation in which wood strength is altered in conjunction with an easily observed `crinkling' of the leaves' surface. Trees from three vigor classes (low growth rate, average growth rate, and high growth rate) of each genotype were sampled. No meaningful tendency of dissimilarities among the different vigor classes was found, nor any pattern in features in a genotype-by-vigor analysis. Wild-type trees exhibited longer vessels and fibers, wider rays, and slightly higher specific gravity. Neither cell wall mechanical properties measured with nanoindentation nor cell wall histochemical properties were statistically or observably different between crinkle-leaf and wild-type wood. The crinkle-leaf mutant has the potential to be a useful model system for wood properties investigation and manipulation if it can serve as a field-observable vegetative marker for altered wood properties.

  17. Implanted Microvessels Progress through Distinct Neovascularization Phenotypes

    PubMed Central

    Nunes, Sara S.; Greer, Kevin A.; Stiening, Chad M.; Chen, Helen YS.; Kidd, Kameha R.; Schwartz, Mark A; Sullivan, Chris J.; Rekapally, Harish; Hoying, James B.

    2009-01-01

    We have previously demonstrated that implanted microvessels form a new microcirculation with minimal host-derived vessel investment. Our objective was to define the vascular phenotypes present during neovascularization in these implants and identify post-angiogenesis events. Morphological, functional and transcriptional assessments identified three distinct vascular phenotypes in the implants: sprouting angiogenesis, neovascular remodeling, and network maturation. A sprouting angiogenic phenotype appeared first, characterized by high proliferation and low mural cell coverage. This was followed by a neovascular remodeling phenotype characterized by a perfused, poorly organized neovascular network, reduced proliferation, and re-associated mural cells. The last phenotype included a vascular network organized into a stereotypical tree structure containing vessels with normal perivascular cell associations. In addition, proliferation was low and was restricted to the walls of larger microvessels. The transition from angiogenesis to neovascular remodeling coincided with the appearance of blood flow in the implant neovasculature. Analysis of vascular-specific and global gene expression indicates that the intermediate, neovascular remodeling phenotype is transcriptionally distinct from the other two phenotypes. Therefore, this vascular phenotype likely is not simply a transitional phenotype but a distinct vascular phenotype involving unique cellular and vascular processes. Furthermore, this neovascular remodeling phase may be a normal aspect of the general neovascularization process. Given that this phenotype is arguably dysfunctional, many of the microvasculatures present within compromised or diseased tissues may not represent a failure to progress appropriately through a normally occurring neovascularization phenotype. PMID:19833141

  18. ELECTRONIC STRUCTURE CALCULATIONS FOR PrFe4P12 FILLED SKUTTERUDITE USING EXTENDED HUCKEL TIGHT-BINDING METHOD

    NASA Astrophysics Data System (ADS)

    GALVAN, DONALD H.

    To gain insight into the electronic properties of PrFe4P12 filled skutterudite, band electronic structure calculations, total and projected density of states, crystal orbital overlap population and Mulliken population analysis were performed. The energy bands yield a semi-metallic behavior with a direct gap (at Γ) of 0.02 eV. Total and Projected Density of States provided information of the contribution from each orbital of each atom to the total Density of States. Moreover, the bonding strength between some atoms within the unit cell was obtained. Mulliken Population Analysis suggests ionic behavior for this filled skutterudite.

  19. A straightforward strategy toward large BN-embedded π-systems: synthesis, structure, and optoelectronic properties of extended BN heterosuperbenzenes.

    PubMed

    Wang, Xiao-Ye; Zhuang, Fang-Dong; Wang, Rui-Bo; Wang, Xin-Chang; Cao, Xiao-Yu; Wang, Jie-Yu; Pei, Jian

    2014-03-12

    A straightforward strategy has been used to construct large BN-embedded π-systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN heteroaromatics to date, have been synthesized in three steps. The molecules exhibit curved π-surfaces, showing two different conformations which are self-organized into a sandwich structure and further packed into a π-stacking column. The assembled microribbons exhibit good charge transport properties and photoconductivity, representing an important step toward the optoelectronic applications of BN-embedded aromatics.

  20. Multivariate Analysis of Genotype-Phenotype Association.

    PubMed

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  1. Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen

    PubMed Central

    Robertson, Anne L.; Ogryzko, Nikolay V.; Henry, Katherine M.; Loynes, Catherine A.; Foulkes, Matthew J.; Meloni, Marco M.; Wang, Xingang; Ford, Christopher; Jackson, Malcolm; Ingham, Philip W.; Wilson, Heather L.; Farrow, Stuart N.; Solari, Roberto; Flower, Roderick J.; Jones, Simon; Whyte, Moira K. B.

    2016-01-01

    ABSTRACT Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments. It is therefore important to develop drug discovery strategies that can identify new therapeutics specifically targeting neutrophils, either by promoting their clearance or by preventing their recruitment. Our recent in vivo chemical genetic screen for accelerators of inflammation resolution identified a subset of compounds sharing a common chemical signature, the bicyclic benzopyrone rings. Here, we further investigate the mechanisms of action of the most active of this chemical series, isopimpinellin, in our zebrafish model of neutrophilic inflammation. We found that this compound targets both the recruitment and resolution phases of the inflammatory response. Neutrophil migration towards a site of injury is reduced by isopimpinellin and this occurs as a result of PI3K inhibition. We also show that isopimpinellin induces neutrophil apoptosis to drive inflammation resolution in vivo using a new zebrafish reporter line detecting in vivo neutrophil caspase-3 activity and allowing quantification of flux through the apoptotic pathway in real time. Finally, our studies reveal that clinically available ‘cromones’ are structurally related to isopimpinellin and have previously undescribed pro-resolution activity in vivo. These findings could have implications for the therapeutic use of benzopyrones in inflammatory disease. PMID:27079522

  2. Do we need an extended evolutionary synthesis?

    PubMed

    Pigliucci, Massimo

    2007-12-01

    The Modern Synthesis (MS) is the current paradigm in evolutionary biology. It was actually built by expanding on the conceptual foundations laid out by its predecessors, Darwinism and neo-Darwinism. For sometime now there has been talk of a new Extended Evolutionary Synthesis (EES), and this article begins to outline why we may need such an extension, and how it may come about. As philosopher Karl Popper has noticed, the current evolutionary theory is a theory of genes, and we still lack a theory of forms. The field began, in fact, as a theory of forms in Darwin's days, and the major goal that an EES will aim for is a unification of our theories of genes and of forms. This may be achieved through an organic grafting of novel concepts onto the foundational structure of the MS, particularly evolvability, phenotypic plasticity, epigenetic inheritance, complexity theory, and the theory of evolution in highly dimensional adaptive landscapes. PMID:17924956

  3. Do we need an extended evolutionary synthesis?

    PubMed

    Pigliucci, Massimo

    2007-12-01

    The Modern Synthesis (MS) is the current paradigm in evolutionary biology. It was actually built by expanding on the conceptual foundations laid out by its predecessors, Darwinism and neo-Darwinism. For sometime now there has been talk of a new Extended Evolutionary Synthesis (EES), and this article begins to outline why we may need such an extension, and how it may come about. As philosopher Karl Popper has noticed, the current evolutionary theory is a theory of genes, and we still lack a theory of forms. The field began, in fact, as a theory of forms in Darwin's days, and the major goal that an EES will aim for is a unification of our theories of genes and of forms. This may be achieved through an organic grafting of novel concepts onto the foundational structure of the MS, particularly evolvability, phenotypic plasticity, epigenetic inheritance, complexity theory, and the theory of evolution in highly dimensional adaptive landscapes.

  4. Extended x-ray absorption fine structure measurements on radio frequency magnetron sputtered HfO2 thin films deposited with different oxygen partial pressures.

    PubMed

    Maidul Haque, S; Nayak, C; Bhattacharyya, Dibyendu; Jha, S N; Sahoo, N K

    2016-03-20

    Two sets of HfO2 thin film have been deposited by the radio frequency magnetron sputtering technique at various oxygen partial pressures, one set without any substrate bias and another set with a 50 W pulsed dc substrate bias. The films have been characterized by extended x-ray absorption fine structure (EXAFS) measurements at the Hf L3 edge, and the structural information obtained from analysis of the EXAFS data has been used to explain the macroscopic behavior of the refractive index obtained from spectroscopic ellipsometry measurements. It has been observed that the variation of refractive index with oxygen partial pressure depends on the Hf-Hf bond length for the set of films deposited without substrate bias, while for the other set of films deposited with pulsed dc substrate bias, it depends on the oxygen coordination of the nearest neighbor shell surrounding Hf sites.

  5. In-situ extended X-ray absorption fine structure study of electrostriction in Gd doped ceria

    SciTech Connect

    Korobko, Roman; Wachtel, Ellen; Lubomirsky, Igor; Lerner, Alyssa; Li, Yuanyuan; Frenkel, Anatoly I.

    2015-01-26

    Studying electric field-induced structural changes in ceramics is challenging due to the very small magnitude of the atomic displacements. We used differential X-ray absorption spectroscopy, an elementally specific and spatially sensitive method, to detect such changes in Gd-doped ceria, recently shown to exhibit giant electrostriction. We found that the large electrostrictive stress generation can be associated with a few percent of unusually short Ce-O chemical bonds that change their length and degree of order under an external electric field. The remainder of the lattice is reduced to the role of passive spectator. This mechanism is fundamentally different from that in electromechanically active materials currently in use.

  6. Deep seismic structure and tectonics of northern Alaska: Crustal-scale duplexing with deformation extending into the upper mantle

    USGS Publications Warehouse

    Fuis, G.S.; Murphy, J.M.; Lutter, W.J.; Moore, T.E.; Bird, K.J.; Christensen, N.I.

    1997-01-01

    Seismic reflection and refraction and laboratory velocity data collected along a transect of northern Alaska (including the east edge of the Koyukuk basin, the Brooks Range, and the North Slope) yield a composite picture of the crustal and upper mantle structure of this Mesozoic and Cenozoic compressional orogen. The following observations are made: (1) Northern Alaska is underlain by nested tectonic wedges, most with northward vergence (i.e., with their tips pointed north). (2) High reflectivity throughout the crust above a basal decollement, which deepens southward from about 10 km depth beneath the northern front of the Brooks Range to about 30 km depth beneath the southern Brooks Range, is interpreted as structural complexity due to the presence of these tectonic wedges, or duplexes. (3) Low reflectivity throughout the crust below the decollement is interpreted as minimal deformation, which appears to involve chiefly bending of a relatively rigid plate consisting of the parautochthonous North Slope crust and a 10- to 15-km-thick section of mantle material. (4) This plate is interpreted as a southward verging tectonic wedge, with its tip in the lower crust or at the Moho beneath the southern Brooks Range. In this interpretation the middle and upper crust, or all of the crust, is detached in the southern Brooks Range by the tectonic wedge, or indentor: as a result, crust is uplifted and deformed above the wedge, and mantle is depressed and underthrust beneath this wedge. (5) Underthrusting has juxtaposed mantle of two different origins (and seismic velocities), giving rise to a prominent sub-Moho reflector. Copyright 1997 by the American Geophysical Union.

  7. Cocrystal Structures of Primed Side-Extending α-Ketoamide Inhibitors Reveal Novel Calpain-Inhibitor Aromatic Interactions

    SciTech Connect

    Qian,J.; Cuerrier, D.; Davies, P.; Li, Z.; Powers, J.; Campbell, R.

    2008-01-01

    Calpains are intracellular cysteine proteases that catalyze the cleavage of target proteins in response to Ca2+ signaling. When Ca2+ homeostasis is disrupted, calpain overactivation causes unregulated proteolysis, which can contribute to diseases such as postischemic injury and cataract formation. Potent calpain inhibitors exist, but of these many cross-react with other cysteine proteases and will need modification to specifically target calpain. Here, we present crystal structures of rat calpain 1 protease core ({mu}I-II) bound to two a-ketoamide-based calpain inhibitors containing adenyl and piperazyl primed-side extensions. An unexpected aromatic-stacking interaction is observed between the primed-side adenine moiety and the Trp298 side chain. This interaction increased the potency of the inhibitor toward {mu}I-II and heterodimeric m-calpain. Moreover, stacking orients the adenine such that it can be used as a scaffold for designing novel primed-side address regions, which could be incorporated into future inhibitors to enhance their calpain specificity.

  8. Th uptake on montmorillonite: a powder and polarized extended X-ray absorption fine structure (EXAFS) study.

    PubMed

    Dähn, Rainer; Scheidegger, André M; Manceau, Alain; Curti, Enzo; Baeyens, Bart; Bradbury, Michael H; Chateigner, Daniel

    2002-05-01

    The uptake process of Th(IV) onto montmorillonite was studied using powder and polarized-EXAFS (P-EXAFS) spectroscopy. Sorption samples were prepared in 0.1 M NaClO(4) solutions either undersaturated (pH 2 and 3, [Th](initial): 2.7x10(-6) to 4x10(-4) M) or supersatured (pH 5, [Th](initial): 4.3x10(-5) to 4x10(-4) M) with respect to amorphous ThO(2). Th loading varied between 1-157 micromol/g at pH 3 and 14-166 micromol/g at pH 5 and equaled 41 micromol/g at pH 2. At pH 5 and high surface loading the EXAFS spectrum resembled that of amorphous Th(OH)(4), suggesting the precipitation of a Th hydrous hydroxide. At low and intermediate surface coverage two O coordination shells at approximately 2.24 and approximately 2.48 A, and one Si shell at 3.81-3.88 A, were systematically observed regardless of pH. The formation of Th nucleation products and Th-Si solution complexes and the sorption of Th on a silica precipitate were excluded from the EXAFS spectra analysis and solution chemistry. In these conditions, Th was shown to bond the montmorillonite surface by sharing double corners with Si tetrahedra. This structural interpretation is consistent with surface coverage calculations which showed that the edge sites were saturated in the two highest concentrated samples (34 and 157 micromol/g) at pH 3.

  9. An example of phenotypic adherence to the island rule? – Anticosti gray jays are heavier but not structurally larger than mainland conspecifics

    PubMed Central

    Strickland, Dan; Norris, D Ryan

    2015-01-01

    The island rule refers to the tendency of small vertebrates to become larger when isolated on islands and the frequent dwarfing of large forms. It implies genetic control, and a necessary linkage, of size and body-mass differences between insular and mainland populations. To examine the island rule, we compared body size and mass of gray jays (Perisoreus canadensis) on Anticosti Island, Québec, located in the Gulf of St. Lawrence, with three mainland populations (2 in Québec and 1 in Ontario). Although gray jays on Anticosti Island were ca 10% heavier, they were not structurally larger, than the three mainland populations. This suggests that Anticosti jays are not necessarily genetically distinct from mainland gray jays and that they may have achieved their greater body masses solely through packing more mass onto mainland-sized body frames. As such, they may be the first-known example of a proposed, purely phenotypic initial step in the adherence to the island rule by an insular population. Greater jay body mass is probably advantageous in Anticosti's high-density, intensely competitive social environment that may have resulted from the island's lack of mammalian nest predators. PMID:26380697

  10. An example of phenotypic adherence to the island rule? - Anticosti gray jays are heavier but not structurally larger than mainland conspecifics.

    PubMed

    Strickland, Dan; Norris, D Ryan

    2015-09-01

    The island rule refers to the tendency of small vertebrates to become larger when isolated on islands and the frequent dwarfing of large forms. It implies genetic control, and a necessary linkage, of size and body-mass differences between insular and mainland populations. To examine the island rule, we compared body size and mass of gray jays (Perisoreus canadensis) on Anticosti Island, Québec, located in the Gulf of St. Lawrence, with three mainland populations (2 in Québec and 1 in Ontario). Although gray jays on Anticosti Island were ca 10% heavier, they were not structurally larger, than the three mainland populations. This suggests that Anticosti jays are not necessarily genetically distinct from mainland gray jays and that they may have achieved their greater body masses solely through packing more mass onto mainland-sized body frames. As such, they may be the first-known example of a proposed, purely phenotypic initial step in the adherence to the island rule by an insular population. Greater jay body mass is probably advantageous in Anticosti's high-density, intensely competitive social environment that may have resulted from the island's lack of mammalian nest predators.

  11. 1-3-A Resolution Structure of Human Glutathione S-Transferase With S-Hexyl Glutathione Bound Reveals Possible Extended Ligandin Binding Site

    SciTech Connect

    Trong, I.Le; Stenkamp, R.E.; Ibarra, C.; Atkins, W.M.; Adman, E.T.

    2005-08-22

    Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathione binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.

  12. Extending Structural Analyses of the Rosenberg Self-Esteem Scale to Consider Criterion-Related Validity: Can Composite Self-Esteem Scores Be Good Enough?

    PubMed

    Donnellan, M Brent; Ackerman, Robert A; Brecheen, Courtney

    2016-01-01

    Although the Rosenberg Self-Esteem Scale (RSES) is the most widely used measure of global self-esteem in the literature, there are ongoing disagreements about its factor structure. This methodological debate informs how the measure should be used in substantive research. Using a sample of 1,127 college students, we test the overall fit of previously specified models for the RSES, including a newly proposed bifactor solution (McKay, Boduszek, & Harvey, 2014 ). We extend previous work by evaluating how various latent factors from these structural models are related to a set of criterion variables frequently studied in the self-esteem literature. A strict unidimensional model poorly fit the data, whereas models that accounted for correlations between negatively and positively keyed items tended to fit better. However, global factors from viable structural models had similar levels of association with criterion variables and with the pattern of results obtained with a composite global self-esteem variable calculated from observed scores. Thus, we did not find compelling evidence that different structural models had substantive implications, thereby reducing (but not eliminating) concerns about the integrity of the self-esteem literature based on overall composite scores for the RSES.

  13. Extended lifetime railgap switch

    SciTech Connect

    Cohn, D.B.; Mendoza, P.J.

    1988-02-02

    In a railgap switch of the type having an elongate blade electrode made of conductive material, an elongate housing made of insulating material for supporting the blade electrode and plate electrode in opposed relation extending in the same direction with the blade centered over the plate and separated therefrom by a gap, and a gas filling the housing and the gap, the gas being selected to breakdown and switch from a highly insulative state to a highly conductive state upon application of a high voltage across the blade and plate electrodes, the improvement is described comprising: forming the blade with laterally extending transverse wing portions at the edge of the blade and adjacent the gap so as to extend in spaced parallel relation to the surface of the plate, the blade generally following the contour thereof to form an inverted T-shape structure with the wing portions extending transversely of the elongate dimension of the blade. The wing portions terminating in a pair of spaced parallel edges extending along the elongate direction of the blade to thereby create two spaced elongate edges along which arcs form serving to divide the erosion effects of discharge between them, the current through each edge being one-half of that in single-edge devices with ablation wear reduced accordingly to give significantly larger switch lifetime. The blade and wing portions limiting ablation erosion of the edges in a direction generally align with the plate contour so that the edge-to-plate separation remains substantially constant.

  14. Extended N-terminal region of the essential phosphorelay signaling protein Ypd1 from Cryptococcus neoformans contributes to structural stability, phosphostability and binding of calcium ions.

    PubMed

    Kennedy, Emily N; Menon, Smita K; West, Ann H

    2016-09-01

    Rapid response to external stimuli is crucial for survival and proliferation of microorganisms. Pathogenic fungi employ histidine-to-aspartate multistep phosphorelay systems to respond to environmental stress, progress through developmental stages and to produce virulence factors. Because these His-to-Asp phosphorelay systems are not found in humans, they are potential targets for the development of new antifungal therapies. Here we report the characterization of the histidine phosphotransfer (HPt) protein Ypd1 from the human fungal pathogen Cryptococcus neoformans Results from this study demonstrate that CnYpd1 indeed functions as a phosphorelay protein in vitro, and that H138 is confirmed as the site of phosphorylation. We found that CnYpd1 exhibits unique characteristics in comparison to other histidine phosphotransfer proteins, such as an extended N-terminal amino acid sequence, which we find contributes to structural integrity, a longer phosphorylated life time and the ability to bind calcium ions. PMID:27549628

  15. Local order of Sb and Bi dopants in hydrogenated amorphous germanium thin films studied by extended x-ray absorption fine structure

    NASA Astrophysics Data System (ADS)

    Dalba, G.; Fornasini, P.; Grisenti, R.; Rocca, F.; Chambouleyron, I.

    2002-07-01

    This letter reports on the investigation of the local order and coordination of Sb and Bi impurities in hydrogenated amorphous germanium thin films. The study uses the extended x-ray absorption fine structure technique in fluorescence mode at room temperature. The investigation includes doping concentrations ranging from 1.1 x1019 to 5 x1020 cm-3. For both impurities, the evidence is that the thermal equilibrium model is not applicable in this case. This result qualitatively follows the behavior of Ga and In impurities in hydrogenated amorphous germanium (a-Ge:H) samples except for Bi. These findings are consistent with data on the transport properties of Sb- and Bi-doped a-Ge:H films.

  16. Analysis of photosynthetic picoeukaryote community structure along an extended Ellett Line transect in the northern North Atlantic reveals a dominance of novel prymnesiophyte and prasinophyte phylotypes

    NASA Astrophysics Data System (ADS)

    Kirkham, Amy R.; Jardillier, Ludwig E.; Holland, Ross; Zubkov, Mikhail V.; Scanlan, Dave J.

    2011-07-01

    Photosynthetic picoeukaryotes (PPEs) of a size <3 μm can contribute significantly to primary production. Here, PPE community structure was analysed along an extended Ellett Line transect, an area in the North Atlantic well studied by physical oceanographers but largely neglected in the field of microalgal ecology. Distribution patterns of specific PPE classes were determined using dot-blot hybridization analysis, while the taxonomic composition of specific PPE classes was revealed by phylogenetic analysis of plastid 16S rRNA gene sequences. In addition, we performed fluorescent in situ hybridization (FISH) analysis of seawater samples collected along the transect to provide a PCR-independent survey of class level PPE distribution patterns. We found the PPE community was dominated by members of the Prymnesiophyceae, Prasinophyceae and Mamiellophyceae. Interestingly, phylogenetic analysis revealed several novel Prymnesiophyceae and Prasinophyceae phylotypes (with only 85-96% identity to neighbouring sequences) within lineages for which cultured counterparts are unknown.

  17. Polyradical Character of Triangular Non-Kekulé Structures, Zethrenes, p-Quinodimethane-Linked Bisphenalenyl, and the Clar Goblet in Comparison: An Extended Multireference Study

    PubMed Central

    2016-01-01

    In this work, two different classes of polyaromatic hydrocarbon (PAH) systems have been investigated in order to characterize the amount of polyradical character and to localize the specific regions of chemical reactivity: (a) the non-Kekulé triangular structures phenalenyl, triangulene and a π-extended triangulene system with high-spin ground state and (b) PAHs based on zethrenes, p-quinodimethane-linked bisphenalenyl, and the Clar goblet containing varying polyradical character in their singlet ground state. The first class of structures already have open-shell character because of their high-spin ground state, which follows from the bonding pattern, whereas for the second class the open-shell character is generated either because of the competition between the closed-shell quinoid Kekulé and the open-shell singlet biradical resonance structures or the topology of the π-electron arrangement of the non-Kekulé form. High-level ab initio calculations based on multireference theory have been carried out to compute singlet–triplet splitting for the above-listed compounds and to provide insight into their chemical reactivity based on the polyradical character by means of unpaired densities. Unrestricted density functional theory and Hartree–Fock calculations have been performed for comparison also in order to obtain better insight into their applicability to these types of complicated radical systems. PMID:26859789

  18. The Bactofilin Cytoskeleton Protein BacM of Myxococcus xanthus Forms an Extended β-Sheet Structure Likely Mediated by Hydrophobic Interactions

    PubMed Central

    Xie, Kefang; Engelhardt, Harald; Bosch, Jürgen; Hoiczyk, Egbert

    2015-01-01

    Bactofilins are novel cytoskeleton proteins that are widespread in Gram-negative bacteria. Myxococcus xanthus, an important predatory soil bacterium, possesses four bactofilins of which one, BacM (Mxan_7475) plays an important role in cell shape maintenance. Electron and fluorescence light microscopy, as well as studies using over-expressed, purified BacM, indicate that this protein polymerizes in vivo and in vitro into ~3 nm wide filaments that further associate into higher ordered fibers of about 10 nm. Here we use a multipronged approach combining secondary structure determination, molecular modeling, biochemistry, and genetics to identify and characterize critical molecular elements that enable BacM to polymerize. Our results indicate that the bactofilin-determining domain DUF583 folds into an extended β-sheet structure, and we hypothesize a left-handed β-helix with polymerization into 3 nm filaments primarily via patches of hydrophobic amino acid residues. These patches form the interface allowing head-to-tail polymerization during filament formation. Biochemical analyses of these processes show that folding and polymerization occur across a wide variety of conditions and even in the presence of chaotropic agents such as one molar urea. Together, these data suggest that bactofilins are comprised of a structure unique to cytoskeleton proteins, which enables robust polymerization. PMID:25803609

  19. In situ surface extended x-ray absorption fine structure spectroscopy of a lead monolayer at a silver(111) electrode/electrolyte interface

    SciTech Connect

    Samant, M.G.; Borges, G.L.; Gordon J.G. II; Melroy, O.R.; Blum, L.

    1987-09-30

    With use of fluorescence detection and grazing incidence excitation, the X-ray absorption spectrum was obtained, at the PbL/sub III/ edge, of a monoatomic adlayer of lead on a silver (111) electrode immersed in solution. The adlayer was produced by under potential deposition from aqueous lead acetate/sodium acetate electrolyte. The edge position and the near-edge structure confirm that the lead is fully reduced to the zerovalent state. The extended X-ray absorption fine structure (EXAFS) contains no detectable contribution from lead-silver scattering, either because the lead layer is incommensurate with the underlying silver lattice or because there is large thermal motion of the lead atoms. Instead, the fine structure is due to scattering from a single type of light atom, most likely oxygen. This oxygen must arise from adsorbed water molecules or acetate ions. The lead-oxygen distance changes with the electrode potential from 2.33 +/- 0.02 A at -0.53 V to 2.38 +/- 0.02 A at -1 V (vs. Ag/AgCl, 3 M KCl).

  20. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

    PubMed Central

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D.; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G.

    2013-01-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited down-regulation and mislocalization of α3- and α5-integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre-negative littermate controls. β1-cKO mice were incontinent, as judged by random urine leakage on filter paper (4-fold higher spotting, P<0.01; 2.5-fold higher urine area percentage, P<0.05). Urodynamic function assessed by cystometry revealed bladder overfilling with 80% longer intercontractile intervals (P<0.05) and detrusor hyperactivity (3-fold more prevoid contractions, P<0.05), but smooth muscle contractility remained intact. ATP secretion into the lumen was elevated (49 vs. 22 nM, P<0.05), indicating abnormal filling-induced purinergic signaling, and short-circuit currents (measured in Ussing chambers) revealed 2-fold higher stretch-activated ion channel conductances in response to hydrostatic pressure of 1 cmH2O (P<0.05). We conclude that loss of integrin signaling from urothelium results in incontinence and overactive bladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding.—Kanasaki, K., Yu, W., von Bodungen, M., Larigakis, J. D., Kanasaki, M., Ayala de la Pena, F., Kalluri, R., Hill, W.G. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype. PMID:23395910

  1. Characterization of structure and dynamics of an aqueous scandium(III) ion by an extended ab initio QM/MM molecular dynamics simulation.

    PubMed

    Vchirawongkwin, Viwat; Kritayakornupong, Chinapong; Tongraar, Anan; Rode, Bernd M

    2012-10-14

    Hydration structure and dynamics of an aqueous Sc(III) solution were characterized by means of an extended ab initio quantum mechanical/molecular dynamical (QM/MM) molecular dynamics simulation at Hartree-Fock level. A monocapped trigonal prismatic structure composed of seven water molecules surrounding scandium(III) ion was proposed by the QM/MM simulation including the quantum mechanical effects for the first and second hydration shells. The mean Sc(III)-O bond length of 2.14 Å was identified for six prism water molecules with one capping water located at around 2.26 Å, reproducing well the X-ray diffraction data. The Sc(III)-O stretching frequency of 432 cm(-1) corresponding to a force constant of 130 N m(-1), evaluated from the enlarged QM/MM simulation, is in good agreement with the experimentally determined value of 430 cm(-1) (128 N m(-1)). Various water exchange processes in the second hydration shell of the hydrated Sc(III) ion predict a mean ligand residence time of 7.3 ps.

  2. Low-temperature adsorption of H2S on Ni(001) studied by near-edge- and surface-extended-x-ray-absorption fine structure

    NASA Astrophysics Data System (ADS)

    McGrath, R.; MacDowell, A. A.; Hashizume, T.; Sette, F.; Citrin, P. H.

    1989-11-01

    The adsorption of H2S on Ni(001) has been studied with surface-extended x-ray-absorption fine structure and near-edge x-ray-absorption fine structure (NEXAFS) using the AT&T Bell Laboratories X15B beamline at the National Synchrotron Light Source. At 95 K and full saturation coverage, ~0.45 monolayer (ML) of S atoms in fourfold-hollow sites are produced, characteristic of room-temperature adsorption, accompanied by ~0.05 ML of oriented molecular H2S. Both these atomic and molecular chemisorbed species are buried under ~0.9 ML of disordered physisorbed H2S. No evidence for HS is found. Above 190 K the two molecular H2S phases desorb, leaving only dissociated S. These findings differ from previously reported interpretations of data obtained with high-resolution electron-energy-loss spectroscopy. They also exemplify the utility of NEXAFS for identifying and quantifying atomic and molecular surface species even when their difference involves only H and the two species coexist.

  3. In situ extended X-ray absorption fine structure study during selective alcohol oxidation over Pd/Al2O3 in supercritical carbon dioxide.

    PubMed

    Grunwaldt, Jan-Dierk; Caravati, Matteo; Baiker, Alfons

    2006-05-25

    High-pressure in situ X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) data are reported during the selective oxidation of benzyl alcohol to benzaldehyde in supercritical carbon dioxide over a Pd/Al(2)O(3) catalyst (shell impregnated). For this purpose, a continuous-flow system with a spectroscopic cell suitable for in situ X-ray absorption studies on heterogeneous catalysts up to 200 degrees C and 200 bar has been developed. Due to the high contribution of the dense fluid to the overall X-ray absorption, high stability of the process pressure is mandatory, particularly when recording EXAFS spectra. According to EXAFS and XANES results, the palladium particles were fully reduced after exposure to benzyl alcohol in scCO(2). In contrast to Pd-catalyzed liquid-phase oxidation, a higher oxygen tolerance of the catalyst was observed. Palladium was partially oxidized on the surface under typical reaction conditions (0.9 mol % benzyl alcohol/0.5 mol % O(2) in carbon dioxide), which gradually increased when the concentration of oxygen in the feed was raised. Both XANES and EXAFS data uncovered that palladium is mainly oxidized on the surface or within the outermost layers. These results are in accordance with simulations of the XANES data using the FEFF8.20 code (program for ab initio calculations on multiple scattering XAS) and EXAFS data fitting/simulation. PMID:16706447

  4. Angle-resolved photoemission extended fine structure of the Ni 3p, Cu 3s, and Cu 3p core levels of the respective clean (111) surfaces

    SciTech Connect

    Huff, W.R. |; Chen, Y.; Kellar, S.A.; Moler, E.J. |; Hussain, Z.; Huang, Z.Q.; Zheng, Y.; Shirley, D.A.

    1997-07-01

    We report a non-s initial-state angle-resolved photoemission extended fine-structure (ARPEFS) study of clean surfaces for the purpose of further understanding the technique. The surface structure sensitivity of ARPEFS applied to clean surfaces and to arbitrary initial states is studied using normal photoemission data taken from the Ni 3p core levels of a Ni(111) single crystal and the Cu 3s and the Cu 3p core levels of a Cu(111) single crystal. The Fourier transforms of these clean surface data are dominated by backscattering. Unlike the s initial-state data, the p initial-state data show a peak in the Fourier transform corresponding to in-plane scattering from the six nearest neighbors to the emitter. Evidence was seen for single-scattering events from the same plane as the emitters and double-scattering events. Using a recently developed, multiple-scattering calculation program, ARPEFS data from clean surfaces and from p initial states can be modeled to high precision. Although there are many layers of emitters when measuring photoemission from a clean surface, test calculations show that the ARPEFS signal is dominated by photoemission from atoms in the first two crystal layers. Thus ARPEFS applied to clean surfaces is sensitive to surface reconstruction. The best-fit calculation for clean Ni(111) indicates an expansion of the first two layers. {copyright} {ital 1997} {ital The American Physical Society}

  5. Estimation method of state-of-charge for lithium-ion battery used in hybrid electric vehicles based on variable structure extended kalman filter

    NASA Astrophysics Data System (ADS)

    Sun, Yong; Ma, Zilin; Tang, Gongyou; Chen, Zheng; Zhang, Nong

    2016-03-01

    Since the main power source of hybrid electric vehicle(HEV) is supplied by the power battery, the predicted performance of power battery, especially the state-of-charge(SOC) estimation has attracted great attention in the area of HEV. However, the value of SOC estimation could not be greatly precise so that the running performance of HEV is greatly affected. A variable structure extended kalman filter(VSEKF)-based estimation method, which could be used to analyze the SOC of lithium-ion battery in the fixed driving condition, is presented. First, the general lower-order battery equivalent circuit model(GLM), which includes column accumulation model, open circuit voltage model and the SOC output model, is established, and the off-line and online model parameters are calculated with hybrid pulse power characteristics(HPPC) test data. Next, a VSEKF estimation method of SOC, which integrates the ampere-hour(Ah) integration method and the extended Kalman filter(EKF) method, is executed with different adaptive weighting coefficients, which are determined according to the different values of open-circuit voltage obtained in the corresponding charging or discharging processes. According to the experimental analysis, the faster convergence speed and more accurate simulating results could be obtained using the VSEKF method in the running performance of HEV. The error rate of SOC estimation with the VSEKF method is focused in the range of 5% to 10% comparing with the range of 20% to 30% using the EKF method and the Ah integration method. In Summary, the accuracy of the SOC estimation in the lithium-ion battery cell and the pack of lithium-ion battery system, which is obtained utilizing the VSEKF method has been significantly improved comparing with the Ah integration method and the EKF method. The VSEKF method utilizing in the SOC estimation in the lithium-ion pack of HEV can be widely used in practical driving conditions.

  6. Estimation method of state-of-charge for lithium-ion battery used in hybrid electric vehicles based on variable structure extended kalman filter

    NASA Astrophysics Data System (ADS)

    Sun, Yong; Ma, Zilin; Tang, Gongyou; Chen, Zheng; Zhang, Nong

    2016-07-01

    Since the main power source of hybrid electric vehicle(HEV) is supplied by the power battery, the predicted performance of power battery, especially the state-of-charge(SOC) estimation has attracted great attention in the area of HEV. However, the value of SOC estimation could not be greatly precise so that the running performance of HEV is greatly affected. A variable structure extended kalman filter(VSEKF)-based estimation method, which could be used to analyze the SOC of lithium-ion battery in the fixed driving condition, is presented. First, the general lower-order battery equivalent circuit model(GLM), which includes column accumulation model, open circuit voltage model and the SOC output model, is established, and the off-line and online model parameters are calculated with hybrid pulse power characteristics(HPPC) test data. Next, a VSEKF estimation method of SOC, which integrates the ampere-hour(Ah) integration method and the extended Kalman filter(EKF) method, is executed with different adaptive weighting coefficients, which are determined according to the different values of open-circuit voltage obtained in the corresponding charging or discharging processes. According to the experimental analysis, the faster convergence speed and more accurate simulating results could be obtained using the VSEKF method in the running performance of HEV. The error rate of SOC estimation with the VSEKF method is focused in the range of 5% to 10% comparing with the range of 20% to 30% using the EKF method and the Ah integration method. In Summary, the accuracy of the SOC estimation in the lithium-ion battery cell and the pack of lithium-ion battery system, which is obtained utilizing the VSEKF method has been significantly improved comparing with the Ah integration method and the EKF method. The VSEKF method utilizing in the SOC estimation in the lithium-ion pack of HEV can be widely used in practical driving conditions.

  7. Structural basis for the extended substrate spectrum of AmpC BER and structure-guided discovery of the inhibition activity of citrate against the class C β-lactamases AmpC BER and CMY-10.

    PubMed

    Na, Jung Hyun; Cha, Sun Shin

    2016-08-01

    AmpC BER is an extended substrate spectrum class C β-lactamase with a two-amino-acid insertion in the R2 loop compared with AmpC EC2. The crystal structures of AmpC BER (S64A mutant) and AmpC EC2 were determined. Structural comparison of the two proteins revealed that the insertion increases the conformational flexibility of the R2 loop. Two citrate molecules originating from the crystallization solution were observed in the active site of the S64A mutant. One citrate molecule makes extensive interactions with active-site residues that are highly conserved among class C β-lactamases, whereas the other one is weakly bound. Based on this structural observation, it is demonstrated that citrate, a primary metabolite that is widely used as a food additive, is a competitive inhibitor of two class C β-lactamases (AmpC BER and CMY-10). Consequently, the data indicate enhancement of the flexibility of the R2 loop as an operative strategy for molecular evolution of extended-spectrum class C β-lactamases, and also suggest that the citrate scaffold is recognized by the active sites of class C β-lactamases. PMID:27487828

  8. Measurement of the Neutron (3He) Spin Structure at Low Q2 and the Extended Gerasimov-Drell-Hearn Sum Rule

    SciTech Connect

    Kominis, Ioannis

    2001-01-31

    This thesis presents the results of E-94010, an experiment at Thomas Jefferson National Accelerator Facility (TJNAF) designed to study the spin structure of the neutron at low momentum transfer, and to test the “extended” Gerasimov-Drell-Hearn (GDH) sum rule. The first experiment of its kind, it was performed in experimental Hall-A of TJNAF using a new polarized 3He facility. It has recently been shown that the GDH sum rule and the Bjorken sum rule are both special examples of a more general sum rule that applies to polarized electron scattering off nucleons. This generalized sum rule, due to Ji and Osborne, reduces to the GDH sum rule at Q2 = 0 and to the Bjorken sum rule at Q2 >> 1 GeV2. By studying the Q2 evolution of the extended GDH sum, one learns about the transition from quark-like behavior to hadronic-like behavior. We measured inclusive polarized cross sections by scattering high energy polarized electrons off the new TJNAF polarized 3He target with both longitudinal and transverse target orientations. The high density 3He target, based on optical pumping and spin exchange, was used as an effective neutron target. The target maintained a polarization of about 35% at beam currents as high as 151tA. We describe the precision 3He polarimetry leading to a systematic uncertainty of the target polarization of 4% (relative). A strained GaAs photocathode was utilized in the polarized electron gun, which provided an electron beam with a polarization of about 70%, known to 3% (relative). By using six different beam energies (between 0.86 and 5.06 GeV) and a fixed scattering angle of 15.5°, a wide kinematic coverage was achieved, with 0.02 GeV2< Q2 <1 GcV2 and 0.5 GeV< W < 2.5 GeV for the squared momentum transfer and invariant mass, respectively. From the measured cross sections we extract the 3He spin structure functions He and g1e Finally, we determine the extended GDH sum for the range 0.1 GeV2< Q2 <1 GeV2 for 3He and the neutron.

  9. The extended structure of the dwarf irregular galaxies Sextans A and Sextans B. Signatures of tidal distortion in the outskirts of the Local Group

    NASA Astrophysics Data System (ADS)

    Bellazzini, M.; Beccari, G.; Fraternali, F.; Oosterloo, T. A.; Sollima, A.; Testa, V.; Galleti, S.; Perina, S.; Faccini, M.; Cusano, F.

    2014-06-01

    We present a detailed study of the stellar and H i structure of the dwarf irregular galaxies Sextans A and Sextans B, members of the NGC 3109 association. We use newly obtained deep (r ≃ 26.5) and wide-field g and r photometry to extend the surface brightness (SB) profiles of the two galaxies down to μV ≃ 31.0 mag/arcsec2. We find that both galaxies are significantly more extended than previously traced with surface photometry, out to ~4 kpc from their centres along their major axes. Older stars are found to have more extended distribution than younger populations. We obtain the first estimate of the mean metallicity for the old stars in Sex B, from the colour distribution of the red giant branch, ⟨[Fe/H]⟩ = -1.6. The SB profiles show significant changes of slope and cannot be fitted with a single Sérsic model. Both galaxies have HI discs as massive as their respective stellar components. In both cases the H i discs display solid-body rotation with maximum amplitude of ~50 km s-1 (albeit with significant uncertainty due to the poorly constrained inclination), implying a dynamical mass ~109 M⊙, a mass-to-light ratio M / LV ~ 25, and a dark-to-baryonic mass ratio of ~10. The distribution of the stellar components is more extended than the gaseous disc in both galaxies. We find that the main, approximately round, stellar body of Sex A is surrounded by an elongated low-SB stellar halo that can be interpreted as a tidal tail, similar to that found in another member of the same association (Antlia). We discuss these, as well as other evidence of tidal disturbance, in the framework of a past passage of the NGC 3109 association close to the Milky Way, which has been hypothesised by several authors and is also supported by the recently discovered filamentary configuration of the association itself. Appendices are available in electronic form at http://www.aanda.orgTable of stellar photometry is only available at the CDS via anonymous ftp to http

  10. [Intermediate phenotype of schizophrenia].

    PubMed

    Hashimoto, Ryota

    2013-04-01

    Genes are major contributors to schizophrenia. The intermediate phenotype concept represents a strategy for identifying risk genes for schizophrenia and for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in schizophrenia. Intermediate phenotypes are defined by being heritable, being able to measure quantitatively; being related to the disorder and its symptoms in the general population; being stable over time; showing increased expression in unaffected relatives of probands; and cosegregation with the disorder in families. Intermediate phenotypes in schizophrenia are neurocognition, neuroimaging, neurophysiology, etc. In this review, we present concept, recent work, and future perspective of intermediate phenotype.

  11. Local vibrational dynamics of hematite (α-Fe{sub 2}O{sub 3}) studied by extended x-ray absorption fine structure and molecular dynamics

    SciTech Connect

    Sanson, A.; Mathon, O.; Pascarelli, S.

    2014-06-14

    The local vibrational dynamics of hematite (α-Fe{sub 2}O{sub 3}) has been investigated by temperature-dependent extended x-ray absorption fine structure spectroscopy and molecular dynamics simulations. The local dynamics of both the short and long nearest-neighbor Fe–O distances has been singled out, i.e., their local thermal expansion and the parallel and perpendicular mean-square relative atomic displacements have been determined, obtaining a partial agreement with molecular dynamics. No evidence of the Morin transition has been observed. More importantly, the strong anisotropy of relative thermal vibrations found for the short Fe–O distance has been related to its negative thermal expansion. The differences between the local dynamics of short and long Fe–O distances are discussed in terms of projection and correlation of atomic motion. As a result, we can conclude that the short Fe–O bond is stiffer to stretching and softer to bending than the long Fe–O bond.

  12. Lead is not off center in PbTe: the importance of r-space phase information in extended x-ray absorption fine structure spectroscopy.

    PubMed

    Keiber, T; Bridges, F; Sales, B C

    2013-08-30

    PbTe is a well-known thermoelectric material. Recent x-ray total scattering studies suggest that Pb moves off center along 100 in PbTe, by ∼0.2  Å at 300 K, producing a split Pb-Te pair distribution. We present an extended x-ray absorption fine structure spectroscopy (EXAFS) study of PbTe (and Tl doped PbTe) to determine if Pb or Te is off center. EXAFS provides sensitive r- or k-space phase information which can differentiate between a split peak for the Pb-Te distribution (indicative of off-center Pb) and a thermally broadened peak. We find no evidence for a split peak for Pb-Te or Te-Pb. At 300 K, the vibration amplitude for Pb-Te (or Te-Pb) is large; this thermally induced disorder is indicative of weak bonds, and the large disorder is consistent with the low thermal conductivity at 300 K. We also find evidence of an anharmonic potential for the nearest Pb-Te bonds, consistent with the overall anharmonicity found for the phonon modes. This effect is modeled by a "skew" factor (C3) which significantly improves the fit of the Pb-Te and Te-Pb peaks for the high temperature EXAFS data; C3 becomes significant above approximately 150-200 K. The consequences of these results will be discussed.

  13. Extended X- ray absorption fine structure study at the K-edge of copper in mixed ligand complexes having benzimidazole as one of the ligands

    NASA Astrophysics Data System (ADS)

    Hinge, V. K.; Joshi, S. K.; Nitin Nair, N.; Singh Verma, Vikram; Shrivastava, B. D.; Prasad, J.; Srivastava, K.

    2014-09-01

    Extended X-ray absorption fine structure (EXAFS) spectra have been studied at the K-edge of copper in some of its biologically important complexes, viz., [Cu(BzImH)4X2] and [Cu(BzIm)2], where X= Cl, Br, 1/2SO4, ClO4, NO3, and BzIm = Benzimidazolato anion. The spectra have been recorded using a bent crystal 0.4 m Cauchois-type transmission spectrograph. The positions of EXAFS maxima and minima have been used to determine the bond lengths in the complexes with the help of three different methods, namely, Levy's, Lytle's and Lytle, Sayers and Stern's (L.S.S.) methods. The phase uncorrected bond lengths have also been determined from Fourier transforms of the experimental spectra. The results obtained from these methods have been discussed and it has been found that the results obtained by L.S.S. method are comparable with the results obtained by Fourier transformation method and that these two methods give phase uncorrected bond lengths.

  14. EXAFS (Extended X-ray Absorption Fine-Structure Spectroscopy) study of the position of Zr within the unit cell of Sm sub 2 Co sub 17

    SciTech Connect

    Rabenberg, L. . Center for Materials Science and Engineering); Barrera, E.V. . Dept. of Mechanical Engineering and Materials Science); Maury, C.E.; Allibert, C.H. . Lab. de Thermodynamique et PhysicoChimie Metallurgiques); Heald, S.M. (Brookhaven National Lab

    1990-01-01

    Extended X-ray Absorption Fine-Structure Spectroscopy (EXAFS) has been used to determine the position of Zr within the unit cell of Sm{sub 2}Co{sub 17}. Zr is routinely added to Sm{sub 2}Co{sub 17} permanent magnet alloys because of its effects on their metallurgical development, but the details of its behavior remain controversial. Induction melted Sm{sub 2}Co{sub 17}:Zr ternary alloys, aged at 1180{degrees}C, then quenched, consisted of intimately mixed H2:17 and R2:17 having Zr in solid solution as well some regions of R2:17 that were poor in Zr. EXAFS spectroscopy of these specimens indicates that the most probable position for Zr is a site having two Sm near neighbor atoms and 11 Co atoms distributed over three different interatomic distances. This is consistent with a direct substitution of Zr for Co in the Co site in the mixed planes (12j in P6{sub 3}/mmc, or 18f in R3m). These results are discussed in terms of the metallurgy of 2:17 magnet alloys. 20 refs., 2 figs.

  15. Real-time object recognition in multidimensional images based on joined extended structural tensor and higher-order tensor decomposition methods

    NASA Astrophysics Data System (ADS)

    Cyganek, Boguslaw; Smolka, Bogdan

    2015-02-01

    In this paper a system for real-time recognition of objects in multidimensional video signals is proposed. Object recognition is done by pattern projection into the tensor subspaces obtained from the factorization of the signal tensors representing the input signal. However, instead of taking only the intensity signal the novelty of this paper is first to build the Extended Structural Tensor representation from the intensity signal that conveys information on signal intensities, as well as on higher-order statistics of the input signals. This way the higher-order input pattern tensors are built from the training samples. Then, the tensor subspaces are built based on the Higher-Order Singular Value Decomposition of the prototype pattern tensors. Finally, recognition relies on measurements of the distance of a test pattern projected into the tensor subspaces obtained from the training tensors. Due to high-dimensionality of the input data, tensor based methods require high memory and computational resources. However, recent achievements in the technology of the multi-core microprocessors and graphic cards allows real-time operation of the multidimensional methods as is shown and analyzed in this paper based on real examples of object detection in digital images.

  16. Local structural studies of the cubic Cd1–xCaxO system through Cd K-edge extended X-ray absorption spectroscopic studies

    PubMed Central

    Srihari, Velaga; Sridharan, V.; Nomura, Masaharu; Sastry, V. Sankara; Sundar, C. S

    2012-01-01

    Cd K-edge extended X-ray absorption fine-structure spectroscopic studies were carried out on Cd1–xCaxO (0 ≤ x ≤0.9) solid solutions and the first and second nearest neighbour (NN) distances and their mean square relative displacement σ2 were estimated. The first NN distance, d Cd–O(x), was found to be smaller than its expected value, a(x)/2, obtained from the X-ray diffraction measurements. It increases monotonically and non-linearly with a negative curvature, comparable with that of the a(x) value variation. The variation σ2 of the 1NN with x is consistent with a disordered solid solution model. The 2NN distances d Cd–Cd(x) and d Cd–Ca(x) are found to follow the average values obtained by X-ray diffraction with d Cd–Ca(x) > d Cd–Cd(x). From detailed analysis it is argued that the solid solution exhibits a bimodal distribution of the 1NN distances, d Cd–O(x) and d Ca–O(x), and that the system belongs to a persistent type. PMID:22713887

  17. Local vibrational dynamics of hematite (α-Fe2O3) studied by extended x-ray absorption fine structure and molecular dynamics

    NASA Astrophysics Data System (ADS)

    Sanson, A.; Mathon, O.; Pascarelli, S.

    2014-06-01

    The local vibrational dynamics of hematite (α-Fe2O3) has been investigated by temperature-dependent extended x-ray absorption fine structure spectroscopy and molecular dynamics simulations. The local dynamics of both the short and long nearest-neighbor Fe-O distances has been singled out, i.e., their local thermal expansion and the parallel and perpendicular mean-square relative atomic displacements have been determined, obtaining a partial agreement with molecular dynamics. No evidence of the Morin transition has been observed. More importantly, the strong anisotropy of relative thermal vibrations found for the short Fe-O distance has been related to its negative thermal expansion. The differences between the local dynamics of short and long Fe-O distances are discussed in terms of projection and correlation of atomic motion. As a result, we can conclude that the short Fe-O bond is stiffer to stretching and softer to bending than the long Fe-O bond.

  18. Structure of GES-1 at Atomic Resolution: Insights Into the Evolution of Carbapenamase Activity in the Class a Extended-Spectrum Beta-Lactamases

    SciTech Connect

    Smith, C.A.; Caccamo, M.; Kantardjieff, K.A.; Vakulenko, S.; /Notre Dame U.

    2007-10-08

    The structure of the class A extended-spectrum {beta}-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 Angstrom resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of {beta}-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the {beta}-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A {beta}-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of {beta}-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5.

  19. Temporal abstraction-based clinical phenotyping with Eureka!

    PubMed

    Post, Andrew R; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW's web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption. PMID:24551400

  20. Temporal Abstraction-based Clinical Phenotyping with Eureka!

    PubMed Central

    Post, Andrew R.; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M.; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H.

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW’s web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption. PMID:24551400

  1. Temporal abstraction-based clinical phenotyping with Eureka!

    PubMed

    Post, Andrew R; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW's web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption.

  2. Temperature-dependent local structure of NdFeAsO(1-x)F(x) system using arsenic K-edge extended x-ray absorption fine structure.

    PubMed

    Joseph, B; Iadecola, A; Malavasi, L; Saini, N L

    2011-07-01

    Local structure of NdFeAsO(1-x)F(x) (x = 0.0, 0.05, 0.15 and 0.18) high temperature iron-pnictide superconductor system is studied using arsenic K-edge extended x-ray absorption fine structure measurements as a function of temperature. Fe-As bond length shows only a weak temperature and F-substitution dependence, consistent with the strong covalent nature of this bond. The temperature dependence of the mean square relative displacements of the Fe-As bond length are well described by the correlated Einstein model for all the samples, but with different Einstein temperatures for the superconducting and non-superconducting samples. The results indicate distinct local Fe-As lattice dynamics in the superconducting and non-superconducting iron-pnictide systems.

  3. Extended x-ray absorption fine structure study of arsenic in HgCdTe: p-type doping linked to nonsubstitutional As incorporation in an unknown AsHg{sub 8} structure

    SciTech Connect

    Biquard, X.; Alliot, I.; Ballet, P.

    2009-11-15

    An extended x-ray absorption fine structure (EXAFS) investigation has been carried out on arsenic-doped Hg{sub 70}Cd{sub 30}Te samples. The incorporation of atomic arsenic has been achieved using a nonconventional radio-frequency plasma source in a molecular beam epitaxy reactor. Two samples from the same epitaxial wafer have been studied. One underwent a 400 deg. C activation annealing under Hg pressure, leading to n to p-type conversion. In the commonly admitted scenario, this conversion is associated with the annealing-induced migration of As from a Hg site to a Te site. This study shows that this is not the case. Before annealing, As is found to be involved in noncrystalline structures: 50% inside an As{sub 2}Te{sub 3} chalcogenide glass and 50% inside a new AsHg{sub 8} compact structure. After annealing, the As{sub 2}Te{sub 3} chalcogenide glass disappears, 31% of As occupies Hg sites and 69% incorporates inside this new AsHg{sub 8} compact structure that occupies Te sites. The EXAFS results are in excellent agreement with 77 K Hall-effect measurements. The new AsHg{sub 8} structure is found to have an acceptor behavior. Overall, this study provides an entirely new vision of extrinsic p-type doping of HgCdTe as well as the first experimental evidence of As site transfer induced by annealing.

  4. Phenotype definition in epilepsy.

    PubMed

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  5. The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity.

    PubMed

    Chen, Xiufang; Wang, Yue; Feng, Tianquan; Yi, Ming; Zhang, Xingan; Zhou, Da

    2016-02-01

    The paradigm of phenotypic plasticity indicates reversible relations of different cancer cell phenotypes, which extends the cellular hierarchy proposed by the classical cancer stem cell (CSC) theory. Since it is still questionable if the phenotypic plasticity is a crucial improvement to the hierarchical model or just a minor extension to it, it is worthwhile to explore the dynamic behavior characterizing the reversible phenotypic plasticity. In this study we compare the hierarchical model and the reversible model in predicting the cell-state dynamics observed in biological experiments. Our results show that the hierarchical model shows significant disadvantages over the reversible model in describing both long-term stability (phenotypic equilibrium) and short-term transient dynamics (overshoot) in cancer cell populations. In a very specific case in which the total growth of population due to each cell type is identical, the hierarchical model predicts neither phenotypic equilibrium nor overshoot, whereas the reversible model succeeds in predicting both of them. Even though the performance of the hierarchical model can be improved by relaxing the specific assumption, its prediction to the phenotypic equilibrium strongly depends on a precondition that may be unrealistic in biological experiments. Moreover, it still does not show as rich dynamics as the reversible model in capturing the overshoots of both CSCs and non-CSCs. By comparison, it is more likely for the reversible model to correctly predict the stability of the phenotypic mixture and various types of overshoot behavior.

  6. Reduced Extended MHD

    NASA Astrophysics Data System (ADS)

    Morrison, P. J.; Abdelhamid, H. M.; Grasso, D.; Hazeltine, R. D.; Lingam, M.; Tassi, E.

    2015-11-01

    Over the years various reduced fluid models have been obtained for modeling plasmas, with the goal of capturing important physics while maintaining computability. Such models have included the physics contained in various generalizations of Ohm's law, including Hall drift and electron inertia. In a recent publication it was shown that full 3D extended MHD is a Hamiltonian system by finding its noncanonical Poisson bracket. Subsequently, this bracket was shown to be derivable from that for Hall MHD by a series of remarkable transformations, which greatly simplifies the proof of the Jacobi identity and allows one to immediately obtain generalizations of the helicity and cross helicity. In this poster we use this structure to obtain exact reduced fluid models with the effects of full two-fluid theory. Results of numerical computations of collisionless reconnection using an exact reduced 4-field model will be presented and analytical comparisons of mode structure of previous reduced models will be made.

  7. Extending quantum mechanics entails extending special relativity

    NASA Astrophysics Data System (ADS)

    Aravinda, S.; Srikanth, R.

    2016-05-01

    The complementarity between signaling and randomness in any communicated resource that can simulate singlet statistics is generalized by relaxing the assumption of free will in the choice of measurement settings. We show how to construct an ontological extension for quantum mechanics (QMs) through the oblivious embedding of a sound simulation protocol in a Newtonian spacetime. Minkowski or other intermediate spacetimes are ruled out as the locus of the embedding by virtue of hidden influence inequalities. The complementarity transferred from a simulation to the extension unifies a number of results about quantum non-locality, and implies that special relativity has a different significance for the ontological model and for the operational theory it reproduces. Only the latter, being experimentally accessible, is required to be Lorentz covariant. There may be certain Lorentz non-covariant elements at the ontological level, but they will be inaccessible at the operational level in a valid extension. Certain arguments against the extendability of QM, due to Conway and Kochen (2009) and Colbeck and Renner (2012), are attributed to their assumption that the spacetime at the ontological level has Minkowski causal structure.

  8. Topological defects in extended inflation

    NASA Technical Reports Server (NTRS)

    Copeland, Edmund J.; Kolb, Edward W.; Liddle, Andrew R.

    1990-01-01

    The production of topological defects, especially cosmic strings, in extended inflation models was considered. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large scale structure via cosmic strings.

  9. Extended X-ray absorption fine structure investigation of Sn local environment in strained and relaxed epitaxial Ge{sub 1−x}Sn{sub x} films

    SciTech Connect

    Gencarelli, F. Heyns, M.; Grandjean, D.; Shimura, Y.; Vandervorst, W.; Vincent, B.; Loo, R.; Banerjee, D.; Vantomme, A.; Temst, K.

    2015-03-07

    We present an extended X-ray absorption fine structure investigation of the local environment of Sn atoms in strained and relaxed Ge{sub 1−x}Sn{sub x} layers with different compositions. We show that the preferred configuration for the incorporation of Sn atoms in these Ge{sub 1−x}Sn{sub x} layers is that of a α-Sn defect, with each Sn atom covalently bonded to four Ge atoms in a classic tetrahedral configuration. Sn interstitials, Sn-split vacancy complexes, or Sn dimers, if present at all, are not expected to involve more than 2.5% of the total Sn atoms. This finding, along with a relative increase of Sn atoms in the second atomic shell around a central Sn atom in Ge{sub 1−x}Sn{sub x} layers with increasing Sn concentrations, suggests that the investigated materials are homogeneous random substitutional alloys. Within the accuracy of the measurements, the degree of strain relaxation of the Ge{sub 1−x}Sn{sub x} layers does not have a significant impact on the local atomic surrounding of the Sn atoms. Finally, the calculated topological rigidity parameter a** = 0.69 ± 0.29 indicates that the strain due to alloying in Ge{sub 1−x}Sn{sub x} is accommodated via bond stretching and bond bending, with a slight predominance of the latter, in agreement with ab initio calculations reported in literature.

  10. Structure and function of starch and resistant starch from corn with different doses of mutant amylose-extender and floury-1 alleles.

    PubMed

    Yao, Ni; Paez, Alix V; White, Pamela J

    2009-03-11

    Four corn types with different doses of mutant amylose-extender (ae) and floury-1 (fl1) alleles, in the endosperm, including no. 1, aeaeae; no. 2, fl1fl1fl1; no. 3, aeaefl1; and no. 4, fl1fl1ae, were developed for use in making Hispanic food products with high resistant starch (RS) content. The RS percentages in the native starch (NS) of 1-4 were 55.2, 1.1, 5.7, and 1.1%, respectively. All NS were evaluated for pasting properties with a rapid viscoanalyzer (RVA) and for thermal properties with a differential scanning calorimeter (DSC). NS 1 had a low peak viscosity (PV) caused by incomplete gelatinization, whereas NS 3 had the greatest PV and breakdown of all four starch types. On the DSC, NS 2 had the lowest onset temperature and greatest enthalpy. NS 1 and 3 had similar onset and peak temperatures, both higher than those of NS 2 and 4. The gel strength of NS heated with a RVA was evaluated by using a texture analyzer immediately after RVA heating (fresh, RVA-F) and after the gel had been stored at 4 degrees C for 10 days (retrograded, RVA-R). NS 1 gel was watery and had the lowest strength (30 g) among starch gel types. NS 3 gel, although exhibiting syneresis, had greater gel strength than NS 2 and 4. The structures of the NS, the RS isolated from the NS (RS-NS), the RS isolated from RVA-F (RS-RVA-F), and the RS isolated from RVA-R (RS-RVA-R) were evaluated by using size exclusion chromatography. NS 1 had a greater percentage of amylose (AM) (58.3%) than the other NS (20.4-26.8%). The RS from all NS types (RS-NS) had a lower percentage of amylopectin (AP) and a greater percentage of low molecular weight (MW) AM than was present in the original NS materials. The RS-RVA-R from all starches had no AP or high MW AM. The percentages of longer chain lengths (DP 35-60) of NS were greater in 1 and 3 than in 2 and 4, and the percentages of smaller chain lengths (DP 10-20) were greater in 2 and 4 than in 1 and 3. In general, NS 3 seemed to have inherited some pasting

  11. Syntheses and Solid-State Structures of Molecular and Extended Silver(I) Complexes of 4-Isocyano-3,5-diisopropylbenzonitrile

    NASA Astrophysics Data System (ADS)

    Li, Ming-Xing; Cheung, Kung-Kai; Mayr, Andreas

    2000-06-01

    The molecular complexes [Ag(4-CN-3,5-i-Pr2-C6H2CN)2]X, 1 (a, X=BF4; b, X=SO3CF3), have been prepared by reaction of the respective silver(I) salts with 2 equivalents of the isocyanide in benzene solution. Reaction of 1b with an equivalent amount of AgSO3CF3 in benzene solution gave the extended molecular solid {[Ag(4-CN-3,5-i-Pr2-C6H2CN)2]SO3CF3}n, 2. The solid-state structures of 1a and 2 have been determined by single-crystal X-ray crystallography. Compound 1a crystallizes in the triclinic space group Poverline1 with a=10.506(2) Å, b=12.838(2) Å, c=12.974(2) Å, α=100.65(2)°, β=101.52(2)°, γ=105.37(2)°, V=1600.1(7) Å3, and Z=2 with R=0.056 and wR=0.087. Compound 2 crystallizes in the triclinic space group Poverline1 with a=9.6868(8) Å, b=10.551(1) Å, c=11.559(1) Å, α=76.350(9)°, β=82.037(9)°, γ=71.481(9)°, V=1086.0(4) Å3, and Z=1 with R=0.027 and wR=0.036. Compound 1a may be described as a dicoordinate silver(I) complex with a significantly bent linear coordination geometry (C-Ag-C 156.1(2)°). The bending of the diisocyanide metal group is caused by the interaction with the BF4 anion (shortest Ag-F distance 2.534(8) Å). The nitrile groups in 1b are not engaged in any directional intermolecular interaction. The solid-state structure of 2 consists of linear chains of [Ag(4-CN-3,5-i-Pr2-C6H2CN)2]SO3CF3 units, whereby each silver ion is coordinated to one isocyano group and one nitrile group of consecutive cyanoisocyanoarene ligands. These linear chains are arranged in antiparallel fashion to form infinite sheets. Within the sheets, the silver ions of pairs of chains are pulled near each other by electrostatic interactions with the SO3CF3 anions. These double chains are held together primarily by π interactions of the cyanoisocyanoarene groups.

  12. Surface complexation and precipitate geometry for aqueous Zn(II) sorption on ferrihydrite I: X-ray absorption extended fine structure spectroscopy analysis

    USGS Publications Warehouse

    Waychunas, G.A.; Fuller, C.C.; Davis, J.A.

    2002-01-01

    "Two-line" ferrihydrite samples precipitated and then exposed to a range of aqueous Zn solutions (10-5 to 10-3 M), and also coprecipitated in similar Zn solutions (pH 6.5), have been examined by Zn and Fe K-edge X-ray absorption spectroscopy. Typical Zn complexes on the surface have Zn-O distances of 1.97(0.2) A?? and coordination numbers of about 4.0(0.5), consistent with tetrahedral oxygen coordination. This contrasts with Zn-O distances of 2.11(.02) A?? and coordination numbers of 6 to 7 in the aqueous Zn solutions used in sample preparation. X-ray absorption extended fine structure spectroscopy (EXAFS) fits to the second shell of cation neighbors indicate as many as 4 Zn-Fe neighbors at 3.44(.04) A?? in coprecipitated samples, and about two Zn-Fe neighbors at the same distance in adsorption samples. In both sets of samples, the fitted coordination number of second shell cations decreases as sorption density increases, indicating changes in the number and type of available complexing sites or the onset of competitive precipitation processes. Comparison of our results with the possible geometries for surface complexes and precipitates suggests that the Zn sorption complexes are inner sphere and at lowest adsorption densities are bidentate, sharing apical oxygens with adjacent edge-sharing Fe(O,OH)6 octahedra. Coprecipitation samples have complexes with similar geometry, but these are polydentate, sharing apices with more than two adjacent edge-sharing Fe(O,OH)6 polyhedra. The results are inconsistent with Zn entering the ferrihydrite structure (i.e., solid solution formation) or formation of other Zn-Fe precipitates. The fitted Zn-Fe coordination numbers drop with increasing Zn density with a minimum of about 0.8(.2) at Zn/(Zn + Fe) of 0.08 or more. This change appears to be attributable to the onset of precipitation of zinc hydroxide polymers with mainly tetrahedral Zn coordination. At the highest loadings studied, the nature of the complexes changes further

  13. Structure-based investigation into the functional roles of the extended loop and substrate-recognition sites in an endo-β-1,4-D-mannanase from the Antarctic springtail, Cryptopygus antarcticus.

    PubMed

    Kim, Min-Kyu; An, Young Jun; Song, Jung Min; Jeong, Chang-Sook; Kang, Mee Hye; Kwon, Kae Kyoung; Lee, Youn-Ho; Cha, Sun-Shin

    2014-11-01

    Endo-β-1,4-D-mannanase from the Antarctic springtail, Cryptopygus antarcticus (CaMan), is a cold-adapted β-mannanase that has the lowest optimum temperature (30°C) of all known β-mannanases. Here, we report the apo- and mannopentaose (M5) complex structures of CaMan. Structural comparison of CaMan with other β-mannanases from the multicellular animals reveals that CaMan has an extended loop that alters topography of the active site. Structural and mutational analyses suggest that this extended loop is linked to the cold-adapted enzymatic activity. From the CaMan-M5 complex structure, we defined the mannose-recognition subsites and observed unreported M5 binding site on the surface of CaMan. PMID:25082572

  14. In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl−/−) mice

    PubMed Central

    Chen, Jeffrey; Kaiyala, Karl J; Lam, Jennifer; Agrawal, Nalini; Nguyen, Lisa; Ogimoto, Kayoko; Spencer, Dean; Morton, Gregory J; Schwartz, Michael W; Dichek, Helén L

    2015-01-01

    The lean body weight phenotype of hepatic lipase (HL)–deficient mice (hl−/−) suggests that HL is required for normal weight gain, but the underlying mechanisms are unknown. HL plays a unique role in lipoprotein metabolism performing bridging as well as catalytic functions, either of which could participate in energy homeostasis. To determine if both the catalytic and bridging functions or the catalytic function alone are required for the effect of HL on body weight, we studied (hl−/−) mice that transgenically express physiologic levels of human (h)HL (with catalytic and bridging functions) or a catalytically-inactive (ci)HL variant (with bridging function only) in which the catalytic Serine 145 was mutated to Alanine. As expected, HL activity in postheparin plasma was restored to physiologic levels only in hHL-transgenic mice (hl−/−hHL). During high-fat diet feeding, hHL-transgenic mice exhibited increased body weight gain and body adiposity relative to hl−/−ciHL mice. A similar, albeit less robust effect was observed in female hHL-transgenic relative to hl−/−ciHL mice. To delineate the basis for this effect, we determined cumulative food intake and measured energy expenditure using calorimetry. Interestingly, in both genders, food intake was 5–10% higher in hl−/−hHL mice relative to hl−/−ciHL controls. Similarly, energy expenditure was ∼10% lower in HL-transgenic mice after adjusting for differences in total body weight. Our results demonstrate that (1) the catalytic function of HL is required to rescue the lean body weight phenotype of hl−/− mice; (2) this effect involves complementary changes in both sides of the energy balance equation; and (3) the bridging function alone is insufficient to rescue the lean phenotype of hl−/−ciHL mice. PMID:25862097

  15. Structural Analysis of the Mn(IV)/Fe(III) Cofactor of Chlamydia Trachomatis Ribonucleotide Reductase By Extended X-Ray Absorption Fine Structure Spectroscopy And Density Functional Theory Calculations

    SciTech Connect

    Younker, J.M.; Krest, C.M.; Jiang, W.; Krebs, C.; Bollinger, J.M.Jr.; Green, M.T.

    2009-05-28

    The class Ic ribonucleotide reductase from Chlamydia trachomatis (C{bar A}) uses a stable Mn(lV)/ Fe(lll) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of -2.92 {angstrom}. The Mn data also suggest the presence of a short 1.74 {angstrom} Mn-O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe2(lll/ III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OH{sub x} ligands as well as the location of the Mn(lV) ion (site 1 or 2). The models that agree best with experimental observation feature a{mu}-1, 3-carboxylate bridge (E120), terminal solvent (H{sub 2}O/OH) to site 1, one {mu}-O bridge, and one {mu}-OH bridge. The site-placement of the metal ions cannot be discerned from the available data.

  16. The integrated phenotype.

    PubMed

    Murren, Courtney J

    2012-07-01

    Proper functioning of complex phenotypes requires that multiple traits work together. Examination of relationships among traits within and between complex characters and how they interact to function as a whole organism is critical to advancing our understanding of evolutionary developmental plasticity. Phenotypic integration refers to the relationships among multiple characters of a complex phenotype, and their relationships with other functional units (modules) in an organism. In this review, I summarize a brief history of the concept of phenotypic integration in plant and animal biology. Following an introduction of concepts, including modularity, I use an empirical case-study approach to highlight recent advance in clarifying the developmental and genomic basis of integration. I end by highlighting some novel approaches to genomic and epigenetic perturbations that offer promise in further addressing the role of phenotypic integration in evolutionary diversification. In the age of the phenotype, studies that examine the genomic and developmental changes in relationships of traits across environments will shape the next chapter in our quest for understanding the evolution of complex characters.

  17. [Phenotypic heterogeneity of chronic obstructive pulmonary disease].

    PubMed

    Garcia-Aymerich, Judith; Agustí, Alvar; Barberà, Joan A; Belda, José; Farrero, Eva; Ferrer, Antoni; Ferrer, Jaume; Gáldiz, Juan B; Gea, Joaquim; Gómez, Federico P; Monsó, Eduard; Morera, Josep; Roca, Josep; Sauleda, Jaume; Antó, Josep M

    2009-03-01

    A functional definition of chronic obstructive pulmonary disease (COPD) based on airflow limitation has largely dominated the field. However, a view has emerged that COPD involves a complex array of cellular, organic, functional, and clinical events, with a growing interest in disentangling the phenotypic heterogeneity of COPD. The present review is based on the opinion of the authors, who have extensive research experience in several aspects of COPD. The starting assumption of the review is that current knowledge on the pathophysiology and clinical features of COPD allows us to classify phenotypic information in terms of the following dimensions: respiratory symptoms and health status, acute exacerbations, lung function, structural changes, local and systemic inflammation, and systemic effects. Twenty-six phenotypic traits were identified and assigned to one of the 6 dimensions. For each dimension, a summary is provided of the best evidence on the relationships among phenotypic traits, in particular among those corresponding to different dimensions, and on the relationship between these traits and relevant events in the natural history of COPD. The information has been organized graphically into a phenotypic matrix where each cell representing a pair of phenotypic traits is linked to relevant references. The information provided has the potential to increase our understanding of the heterogeneity of COPD phenotypes and help us plan future studies on aspects that are as yet unexplored.

  18. Spatial structure determination of ({radical}3 x {radical}3)R30{degrees} and (1.5 x 1.5)R18{degrees}CO on Cu(111) using angle-resolved photoemission extended fine structure

    SciTech Connect

    Moler, E.J.; Kellar, S.A.; Huff, W.R.A.

    1997-04-01

    The authors report a study of the spatial structure of ({radical}3 x {radical}3)R30{degrees} (low coverage) and (1.5 x 1.5)R18{degrees} (intermediate coverage) CO adsorbed on Cu(111), using the Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) technique at beamline 9.3.2 at the Advanced Light Source. The CO molecule adsorbs on an atop site for both adsorption phases. Full multiple-scattering spherical-wave (MSSW) calculations were used to extract the C-Cu. bond length and the first Cu-Cu layer spacing for each adsorption phase. The authors find that the C-Cu bond length remains unchanged with increasing coverage, but the 1st Cu-Cu layer spacing contracts at the intermediate coverage. They calculate the bending mode force constant in the (1.5 x 1.5)R18{degrees} phase to be K{sub {delta}} = 2.2 (1) x 10{sup {minus}12} dyne-cm/rad from their experimentally determined bond lengths combined with previously published infra-red absorption frequencies.

  19. Phenotypic switching in gene regulatory networks.

    PubMed

    Thomas, Philipp; Popović, Nikola; Grima, Ramon

    2014-05-13

    Noise in gene expression can lead to reversible phenotypic switching. Several experimental studies have shown that the abundance distributions of proteins in a population of isogenic cells may display multiple distinct maxima. Each of these maxima may be associated with a subpopulation of a particular phenotype, the quantification of which is important for understanding cellular decision-making. Here, we devise a methodology which allows us to quantify multimodal gene expression distributions and single-cell power spectra in gene regulatory networks. Extending the commonly used linear noise approximation, we rigorously show that, in the limit of slow promoter dynamics, these distributions can be systematically approximated as a mixture of Gaussian components in a wide class of networks. The resulting closed-form approximation provides a practical tool for studying complex nonlinear gene regulatory networks that have thus far been amenable only to stochastic simulation. We demonstrate the applicability of our approach in a number of genetic networks, uncovering previously unidentified dynamical characteristics associated with phenotypic switching. Specifically, we elucidate how the interplay of transcriptional and translational regulation can be exploited to control the multimodality of gene expression distributions in two-promoter networks. We demonstrate how phenotypic switching leads to birhythmical expression in a genetic oscillator, and to hysteresis in phenotypic induction, thus highlighting the ability of regulatory networks to retain memory. PMID:24782538

  20. Extender for securing a closure

    SciTech Connect

    Thomas, II, Patrick A.

    2012-10-02

    An apparatus for securing a closure such as door or a window that opens and closes by movement relative to a fixed structure such as a wall or a floor. Many embodiments provide a device for relocating a padlock from its normal location where it secures a fastener (such as a hasp) to a location for the padlock that is more accessible for locking and unlocking the padlock. Typically an extender is provided, where the extender has a hook at a first end that is disposed through the eye of the staple of the hasp, and at an opposing second end the extender has an annulus, such as a hole in the extender or a loop or ring affixed to the extender. The shackle of the padlock may be disposed through the annulus and may be disposed through the eye of a second staple to secure the door or window in a closed or open position. Some embodiments employ a rigid sheath to enclose at least a portion of the extender. Typically the rigid sheath has an open state where the hook is exposed outside the sheath and a closed state where the hook is disposed within the sheath.

  1. X-ray absorption near edge structure and extended X-ray absorption fine structure analysis of standards and biological samples containing mixed oxidation states of chromium(III) and chromium(VI).

    PubMed

    Parsons, J G; Dokken, K; Peralta-Videa, J R; Romero-Gonzalez, J; Gardea-Torresdey, J L

    2007-03-01

    For the first time a method has been developed for the extended X-ray absorption fine structure (EXAFS) data analyses of biological samples containing multiple oxidation states of chromium. In this study, the first shell coordination and interatomic distances based on the data analysis of known standards of potassium chromate (Cr(VI)) and chromium nitrate hexahydrate (Cr(III)) were investigated. The standards examined were mixtures of the following molar ratios of Cr(VI):Cr(III), 0:1, 0.25:0.75, 0.5:0.5, 0.75:0.25, and 1:0. It was determined from the calibration data that the fitting error associated with linear combination X-ray absorption near edge structure (LC-XANES) fittings was approximately +/-10% of the total fitting. The peak height of the Cr(VI) pre-edge feature after normalization of the X-ray absorption (XAS) spectra was used to prepare a calibration curve. The EXAFS fittings of the standards were also investigated and fittings to lechuguilla biomass samples laden with different ratios of Cr(III) and Cr(VI) were performed as well. An excellent agreement between the XANES data and the data presented in the EXAFS spectra was observed. The EXFAS data also presented mean coordination numbers directly related to the ratios of the different chromium oxidation states in the sample. The chromium oxygen interactions had two different bond lengths at approximately 1.68 and 1.98 A for the Cr(VI) and Cr(III) in the sample, respectively. PMID:17389076

  2. X-Ray Absorption Near Edge Structure And Extended X-Ray Absorption Fine Structure Analysis of Standards And Biological Samples Containing Mixed Oxidation States of Chromium(III) And Chromium(VI)

    SciTech Connect

    Parsons, J.G.; Dokken, K.; Peralta-Videa, J.R.; Romero-Gonzalez, J.; Gardea-Torresdey, J.L.

    2009-06-02

    For the first time a method has been developed for the extended X-ray absorption fine structure (EXAFS) data analyses of biological samples containing multiple oxidation states of chromium. In this study, the first shell coordination and interatomic distances based on the data analysis of known standards of potassium chromate (Cr(VI)) and chromium nitrate hexahydrate (Cr(III)) were investigated. The standards examined were mixtures of the following molar ratios of Cr(VI):Cr(III), 0:1, 0.25:0.75, 0.5:0.5, 0.75:0.25, and 1:0. It was determined from the calibration data that the fitting error associated with linear combination X-ray absorption near edge structure (LC-XANES) fittings was approximately {+-}10% of the total fitting. The peak height of the Cr(VI) pre-edge feature after normalization of the X-ray absorption (XAS) spectra was used to prepare a calibration curve. The EXAFS fittings of the standards were also investigated and fittings to lechuguilla biomass samples laden with different ratios of Cr(III) and Cr(VI) were performed as well. An excellent agreement between the XANES data and the data presented in the EXAFS spectra was observed. The EXFAS data also presented mean coordination numbers directly related to the ratios of the different chromium oxidation states in the sample. The chromium oxygen interactions had two different bond lengths at approximately 1.68 and 1.98 {angstrom} for the Cr(VI) and Cr(III) in the sample, respectively.

  3. Down Syndrome: Cognitive Phenotype

    ERIC Educational Resources Information Center

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  4. The broad autism phenotype questionnaire: prevalence and diagnostic classification.

    PubMed

    Sasson, Noah J; Lam, Kristen S L; Childress, Debra; Parlier, Morgan; Daniels, Julie L; Piven, Joseph

    2013-04-01

    The Broad Autism Phenotype Questionnaire (BAPQ) was administered to a large community-based sample of biological parents of children with autism (PCAs) and comparison parents (CPs) (n = 1,692). Exploratory factor analysis and internal consistency parameters confirmed a robust three-factor structure of the BAPQ, corresponding to the proposed aloof, pragmatic language and rigidity subscales. Based upon the distribution of Broad Autism Phenotype (BAP) features in the general population, new normative cutoff values for BAPQ subscales were established that provide increased specificity relative to those previously reported, and thus enhance the utility of the BAPQ for diagnostically classifying the BAP. These cutoffs were also used to estimate prevalence of the BAP and its three components, with rates ranging between 14-23% for PCAs and between 5-9% for CPs. Analysis of patterns of BAP characteristics within family members revealed that BAP features were more likely to co-occur in PCAs relative to CPs. Collectively, these findings extend the utility of the BAPQ and provide additional evidence that it is an efficient and reliable tool for disaggregating the heterogeneity of autism through the identification of meaningful subgroups of parents. Autism Res 2013, 6: 134-143. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  5. Mapping structural landmarks, ligand binding sites and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions and variation in phenotypes in inherited diseases affecting basement membranes

    PubMed Central

    Des Parkin, J.; San Antonio, James D.; Pedchenko, Vadim; Hudson, Billy; Jensen, Shane T.; Savige, Judy

    2016-01-01

    Collagen IV is the major protein found in basement membranes. It comprises 3 heterotrimers (α1α1α2, α3α4α5, and α5α5α6) that form distinct networks, and are responsible for membrane strength and integrity. We constructed linear maps of the collagen IV heterotrimers (‘interactomes’) that indicated major structural landmarks, known and predicted ligand-binding sites, and missense mutations, in order to identify functional and disease-associated domains, potential interactions between ligands, and genotype-phenotype relationships. The maps documented more than 30 known ligand-binding sites as well as motifs for integrins, heparin, von Willebrand factor (VWF), decorin and bone morphogenetic protein (BMP). They predicted functional domains for angiogenesis and haemostasis, and disease domains for autoimmunity, tumor growth and inhibition, infection and glycation. Cooperative ligand interactions were indicated by binding site proximity, for example, between integrins, matrix metalloproteinases and heparin. The maps indicated that mutations affecting major ligand-binding sites, for example for Von Hippel Lindau (VHL) protein in the α1 chain or integrins in the α5 chain, resulted in distinctive phenotypes (Hereditary Angiopathy, Nephropathy, Aneurysms and muscle Cramps (HANAC) syndrome, and early onset Alport syndrome respectively). These maps further our understanding of basement membrane biology and disease, and suggest novel membrane interactions, functions, and therapeutic targets. PMID:21280145

  6. Analysis of Pena Shokeir phenotype.

    PubMed

    Hall, J G

    1986-09-01

    At this point in time, we recognize that "Pena Shokeir" is not a diagnosis or a specific syndrome but rather a description of a phenotype produced by fetal akinesia or decreased in utero movement. In its "full blown" form, it is characterized by polyhydramnios, intrauterine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, congenital contractures, short umbilical cord, and lethality. From the cases thus far reported, we would anticipate that the phenotype is present in a very heterogeneous group of disorders--heterogeneous both with regard to the specific anomalies present and with regard to the causes (which must include many environmental agents and multiple genetic forms). One challenge for the future is to better describe and delineate specific entities. In the meantime, we would do well to use the terms "Pena Shokeir phenotype" or "fetal akinesia/hypokinesia sequence," which do not imply a single entity. There are many practical aspects of recognizing this phenotype. The presence of any one of the cardinal signs of the fetal akinesia/hypokinesia sequence should alert the physician to look for the other associated anomalies, since specific treatment may be indicated, and catch-up or compensatory growth may occur, if given a chance. The ability to provide prenatal diagnosis and perhaps prenatal treatment in the future may allow us to alter dramatically the natural history of some cases. In others, we need to establish when treatment is possible and when it gives no benefit. Perhaps the most important insight gained from the study of the fetal akinesia sequence is the reaffirmation of the concept that function is an integral part of normal development. Specific structures do not develop in isolation but are part of a carefully timed and integrated system. The "use" of a structure in utero is necessary for its continuing and normal development. The old adage "use it or lose it" seems to apply just as appropriately to prenatal normal

  7. Phenotypic clustering in MPZ mutations.

    PubMed

    Shy, Michael E; Jáni, Agnes; Krajewski, Karen; Grandis, Marina; Lewis, Richard A; Li, Jun; Shy, Rosemary R; Balsamo, Janne; Lilien, Jack; Garbern, James Y; Kamholz, John

    2004-02-01

    Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily with single extracellular, transmembrane and cytoplasmic domains. Homotypic interactions between extracellular domains of MPZ adhere adjacent myelin wraps to each other. MPZ is also necessary for myelin compaction since mice which lack MPZ develop severe dysmyelinating neuropathies in which compaction is dramatically disrupted. MPZ mutations in humans cause the inherited demyelinating neuropathy CMT1B. Some mutations cause the severe neuropathies of infancy designated as Dejerine-Sottas disease, while others cause a 'classical' Charcot-Marie-Tooth (CMT) disease Type 1B (CMT1B) phenotype with normal early milestones but development of disability during the first two decades of life. Still other mutations cause a neuropathy that presents in adults, with normal nerve conduction velocities, designated as a 'CMT2' form of CMT1B. To correlate the phenotype of patients with MPZ mutations with their genotype, we identified and evaluated 13 patients from 12 different families with eight different MPZ mutations. In addition, we re-analysed the clinical data from 64 cases of CMT1B from the literature. Contrary to our expectations, we found that most patients presented with either an early onset neuropathy with signs and symptoms prior to the onset of walking or a late onset neuropathy with signs and symptoms at around age 40 years. Only occasional patients presented with a 'classical' CMT phenotype. Correlation of specific MPZ mutations with their phenotypes demonstrated that addition of either a charged amino acid or altering a cysteine residue in the extracellular domain caused a severe early onset neuropathy. Severe neuropathy was also caused by truncation of the cytoplasmic domain or alteration of an evolutionarily conserved amino acid. Taken together, these data suggest that early onset neuropathy is caused by MPZ mutations that significantly disrupt the tertiary structure of MPZ and thus

  8. Extended chameleon models

    NASA Astrophysics Data System (ADS)

    Brax, Philippe; Tamanini, Nicola

    2016-05-01

    We extend the chameleon models by considering scalar-fluid theories where the coupling between matter and the scalar field can be represented by a quadratic effective potential with density-dependent minimum and mass. In this context, we study the effects of the scalar field on Solar System tests of gravity and show that models passing these stringent constraints can still induce large modifications of Newton's law on galactic scales. On these scales we analyze models which could lead to a percent deviation of Newton's law outside the virial radius. We then model the dark matter halo as a Navarro-Frenk-White profile and explicitly find that the fifth force can give large contributions around the galactic core in a particular model where the scalar field mass is constant and the minimum of its potential varies linearly with the matter density. At cosmological distances, we find that this model does not alter the growth of large scale structures and therefore would be best tested on galactic scales, where interesting signatures might arise in the galaxy rotation curves.

  9. Extending the extended V-Y flap.

    PubMed

    Prowse, Phoebe; Morton, Jonathan

    2012-06-01

    This case report demonstrates a modification of the so-called 'Extended V-Y Flap' used to simultaneously reconstruct a defect involving the upper lip, floor of nose and alar rim following tumour excision. We hope that this case serves as a reminder of the versatility of the V-Y flap in the nasolabial region, and its considerable capacity for augmentation. PMID:22018837

  10. Fitness of multidimensional phenotypes in dynamic adaptive landscapes.

    PubMed

    Laughlin, Daniel C; Messier, Julie

    2015-08-01

    Phenotypic traits influence species distributions, but ecology lacks established links between multidimensional phenotypes and fitness for predicting species responses to environmental change. The common focus on single traits rather than multiple trait combinations limits our understanding of their adaptive value, and intraspecific trait covariation has been neglected in ecology despite its importance in evolutionary theory and its likely impact on species distributions. Here, we extend the adaptive landscape framework to ecological sorting of multidimensional phenotypes across environments and discuss how two analytical approaches can be used to quantify fitness as a function of the interaction between the phenotype and the environment. We encourage ecologists to consider how phenotypic integration will constrain species responses to environmental change.

  11. The Effect of an Extended Wilderness Education Experience on Ill-Structured Problem-Solving Skill Development in Emerging Adult Students

    ERIC Educational Resources Information Center

    Collins, Rachel H.

    2014-01-01

    In a society that is becoming more dynamic, complex, and diverse, the ability to solve ill-structured problems has become an increasingly critical skill. Emerging adults are at a critical life stage that is an ideal time to develop the skills needed to solve ill-structured problems (ISPs) as they are transitioning to adult roles and starting to…

  12. Rapamycin extends murine lifespan but has limited effects on aging

    PubMed Central

    Neff, Frauke; Flores-Dominguez, Diana; Ryan, Devon P.; Horsch, Marion; Schröder, Susanne; Adler, Thure; Afonso, Luciana Caminha; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Garrett, Lillian; Hans, Wolfgang; Hettich, Moritz M.; Holtmeier, Richard; Hölter, Sabine M.; Moreth, Kristin; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Naton, Beatrix; Ordemann, Rainer; Adamski, Jerzy; Beckers, Johannes; Bekeredjian, Raffi; Busch, Dirk H.; Ehninger, Gerhard; Graw, Jochen; Höfler, Heinz; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Stypmann, Jörg; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabe de Angelis, Martin; Ehninger, Dan

    2013-01-01

    Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin’s effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin’s longevity effects from effects on aging itself. PMID:23863708

  13. Characterizing xBa(Mg1/3Ta2/3)O3+(1-x )Ba(Mg1/3Nb2/3)O3 microwave ceramics using extended x-ray absorption fine structure method

    NASA Astrophysics Data System (ADS)

    Chang, P.-J.; Chia, C.-T.; Lin, I.-N.; Lee, J.-F.; Lin, C. M.; Wu, K. T.

    2006-06-01

    The structures of TaO6 and NbO6 oxygen octahedra in xBa(Mg1/3Ta2/3)O3+(1-x )Ba(Mg1/3Nb2/3)O3 perovskite ceramics with x =0, 0.25, 0.50, 0.75, and 1.0 were investigated by the extended x-ray absorption fine structure method. The decline in the microwave dielectric constant as x increases is caused mainly by the decrease of the mean volume of the oxygen octahedra, regardless of the 1:2 ordered structure and the distortion of the oxygen octahedron. The low Qf values of the TaO6 and NbO6 mixed samples are caused by not only the degrading of the 1:2 ordered structure but also the distortion of oxygen octahedral cages.

  14. Functional Extended Redundancy Analysis

    ERIC Educational Resources Information Center

    Hwang, Heungsun; Suk, Hye Won; Lee, Jang-Han; Moskowitz, D. S.; Lim, Jooseop

    2012-01-01

    We propose a functional version of extended redundancy analysis that examines directional relationships among several sets of multivariate variables. As in extended redundancy analysis, the proposed method posits that a weighed composite of each set of exogenous variables influences a set of endogenous variables. It further considers endogenous…

  15. Extended or Restricted Childhood?

    ERIC Educational Resources Information Center

    Richards, Colin

    2005-01-01

    This article discusses the Government's proposals for "extended" primary schools, an important element in the recently-published five-year plan for education. The author expresses concern that extended primary schools will not provide a variety of experiences, including "play" experiences for young children.

  16. Extended conformal field theories

    NASA Astrophysics Data System (ADS)

    Taormina, Anne

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c≥1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification.

  17. Recovery act. Characterizing structural controls of EGS-candidate and conventional geothermal reservoirs in the Great Basin. Developing successful exploration strategies in extended terranes

    SciTech Connect

    Faulds, James

    2015-06-25

    We conducted a comprehensive analysis of the structural controls of geothermal systems within the Great Basin and adjacent regions. Our main objectives were to: 1) Produce a catalogue of favorable structural environments and models for geothermal systems. 2) Improve site-specific targeting of geothermal resources through detailed studies of representative sites, which included innovative techniques of slip tendency analysis of faults and 3D modeling. 3) Compare and contrast the structural controls and models in different tectonic settings. 4) Synthesize data and develop methodologies for enhancement of exploration strategies for conventional and EGS systems, reduction in the risk of drilling non-productive wells, and selecting the best EGS sites.

  18. Advances in Phenotyping of Functional Traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In plants, functional traits are morphological, biochemical, physiological, structural, phenological, or behavioral characteristics that are expressed in phenotypes of individual plants,that are relevant to the plant’s role in the ecosystem or its agronomic performance. By themselves, functional tra...

  19. PRIMARY CILIARY DYSKINESIA: DIAGNOSTIC AND PHENOTYPIC FEATURES

    EPA Science Inventory

    Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. We hypothesized that the major clinical and biologic phenotypic markers of the disease could be evaluated by studying a cohort of subjects suspected of having PCD. ...

  20. Single cell dynamic phenotyping

    PubMed Central

    Patsch, Katherin; Chiu, Chi-Li; Engeln, Mark; Agus, David B.; Mallick, Parag; Mumenthaler, Shannon M.; Ruderman, Daniel

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype tracking, and data filtering to remove erroneous cell tracks using the novel Tracking Aberration Measure (TrAM). Our workflow is broadly applicable across imaging platforms and analysis software. By applying this workflow to cancer cell assays, we reduced aberrant cell track prevalence from 17% to 2%. The cost of this improvement was removing 15% of the well-tracked cells. This enabled detection of significant motility differences between cell lines. Similarly, we avoided detecting a false change in translocation kinetics by eliminating the true cause: varied proportions of unresponsive cells. Finally, by systematically seeking heterogeneous behaviors, we detected subpopulations that otherwise could have been missed, including early apoptotic events and pre-mitotic cells. We provide optimized protocols for specific applications and step-by-step guidelines for adapting them to a variety of biological systems. PMID:27708391

  1. A new method to infer causal phenotype networks using QTL and phenotypic information.

    PubMed

    Wang, Huange; van Eeuwijk, Fred A

    2014-01-01

    In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at quantitative trait loci (QTLs) to learn about causal relationships among phenotypic traits. A requirement for using these approaches is that at least one unique QTL has been identified for each trait studied. However, in practice, especially for molecular phenotypes such as metabolites, this prerequisite is often not met due to limited sample sizes, high noise levels and small QTL effects. Here, we present a novel heuristic search algorithm called the QTL+phenotype supervised orientation (QPSO) algorithm to infer causal directions for edges in undirected phenotype networks. The two main advantages of this algorithm are: first, it does not require QTLs for each and every trait; second, it takes into account associated phenotypic interactions in addition to detected QTLs when orienting undirected edges between traits. We evaluate and compare the performance of QPSO with another state-of-the-art approach, the QTL-directed dependency graph (QDG) algorithm. Simulation results show that our method has broader applicability and leads to more accurate overall orientations. We also illustrate our method with a real-life example involving 24 metabolites and a few major QTLs measured on an association panel of 93 tomato cultivars. Matlab source code implementing the proposed algorithm is freely available upon request. PMID:25144184

  2. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure.

    PubMed

    Sun, Bo; Roh, Kyung-Hwan; Lee, Sae-Rom; Lee, Yong-Soon; Kang, Kyung-Sun

    2007-03-23

    Success in islet-transplantation-based therapies for type I diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Embryonic stem cells (ESCs) have been successfully induced into insulin producing islet-like structure in several studies. However, the source of the ESCs has presented ethical and technical concerns. Here, we isolated a population of stem cells from human cord blood (UCB), which expressed embryo stage specific maker, SSEA-4, and the multi-potential stem cell marker, Oct4. Subsequently, we successfully induced them into insulin-producing islet-like structures, which co-express insulin and C-peptide. These findings might have a significant potential to advance human UCB derived stem-cell-based therapeutics for diabetes.

  3. π-Extended and six-coordinate iron(II) complexes: structures, magnetic properties, and the electrochemical synthesis of a conducting iron(II) metallopolymer.

    PubMed

    Djukic, Brandon; Seda, Takele; Gorelsky, Serge I; Lough, Alan J; Lemaire, Martin T

    2011-08-01

    Herein, we describe the preparation of three new bidentate π-extended derivatives of the ligand N-phenyl-2-pyridinalimine (ppi) containing a 3-thienyl (4) substituent at position 4 of the aniline ring or 2-thienyl (6) or phenyl (2) substituents at each of the 2,5 positions of the aniline rings. Three iron(2+) complexes (7-9) containing these ligands were prepared by combining two equivalents each of 2, 4, or 6 with Fe(NCS)(2), and the resulting neutral, six-coordinate complexes were fully characterized, including with single crystal X-ray diffraction experiments in the case of complexes 7 and 9. Variable temperature magnetic susceptibility and Mössbauer experiments confirm the presence of spin-crossover in complexes 7 and 8, and the unusual solid state variable temperature magnetic properties of complex 9 likely result from crystal packing forces. Electropolymerization of the 2,5-dithienyl-substituted complex (9) produces a conducting and electrochromic metallopolymer film (poly-9).

  4. Extending mine life

    SciTech Connect

    Not Available

    1984-06-01

    Mine layouts, new machines and techniques, research into problem areas of ground control and so on, are highlighted in this report on extending mine life. The main resources taken into account are coal mining, uranium mining, molybdenum and gold mining.

  5. High-accuracy vapor pressure data of the extended [C(n)C1im][Ntf2] ionic liquid series: trend changes and structural shifts.

    PubMed

    Rocha, Marisa A A; Lima, Carlos F R A C; Gomes, Lígia R; Schröder, Bernd; Coutinho, João A P; Marrucho, Isabel M; Esperança, José M S S; Rebelo, Luís P N; Shimizu, Karina; Lopes, José N Canongia; Santos, Luís M N B F

    2011-09-22

    For the first time, two distinct trends are clearly evidenced for the enthalpies and entropies of vaporization along the [Cnmim][Ntf2] ILs series. The trend shifts observed for Δ(l)(g)H(m)(o) and Δ(l)(g)S(m)(o), which occur at [C6mim][Ntf2], are related to structural modifications. The thermodynamic results reported in the present article constitute the first quantitative experimental evidence of the structural percolation phenomenon and make a significant contribution to better understanding of the relationship among cohesive energies, volatilities, and liquid structures of ionic liquids. A new Knudsen effusion apparatus, combined with a quartz crystal microbalance, was used for the high-accuracy volatility study of the 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide series ([Cnmim][Ntf2], where n = 2, 3, 4, 5, 6, 7, 8, 10, 12). Vapor pressures in the (450–500) K temperature range were measured, and the molar standard enthalpies, entropies, and Gibbs energies of vaporization were derived. The thermodynamic parameters of vaporization were reported, along with molecular dynamic simulations of the liquid phase structure, allowing the establishment of a link between the thermodynamic properties and the percolation phenomenon in ILs.

  6. Dicyanometallates as Model Extended Frameworks

    PubMed Central

    2016-01-01

    We report the structures of eight new dicyanometallate frameworks containing molecular extra-framework cations. These systems include a number of hybrid inorganic–organic analogues of conventional ceramics, such as Ruddlesden–Popper phases and perovskites. The structure types adopted are rationalized in the broader context of all known dicyanometallate framework structures. We show that the structural diversity of this family can be understood in terms of (i) the charge and coordination preferences of the particular metal cation acting as framework node, and (ii) the size, shape, and extent of incorporation of extra-framework cations. In this way, we suggest that dicyanometallates form a particularly attractive model family of extended frameworks in which to explore the interplay between molecular degrees of freedom, framework topology, and supramolecular interactions. PMID:27057759

  7. `Weak A' phenotypes

    PubMed Central

    Cartron, J. P.; Gerbal, A.; Hughes-Jones, N. C.; Salmon, C.

    1974-01-01

    Thirty-five weak A samples including fourteen A3, eight Ax, seven Aend, three Am and three Ae1 were studied in order to determine their A antigen site density, using an IgG anti-A labelled with 125I. The values obtained ranged between 30,000 A antigen sites for A3 individuals, and 700 sites for the Ae1 red cells. The hierarchy of values observed made it possible to establish a quantitative relationship between the red cell agglutinability of these phenotypes measured under standard conditions, and their antigen site density. PMID:4435836

  8. Observations and Modeling of the Near Surface Vertical Structure of the Atmosphere in the Southern Appalachians during the Integrated Precipitation and Hydrology Experiment (IPHEx) Extended Observing Period

    NASA Astrophysics Data System (ADS)

    Wilson, A. M.; Barros, A. P.

    2014-12-01

    Accurate, high resolution observations of precipitation accumulations and intensity in regions of complex terrain are largely unavailable, due to a lack of existing in situ observations and obstacles to remote sensing (radar and satellite observations) such as beam blockage and ground clutter. For the past six years, a high-elevation, high-density rain gauge network has been recording precipitation observations along ridgelines in the Pigeon River Basin in the Southern Appalachians. These longer term observations complement the 4-D database of observations, which are being collected in support of the Global Precipitation Mission (GPM) during the first field campaign after the launch of the GPM satellite, the Integrated Precipitation and Hydrology Experiment (IPHEx). The observations focused on here are those at the near surface, within 2 kilometers of the ground level. The IPHEx extended observation period lasts until the end of 2014. This presentation will focus on ground-based measurements made by MicroRain Radars, disdrometers, radiometers, rain gauges, fog collectors and aerosol spectrometers among others during the spring, summer and fall of 2014. These measurements will be analyzed to provide information on the diurnal cycle of microphysical and dynamical processes and properties in the region, with an emphasis on describing the characteristics of local cloud and fog. These observations will be discussed in the context of previous findings based on observations and model results (stochastic column model and the Advanced Research Weather and Forecasting Model (WRF)). Specifically, this presentation will address whether the IPHEx observations support the hypothesis, validated for specific case studies in previous work, that Bergeron processes govern the enhancement of light rainfall in the Southern Appalachians through increased coalescence efficiency in stratiform rainfall due to the interactions with low level clouds and topography modulated fog. WRF

  9. A Group 6 Late Embryogenesis Abundant Protein from Common Bean Is a Disordered Protein with Extended Helical Structure and Oligomer-forming Properties*

    PubMed Central

    Rivera-Najera, Lucero Y.; Saab-Rincón, Gloria; Battaglia, Marina; Amero, Carlos; Pulido, Nancy O.; García-Hernández, Enrique; Solórzano, Rosa M.; Reyes, José L.; Covarrubias, Alejandra A.

    2014-01-01

    Late embryogenesis-abundant proteins accumulate to high levels in dry seeds. Some of them also accumulate in response to water deficit in vegetative tissues, which leads to a remarkable association between their presence and low water availability conditions. A major sub-group of these proteins, also known as typical LEA proteins, shows high hydrophilicity and a high percentage of glycine and other small amino acid residues, distinctive physicochemical properties that predict a high content of structural disorder. Although all typical LEA proteins share these characteristics, seven groups can be distinguished by sequence similarity, indicating structural and functional diversity among them. Some of these groups have been extensively studied; however, others require a more detailed analysis to advance in their functional understanding. In this work, we report the structural characterization of a group 6 LEA protein from a common bean (Phaseolus vulgaris L.) (PvLEA6) by circular dichroism and nuclear magnetic resonance showing that it is a disordered protein in aqueous solution. Using the same techniques, we show that despite its unstructured nature, the addition of trifluoroethanol exhibited an intrinsic potential in this protein to gain helicity. This property was also promoted by high osmotic potentials or molecular crowding. Furthermore, we demonstrate that PvLEA6 protein is able to form soluble homo-oligomeric complexes that also show high levels of structural disorder. The association between PvLEA6 monomers to form dimers was shown to occur in plant cells by bimolecular fluorescence complementation, pointing to the in vivo functional relevance of this association. PMID:25271167

  10. A group 6 late embryogenesis abundant protein from common bean is a disordered protein with extended helical structure and oligomer-forming properties.

    PubMed

    Rivera-Najera, Lucero Y; Saab-Rincón, Gloria; Battaglia, Marina; Amero, Carlos; Pulido, Nancy O; García-Hernández, Enrique; Solórzano, Rosa M; Reyes, José L; Covarrubias, Alejandra A

    2014-11-14

    Late embryogenesis-abundant proteins accumulate to high levels in dry seeds. Some of them also accumulate in response to water deficit in vegetative tissues, which leads to a remarkable association between their presence and low water availability conditions. A major sub-group of these proteins, also known as typical LEA proteins, shows high hydrophilicity and a high percentage of glycine and other small amino acid residues, distinctive physicochemical properties that predict a high content of structural disorder. Although all typical LEA proteins share these characteristics, seven groups can be distinguished by sequence similarity, indicating structural and functional diversity among them. Some of these groups have been extensively studied; however, others require a more detailed analysis to advance in their functional understanding. In this work, we report the structural characterization of a group 6 LEA protein from a common bean (Phaseolus vulgaris L.) (PvLEA6) by circular dichroism and nuclear magnetic resonance showing that it is a disordered protein in aqueous solution. Using the same techniques, we show that despite its unstructured nature, the addition of trifluoroethanol exhibited an intrinsic potential in this protein to gain helicity. This property was also promoted by high osmotic potentials or molecular crowding. Furthermore, we demonstrate that PvLEA6 protein is able to form soluble homo-oligomeric complexes that also show high levels of structural disorder. The association between PvLEA6 monomers to form dimers was shown to occur in plant cells by bimolecular fluorescence complementation, pointing to the in vivo functional relevance of this association. PMID:25271167

  11. The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site

    PubMed Central

    Taylor, Alexander B.; Meyer, Britta; Leal, Belinda Z.; Kötter, Peter; Schirf, Virgil; Demeler, Borries; Hart, P. John; Entian, Karl-Dieter; Wöhnert, Jens

    2008-01-01

    Ribosome biogenesis in eukaryotes requires the participation of a large number of ribosome assembly factors. The highly conserved eukaryotic nucleolar protein Nep1 has an essential but unknown function in 18S rRNA processing and ribosome biogenesis. In Saccharomyces cerevisiae the malfunction of a temperature-sensitive Nep1 protein (nep1-1ts) was suppressed by the addition of S-adenosylmethionine (SAM). This suggests the participation of Nep1 in a methyltransferase reaction during ribosome biogenesis. In addition, yeast Nep1 binds to a 6-nt RNA-binding motif also found in 18S rRNA and facilitates the incorporation of ribosomal protein Rps19 during the formation of pre-ribosomes. Here, we present the X-ray structure of the Nep1 homolog from the archaebacterium Methanocaldococcus jannaschii in its free form (2.2 Å resolution) and bound to the S-adenosylmethionine analog S-adenosylhomocysteine (SAH, 2.15 Å resolution) and the antibiotic and general methyltransferase inhibitor sinefungin (2.25 Å resolution). The structure reveals a fold which is very similar to the conserved core fold of the SPOUT-class methyltransferases but contains a novel extension of this common core fold. SAH and sinefungin bind to Nep1 at a preformed binding site that is topologically equivalent to the cofactor-binding site in other SPOUT-class methyltransferases. Therefore, our structures together with previous genetic data suggest that Nep1 is a genuine rRNA methyltransferase. PMID:18208838

  12. A codon change in beta-tubulin which drastically affects microtubule structure in Drosophila melanogaster fails to produce a significant phenotype in Saccharomyces cerevisiae.

    PubMed

    Praitis, V; Katz, W S; Solomon, F

    1991-09-01

    The relative uniformity of microtubule ultrastructure in almost all eukaryotic cells is thought to be a consequence of the conserved elements of tubulin sequence. In support of this idea, a mutation in a beta-tubulin gene of Drosophila melanogaster, occurring at a highly conserved position, produces U-shaped microtubules, suggesting a defect in either nucleation or packing during assembly (M. T. Fuller, J. H. Caulton, J. A. Hutchens, T. C. Kaufman, and E. C. Raff, J. Cell Biol. 104:385-394, 1987, and J. E. Rudolph, M. Kimble, H. D. Hoyle, M. A. Subler, and E. C. Raff, Mol. Cell. Biol. 7:2231-2242, 1987). Surprisingly, we find that introducing the same mutation into the sole beta-tubulin gene of Saccharomyces cerevisiae has virtually no consequences for microtubule structure or function in that organism. PMID:1908555

  13. The Impact of Herbicide-Resistant Rice Technology on Phenotypic Diversity and Population Structure of United States Weedy Rice1[W][OPEN

    PubMed Central

    Burgos, Nilda Roma; Singh, Vijay; Tseng, Te Ming; Black, Howard; Young, Nelson D.; Huang, Zhongyun; Hyma, Katie E.; Gealy, David R.; Caicedo, Ana L.

    2014-01-01

    The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw-colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management. PMID:25122473

  14. Reprogramming of fibroblast nuclei in cloned bovine embryos involves major structural remodeling with both striking similarities and differences to nuclear phenotypes of in vitro fertilized embryos.

    PubMed

    Popken, Jens; Brero, Alessandro; Koehler, Daniela; Schmid, Volker J; Strauss, Axel; Wuensch, Annegret; Guengoer, Tuna; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Zakhartchenko, Valeri; Wolf, Eckhard; Cremer, Thomas

    2014-01-01

    Nuclear landscapes were studied during preimplantation development of bovine embryos, generated either by in vitro fertilization (IVF), or generated as cloned embryos by somatic cell nuclear transfer (SCNT) of bovine fetal fibroblasts, using 3-dimensional confocal laser scanning microscopy (3D-CLSM) and structured illumination microscopy (3D-SIM). Nuclear landscapes of IVF and SCNT embryonic nuclei were compared with each other and with fibroblast nuclei. We demonstrate that reprogramming of fibroblast nuclei in cloned embryos requires changes of their landscapes similar to nuclei of IVF embryos. On the way toward the 8-cell stage, where major genome activation occurs, a major lacuna, enriched with splicing factors, was formed in the nuclear interior and chromosome territories (CTs) were shifted toward the nuclear periphery. During further development the major lacuna disappeared and CTs were redistributed throughout the nuclear interior forming a contiguous higher order chromatin network. At all stages of development CTs of IVF and SCNT embryonic nuclei were built up from chromatin domain clusters (CDCs) pervaded by interchromatin compartment (IC) channels. Quantitative analyses revealed a highly significant enrichment of RNA polymerase II and H3K4me3, a marker for transcriptionally competent chromatin, at the periphery of CDCs. In contrast, H3K9me3, a marker for silent chromatin, was enriched in the more compacted interior of CDCs. Despite these striking similarities, we also detected major differences between nuclear landscapes of IVF and cloned embryos. Possible implications of these differences for the developmental potential of cloned animals remain to be investigated. We present a model, which integrates generally applicable structural and functional features of the nuclear landscape.

  15. Reprogramming of fibroblast nuclei in cloned bovine embryos involves major structural remodeling with both striking similarities and differences to nuclear phenotypes of in vitro fertilized embryos

    PubMed Central

    Popken, Jens; Brero, Alessandro; Koehler, Daniela; Schmid, Volker J; Strauss, Axel; Wuensch, Annegret; Guengoer, Tuna; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Zakhartchenko, Valeri; Wolf, Eckhard; Cremer, Thomas

    2014-01-01

    Nuclear landscapes were studied during preimplantation development of bovine embryos, generated either by in vitro fertilization (IVF), or generated as cloned embryos by somatic cell nuclear transfer (SCNT) of bovine fetal fibroblasts, using 3-dimensional confocal laser scanning microscopy (3D-CLSM) and structured illumination microscopy (3D-SIM). Nuclear landscapes of IVF and SCNT embryonic nuclei were compared with each other and with fibroblast nuclei. We demonstrate that reprogramming of fibroblast nuclei in cloned embryos requires changes of their landscapes similar to nuclei of IVF embryos. On the way toward the 8-cell stage, where major genome activation occurs, a major lacuna, enriched with splicing factors, was formed in the nuclear interior and chromosome territories (CTs) were shifted toward the nuclear periphery. During further development the major lacuna disappeared and CTs were redistributed throughout the nuclear interior forming a contiguous higher order chromatin network. At all stages of development CTs of IVF and SCNT embryonic nuclei were built up from chromatin domain clusters (CDCs) pervaded by interchromatin compartment (IC) channels. Quantitative analyses revealed a highly significant enrichment of RNA polymerase II and H3K4me3, a marker for transcriptionally competent chromatin, at the periphery of CDCs. In contrast, H3K9me3, a marker for silent chromatin, was enriched in the more compacted interior of CDCs. Despite these striking similarities, we also detected major differences between nuclear landscapes of IVF and cloned embryos. Possible implications of these differences for the developmental potential of cloned animals remain to be investigated. We present a model, which integrates generally applicable structural and functional features of the nuclear landscape. PMID:25482066

  16. The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data.

    PubMed

    Koscielny, Gautier; Yaikhom, Gagarine; Iyer, Vivek; Meehan, Terrence F; Morgan, Hugh; Atienza-Herrero, Julian; Blake, Andrew; Chen, Chao-Kung; Easty, Richard; Di Fenza, Armida; Fiegel, Tanja; Grifiths, Mark; Horne, Alan; Karp, Natasha A; Kurbatova, Natalja; Mason, Jeremy C; Matthews, Peter; Oakley, Darren J; Qazi, Asfand; Regnart, Jack; Retha, Ahmad; Santos, Luis A; Sneddon, Duncan J; Warren, Jonathan; Westerberg, Henrik; Wilson, Robert J; Melvin, David G; Smedley, Damian; Brown, Steve D M; Flicek, Paul; Skarnes, William C; Mallon, Ann-Marie; Parkinson, Helen

    2014-01-01

    The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and standardized protocols for the experimentation, collection and dissemination of data. Dedicated 'data wranglers' work with each phenotyping center to collate data and perform quality control of data. An automated statistical analysis pipeline has been developed to identify knockout strains with a significant change in the phenotype parameters. Annotation with biomedical ontologies allows biologists and clinicians to easily find mouse strains with phenotypic traits relevant to their research. Data integration with other resources will provide insights into mammalian gene function and human disease. As phenotype data become available for every gene in the mouse, the IMPC web portal will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases.

  17. The Phenotype of Loneliness

    PubMed Central

    Cacioppo, John T.; Cacioppo, Stephanie

    2012-01-01

    Goossens’ (in press) review nicely maps the progression of scientific research from its early focus on loneliness as a dysphoric state that results from the discrepancy between a person's ideal and actual social relationships to its current emphasis on the centrality of loneliness to our very nature as a social species, and he argues that developmental science throughout Europe has a great deal to contribute to our understanding of this construct. He concludes that psychologists should care about research on loneliness for five reasons: (i) it is a well-defined phenotype, (ii) it shows both high stability and individual differences in rates of change across years, (iii) it has adaptive value and evolutionary significance, (iv) it has a genetic substrate that is moderated by social environments, and (v) it has self-maintaining features that can lead to adverse mental health outcomes. Goossen's (2012) review is rife with information and ideas. We focus here on two additional important reasons and on the phenotype of loneliness. PMID:23024688

  18. [Predisposition - obesity phenotype].

    PubMed

    Blüher, M

    2014-05-01

    Obesity belongs to the five most important health burdens in modern societies and reaches with ~20 % prevalence in Germany epidemic proportions. Obesity significantly increases the risk of developing metabolic (e. g. type 2 diabetes), cardiovascular, orthopaedic, psychologic and other disorders. Despite the well established epidemiologic relationship between obesity and these co-morbidities, there is a subgroup of metabolically healthy obese patients, which seems to be protected against metabolic and cardiovascular obesity related disorders. Compared to metabolically unhealthy or high risk obese patients, metabolically healthy obese individuals are characterized by preserved insulin sensitivity, lower liver fat content, lower visceral fat mass, as well as normal adipose tissue function. Noteworthy, metabolically healthy obese individuals do not significantly improve their obesity-associated risk for the development of type 2 diabetes and vascular diseases. Therefore, distinction between metabolically healthy from high-risk obese phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, pharmacological or bariatric surgery interventions. A stratified treatment approach considering these different obesity phenotypes should be introduced into clinical management of obese patients.

  19. Protein expression and genetic structure of the coral Porites lobata in an environmentally extreme Samoan back reef: Does host genotype limit phenotypic plasticity?

    USGS Publications Warehouse

    Barshis, D.J.; Stillman, J.H.; Gates, R.D.; Toonen, R.J.; Smith, L.W.; Birkeland, C.

    2010-01-01

    The degree to which coral reef ecosystems will be impacted by global climate change depends on regional and local differences in corals' susceptibility and resilience to environmental stressors. Here, we present data from a reciprocal transplant experiment using the common reef building coral Porites lobata between a highly fluctuating back reef environment that reaches stressful daily extremes, and a more stable, neighbouring forereef. Protein biomarker analyses assessing physiological contributions to stress resistance showed evidence for both fixed and environmental influence on biomarker response. Fixed influences were strongest for ubiquitin-conjugated proteins with consistently higher levels found in back reef source colonies both pre and post-transplant when compared with their forereef conspecifics. Additionally, genetic comparisons of back reef and forereef populations revealed significant population structure of both the nuclear ribosomal and mitochondrial genomes of the coral host (FST = 0.146 P < 0.0001, FST = 0.335 P < 0.0001 for rDNA and mtDNA, respectively), whereas algal endosymbiont populations were genetically indistinguishable between the two sites. We propose that the genotype of the coral host may drive limitations to the physiological responses of these corals when faced with new environmental conditions. This result is important in understanding genotypic and environmental interactions in the coral algal symbiosis and how corals may respond to future environmental changes. ?? 2010 Blackwell Publishing Ltd.

  20. Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder.

    PubMed

    Leuchter, Andrew F; Hunter, Aimee M; Krantz, David E; Cook, Ian A

    2014-12-01

    Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness.

  1. Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder

    PubMed Central

    Leuchter, Andrew F.; Hunter, Aimee M.; Krantz, David E.; Cook, Ian A.

    2014-01-01

    Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness. PMID:25733956

  2. Syntheses, structural variations and fluorescence studies of two dinuclear zinc(II) complexes of a Schiff base ligand with an extended carboxylate side arm

    NASA Astrophysics Data System (ADS)

    Shit, Shyamapada; Sasmal, Ashok; Dhal, Piu; Rizzoli, Corrado; Mitra, Samiran

    2016-03-01

    A potentially tetradentate Schiff base ligand containing carboxylic acid group, HL, (E)-2-((pyridin-2-yl)methyleneamino)-5-chlorobenzoic acid is synthesized and characterized. Reaction of HL with hydrated zinc(II) trichloroacetate and zinc(II) trifluoroacetate under similar reaction condition yields two discrete dinuclear complexes, [Zn(L)(Cl)]2 (1) and [Zn(L)(CF3COO)]2 (2) and characterized by different physicochemical methods. Single crystal X-ray structural characterization reveals different ligating properties of the coordinated anionic ligand (L-) in its zinc(II) complexes. The side arm carboxylate of L- shows μ1,3-carboxylato-bridging mode in 1 and connects zinc(II) atoms in syn-anti fashion while it exhibits a μ1,1-carboxylato-bridging mode in 2. The metal ions display distorted square pyramidal geometries in both the structures and associated with different degrees of distortions. The fluorescence spectra of HL and its zinc(II) complexes recorded in methanol at room temperature which reveal the enhancement of emission intensity for the complexes compared to that of the free ligand. Thermogravimetric analyses (TGA) reveal high thermal stabilities of the complexes.

  3. Comprehensive study on the structure of the BSA from extended-to aged form in wide (2-12) pH range.

    PubMed

    Varga, N; Hornok, V; Sebők, D; Dékány, I

    2016-07-01

    In this work we studied the structure of the bovine serum albumin (BSA) and the protein-ligand interactions since researchers prefer to use them as carriers in drug delivery systems. Systematic study (between pH 2-12, in double distilled water and physiological salt solution) was carried out to determine the changes in the secondary and the tertiary structures of the BSA, the apparent molecular weight (Mw), the size (dLS) and the electrokinetic potential (ζ). At pH 7, the BSA has higher stability in the absence (ζ=-69mV, dLS=2.2nm, A2=1.4×10(-3)mlmol/g(2)) than in the presence of salt solution (ζ=-2.4mV, dLS=5.3nm, A2=-3.2×10(-4)mlmol/g(2)). The Mw strongly depends on the pH and the ionic strength (at pH 3 in the absence of salt, the Mw is 54.6kDa while in the presence of salt is 114kDa) which determines the geometry of the protein. The protein-ligand interactions were characterized by fluorescence (FL) and isothermal microcalorimetry (ITC) methods; these independent techniques provided similar thermodynamic parameters such as the binding constant (K) and the Gibbs free energy (ΔG). PMID:26995614

  4. Comprehensive study on the structure of the BSA from extended-to aged form in wide (2-12) pH range.

    PubMed

    Varga, N; Hornok, V; Sebők, D; Dékány, I

    2016-07-01

    In this work we studied the structure of the bovine serum albumin (BSA) and the protein-ligand interactions since researchers prefer to use them as carriers in drug delivery systems. Systematic study (between pH 2-12, in double distilled water and physiological salt solution) was carried out to determine the changes in the secondary and the tertiary structures of the BSA, the apparent molecular weight (Mw), the size (dLS) and the electrokinetic potential (ζ). At pH 7, the BSA has higher stability in the absence (ζ=-69mV, dLS=2.2nm, A2=1.4×10(-3)mlmol/g(2)) than in the presence of salt solution (ζ=-2.4mV, dLS=5.3nm, A2=-3.2×10(-4)mlmol/g(2)). The Mw strongly depends on the pH and the ionic strength (at pH 3 in the absence of salt, the Mw is 54.6kDa while in the presence of salt is 114kDa) which determines the geometry of the protein. The protein-ligand interactions were characterized by fluorescence (FL) and isothermal microcalorimetry (ITC) methods; these independent techniques provided similar thermodynamic parameters such as the binding constant (K) and the Gibbs free energy (ΔG).

  5. Synthesis, structures and properties of Ag+ complexes containing polyphosphine ligands with extended Ag⋯C, N-O⋯π and C-H⋯π interactions

    NASA Astrophysics Data System (ADS)

    Huang, Ting-Hong; Yang, Hu; Yang, Guo; Li, Yanfen; Huang, Li-Li

    2016-08-01

    Based on ligands of N,N-bis((diphenylphosphino)methyl)benzenamine (pba), 4-(4-(bis((diphenylphosphino)methyl)amino)benzyl)-N-((diphenylphosphino)methyl)benzenamine (dptp) and N,N,N‧,N‧-tetrakis((diphenylphosphino)methyl)benzene-1,4-diamine (pbaa), three new silver(I) complexes [Ag(pba)2]ClO4 (1), [Ag2(dptp)2](ClO4)2·2DMF (2) and [Ag4(pbaa)(NO3)4]n (3), have been synthesized and characterized. Structural analysis reveals that all of these complexes contain the 1D infinite chains, with different variations in the weak interactions. Complexes 1 and 2 are interconnected by intermolecular C-H⋯π interactions to form 1D infinite chains and 2D networks, and the ordered-layer-lattic ClO4- and DMF in 2 are between 2D networks. For 3, the pbaa ligand adopts a tetradentate coordination mode to link two adjacent stair-like [Ag4O4] cores resulting in a 1D chain, respectively, with Ag⋯C, N-O⋯π and C-H⋯π interactions. All these show that phosphine ligands play an important role in the construction of interesting topological structures with different types of the weak interactions.

  6. Extendable pipe crawler

    DOEpatents

    Hapstack, Mark

    1991-01-01

    A pipe crawler having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by "inchworm"-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward.

  7. Extendable pipe crawler

    DOEpatents

    Hapstack, M.

    1991-05-28

    A pipe crawler is described having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by inchworm'-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward. 5 figures.

  8. Aspergillus parasiticus SU-1 genome sequence, predicted chromosome structure, and comparative gene expression under aflatoxin-inducing conditions: evidence that differential expression contributes to species phenotype.

    PubMed

    Linz, John E; Wee, Josephine; Roze, Ludmila V

    2014-08-01

    The filamentous fungi Aspergillus parasiticus and Aspergillus flavus produce the carcinogenic secondary metabolite aflatoxin on susceptible crops. These species differ in the quantity of aflatoxins B1, B2, G1, and G2 produced in culture, in the ability to produce the mycotoxin cyclopiazonic acid, and in morphology of mycelia and conidiospores. To understand the genetic basis for differences in biochemistry and morphology, we conducted next-generation sequence (NGS) analysis of the A. parasiticus strain SU-1 genome and comparative gene expression (RNA sequence analysis [RNA Seq]) analysis of A. parasiticus SU-1 and A. flavus strain NRRL 3357 (3357) grown under aflatoxin-inducing and -noninducing culture conditions. Although A. parasiticus SU-1 and A. flavus 3357 are highly similar in genome structure and gene organization, we observed differences in the presence of specific mycotoxin gene clusters and differential expression of specific mycotoxin genes and gene clusters that help explain differences in the type and quantity of mycotoxins synthesized. Using computer-aided analysis of secondary metabolite clusters (antiSMASH), we demonstrated that A. parasiticus SU-1 and A. flavus 3357 may carry up to 93 secondary metabolite gene clusters, and surprisingly, up to 10% of the genome appears to be dedicated to secondary metabolite synthesis. The data also suggest that fungus-specific zinc binuclear cluster (C6) transcription factors play an important role in regulation of secondary metabolite cluster expression. Finally, we identified uniquely expressed genes in A. parasiticus SU-1 that encode C6 transcription factors and genes involved in secondary metabolism and stress response/cellular defense. Future work will focus on these differentially expressed A. parasiticus SU-1 loci to reveal their role in determining distinct species characteristics. PMID:24951444

  9. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    PubMed Central

    Köhler, Sebastian; Doelken, Sandra C.; Mungall, Christopher J.; Bauer, Sebastian; Firth, Helen V.; Bailleul-Forestier, Isabelle; Black, Graeme C. M.; Brown, Danielle L.; Brudno, Michael; Campbell, Jennifer; FitzPatrick, David R.; Eppig, Janan T.; Jackson, Andrew P.; Freson, Kathleen; Girdea, Marta; Helbig, Ingo; Hurst, Jane A.; Jähn, Johanna; Jackson, Laird G.; Kelly, Anne M.; Ledbetter, David H.; Mansour, Sahar; Martin, Christa L.; Moss, Celia; Mumford, Andrew; Ouwehand, Willem H.; Park, Soo-Mi; Riggs, Erin Rooney; Scott, Richard H.; Sisodiya, Sanjay; Vooren, Steven Van; Wapner, Ronald J.; Wilkie, Andrew O. M.; Wright, Caroline F.; Vulto-van Silfhout, Anneke T.; de Leeuw, Nicole; de Vries, Bert B. A.; Washingthon, Nicole L.; Smith, Cynthia L.; Westerfield, Monte; Schofield, Paul; Ruef, Barbara J.; Gkoutos, Georgios V.; Haendel, Melissa; Smedley, Damian; Lewis, Suzanna E.; Robinson, Peter N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online. PMID:24217912

  10. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data.

    PubMed

    Köhler, Sebastian; Doelken, Sandra C; Mungall, Christopher J; Bauer, Sebastian; Firth, Helen V; Bailleul-Forestier, Isabelle; Black, Graeme C M; Brown, Danielle L; Brudno, Michael; Campbell, Jennifer; FitzPatrick, David R; Eppig, Janan T; Jackson, Andrew P; Freson, Kathleen; Girdea, Marta; Helbig, Ingo; Hurst, Jane A; Jähn, Johanna; Jackson, Laird G; Kelly, Anne M; Ledbetter, David H; Mansour, Sahar; Martin, Christa L; Moss, Celia; Mumford, Andrew; Ouwehand, Willem H; Park, Soo-Mi; Riggs, Erin Rooney; Scott, Richard H; Sisodiya, Sanjay; Van Vooren, Steven; Wapner, Ronald J; Wilkie, Andrew O M; Wright, Caroline F; Vulto-van Silfhout, Anneke T; de Leeuw, Nicole; de Vries, Bert B A; Washingthon, Nicole L; Smith, Cynthia L; Westerfield, Monte; Schofield, Paul; Ruef, Barbara J; Gkoutos, Georgios V; Haendel, Melissa; Smedley, Damian; Lewis, Suzanna E; Robinson, Peter N

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online. PMID:24217912

  11. Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii

    DOE PAGES

    Mitchell, Joshua M.; Clasman, Jozlyn R.; June, Cynthia M.; Kaitany, Kip-Chumba J.; LaFleur, James R.; Taracila, Magdalena A.; Klinger, Neil V.; Bonomo, Robert A.; Wymore, Troy; Szarecka, Agnieszka; et al

    2015-02-24

    The carbapenem-hydrolyzing class D β-lactamases OXA-23 and OXA-24/40 have emerged world-wide as causative agents for β-lactam antibiotic resistance in Acinetobacter species. Many variants of these enzymes have appeared clinically, including OXA-160 and OXA-225, which both contain a P→S substitution at homologous positions in the OXA-24/40 and OXA-23 backgrounds respectively. We purified OXA-160 and OXA-225 and used steady-state kinetic analysis to compare the substrate profiles of these variants to their parental enzymes, OXA-24/40 and OXA-23. OXA-160 and OXA-225 possess greatly enhanced hydrolytic activities against aztreonam, ceftazidime, cefotaxime and ceftriaxone when compared to OXA-24/40 and OXA-23. These enhanced activities are the resultmore » of much lower Km values, suggesting that the P→S substitution enhances the binding affinity of these drugs. We have determined the structures of the acylated forms of OXA-160 (with ceftazidime and aztreonam) and OXA-225 (ceftazidime). These structures show that the R1 oxyimino side-chain of these drugs occupies a space near the β5-β6 loop and the omega loop of the enzymes. The P→S substitution found in OXA-160 and OXA-225 results in a deviation of the β5-β6 loop, relieving the steric clash with the R1 side-chain carboxypropyl group of aztreonam and ceftazidime. We found that these results reveal worrying trends in the enhancement of substrate spectrum of class D β-lactamases, but may also provide a map for β-lactam improvement.« less

  12. NRC Job Code V6060: Extended in-situ and real time monitoring. Task 4: Detection and monitoring of leaks at nuclear power plants external to structures

    SciTech Connect

    Sheen, S. H.

    2012-08-01

    In support of Task 4 of the NRC study on compliance with 10 CFR part 20.1406, minimization of contamination, Argonne National Laboratory (ANL) conducted a one-year scoping study, in concert with a parallel study performed by NRC/NRR staff, on monitoring for leaks at nuclear power plants (NPPs) external to structures. The objective of this task-4 study is to identify and assess those sensors and monitoring techniques for early detection of abnormal radioactive releases from the engineered facility structures, systems and components (SSCs) to the surrounding underground environment in existing NPPs and planned new reactors. As such, methods of interest include: (1) detection of anomalous water content of soils surrounding SSCs, (2) radionuclides contained in the leaking water, and (3) secondary signals such as temperature. ANL work scope includes mainly to (1) identify, in concert with the nuclear industry, the sensors and techniques that have most promise to detect radionuclides and/or associated chemical releases from SSCs of existing NPPs and (2) review and provide comments on the results of the NRC/NRR staff scoping study to identify candidate technologies. This report constitutes the ANL deliverable of the task-4 study. It covers a survey of sensor technologies and leak detection methods currently applied to leak monitoring at NPPs. The survey also provides a technology evaluation that identifies their strength and deficiency based on their detection speed, sensitivity, range and reliability. Emerging advanced technologies that are potentially capable of locating releases, identifying the radionuclides, and estimating their concentrations and distributions are also included in the report along with suggestions of required further research and development.

  13. Structural and Catalytic Effects of Proline Substitution and Surface Loop Deletion in the Extended Active Site of Human Carbonic Anhydrase II

    PubMed Central

    Boone, Christopher D.; Rasi, Valerio; Tu, Chingkuang; McKenna, Robert

    2015-01-01

    The bioengineering of a thermophilic enzyme starting from a mesophilic scaffold has proven to be a significant challenge as several stabilizing elements have been proposed to be the foundation of thermal stability including disulfide bridges, surface loop reduction, ionic pair networks, proline substitutions, and aromatic clusters. This study emphasizes the impact of increasing the rigidity of human carbonic anhydrase II (HCA II) via incorporation of proline residues at positions 170 and 234, which are located in surface loops that are able to accommodate restrictive main-chain conformations without rearrangement of the surrounding peptide backbone. Additionally, the effect of compactness of HCA II was examined by way of deletion of a surface loop (residues 230 through 240), which had been previously identified as a possible source of thermal stability for the hyperthermophilic CA isolated from the bacterium Sulfurihydrogenibium yellowstonense YO3AOP1. Differential scanning calorimetry analysis of these HCA II variants revealed that these structural modifications had a minimum effect on the thermal stability of the enzyme while kinetic studies showed unexpected effects on the catalytic efficiency and proton transfer rates. X-ray crystallographic analysis of these HCA II variants showed the electrostatic potential and configuration of the highly acidic loop (residues 230 and 240) plays an important role in its high catalytic activity. Based on these observations and the literature, a picture is emerging of the various components within the general structural architecture of HCA II that are key to stability. These elements could provide the blueprints for the rational thermal stability engineering of other enzymes. PMID:25683338

  14. Structural