WorldWideScience

Sample records for regional domain differentiation

  1. Process- and Domain-Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation

    Science.gov (United States)

    Collins, Heather R.; Zhu, Xun; Bhatt, Ramesh S.; Clark, Jonathan D.; Joseph, Jane E.

    2015-01-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. The present study parametrically varied demands on featural, first-order configural or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing) or reflected generalized perceptual differentiation (i.e. differentiation that crosses category and processing type boundaries). Regions of interest were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process-specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex, and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain-specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories. PMID:22849402

  2. Process and domain specificity in regions engaged for face processing: an fMRI study of perceptual differentiation.

    Science.gov (United States)

    Collins, Heather R; Zhu, Xun; Bhatt, Ramesh S; Clark, Jonathan D; Joseph, Jane E

    2012-12-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.

  3. Euchromatin islands in large heterochromatin domains are enriched for CTCF binding and differentially DNA-methylated regions

    Directory of Open Access Journals (Sweden)

    Wen Bo

    2012-10-01

    Full Text Available Abstract Background The organization of higher order chromatin is an emerging epigenetic mechanism for understanding development and disease. We and others have previously observed dynamic changes during differentiation and oncogenesis in large heterochromatin domains such as Large Organized Chromatin K (lysine modifications (LOCKs, of histone H3 lysine-9 dimethylation (H3K9me2 or other repressive histone posttranslational modifications. The microstructure of these regions has not previously been explored. Results We analyzed the genome-wide distribution of H3K9me2 in two human pluripotent stem cell lines and three differentiated cells lines. We identified > 2,500 small regions with very low H3K9me2 signals in the body of LOCKs, which were termed as euchromatin islands (EIs. EIs are 6.5-fold enriched for DNase I Hypersensitive Sites and 8-fold enriched for the binding of CTCF, the major organizer of higher-order chromatin. Furthermore, EIs are 2–6 fold enriched for differentially DNA-methylated regions associated with tissue types (T-DMRs, reprogramming (R-DMRs and cancer (C-DMRs. Gene ontology (GO analysis suggests that EI-associated genes are functionally related to organ system development, cell adhesion and cell differentiation. Conclusions We identify the existence of EIs as a finer layer of epigenomic architecture within large heterochromatin domains. Their enrichment for CTCF sites and DNAse hypersensitive sites, as well as association with DMRs, suggest that EIs play an important role in normal epigenomic architecture and its disruption in disease.

  4. Fiscal competition and regional differentiation

    OpenAIRE

    Justman, Moshe; Thisse, Jacques-François; Van Ypersele, Tanguy

    2001-01-01

    Regions can benefit by offering infrastructure services that are differentiated. Competition between regions over potential investors is then less direct, allowing them to realize greater benefits from external investors. The two polar cases of full and incomplete information about investors' needs are studied. In both cases, there is regional differentiation. However, fiscal competition is efficient in the former case but not in the latter. Finally, it is shown that free entry in the loc...

  5. Regional climate model sensitivity to domain size

    Science.gov (United States)

    Leduc, Martin; Laprise, René

    2009-05-01

    Regional climate models are increasingly used to add small-scale features that are not present in their lateral boundary conditions (LBC). It is well known that the limited area over which a model is integrated must be large enough to allow the full development of small-scale features. On the other hand, integrations on very large domains have shown important departures from the driving data, unless large scale nudging is applied. The issue of domain size is studied here by using the “perfect model” approach. This method consists first of generating a high-resolution climatic simulation, nicknamed big brother (BB), over a large domain of integration. The next step is to degrade this dataset with a low-pass filter emulating the usual coarse-resolution LBC. The filtered nesting data (FBB) are hence used to drive a set of four simulations (LBs for Little Brothers), with the same model, but on progressively smaller domain sizes. The LB statistics for a climate sample of four winter months are compared with BB over a common region. The time average (stationary) and transient-eddy standard deviation patterns of the LB atmospheric fields generally improve in terms of spatial correlation with the reference (BB) when domain gets smaller. The extraction of the small-scale features by using a spectral filter allows detecting important underestimations of the transient-eddy variability in the vicinity of the inflow boundary, which can penalize the use of small domains (less than 100 × 100 grid points). The permanent “spatial spin-up” corresponds to the characteristic distance that the large-scale flow needs to travel before developing small-scale features. The spin-up distance tends to grow in size at higher levels in the atmosphere.

  6. Regional climate model sensitivity to domain size

    Energy Technology Data Exchange (ETDEWEB)

    Leduc, Martin [Universite du Quebec a Montreal, Canadian Regional Climate Modelling and Diagnostics (CRCMD) Network, ESCER Centre, Montreal (Canada); UQAM/Ouranos, Montreal, QC (Canada); Laprise, Rene [Universite du Quebec a Montreal, Canadian Regional Climate Modelling and Diagnostics (CRCMD) Network, ESCER Centre, Montreal (Canada)

    2009-05-15

    Regional climate models are increasingly used to add small-scale features that are not present in their lateral boundary conditions (LBC). It is well known that the limited area over which a model is integrated must be large enough to allow the full development of small-scale features. On the other hand, integrations on very large domains have shown important departures from the driving data, unless large scale nudging is applied. The issue of domain size is studied here by using the ''perfect model'' approach. This method consists first of generating a high-resolution climatic simulation, nicknamed big brother (BB), over a large domain of integration. The next step is to degrade this dataset with a low-pass filter emulating the usual coarse-resolution LBC. The filtered nesting data (FBB) are hence used to drive a set of four simulations (LBs for Little Brothers), with the same model, but on progressively smaller domain sizes. The LB statistics for a climate sample of four winter months are compared with BB over a common region. The time average (stationary) and transient-eddy standard deviation patterns of the LB atmospheric fields generally improve in terms of spatial correlation with the reference (BB) when domain gets smaller. The extraction of the small-scale features by using a spectral filter allows detecting important underestimations of the transient-eddy variability in the vicinity of the inflow boundary, which can penalize the use of small domains (less than 100 x 100 grid points). The permanent ''spatial spin-up'' corresponds to the characteristic distance that the large-scale flow needs to travel before developing small-scale features. The spin-up distance tends to grow in size at higher levels in the atmosphere. (orig.)

  7. Differential coincidence circuit in the 10{sup -10} second region (1960); Circuit de coincidence differentiel dans le domaine de 10{sup -10} seconde (1960)

    Energy Technology Data Exchange (ETDEWEB)

    Van Zurk, R [Commissariat a l' Energie Atomique, Lab. de Physique Nucleaire, Grenoble (France).Centre d' Etudes Nucleaires; [Grenoble-1 Univ., 38 (France); [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1960-07-01

    A coincidence circuit of low resolution time using the differential coincidence Bay principle is described. It uses three 6BN6 tubes ordered to chronotron structure. Results with Radiotechnique 56 AVP photomultipliers and for {sup 60}Co {gamma}-{gamma} coincidences are 4,6.10{sup -10} s (full width at half maximum) if the efficiency is {epsilon} = 40 per cent and also 7,2.10{sup -10} s if {epsilon} = 85 per cent. (author) [French] Un circuit de coincidence differentiel du type de Bay, utilise en selecteur en temps a canal mobile, a ete construit pour la mesure des periodes {gamma} et des periodes d'annihilation du positon dans differents materiaux. Il comporte trois tubes 6BN6 disposes en structure chronotron. On a utilise les nouveaux photomultiplicateurs 56 AVP avec scintillateur plastique. Avec les coincidences {gamma}-{gamma} du {sup 60}Co, on obtient 2T 4,6.10{sup -10} s avec une efficacite de 40 pour cent et 2T = 7,2.10{sup -10} s avec une efficacite de 85 pour cent. (auteur)

  8. Existence of anti-periodic (differentiable) mild solutions to semilinear differential equations with nondense domain.

    Science.gov (United States)

    Liu, Jinghuai; Zhang, Litao

    2016-01-01

    In this paper, we investigate the existence of anti-periodic (or anti-periodic differentiable) mild solutions to the semilinear differential equation [Formula: see text] with nondense domain. Furthermore, an example is given to illustrate our results.

  9. The death effector domains of caspase-8 induce terminal differentiation.

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    Ainhoa Mielgo

    2009-11-01

    Full Text Available The differentiation and senescence programs of metazoans play key roles in regulating normal development and preventing aberrant cell proliferation, such as cancer. These programs are intimately associated with both the mitotic and apoptotic pathways. Caspase-8 is an apical apoptotic initiator that has recently been appreciated to coordinate non-apoptotic roles in the cell. Most of these functions are attributed to the catalytic domain, however, the amino-terminal death effector domains (DEDs, which belong to the death domain superfamily of proteins, can also play key roles during development. Here we describe a novel role for caspase-8 DEDs in regulating cell differentiation and senescence. Caspase-8 DEDs accumulate during terminal differentiation and senescence of epithelial, endothelial and myeloid cells; genetic deletion or shRNA suppression of caspase-8 disrupts cell differentiation, while re-expression of DEDs rescues this phenotype. Among caspase-8 deficient neuroblastoma cells, DED expression attenuated tumor growth in vivo and proliferation in vitro via disruption of mitosis and cytokinesis, resulting in upregulation of p53 and induction of differentiation markers. These events occur independent of caspase-8 catalytic activity, but require a critical lysine (K156 in a microtubule-binding motif in the second DED domain. The results demonstrate a new function for the DEDs of caspase-8, and describe an unexpected mechanism that contributes to cell differentiation and senescence.

  10. Optimal Control Problems for Partial Differential Equations on Reticulated Domains

    CERN Document Server

    Kogut, Peter I

    2011-01-01

    In the development of optimal control, the complexity of the systems to which it is applied has increased significantly, becoming an issue in scientific computing. In order to carry out model-reduction on these systems, the authors of this work have developed a method based on asymptotic analysis. Moving from abstract explanations to examples and applications with a focus on structural network problems, they aim at combining techniques of homogenization and approximation. Optimal Control Problems for Partial Differential Equations on Reticulated Domains is an excellent reference tool for gradu

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

    Science.gov (United States)

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

    2013-03-01

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

  12. CORAL: aligning conserved core regions across domain families.

    Science.gov (United States)

    Fong, Jessica H; Marchler-Bauer, Aron

    2009-08-01

    Homologous protein families share highly conserved sequence and structure regions that are frequent targets for comparative analysis of related proteins and families. Many protein families, such as the curated domain families in the Conserved Domain Database (CDD), exhibit similar structural cores. To improve accuracy in aligning such protein families, we propose a profile-profile method CORAL that aligns individual core regions as gap-free units. CORAL computes optimal local alignment of two profiles with heuristics to preserve continuity within core regions. We benchmarked its performance on curated domains in CDD, which have pre-defined core regions, against COMPASS, HHalign and PSI-BLAST, using structure superpositions and comprehensive curator-optimized alignments as standards of truth. CORAL improves alignment accuracy on core regions over general profile methods, returning a balanced score of 0.57 for over 80% of all domain families in CDD, compared with the highest balanced score of 0.45 from other methods. Further, CORAL provides E-values to aid in detecting homologous protein families and, by respecting block boundaries, produces alignments with improved 'readability' that facilitate manual refinement. CORAL will be included in future versions of the NCBI Cn3D/CDTree software, which can be downloaded at http://www.ncbi.nlm.nih.gov/Structure/cdtree/cdtree.shtml. Supplementary data are available at Bioinformatics online.

  13. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

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    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  14. LOCAL DEVELOPMENT IN NORTHEST REGION THROUGH ACTIVITIES IN ITC DOMAIN

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    Daniela\tENACHESCU

    2015-06-01

    Full Text Available Economic areas with high technology are key drivers in sustainable regional development, including unemployment and consequently decreasing population migration in the region. Northeast Region is the largest development region of Romania in terms of number of inhabitants and the owned area. On 01/01/2014, according to balance employment, labor resources of the region were numbered 2,428,700, which represent 49.6% of employed population. The registered unemployment rate at 31 August 2014 was 6.5%, with 82 thousand unemployed registered. In terms of participation in the main economic activities, civilian employment in agriculture, forestry and fishing is predominant (40.1% while in service, civilian employment is 37.1%, while industry and construction is 22.8%. The paper aims to analyze the situation that the potential employment and development opportunities for the Northeast region through activities in the field of ITC domain. Unfortunately, this area was the worst in most indicators, the use of computers and the internet to the turnover of companies and investments in the IT & C and unfortunately in terms of employment population that is under 50%

  15. Numerical solutions of ordinary and partial differential equations in the frequency domain

    International Nuclear Information System (INIS)

    Hazi, G.; Por, G.

    1997-01-01

    Numerical problems during the noise simulation in a nuclear power plant are discussed. The solutions of ordinary and partial differential equations are studied in the frequency domain. Numerical methods by the transfer function method are applied. It is shown that the correctness of the numerical methods is limited for ordinary differential equations in the frequency domain. To overcome the difficulties, step-size selection is suggested. (author)

  16. Differentiation of illicit drugs with THz time-domain spectroscopy

    International Nuclear Information System (INIS)

    Liu Guifeng; Ma Shihua; Ji Te; Zhao Hongwei; Wang Wenfeng

    2010-01-01

    The tera hertz time-domain spectroscopy (THz-TDS) was used for sensing and identifying illicit drugs. The absorption spectra of seven illicit drug samples(morphine and its hydrochloride, cocaine hydrochloride, codeine phosphate, papaverine hydrochloride, pethidine hydrochloride, and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature. The geometric structure and vibration frequencies of morphine were calculated by density functional theory. The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes. Each illicit drug has a distinct signature in its THz spectra. The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints. (authors)

  17. Causality between regional stock markets: A frequency domain approach

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    Gradojević Nikola

    2013-01-01

    Full Text Available Using a data set from five regional stock exchanges (Serbia, Croatia, Slovenia, Hungary and Germany, this paper presents a frequency domain analysis of a causal relationship between the returns on the CROBEX, SBITOP, CETOP and DAX indices, and the return on the major Serbian stock exchange index, BELEX 15. We find evidence of a somewhat dominant effect of the CROBEX and CETOP stock indices on the BELEX 15 stock index across a range of frequencies. The results also indicate that the BELEX 15 index and the SBITOP index interact in a bi-directional causal fashion. Finally, the DAX index movements consistently drive the BELEX 15 index returns for cycle lengths between 3 and 11 days without any feedback effect.

  18. A multi-domain spectral method for time-fractional differential equations

    Science.gov (United States)

    Chen, Feng; Xu, Qinwu; Hesthaven, Jan S.

    2015-07-01

    This paper proposes an approach for high-order time integration within a multi-domain setting for time-fractional differential equations. Since the kernel is singular or nearly singular, two main difficulties arise after the domain decomposition: how to properly account for the history/memory part and how to perform the integration accurately. To address these issues, we propose a novel hybrid approach for the numerical integration based on the combination of three-term-recurrence relations of Jacobi polynomials and high-order Gauss quadrature. The different approximations used in the hybrid approach are justified theoretically and through numerical examples. Based on this, we propose a new multi-domain spectral method for high-order accurate time integrations and study its stability properties by identifying the method as a generalized linear method. Numerical experiments confirm hp-convergence for both time-fractional differential equations and time-fractional partial differential equations.

  19. Regionally and seasonally differentiated primary production in the North Atlantic

    Science.gov (United States)

    Sathyendranath, Shubha; Longhurst, Alan; Caverhill, Carla M.; Platt, Trevor

    1995-10-01

    A bio-geochemical classification of the N. Atlantic Basin is presented according to which the basin is first divided into four primary algal domains: Polar, West-Wind, Trades and Coastal. These are in turn sub-divided into smaller provinces. The classification is based on differences in the physical environment which are likely to influence regional algal dynamics. The seasonally-differentiated parameters of the photosynthesis-light curve ( P-I curve) and parameters that define the vertical structure in chlorophyll profile are then established for each province, based on an analysis of an archive of over 6000 chlorophyll profiles, and over 1800 P-I curves. These are then combined with satellite-derived chlorophyll data for the N. Atlantic, and information on cloud cover, to compute primary production at the annual scale. using a model that computes spectral transmission of light underwater, and spectral, photosynthetic response of phytoplankton to available light. The results are compared with earlier, satellite-derived, estimates of basin-scale primary production.

  20. D1/D2 domain of large-subunit ribosomal DNA for differentiation of Orpinomyces spp.

    Science.gov (United States)

    Dagar, Sumit S; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K

    2011-09-01

    This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation.

  1. Focus on Membrane Differentiation and Membrane Domains in the Prokaryotic Cell

    NARCIS (Netherlands)

    Boekema, Egbert J.; Scheffers, Dirk-Jan; van Bezouwen, Laura S.; Bolhuis, Henk; Folea, I. Mihaela

    2013-01-01

    A summary is presented of membrane differentiation in the prokaryotic cell, with an emphasis on the organization of proteins in the plasma/cell membrane. Many species belonging to the Eubacteria and Archaea have special membrane domains and/or membrane proliferation, which are vital for different

  2. Ordinary differential equations introduction to the theory of ordinary differential equations in the real domain

    CERN Document Server

    Kurzweil, J

    1986-01-01

    The author, Professor Kurzweil, is one of the world's top experts in the area of ordinary differential equations - a fact fully reflected in this book. Unlike many classical texts which concentrate primarily on methods of integration of differential equations, this book pursues a modern approach: the topic is discussed in full generality which, at the same time, permits us to gain a deep insight into the theory and to develop a fruitful intuition. The basic framework of the theory is expanded by considering further important topics like stability, dependence of a solution on a parameter, Car

  3. DIFFERENTIAL EFFECT OF NATIONAL VS. REGIONAL CELEBRITIES ON CONSUMER ATTITUDES

    OpenAIRE

    Varsha JAIN; Subhadip ROY; Abhishek KUMAR; Anusha KABRA

    2010-01-01

    The present study explores the differential effects of having a National/Regional celebrity in an advertisement/ endorsement. More specifically the study intends to find out whether a National celebrity would have a more favorable impact on consumer attitudes than a Regional celebrity when endorsing the same product. Experimental design was used as the research methodology. A 3 (National Celebrity/Regional Celebrity/No Celebrity) X 2 (High/Low Involvement Product) design was conducted on stud...

  4. Eps homology domain endosomal transport proteins differentially localize to the neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2012-09-01

    Full Text Available Abstract Background Recycling of endosomes is important for trafficking and maintenance of proteins at the neuromuscular junction (NMJ. We have previously shown high expression of the endocytic recycling regulator Eps15 homology domain-containing (EHD1 proteinin the Torpedo californica electric organ, a model tissue for investigating a cholinergic synapse. In this study, we investigated the localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal muscle, and assessed the morphological changes in EHD1−/− NMJs. Methods Localization of the candidate NMJ protein EHD1 was assessed by confocal microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene transfer and immunolabeling. The potential function of EHD1 was assessed by specific force measurement and α-bungarotoxin-based endplate morphology mapping in EHD1−/− mouse skeletal muscle. Results Endogenous EHD1 localized to primary synaptic clefts of murine NMJ, and this localization was confirmed by expression of recombinant green fluorescent protein labeled-EHD1 in murine skeletal muscle in vivo. EHD1−/− mouse skeletal muscle had normal histology and NMJ morphology, and normal specific force generation during muscle contraction. The EHD 1–4 proteins showed differential localization in skeletal muscle: EHD2 to muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions and to primary synaptic clefts, but at lower levels than EHD1. Additionally, specific antibodies raised against mammalian EHD1-4 recognized proteins of the expected mass in the T. californica electric organ. Finally, we found that EHD4 expression was more abundant in EHD1−/− mouse skeletal muscle than in wild-type skeletal muscle. Conclusion EHD1 and EHD4 localize to the primary synaptic clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function in EHD1−/− muscle may be due to functional compensation by other EHD paralogs.

  5. The consequences of price differentiation for regional development in Poland

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    Grzegorz Przekota

    2017-07-01

    Full Text Available Each region in Poland has a different economic potential due to its own specific features. Taking account of the specific nature of individual regions is important for the management of the country as a whole and of its particular regions. Existing disparities in the economic development may lead to many negative phenomena, such as internal migration or regional marginalization. Excessive price and income inequalities may weaken economic growth throughout the country. It is important for the coherence of the whole country that the disparities between regions are not too big. The study determines the consequences of price differentiation for regional development in Poland. The analysis was conducted using the coefficient of variation, correlation coefficient, regression coefficient and medium pace. The regions differ in terms of development, dynamic growth and wages. However, prices are much less diverse.

  6. Incremental localized boundary-domain integro-differential equations of elastic damage mechanics for inhomogeneous body

    OpenAIRE

    Mikhailov, SE

    2006-01-01

    Copyright @ 2006 Tech Science Press A quasi-static mixed boundary value problem of elastic damage mechanics for a continuously inhomogeneous body is considered. Using the two-operator Green-Betti formula and the fundamental solution of an auxiliary homogeneous linear elasticity with frozen initial, secant or tangent elastic coe±cients, a boundary-domain integro-differential formulation of the elasto-plastic problem with respect to the displacement rates and their gradients is derived. Usin...

  7. MR differentiation of cystic lesions in the maxillomandibular region

    International Nuclear Information System (INIS)

    Minami, M.; Kaneda, T.; Ozawa, K.; Ozawa, M.; Itaz, Y.; Sasaki, Y.

    1991-01-01

    This paper examines the capability of MR imaging in differentiating cystic lesions in the maxillomandibular region. MR imaging of 34 patients with cystic lesions in the maxillomandibular region was performed prospectively. After T1-weighted axial imaging, T1-weighted axial and sagittal/coronal imaging with Gd-DTPA and T2-weighted axial imaging was performed. The pathologic examinations of the cases showed 9 ameloblastomas, 13 odontogenic keratocysts, and 11 other types of cysts. MR differentiation between ameloblastoma and cysts was possible in all cases but one. MR images of ameloblastoma showed solid and cystic components, multilocularity, irregularly thickened walls, mural nodules, marked Gd-DTPA enhancement of the wall, and low T1-weighted signal fluids. MR differentiation between various kinds of cysts was difficult without information from conventional radiography, except odontogenic keratocysts. MR images of 17 keratocysts showed cystic patterns, regularly thin walls monolocular cysts, weak Gd-DTPA enhancement of the walls, and inhomogeneous intensity of the contents

  8. Stable multi-domain spectral penalty methods for fractional partial differential equations

    Science.gov (United States)

    Xu, Qinwu; Hesthaven, Jan S.

    2014-01-01

    We propose stable multi-domain spectral penalty methods suitable for solving fractional partial differential equations with fractional derivatives of any order. First, a high order discretization is proposed to approximate fractional derivatives of any order on any given grids based on orthogonal polynomials. The approximation order is analyzed and verified through numerical examples. Based on the discrete fractional derivative, we introduce stable multi-domain spectral penalty methods for solving fractional advection and diffusion equations. The equations are discretized in each sub-domain separately and the global schemes are obtained by weakly imposed boundary and interface conditions through a penalty term. Stability of the schemes are analyzed and numerical examples based on both uniform and nonuniform grids are considered to highlight the flexibility and high accuracy of the proposed schemes.

  9. Nanosecond Characterization of Regional Domain Imprint from Fast Domain Switching Currents in Pb(Zr,Ti)O_3 Thin Films

    International Nuclear Information System (INIS)

    Jun Jiang; An-Quan Jiang

    2016-01-01

    The traditional imprint characterization of ferroelectric thin films estimates imprint time dependence of the mean coercive voltage of all domains from a polarization-voltage hysteresis loop, which shows a semilogarithmic time dependence above an initial imprint time of τ_0 > 1 μs at room temperature. Below τ_0, the imprint effect is believed to be weak. In consideration of region-by-region domain reversal under a rising pulsed voltage with ordered coercive voltages increasing from zero up to the maximum applied voltage during capacitor charging time, we can estimate the imprinted coercive voltage of each domain from domain switching current transient separately with imprint time as short as 20 ns. In disagreement with the previous observations, all imprinted coercive voltages for the domains in Pt/Pb(Zr_0_._4Ti_0_._6)O_3/Pt thin-film capacitors show step-like increases at two characteristic times of 300 ns and 0.27s. The imprint effect is surprisingly strong enough even at shortened time down to 20 ns without any evidence of weakening. (paper)

  10. Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Roberta eHaddad-Tóvolli

    2015-03-01

    Full Text Available Secreted protein Sonic hedgehog (Shh ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e. we wanted to clarify the hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: 1 hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; 2 another source of diversity are differential requirements for Shh of neural vs non-neural origin; 3 Gli2 is indispensable for the specification of a medial progenitor domain generating several essential hypothalamic nuclei plus the pituitary and median eminence; 4 the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

  11. Fine-tuning of protein domain boundary by minimizing potential coiled coil regions

    International Nuclear Information System (INIS)

    Iwaya, Naoko; Goda, Natsuko; Unzai, Satoru; Fujiwara, Kenichiro; Tanaka, Toshiki; Tomii, Kentaro; Tochio, Hidehito; Shirakawa, Masahiro; Hiroaki, Hidekazu

    2007-01-01

    Structural determination of individual protein domains isolated from multidomain proteins is a common approach in the post-genomic era. Novel and thus uncharacterized domains liberated from intact proteins often self-associate due to incorrectly defined domain boundaries. Self-association results in missing signals, poor signal dispersion and a low signal-to-noise ratio in 1 H- 15 N HSQC spectra. We have found that a putative, non-canonical coiled coil region close to a domain boundary can cause transient hydrophobic self-association and monomer-dimer equilibrium in solution. Here we propose a rational method to predict putative coiled coil regions adjacent to the globular core domain using the program COILS. Except for the amino acid sequence, no preexisting knowledge concerning the domain is required. A small number of mutant proteins with a minimized coiled coil region have been rationally designed and tested. The engineered domains exhibit decreased self-association as assessed by 1 H- 15 N HSQC spectra with improved peak dispersion and sharper cross peaks. Two successful examples of isolating novel N-terminal domains from AAA-ATPases are demonstrated. Our method is useful for the experimental determination of domain boundaries suited for structural genomics studies

  12. Fine-tuning of protein domain boundary by minimizing potential coiled coil regions.

    Science.gov (United States)

    Iwaya, Naoko; Goda, Natsuko; Unzai, Satoru; Fujiwara, Kenichiro; Tanaka, Toshiki; Tomii, Kentaro; Tochio, Hidehito; Shirakawa, Masahiro; Hiroaki, Hidekazu

    2007-01-01

    Structural determination of individual protein domains isolated from multidomain proteins is a common approach in the post-genomic era. Novel and thus uncharacterized domains liberated from intact proteins often self-associate due to incorrectly defined domain boundaries. Self-association results in missing signals, poor signal dispersion and a low signal-to-noise ratio in (1)H-(15)N HSQC spectra. We have found that a putative, non-canonical coiled coil region close to a domain boundary can cause transient hydrophobic self-association and monomer-dimer equilibrium in solution. Here we propose a rational method to predict putative coiled coil regions adjacent to the globular core domain using the program COILS. Except for the amino acid sequence, no preexisting knowledge concerning the domain is required. A small number of mutant proteins with a minimized coiled coil region have been rationally designed and tested. The engineered domains exhibit decreased self-association as assessed by (1)H-(15)N HSQC spectra with improved peak dispersion and sharper cross peaks. Two successful examples of isolating novel N-terminal domains from AAA-ATPases are demonstrated. Our method is useful for the experimental determination of domain boundaries suited for structural genomics studies.

  13. Income differentials on regional labour markets in Southwest Germany

    Directory of Open Access Journals (Sweden)

    Guyot Alice

    2009-01-01

    Full Text Available The aim of our paper is to identify explanatory variables for income disparities between women and men across different regional types. Using data from the BA Employment Panel (BEP descriptive statistics show that the gender pay gap grows wider from core regions to periphery. The main explanatory variables for the income differentials are vocational education in the men's case and size of enterprise in the women's case. Whereas in the case of women the importance of vocational status increases and the importance of size of enterprise decreases from rural areas to urban areas.

  14. Differential associations between domains of sibling conflict and adolescent emotional adjustment.

    Science.gov (United States)

    Campione-Barr, Nicole; Greer, Kelly Bassett; Kruse, Anna

    2013-01-01

    Issues of equality and fairness and invasion of the personal domain, 2 previously identified topic areas of adolescent sibling conflict (N. Campione-Barr & J. G. Smetana, 2010), were examined in 145 dyads (Mfirst-born = 14.97, SD = 1.69 years; Msecond-born = 12.20, SD = 1.90 years) for their differential effects on youths' emotional adjustment over 1 year. The impact of internalizing symptoms on later sibling conflicts also was tested. Invasion of the personal domain conflicts were associated with higher levels of anxiety and lower self-esteem 1 year later, whereas Equality and Fairness issues were associated with greater depressed mood. Conversely, greater internalizing symptomatology and lower self-esteem predicted more of both types of conflict. Moderating influences of gender and ordinal position were also examined. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

  15. A Domain Specific Embedded Language in C++ for Automatic Differentiation, Projection, Integration and Variational Formulations

    Directory of Open Access Journals (Sweden)

    Christophe Prud'homme

    2006-01-01

    Full Text Available In this article, we present a domain specific embedded language in C++ that can be used in various contexts such as numerical projection onto a functional space, numerical integration, variational formulations and automatic differentiation. Albeit these tools operate in different ways, the language overcomes this difficulty by decoupling expression constructions from evaluation. The language is implemented using expression templates and meta-programming techniques and uses various Boost libraries. The language is exercised on a number of non-trivial examples and a benchmark presents the performance behavior on a few test problems.

  16. Changing the cubic ferrimagnetic domain structure in temperature region of spin flip transition

    International Nuclear Information System (INIS)

    Djuraev, D.R.; Niyazov, L.N.; Saidov, K.S.; Sokolov, B.Yu.

    2011-01-01

    The transformation of cubic ferrimagnetic Tb 0.2 Y 2.8 Fe 5 O 12 domain structure has been studied by magneto optic method in the temperature region of spontaneous spin flip phase transition (SPT). It has been found that SPT occurs in a finite temperature interval where the coexistence of low- and high- temperature magnetic phase domains has observed. A character of domain structure evolution in temperature region of spin flip essentially depends on the presence of mechanical stresses in crystal. Interpretation of experimental results has been carried out within the framework of SPT theory for a cubic crystal. (authors)

  17. An optimized algorithm for detecting and annotating regional differential methylation.

    Science.gov (United States)

    Li, Sheng; Garrett-Bakelman, Francine E; Akalin, Altuna; Zumbo, Paul; Levine, Ross; To, Bik L; Lewis, Ian D; Brown, Anna L; D'Andrea, Richard J; Melnick, Ari; Mason, Christopher E

    2013-01-01

    DNA methylation profiling reveals important differentially methylated regions (DMRs) of the genome that are altered during development or that are perturbed by disease. To date, few programs exist for regional analysis of enriched or whole-genome bisulfate conversion sequencing data, even though such data are increasingly common. Here, we describe an open-source, optimized method for determining empirically based DMRs (eDMR) from high-throughput sequence data that is applicable to enriched whole-genome methylation profiling datasets, as well as other globally enriched epigenetic modification data. Here we show that our bimodal distribution model and weighted cost function for optimized regional methylation analysis provides accurate boundaries of regions harboring significant epigenetic modifications. Our algorithm takes the spatial distribution of CpGs into account for the enrichment assay, allowing for optimization of the definition of empirical regions for differential methylation. Combined with the dependent adjustment for regional p-value combination and DMR annotation, we provide a method that may be applied to a variety of datasets for rapid DMR analysis. Our method classifies both the directionality of DMRs and their genome-wide distribution, and we have observed that shows clinical relevance through correct stratification of two Acute Myeloid Leukemia (AML) tumor sub-types. Our weighted optimization algorithm eDMR for calling DMRs extends an established DMR R pipeline (methylKit) and provides a needed resource in epigenomics. Our method enables an accurate and scalable way of finding DMRs in high-throughput methylation sequencing experiments. eDMR is available for download at http://code.google.com/p/edmr/.

  18. [Differential mortality according to region of residence in Benin].

    Science.gov (United States)

    Laourou, H M

    1995-01-01

    "The first mortality tables of Benin elaborated by direct estimation for the whole country deal with relatively different regional realities. It is in this regard that the data, whether it is death from multiround surveys or information about survival of parents, allows one to distinguish between the North (with a higher mortality) and the South (which has a lower mortality). Moreover, this differential study reveals that the level of male adult mortality after 35 years in the South, is well above the national average, probably because of the increase in deaths through violence (road accident or victim of a fire) in this part of Benin....The originality of this study is to have highlighted the mortality differentials at almost all age groups of life...." (SUMMARY IN ENG AND ITA) excerpt

  19. Earning differentials by occupational categories: Gender, race and regions

    Directory of Open Access Journals (Sweden)

    Ronaldo de Albuquerque e Arraes

    2014-09-01

    Full Text Available Analyzing the income differentials amongst the Brazilian workers’ occupations is the focus of this paper. Due to the wide diversity of occupations cataloged by the IBGE (around 800, a theoretical procedure is applied to reduce them to only seven in order to allow statistical treatment of the data. The methodological approach is based on Mincerian quantile equations to be estimated in various strata of the workers’ income distribution, on which a breakdown is made to check the gap among the individuals’ income with distinct inherent attributes and between those living in both more and less developed regions. The estimation results ensure the importance of breakdown analysis for occupational strata as well as for quantiles, since the effects of explanatory variables are distinct along the income distribution and vary among occupations. Regarding the gaps in this distribution, there is a glass ceiling effect in some occupations, that is, the gap is greater at the top of distribution, although in most cases the wider gap occurs at the bottom of the distribution – sticky floor effect, which makes this a distinguished result from other studies. Moreover, contrary to the gap in gender, which is due to the compensation characteristics of individuals only (discrimination, income differentials between regions and races also occur from the heterogeneous characteristics of workers.

  20. Chapter 4: Regional magnetic domains of the Circum-Arctic: A framework for geodynamic interpretation

    Science.gov (United States)

    Saltus, R.W.; Miller, E.L.; Gaina, C.; Brown, P.J.

    2011-01-01

    We identify and discuss 57 magnetic anomaly pattern domains spanning the Circum-Arctic. The domains are based on analysis of a new Circum-Arctic data compilation. The magnetic anomaly patterns can be broadly related to general geodynamic classification of the crust into stable, deformed (magnetic and nonmagnetic), deep magnetic high, oceanic and large igneous province domains. We compare the magnetic domains with topography/bathymetry, regional geology, regional free air gravity anomalies and estimates of the relative magnetic 'thickness' of the crust. Most of the domains and their geodynamic classification assignments are consistent with their topographic/bathymetric and geological expression. A few of the domains are potentially controversial. For example, the extent of the Iceland Faroe large igneous province as identified by magnetic anomalies may disagree with other definitions for this feature. Also the lack of definitive magnetic expression of oceanic crust in Baffin Bay, the Norwegian-Greenland Sea and the Amerasian Basin is at odds with some previous interpretations. The magnetic domains and their boundaries provide clues for tectonic models and boundaries within this poorly understood portion of the globe. ?? 2011 The Geological Society of London.

  1. Basis adaptation and domain decomposition for steady-state partial differential equations with random coefficients

    Energy Technology Data Exchange (ETDEWEB)

    Tipireddy, R.; Stinis, P.; Tartakovsky, A. M.

    2017-12-01

    We present a novel approach for solving steady-state stochastic partial differential equations (PDEs) with high-dimensional random parameter space. The proposed approach combines spatial domain decomposition with basis adaptation for each subdomain. The basis adaptation is used to address the curse of dimensionality by constructing an accurate low-dimensional representation of the stochastic PDE solution (probability density function and/or its leading statistical moments) in each subdomain. Restricting the basis adaptation to a specific subdomain affords finding a locally accurate solution. Then, the solutions from all of the subdomains are stitched together to provide a global solution. We support our construction with numerical experiments for a steady-state diffusion equation with a random spatially dependent coefficient. Our results show that highly accurate global solutions can be obtained with significantly reduced computational costs.

  2. Differential dynamic and structural behavior of lipid-cholesterol domains in model membranes.

    Directory of Open Access Journals (Sweden)

    Luis F Aguilar

    Full Text Available Changes in the cholesterol (Chol content of biological membranes are known to alter the physicochemical properties of the lipid lamella and consequently the function of membrane-associated enzymes. To characterize these changes, we used steady-state and time resolved fluorescence spectroscopy and two photon-excitation microscopy techniques. The membrane systems were chosen according to the techniques that were used: large unilamellar vesicles (LUVs for cuvette and giant unilamellar vesicles (GUVs for microscopy measurements; they were prepared from dipalmitoyl phosphatidylcholine (DPPC and dioctadecyl phosphatidylcholine (DOPC in mixtures that are well known to form lipid domains. Two fluorescent probes, which insert into different regions of the bilayer, were selected: 1,6-diphenyl-1,3,5-hexatriene (DPH was located at the deep hydrophobic core of the acyl chain regions and 2-dimethylamino-6-lauroylnaphthalene (Laurdan at the hydrophilic-hydrophobic membrane interface. Our spectroscopy results show that (i the changes induced by cholesterol in the deep hydrophobic phospholipid acyl chain domain are different from the ones observed in the superficial region of the hydrophilic-hydrophobic interface, and these changes depend on the state of the lamella and (ii the incorporation of cholesterol into the lamella induces an increase in the orientation dynamics in the deep region of the phospholipid acyl chains with a corresponding decrease in the orientation at the region close to the polar lipid headgroups. The microscopy data from DOPC/DPPC/Chol GUVs using Laurdan generalized polarization (Laurdan GP suggest that a high cholesterol content in the bilayer weakens the stability of the water hydrogen bond network and hence the stability of the liquid-ordered phase (Lo.

  3. Constructing regional advantage: platform policies based on related variety and differentiated knowledge bases.

    NARCIS (Netherlands)

    Asheim, B.T.; Boschma, R.A.; Cooke, P.

    2011-01-01

    Constructing regional advantage: platform policies based on related variety and differentiated knowledge bases, Regional Studies. This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related

  4. Brain region-dependent differential expression of alpha-synuclein.

    Science.gov (United States)

    Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tsujimura, Atsushi; Tanaka, Masaki

    2016-04-15

    α-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α-synuclein was highly expressed in the neuronal cell bodies of some early PD-affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of α-synuclein in the GABAergic inhibitory synapses was different among brain regions. α-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal α-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α-synuclein are different in various brain regions. © 2015 Wiley Periodicals, Inc.

  5. Enhanced performance for differential detection in coherent Brillouin optical time-domain analysis sensors

    Science.gov (United States)

    Shao, Liyang; Zhang, Yunpeng; Li, Zonglei; Zhang, Zhiyong; Zou, Xihua; Luo, Bin; Pan, Wei; Yan, Lianshan

    2016-11-01

    Logarithmic detectors (LogDs) have been used in coherent Brillouin optical time-domain analysis (BOTDA) sensors to reduce the effect of phase fluctuation, demodulation complexities, and measurement time. However, because of the inherent properties of LogDs, a DC component at the level of hundreds of millivolts that prohibits high-gain signal amplification (SA) could be generated, resulting in unacceptable data acquisition (DAQ) inaccuracies and decoding errors in the process of prototype integration. By generating a reference light at a level similar to the probe light, differential detection can be applied to remove the DC component automatically using a differential amplifier before the DAQ process. Therefore, high-gain SA can be employed to reduce quantization errors. The signal-to-noise ratio of the weak Brillouin gain signal is improved from ˜11.5 to ˜21.8 dB. A BOTDA prototype is implemented based on the proposed scheme. The experimental results show that the measurement accuracy of the Brillouin frequency shift (BFS) is improved from ±1.9 to ±0.8 MHz at the end of a 40-km sensing fiber.

  6. D1/D2 Domain of Large-Subunit Ribosomal DNA for Differentiation of Orpinomyces spp.▿

    Science.gov (United States)

    Dagar, Sumit S.; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K.

    2011-01-01

    This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation. PMID:21784906

  7. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale

    Science.gov (United States)

    Portela-Buelvas, Katherin; Oviedo, Heidi C.; Herazo, Edwin; Campo-Arias, Adalberto

    2016-01-01

    Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective. To establish the DIF of the psychological domain of the MRS in Colombian women. Methods. 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation (X ± SD). A p value <0.001 was considered statistically significant. Results. In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women (p < 0.001). Conclusions. The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct. PMID:27847825

  8. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale.

    Science.gov (United States)

    Monterrosa-Castro, Alvaro; Portela-Buelvas, Katherin; Oviedo, Heidi C; Herazo, Edwin; Campo-Arias, Adalberto

    2016-01-01

    Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective . To establish the DIF of the psychological domain of the MRS in Colombian women. Methods . 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation ( X ± SD). A p value <0.001 was considered statistically significant. Results . In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women ( p < 0.001). Conclusions . The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct.

  9. A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding.

    Science.gov (United States)

    Williams, K P; Shoelson, S E

    1993-03-15

    Src homology 2 (SH2) domains are modular phosphotyrosine binding pockets found within a wide variety of cytoplasmic signaling molecules. Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. Each residue except phosphotyrosine (pY) within a tightly binding, IRS-1-derived phosphopeptide (GNGDpYMPMSPKS) was substituted with the photoactive amino acid, benzoylphenylalanine (Bpa). Whereas most substitutions had little effect on binding affinity, Bpa substitution of either Met (+1 and +3 with respect to pY) reduced affinity 50-100-fold to confirm their importance in the pYMXM recognition motif. In three cases photolysis of SH2 domain/Bpa phosphopeptide complexes led to cross-linking of > 50% of the SH2 domain; cross-link positions were identified by microsequence, amino acid composition, and electrospray mass spectrometric analyses. Bpa-1 cross-links within alpha-helix I, whereas Bpa+1 and Bpa+4 cross-link the SH2 domain within the flexible loop C-terminal to alpha-helix II. Moreover, cross-linking at any position prevents SH2 domain cleavage at a trypsin-sensitive site within the flexible loop between beta-strands 1 and 2. Therefore, at least three distinct SH2 regions in addition to the beta-sheet participate in phosphoprotein binding; the loop cross-linked by phosphopeptide residues C-terminal to pY appears to confer specificity to the phosphoprotein/SH2 domain interaction.

  10. Spectral nudging to eliminate the effects of domain position and geometry in regional climate model simulations

    Science.gov (United States)

    Miguez-Macho, Gonzalo; Stenchikov, Georgiy L.; Robock, Alan

    2004-07-01

    It is well known that regional climate simulations are sensitive to the size and position of the domain chosen for calculations. Here we study the physical mechanisms of this sensitivity. We conducted simulations with the Regional Atmospheric Modeling System (RAMS) for June 2000 over North America at 50 km horizontal resolution using a 7500 km × 5400 km grid and NCEP/NCAR reanalysis as boundary conditions. The position of the domain was displaced in several directions, always maintaining the U.S. in the interior, out of the buffer zone along the lateral boundaries. Circulation biases developed a large scale structure, organized by the Rocky Mountains, resulting from a systematic shifting of the synoptic wave trains that crossed the domain. The distortion of the large-scale circulation was produced by interaction of the modeled flow with the lateral boundaries of the nested domain and varied when the position of the grid was altered. This changed the large-scale environment among the different simulations and translated into diverse conditions for the development of the mesoscale processes that produce most of precipitation for the Great Plains in the summer season. As a consequence, precipitation results varied, sometimes greatly, among the experiments with the different grid positions. To eliminate the dependence of results on the position of the domain, we used spectral nudging of waves longer than 2500 km above the boundary layer. Moisture was not nudged at any level. This constrained the synoptic scales to follow reanalysis while allowing the model to develop the small-scale dynamics responsible for the rainfall. Nudging of the large scales successfully eliminated the variation of precipitation results when the grid was moved. We suggest that this technique is necessary for all downscaling studies with regional models with domain sizes of a few thousand kilometers and larger embedded in global models.

  11. Regional climate projections for the MENA-CORDEX domain: analysis of projected temperature and precipitation changes

    Science.gov (United States)

    Hänsler, Andreas; Weber, Torsten; Eggert, Bastian; Saeed, Fahad; Jacob, Daniela

    2014-05-01

    Within the CORDEX initiative a multi-model suite of regionalized climate change information will be made available for several regions of the world. The German Climate Service Center (CSC) is taking part in this initiative by applying the regional climate model REMO to downscale global climate projections of different coupled general circulation models (GCMs) for several CORDEX domains. Also for the MENA-CORDEX domain, a set of regional climate change projections has been established at the CSC by downscaling CMIP5 projections of the Max-Planck-Institute Earth System Model (MPI-ESM) for the scenarios RCP4.5 and RCP8.5 with the regional model REMO for the time period from 1950 to 2100 to a horizontal resolution of 0.44 degree. In this study we investigate projected changes in future climate conditions over the domain towards the end of the 21st century. Focus in the analysis is given to projected changes in the temperature and rainfall characteristics and their differences for the two scenarios will be highlighted.

  12. On parametric domain for asymptotic stability with probability one of zero solution of linear Ito stochastic differential equations

    International Nuclear Information System (INIS)

    Phan Thanh An; Phan Le Na; Ngo Quoc Chung

    2004-05-01

    We describe a practical implementation for finding parametric domain for asymptotic stability with probability one of zero solution of linear Ito stochastic differential equations based on Korenevskij and Mitropolskij's sufficient condition and our sufficient conditions. Numerical results show that all of these sufficient conditions are crucial in the implementation. (author)

  13. T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

    Directory of Open Access Journals (Sweden)

    Usha Bughani

    Full Text Available CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1 specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17 have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab'2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an

  14. Structural domains and conformational changes in nuclear chromatin: a quantitative thermodynamic approach by differential scanning calorimetry.

    Science.gov (United States)

    Balbi, C; Abelmoschi, M L; Gogioso, L; Parodi, S; Barboro, P; Cavazza, B; Patrone, E

    1989-04-18

    A good deal of information on the thermodynamic properties of chromatin was derived in the last few years from optical melting experiments. The structural domains of the polynucleosomal chain, the linker, and the core particle denature as independent units. The differential scanning calorimetry profile of isolated chromatin is made up of three endotherms, at approximately 74, 90, and 107 degrees C, having an almost Gaussian shape. Previous work on this matter, however, was mainly concerned with the dependence of the transition enthalpy on external parameters, such as the ionic strength, or with the melting of nuclei from different sources. In this paper we report the structural assignment of the transitions of rat liver nuclei, observed at 58, 66, 75, 92, and 107 degrees C. They are representative of the quiescent state of the cell. The strategy adopted in this work builds on the method developed for the investigation of complex biological macromolecules. The heat absorption profile of the nucleus was related to the denaturation of isolated nuclear components; electron microscopy and electrophoretic techniques were used for their morphological and molecular characterization. The digestion of chromatin by endogenous nuclease mimics perfectly the decondensation of the higher order structure and represented the source of several misinterpretations. This point was carefully examined in order to define unambiguously the thermal profile of native nuclei. The low-temperature transitions, centered around 58 and 66 degrees C, arise from the melting of scaffolding structures and of the proteins associated with heterogeneous nuclear RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Detection of differentially methylated regions of irradiated fig tree selections

    Directory of Open Access Journals (Sweden)

    Maria Gabriela Fontanetti Rodrigues

    Full Text Available ABSTRACT Fig tree (Ficus carica L. breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, “Roxo-de-Valinhos”, which had previously used methylation-sensitive amplified polymorphism (MSAP and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes.

  16. Detection of differentially methylated regions of irradiated fig tree selections

    International Nuclear Information System (INIS)

    Rodrigues, Maria Gabriela Fontanetti; Soares, Murilo Racy; Gimenez, Daniele Fernanda Jovino; Fonseca, Larissa Fernanda Simielli; Torrieri, Erico; Ramos, Ester Silveira; Giuliatti, Silvana; Universidade de Sao Paulo; Universidade Estadual Paulista Julio de Mesquita Filho

    2017-01-01

    Fig tree (Ficus carica L.) breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, 'Roxo-de-Valinhos', which had previously used methylation-sensitive amplified polymorphism (MSAP) and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP) form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes. (author)

  17. Detection of differentially methylated regions of irradiated fig tree selections

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Maria Gabriela Fontanetti; Soares, Murilo Racy; Gimenez, Daniele Fernanda Jovino; Fonseca, Larissa Fernanda Simielli; Torrieri, Erico; Ramos, Ester Silveira; Giuliatti, Silvana, E-mail: mariagabriela@dracena.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Dracena, SP (Brazil). Faculdade de Agricultura e Ciencias Tecnologicas; Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Dept. de Genetica; Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Jaboticabal, SP (Brazil). Faculdade de Agricultura e Ciencias Veterinarias

    2017-07-15

    Fig tree (Ficus carica L.) breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, 'Roxo-de-Valinhos', which had previously used methylation-sensitive amplified polymorphism (MSAP) and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP) form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes. (author)

  18. Income differentiation of agricultural households in regions of Czech Republic

    Directory of Open Access Journals (Sweden)

    Zuzana Procházková

    2012-01-01

    Full Text Available The Czech Republic has recently experienced phases of economic growth and periods of economic crisis. This fact affects the standard of living and household behaviour and affects the formation of life-style. This paper deals with the income situation of households. The main source of data is EU SILC survey from the years 2005 to 2008. The result of the enquiry and processing of primary data is information about the average income per household member, the poverty level and the number of households at risk of poverty. For the formulation of income differentiation is used Gini coefficient. Attention is paid to factors that affect income inequality (the number of household members, social group, and age. The analysis and subsequent problem solving of income inequality may be contributed with further analysis of empirical data of this type. Household income is one of the decisive factors determining the style of family life, their priorities, meeting their needs, and ensure-time activities. Differences between regions determine preferences and identify opportunities.

  19. Sensitivity of simulated regional Arctic climate to the choice of coupled model domain

    Directory of Open Access Journals (Sweden)

    Dmitry V. Sein

    2014-07-01

    Full Text Available The climate over the Arctic has undergone changes in recent decades. In order to evaluate the coupled response of the Arctic system to external and internal forcing, our study focuses on the estimation of regional climate variability and its dependence on large-scale atmospheric and regional ocean circulations. A global ocean–sea ice model with regionally high horizontal resolution is coupled to an atmospheric regional model and global terrestrial hydrology model. This way of coupling divides the global ocean model setup into two different domains: one coupled, where the ocean and the atmosphere are interacting, and one uncoupled, where the ocean model is driven by prescribed atmospheric forcing and runs in a so-called stand-alone mode. Therefore, selecting a specific area for the regional atmosphere implies that the ocean–atmosphere system can develop ‘freely’ in that area, whereas for the rest of the global ocean, the circulation is driven by prescribed atmospheric forcing without any feedbacks. Five different coupled setups are chosen for ensemble simulations. The choice of the coupled domains was done to estimate the influences of the Subtropical Atlantic, Eurasian and North Pacific regions on northern North Atlantic and Arctic climate. Our simulations show that the regional coupled ocean–atmosphere model is sensitive to the choice of the modelled area. The different model configurations reproduce differently both the mean climate and its variability. Only two out of five model setups were able to reproduce the Arctic climate as observed under recent climate conditions (ERA-40 Reanalysis. Evidence is found that the main source of uncertainty for Arctic climate variability and its predictability is the North Pacific. The prescription of North Pacific conditions in the regional model leads to significant correlation with observations, even if the whole North Atlantic is within the coupled model domain. However, the inclusion of the

  20. Predicting binding within disordered protein regions to structurally characterised peptide-binding domains.

    Directory of Open Access Journals (Sweden)

    Waqasuddin Khan

    Full Text Available Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear Motif containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58.Next, we trained a bidirectional recurrent neural network (BRNN using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72 showing that multiple sources of information can be combined to produce results which are clearly superior to any single source.We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors.

  1. The PLAC1-homology region of the ZP domain is sufficient for protein polymerisation

    Directory of Open Access Journals (Sweden)

    Litscher Eveline S

    2006-04-01

    Full Text Available Abstract Background Hundreds of extracellular proteins polymerise into filaments and matrices by using zona pellucida (ZP domains. ZP domain proteins perform highly diverse functions, ranging from structural to receptorial, and mutations in their genes are responsible for a number of severe human diseases. Recently, PLAC1, Oosp1-3, Papillote and CG16798 proteins were identified that share sequence homology with the N-terminal half of the ZP domain (ZP-N, but not with its C-terminal half (ZP-C. The functional significance of this partial conservation is unknown. Results By exploiting a highly engineered bacterial strain, we expressed in soluble form the PLAC1-homology region of mammalian sperm receptor ZP3 as a fusion to maltose binding protein. Mass spectrometry showed that the 4 conserved Cys residues within the ZP-N moiety of the fusion protein adopt the same disulfide bond connectivity as in full-length native ZP3, indicating that it is correctly folded, and electron microscopy and biochemical analyses revealed that it assembles into filaments. Conclusion These findings provide a function for PLAC1-like proteins and, by showing that ZP-N is a biologically active folding unit, prompt a re-evaluation of the architecture of the ZP domain and its polymers. Furthermore, they suggest that ZP-C might play a regulatory role in the assembly of ZP domain protein complexes.

  2. Sequential assignment of proline-rich regions in proteins: Application to modular binding domain complexes

    International Nuclear Information System (INIS)

    Kanelis, Voula; Donaldson, Logan; Muhandiram, D.R.; Rotin, Daniela; Forman-Kay, Julie D.; Kay, Lewis E.

    2000-01-01

    Many protein-protein interactions involve amino acid sequences containing proline-rich motifs and even poly-proline stretches. The lack of amide protons in such regions complicates assignment, since 1 HN-based triple-resonance assignment strategies cannot be employed. Two such systems that we are currently studying include an SH2 domain from the protein Crk with a region containing 9 prolines in a 14 amino acid sequence, as well as a WW domain that interacts with a proline-rich target. A modified version of the HACAN pulse scheme, originally described by Bax and co-workers [Wang et al. (1995) J. Biomol. NMR, 5, 376-382], and an experiment which correlates the intra-residue 1 H α , 13 C α / 13 C β chemical shifts with the 15 N shift of the subsequent residue are presented and applied to the two systems listed above, allowing sequential assignment of the molecules

  3. Sarcocystis neurona: molecular characterization of enolase domain I region and a comparison to other protozoa.

    Science.gov (United States)

    Bolten, K E; Marsh, A E; Reed, S M; Dubey, J P; Toribio, R E; Saville, W J A

    2008-09-01

    Sarcocystis neurona causes protozoal myeloencephalitis and has the ability to infect a wide host range in contrast to other Sarcocystis species. In the current study, five S. neurona isolates from a variety of sources, three Sarcocystis falcatula, one Sarcocystis dasypi/S. neurona-like isolate, and one Besnoitia darlingi isolate were used to compare the enolase 2 gene segment containing the domain I region to previously sequenced enolase genes from Neospora caninum, Neospora hughesi, Toxoplasma gondii, Plasmodium falciparum, and Trypanosoma cruzi; enolase 2 segment containing domain I region is highly conserved amongst these parasites of veterinary and medical importance. Immunohistochemistry results indicates reactivity of T. gondii enolase 1 and 2 antibodies to S. neurona merozoites and metrocytes, but no reactivity of anti-enolase 1 to the S. neurona bradyzoite stage despite reactivity to T. gondii bradyzoites, suggesting expression differences between organisms.

  4. Pod systems: an equivariant ordinary differential equation approach to dynamical systems on a spatial domain

    International Nuclear Information System (INIS)

    Elmhirst, Toby; Stewart, Ian; Doebeli, Michael

    2008-01-01

    We present a class of systems of ordinary differential equations (ODEs), which we call 'pod systems', that offers a new perspective on dynamical systems defined on a spatial domain. Such systems are typically studied as partial differential equations, but pod systems bring the analytic techniques of ODE theory to bear on the problems, and are thus able to study behaviours and bifurcations that are not easily accessible to the standard methods. In particular, pod systems are specifically designed to study spatial dynamical systems that exhibit multi-modal solutions. A pod system is essentially a linear combination of parametrized functions in which the coefficients and parameters are variables whose dynamics are specified by a system of ODEs. That is, pod systems are concerned with the dynamics of functions of the form Ψ(s, t) = y 1 (t) φ(s; x 1 (t)) + ··· + y N (t) φ(s; x N (t)), where s in R n is the spatial variable and φ: R n × R d → R. The parameters x i in R d and coefficients y i in R are dynamic variables which evolve according to some system of ODEs, x-dot i = G i (x, y) and y-dot i = H i (x, y), for i = 1, ..., N. The dynamics of Ψ in function space can then be studied through the dynamics of the x and y in finite dimensions. A vital feature of pod systems is that the ODEs that specify the dynamics of the x and y variables are not arbitrary; restrictions on G i and H i are required to guarantee that the dynamics of Ψ in function space are well defined (that is, that trajectories are unique). One important restriction is symmetry in the ODEs which arises because Ψ is invariant under permutations of the indices of the (x i , y i ) pairs. However, this is not the whole story, and the primary goal of this paper is to determine the necessary structure of the ODEs explicitly to guarantee that the dynamics of Ψ are well defined

  5. Mycoplasma hyopneumoniae and Mycoplasma flocculare differential domains from orthologous surface proteins induce distinct cellular immune responses in mice.

    Science.gov (United States)

    Leal, Fernanda Munhoz Dos Anjos; Virginio, Veridiana Gomes; Martello, Carolina Lumertz; Paes, Jéssica Andrade; Borges, Thiago J; Jaeger, Natália; Bonorino, Cristina; Ferreira, Henrique Bunselmeyer

    2016-07-15

    Mycoplasma hyopneumoniae and Mycoplasma flocculare are two genetically close species found in the swine respiratory tract. Despite their similarities, while M. hyopneumoniae is the causative agent of porcine enzootic pneumonia, M. flocculare is a commensal bacterium. Genomic and transcriptional comparative analyses so far failed to explain the difference in pathogenicity between these two species. We then hypothesized that such difference might be, at least in part, explained by amino acid sequence and immunological or functional differences between ortholog surface proteins. In line with that, it was verified that approximately 85% of the ortholog surface proteins from M. hyopneumoniae 7448 and M. flocculare present one or more differential domains. To experimentally assess possible immunological implications of this kind of difference, the extracellular differential domains from one pair of orthologous surface proteins (MHP7448_0612, from M. hyopneumoniae, and MF_00357, from M. flocculare) were expressed in E. coli and used to immunize mice. The recombinant polypeptides (rMHP61267-169 and rMF35767-196, respectively) induced distinct cellular immune responses. While, rMHP61267-169 induced both Th1 and Th2 responses, rMF35767-196 induced just an early pro-inflammatory response. These results indicate that immunological properties determined by differential domains in orthologous surface protein might play a role in pathogenicity, contributing to elicit specific and differential immune responses against each species. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. The Arctic Marine Pulses Model: Linking Contiguous Domains in the Pacific Arctic Region

    Science.gov (United States)

    Moore, S. E.; Stabeno, P. J.

    2016-02-01

    The Pacific Arctic marine ecosystem extends from the northern Bering Sea, across the Chukchi and into the East Siberian and Beaufort seas. Food webs in this domain are short, a simplicity that belies the biophysical complexity underlying trophic linkages from primary production to humans. Existing biophysical models, such as pelagic-benthic coupling and advective processes, provide frameworks for connecting certain aspects of the marine food web, but do not offer a full accounting of events that occur seasonally across the Pacific Arctic. In the course of the Synthesis of Arctic Research (SOAR) project, a holistic Arctic Marine Pulses (AMP) model was developed that depicts seasonal biophysical `pulses' across a latitudinal gradient, and linking four previously-described contiguous domains, including the: (i) Pacific-Arctic domain = the focal region; (ii) seasonal ice zone domain; (iii) Pacific marginal domain; and (iv) riverine coastal domain. The AMP model provides a spatial-temporal framework to guide research on dynamic ecosystem processes during this period of rapid biophysical changes in the Pacific Arctic. Some of the processes included in the model, such as pelagic-benthic coupling in the Northern Bering and Chukchi seas, and advection and upwelling along the Beaufort shelf, are already the focus of sampling via the Distributed Biological Observatory (DBO) and other research programs. Other aspects such as biological processes associated with the seasonal ice zone and trophic responses to riverine outflow have received less attention. The AMP model could be enhanced by the application of visualization tools to provide a means to watch a season unfold in space and time. The capability to track sea ice dynamics and water masses and to move nutrients, prey and upper-trophic predators in space and time would provide a strong foundation for the development of predictive human-inclusive ecosystem models for the Pacific Arctic.

  7. Generalized query-based active learning to identify differentially methylated regions in DNA.

    Science.gov (United States)

    Haque, Md Muksitul; Holder, Lawrence B; Skinner, Michael K; Cook, Diane J

    2013-01-01

    Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique.

  8. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    Directory of Open Access Journals (Sweden)

    Alvarez-Bolado Gonzalo

    2012-01-01

    Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

  9. The Differential Effects of Task Complexity on Domain-Specific and Peer Assessment Skills

    Science.gov (United States)

    van Zundert, Marjo J.; Sluijsmans, Dominique M. A.; Konings, Karen D.; van Merrienboer, Jeroen J. G.

    2012-01-01

    In this study the relationship between domain-specific skills and peer assessment skills as a function of task complexity is investigated. We hypothesised that peer assessment skills were superposed on domain-specific skills and will therefore suffer more when higher cognitive load is induced by increased task complexity. In a mixed factorial…

  10. Mapping the Landscape of Domain-Wall Pinning in Ferromagnetic Films Using Differential Magneto-Optical Microscopy

    Science.gov (United States)

    Badea, Robert; Berezovsky, Jesse

    2016-06-01

    The propagation of domain walls in a ferromagnetic film is largely determined by domain-wall pinning at defects in the material. In this article, we map the effective potential landscape for domain-wall pinning in permalloy films by raster scanning a single ferromagnetic vortex and monitoring the hysteretic vortex displacement vs applied magnetic field. The measurement is carried out using a differential magneto-optical microscopy technique which yields spatial sensitivity of approximately 10 nm. We present a simple algorithm for extracting an effective pinning potential from the measurement of vortex displacement vs applied field. The resulting maps of the pinning potential reveal distinct types of pinning sites, which we attribute to quasi-zero-, one-, and two-dimensional defects in the permalloy film.

  11. Domain-General Brain Regions Do Not Track Linguistic Input as Closely as Language-Selective Regions.

    Science.gov (United States)

    Blank, Idan A; Fedorenko, Evelina

    2017-10-11

    Language comprehension engages a cortical network of left frontal and temporal regions. Activity in this network is language-selective, showing virtually no modulation by nonlinguistic tasks. In addition, language comprehension engages a second network consisting of bilateral frontal, parietal, cingulate, and insular regions. Activity in this "multiple demand" (MD) network scales with comprehension difficulty, but also with cognitive effort across a wide range of nonlinguistic tasks in a domain-general fashion. Given the functional dissociation between the language and MD networks, their respective contributions to comprehension are likely distinct, yet such differences remain elusive. Prior neuroimaging studies have suggested that activity in each network covaries with some linguistic features that, behaviorally, influence on-line processing and comprehension. This sensitivity of the language and MD networks to local input characteristics has often been interpreted, implicitly or explicitly, as evidence that both networks track linguistic input closely, and in a manner consistent across individuals. Here, we used fMRI to directly test this assumption by comparing the BOLD signal time courses in each network across different people ( n = 45, men and women) listening to the same story. Language network activity showed fewer individual differences, indicative of closer input tracking, whereas MD network activity was more idiosyncratic and, moreover, showed lower reliability within an individual across repetitions of a story. These findings constrain cognitive models of language comprehension by suggesting a novel distinction between the processes implemented in the language and MD networks. SIGNIFICANCE STATEMENT Language comprehension recruits both language-specific mechanisms and domain-general mechanisms that are engaged in many cognitive processes. In the human cortex, language-selective mechanisms are implemented in the left-lateralized "core language network

  12. Towards regional differentiation of rural development policy in the EU

    NARCIS (Netherlands)

    Terluin, I.J.; Venema, G.S.

    2003-01-01

    In this study a comparative analysis of the Rural Development Plans (RDPs) in four intermediate rural regions (Northern Netherlands, Lower Saxony, Wales and Emilia Romagna) and four most urban regions (Southern Netherlands, North Rhine-Westphalia, Flanders and Lombardia) is made. Such plans are

  13. The generation and selection of single-domain, v region libraries from nurse sharks.

    Science.gov (United States)

    Flajnik, Martin F; Dooley, Helen

    2009-01-01

    The cartilaginous fish (sharks, skates, and rays) are the oldest phylogenetic group in which a human-type adaptive immune system and immunoglobulins (Igs) have been found. In addition to their conventional (heavy-light chain heterodimeric) isotypes, IgM and IgW, sharks produce the novel isotype, IgNAR, a heavy chain homodimer that does not associate with light chains. Instead, its variable (V) regions act as independent, soluble units in order to bind antigen. In this chapter, we detail our immunization protocol in order to raise a humoral IgNAR response in the nurse shark (Ginglymostoma cirratum) and the subsequent cloning of the single-domain V regions from this isotype in order to select antigen-specific binders by phage display.

  14. Algorithmic differentiation of pragma-defined parallel regions differentiating computer programs containing OpenMP

    CERN Document Server

    Förster, Michael

    2014-01-01

    Numerical programs often use parallel programming techniques such as OpenMP to compute the program's output values as efficient as possible. In addition, derivative values of these output values with respect to certain input values play a crucial role. To achieve code that computes not only the output values simultaneously but also the derivative values, this work introduces several source-to-source transformation rules. These rules are based on a technique called algorithmic differentiation. The main focus of this work lies on the important reverse mode of algorithmic differentiation. The inh

  15. Requirement of the coiled-coil domain of PML-RARα oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation

    International Nuclear Information System (INIS)

    Kim, Young-Eui; Kim, Dong-Yeon; Lee, Jang-Mi; Kim, Seong-Tae; Han, Tae-Hee; Ahn, Jin-Hyun

    2005-01-01

    Homo-oligomerization via a coiled-coil (C-C) domain has been shown to be necessary for the promyelocytic leukemia (PML)-retinoic acid receptor-α (RARα) fusion protein to acquire oncogenic potential in acute promyelocytic leukemia. We show here that PML(ΔC-C)-RARα, which contains a deletion in its C-C domain, is neither localized as characteristic microspeckles nor modified by small ubiquitin-like modifiers (SUMO). The absence of sumoylation of the ΔC-C mutant was due to the lack of binding to Ubc9, a SUMO conjugation enzyme. The integrity of RING finger domain was also needed for both sumoylation and microspeckle formation. In GAL4-DNA tethering assays, the ΔC-C mutant completely lost the inhibitory effect on retinoic acid (RA)-mediated transactivation. Furthermore, the expression of CD14 in U937 cells expressing the ΔC-C mutant in response to vitamin D3 was markedly higher than in cells expressing PML-RARα. However, the RA-mediated induction of C/EBPβ in cells expressing the ΔC-C mutant was comparable to that of control cells. Thus, our results suggest that the C-C domain-associated functions of sumoylation, localization as microspeckles, and the inhibition of monocyte differentiation all contribute to the oncogenic activity of PML-RARα

  16. Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

    Directory of Open Access Journals (Sweden)

    Jamie A Moroco

    Full Text Available Src-family kinases (SFKs are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12 to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo.

  17. Regional climate simulations with COSMO-CLM over MENA-CORDEX domain

    Science.gov (United States)

    Galluccio, Salvatore; Bucchignani, Edoardo; Mercogliano, Paola; Montesarchio, Myriam

    2014-05-01

    In the frame of WCRP Coordinated Regional Downscaling Experiment (CORDEX), a set of common Regional Climate Downscaling (RCD) domains has been defined, as a prerequisite for the development of model evaluation and climate projection frameworks. CORDEX domains encompass the majority of land areas of the world. In this work, climate simulations have been performed over MENA-CORDEX domain, which includes North-Africa, southern Europe and the whole Arabian peninsula. The non-hydrostatic regional climate model COSMO-CLM has been used. At CMCC, regional climate modelling is a part of an integrated simulation system and it has been used in different European and African projects to provide qualitative and quantitative evaluation of the hydrogeological and public health risks. A series of simulations has been conducted over the MENA-CORDEX area at spatial resolution of 0.44°. A sensitivity analysis was conducted to adjust the model configuration to better reproduce the observed climate data. The numerical simulations were driven by ERA-Interim reanalysis (horizontal resolution of 0.703°) for the period 1979-1984; the first year, was considered as a spin up period. The validation was performed by using several data sets: CRU data set was used to validate temperature, precipitation and cloud cover; MERRA data set was used to validate temperature and precipitation and GPCP for precipitation. The model sensitivity to the external parameters was tested considering two different configurations for the surface albedo. In the first one, albedo is only function of soil-type whereas in the second configuration it is prescribed by two external fields for dry and saturated soil based on MODIS data. Moreover, we tested two aerosol distributions as well, namely the default Tanre aerosol distribution and aerosol maps according to Tegen (NASA/GISS). We found, as expected, a significant sensitivity, in particular on the African region. We also varied tuning and physical parameters, such

  18. Differentiating functional brain regions using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Gil, Daniel A.; Bow, Hansen C.; Shen, Jin-H.; Joos, Karen M.; Skala, Melissa C.

    2017-02-01

    The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

  19. Antibody complementarity-determining regions (CDRs can display differential antimicrobial, antiviral and antitumor activities.

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    Full Text Available BACKGROUND: Complementarity-determining regions (CDRs are immunoglobulin (Ig hypervariable domains that determine specific antibody (Ab binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a a protein epitope of Candida albicans cell wall stress mannoprotein; b a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small

  20. A novel heavy domain antibody library with functionally optimized complementarity determining regions.

    Directory of Open Access Journals (Sweden)

    Ole Aalund Mandrup

    Full Text Available Today a number of synthetic antibody libraries of different formats have been created and used for the selection of a large number of recombinant antibodies. One of the determining factors for successful isolation of recombinant antibodies from libraries lies in the quality of the libraries i.e. the number of correctly folded, functional antibodies contained in the library. Here, we describe the construction of a novel, high quality, synthetic single domain antibody library dubbed Predator. The library is based on the HEL4 domain antibody with the addition of recently reported mutations concerning the amino acid composition at positions critical for the folding characteristics and aggregation propensities of domain antibodies. As a unique feature, the CDR3 of the library was designed to mimic the natural human immune response by designating amino acids known to be prevalent in functional antibodies to the diversity in CDR3. CDR randomizations were performed using trinucleotide synthesis to avoid the presence of stop codons. Furthermore a novel cycle free elongation method was used for the conversion of the synthesized single stranded DNA containing the randomized CDRs into double stranded DNA of the library. In addition a modular approach has been adopted for the scaffold in which each CDR region is flanked by unique restrictions sites, allowing easy affinity maturation of selected clones by CDR shuffling. To validate the quality of the library, one round phage display selections were performed on purified antigens and highly complex antigen mixtures such as cultured eukaryotic cells resulting in several specific binders. The further characterization of some of the selected clones, however, indicates a reduction in thermodynamic stability caused by the inclusion the additional mutations to the HEL4 scaffold.

  1. Differential and Domain-Specific Associations Among Right-Wing Authoritarianism, Social Dominance Orientation, and Adolescent Delinquency.

    Science.gov (United States)

    Oosterhoff, Benjamin; Shook, Natalie J; Clay, Russ; Metzger, Aaron

    2017-09-01

    Using a dual-process model (DPM) framework, this research examined whether right-wing authoritarianism (RWA) and social dominance orientation (SDO) are differentially associated with adolescent delinquency. In Study 1 ( N = 847; M age = 15.96) and Study 2 ( N = 340; M age = 16.64), adolescents completed measures of RWA, SDO, and engagement in different forms of delinquency. In Study 2, adolescents also reported their beliefs about obeying different laws. Across both studies, adolescents who endorsed greater RWA engaged in lower levels of delinquency and those who endorsed greater SDO engaged in higher levels of delinquency. Findings from Study 2 suggest that these associations are contingent on the domain-specific purpose of the law being violated and are also present with adolescents' beliefs about their obligation to obey laws. These results extend the DPM, demonstrating that RWA and SDO are differentially linked with youth delinquency.

  2. Differential susceptibility of brain regions to tributyltin chloride toxicity.

    Science.gov (United States)

    Mitra, Sumonto; Siddiqui, Waseem A; Khandelwal, Shashi

    2015-12-01

    Tributyltin (TBT), a well-known endocrine disruptor, is an omnipresent environmental pollutant and is explicitly used in many industrial applications. Previously we have shown its neurotoxic potential on cerebral cortex of male Wistar rats. As the effect of TBT on other brain regions is not known, we planned this study to evaluate its effect on four brain regions (cerebellum, hippocampus, hypothalamus, and striatum). Four-week-old male Wistar rats were gavaged with a single dose of TBT-chloride (TBTC) (10, 20, and 30 mg/kg) and sacrificed on days 3 and 7, respectively. Effect of TBTC on blood-brain barrier (BBB) permeability and tin (Sn) accumulation were measured. Oxidative stress indexes such as reactive oxygen species (ROS), reduced and oxidized glutathione (GSH/GSSG) ratio, lipid peroxidation, and protein carbonylation were analyzed as they play an imperative role in various neuropathological conditions. Since metal catalyzed reactions are a major source of oxidant generation, levels of essential metals like iron (Fe), zinc (Zn), and calcium (Ca) were estimated. We found that TBTC disrupted BBB and increased Sn accumulation, both of which appear significantly correlated. Altered metal homeostasis and ROS generation accompanied by elevated lipid peroxidation and protein carbonylation indicated oxidative damage which appeared more pronounced in the striatum than in cerebellum, hippocampus, and hypothalamus. This could be associated to the depleted GSH levels in striatum. These results suggest that striatum is more susceptible to TBTC induced oxidative damage as compared with other brain regions under study. © 2014 Wiley Periodicals, Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-01

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

  4. Origins of the Xylella fastidiosa prophage-like regions and their impact in genome differentiation.

    Directory of Open Access Journals (Sweden)

    Alessandro de Mello Varani

    Full Text Available Xylella fastidiosa is a Gram negative plant pathogen causing many economically important diseases, and analyses of completely sequenced X. fastidiosa genome strains allowed the identification of many prophage-like elements and possibly phage remnants, accounting for up to 15% of the genome composition. To better evaluate the recent evolution of the X. fastidiosa chromosome backbone among distinct pathovars, the number and location of prophage-like regions on two finished genomes (9a5c and Temecula1, and in two candidate molecules (Ann1 and Dixon were assessed. Based on comparative best bidirectional hit analyses, the majority (51% of the predicted genes in the X. fastidiosa prophage-like regions are related to structural phage genes belonging to the Siphoviridae family. Electron micrograph reveals the existence of putative viral particles with similar morphology to lambda phages in the bacterial cell in planta. Moreover, analysis of microarray data indicates that 9a5c strain cultivated under stress conditions presents enhanced expression of phage anti-repressor genes, suggesting switches from lysogenic to lytic cycle of phages under stress-induced situations. Furthermore, virulence-associated proteins and toxins are found within these prophage-like elements, thus suggesting an important role in host adaptation. Finally, clustering analyses of phage integrase genes based on multiple alignment patterns reveal they group in five lineages, all possessing a tyrosine recombinase catalytic domain, and phylogenetically close to other integrases found in phages that are genetic mosaics and able to perform generalized and specialized transduction. Integration sites and tRNA association is also evidenced. In summary, we present comparative and experimental evidence supporting the association and contribution of phage activity on the differentiation of Xylella genomes.

  5. Multivariate analysis of regional differentials of nuptiality in Bangladesh.

    Science.gov (United States)

    Chowdhury, A A; Islam, M A

    1981-01-01

    The importance of socioeconomics differentials in nuptiality has occupied a very important position in recent demographic research. An effort has been made in this paper to find out the nature and extent of the causal relationship between the dependent variable--nuptiality, and its determinants. Our findings suggest that education may play a vital role in raising mean age at marriage. This may be done by extending free and compulsory mass and primary education throughout the country. It has further been observed that urbanization through economic development is a precondition to increase the literacy rate and hence female labor force participation in the country's economy. Thus proper education will increase the female employment rate which in turn will raise the age at marriage. Equal distribution of population and insurance schemes for childless couples may also indirectly put a positive effect on nuptiality. Finally, this paper provides a guideline for using the path analysis technique in determining the factors causing the changes and the effects of these factors on nuptiality in Bangladesh. However, caution should be made in taking into account the causal ordering of the indices. Different ordering may give different results.

  6. Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.

    Science.gov (United States)

    Kim, Han Ie; Jung, Jinwon; Lee, Eun-Saem; Kim, Yong-Chul; Lee, Weontae; Lee, Seung-Taek

    2007-11-03

    PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

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

    Science.gov (United States)

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

    2018-01-01

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

  8. The Adomian decomposition method for solving partial differential equations of fractal order in finite domains

    Energy Technology Data Exchange (ETDEWEB)

    El-Sayed, A.M.A. [Faculty of Science University of Alexandria (Egypt)]. E-mail: amasyed@hotmail.com; Gaber, M. [Faculty of Education Al-Arish, Suez Canal University (Egypt)]. E-mail: mghf408@hotmail.com

    2006-11-20

    The Adomian decomposition method has been successively used to find the explicit and numerical solutions of the time fractional partial differential equations. A different examples of special interest with fractional time and space derivatives of order {alpha}, 0<{alpha}=<1 are considered and solved by means of Adomian decomposition method. The behaviour of Adomian solutions and the effects of different values of {alpha} are shown graphically for some examples.

  9. Molecular Dynamics Simulations of the STAS Domains of Rat Prestin and Human Pendrin Reveal Conformational Motions in Conserved Flexible Regions

    Directory of Open Access Journals (Sweden)

    Alok K. Sharma

    2014-02-01

    Full Text Available Background: Molecular dynamics (MD simulations provide valuable information on the conformational changes that accompany time-dependent motions in proteins. The reported crystal structure of rat prestin (PDB 3LLO is remarkable for an α1-α2 inter-helical angle that differs substantially from those observed in bacterial STAS domains of SulP anion transporters and anti-sigma factor antagonists. However, NMR data on the rat prestin STAS domain in solution suggests dynamic features at or near the α1-α2 helical region (Pasqualetto et al JMB, 2010. We therefore performed a 100 ns 300K MD simulation study comparing the STAS domains of rat prestin and (modeled human pendrin, to explore possible conformational flexibility in the region of the α1 and α2 helices. Methods: The conformation of the loop missing in the crystal structure of rat prestin STAS (11 amino acids between helix α1 and strand β3 was built using Modeller. MD simulations were performed with GROMACSv4.6 using GROMOS96 53a6 all-atom force field. Results: A subset of secondary structured elements of the STAS domains exhibits significant conformational changes during the simulation time course. The conformationally perturbed segments include the majority of loop regions, as well as the α1 and α2 helices. A significant decrease in the α1-α2 inter-helical angle observed across the simulation trajectory leads to closer helical packing at their C-termini. The end-simulation conformations of the prestin and pendrin STAS domains, including their decreased α1-α2 inter-helical angles, resemble more closely the packing of corresponding helices in the STAS structures of bacterial SulP transporters Rv1739c and ychM, as well as those of the anti-sigma factor antagonists. Several structural segments of the modeled human pendrin STAS domain exhibit larger atomic motions and greater conformational deviations than the corresponding regions of rat prestin, predicting that the human pendrin STAS

  10. Effective crop evapotranspiration measurement using time-domain reflectometry technique in a sub-humid region

    Science.gov (United States)

    Srivastava, R. K.; Panda, R. K.; Halder, Debjani

    2017-08-01

    The primary objective of this study was to evaluate the performance of the time-domain reflectometry (TDR) technique for daily evapotranspiration estimation of peanut and maize crop in a sub-humid region. Four independent methods were used to estimate crop evapotranspiration (ETc), namely, soil water balance budgeting approach, energy balance approach—(Bowen ratio), empirical methods approach, and Pan evaporation method. The soil water balance budgeting approach utilized the soil moisture measurement by gravimetric and TDR method. The empirical evapotranspiration methods such as combination approach (FAO-56 Penman-Monteith and Penman), temperature-based approach (Hargreaves-Samani), and radiation-based approach (Priestley-Taylor, Turc, Abetw) were used to estimate the reference evapotranspiration (ET0). The daily ETc determined by the FAO-56 Penman-Monteith, Priestley-Taylor, Turc, Pan evaporation, and Bowen ratio were found to be at par with the ET values derived from the soil water balance budget; while the methods Abetw, Penman, and Hargreaves-Samani were not found to be ideal for the determination of ETc. The study illustrates the in situ applicability of the TDR method in order to make it possible for a user to choose the best way for the optimum water consumption for a given crop in a sub-humid region. The study suggests that the FAO-56 Penman-Monteith, Turc, and Priestley-Taylor can be used for the determination of crop ETc using TDR in comparison to soil water balance budget.

  11. Sensitivity analysis with the regional climate model COSMO-CLM over the CORDEX-MENA domain

    Science.gov (United States)

    Bucchignani, E.; Cattaneo, L.; Panitz, H.-J.; Mercogliano, P.

    2016-02-01

    The results of a sensitivity work based on ERA-Interim driven COSMO-CLM simulations over the Middle East-North Africa (CORDEX-MENA) domain are presented. All simulations were performed at 0.44° spatial resolution. The purpose of this study was to ascertain model performances with respect to changes in physical and tuning parameters which are mainly related to surface, convection, radiation and cloud parameterizations. Evaluation was performed for the whole CORDEX-MENA region and six sub-regions, comparing a set of 26 COSMO-CLM runs against a combination of available ground observations, satellite products and reanalysis data to assess temperature, precipitation, cloud cover and mean sea level pressure. The model proved to be very sensitive to changes in physical parameters. The optimized configuration allows COSMO-CLM to improve the simulated main climate features of this area. Its main characteristics consist in the new parameterization of albedo, based on Moderate Resolution Imaging Spectroradiometer data, and the new parameterization of aerosol, based on NASA-GISS AOD distributions. When applying this configuration, Mean Absolute Error values for the considered variables are as follows: about 1.2 °C for temperature, about 15 mm/month for precipitation, about 9 % for total cloud cover, and about 0.6 hPa for mean sea level pressure.

  12. Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jung Hwan; Choi, Yoo Jin; Choi, Won Suk; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang, E-mail: wonsang@catholic.ac.kr

    2013-11-01

    Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

  13. Distributed HUC-based modeling with SUMMA for ensemble streamflow forecasting over large regional domains.

    Science.gov (United States)

    Saharia, M.; Wood, A.; Clark, M. P.; Bennett, A.; Nijssen, B.; Clark, E.; Newman, A. J.

    2017-12-01

    Most operational streamflow forecasting systems rely on a forecaster-in-the-loop approach in which some parts of the forecast workflow require an experienced human forecaster. But this approach faces challenges surrounding process reproducibility, hindcasting capability, and extension to large domains. The operational hydrologic community is increasingly moving towards `over-the-loop' (completely automated) large-domain simulations yet recent developments indicate a widespread lack of community knowledge about the strengths and weaknesses of such systems for forecasting. A realistic representation of land surface hydrologic processes is a critical element for improving forecasts, but often comes at the substantial cost of forecast system agility and efficiency. While popular grid-based models support the distributed representation of land surface processes, intermediate-scale Hydrologic Unit Code (HUC)-based modeling could provide a more efficient and process-aligned spatial discretization, reducing the need for tradeoffs between model complexity and critical forecasting requirements such as ensemble methods and comprehensive model calibration. The National Center for Atmospheric Research is collaborating with the University of Washington, the Bureau of Reclamation and the USACE to implement, assess, and demonstrate real-time, over-the-loop distributed streamflow forecasting for several large western US river basins and regions. In this presentation, we present early results from short to medium range hydrologic and streamflow forecasts for the Pacific Northwest (PNW). We employ a real-time 1/16th degree daily ensemble model forcings as well as downscaled Global Ensemble Forecasting System (GEFS) meteorological forecasts. These datasets drive an intermediate-scale configuration of the Structure for Unifying Multiple Modeling Alternatives (SUMMA) model, which represents the PNW using over 11,700 HUCs. The system produces not only streamflow forecasts (using the Mizu

  14. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project).

    Science.gov (United States)

    Compernolle, Sofie; De Cocker, Katrien; Roda, Célina; Oppert, Jean-Michel; Mackenbach, Joreintje D; Lakerveld, Jeroen; Glonti, Ketevan; Bardos, Helga; Rutter, Harry; Cardon, Greet; De Bourdeaudhuij, Ilse

    2016-01-01

    The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level. In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London), a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables. Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use) were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours. Preliminary evidence was found for

  15. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project.

    Directory of Open Access Journals (Sweden)

    Sofie Compernolle

    Full Text Available The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level.In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London, a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables.Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours.Preliminary evidence was

  16. Prostate segmentation by feature enhancement using domain knowledge and adaptive region based operations

    International Nuclear Information System (INIS)

    Nanayakkara, Nuwan D; Samarabandu, Jagath; Fenster, Aaron

    2006-01-01

    Estimation of prostate location and volume is essential in determining a dose plan for ultrasound-guided brachytherapy, a common prostate cancer treatment. However, manual segmentation is difficult, time consuming and prone to variability. In this paper, we present a semi-automatic discrete dynamic contour (DDC) model based image segmentation algorithm, which effectively combines a multi-resolution model refinement procedure together with the domain knowledge of the image class. The segmentation begins on a low-resolution image by defining a closed DDC model by the user. This contour model is then deformed progressively towards higher resolution images. We use a combination of a domain knowledge based fuzzy inference system (FIS) and a set of adaptive region based operators to enhance the edges of interest and to govern the model refinement using a DDC model. The automatic vertex relocation process, embedded into the algorithm, relocates deviated contour points back onto the actual prostate boundary, eliminating the need of user interaction after initialization. The accuracy of the prostate boundary produced by the proposed algorithm was evaluated by comparing it with a manually outlined contour by an expert observer. We used this algorithm to segment the prostate boundary in 114 2D transrectal ultrasound (TRUS) images of six patients scheduled for brachytherapy. The mean distance between the contours produced by the proposed algorithm and the manual outlines was 2.70 ± 0.51 pixels (0.54 ± 0.10 mm). We also showed that the algorithm is insensitive to variations of the initial model and parameter values, thus increasing the accuracy and reproducibility of the resulting boundaries in the presence of noise and artefacts

  17. On the solution of elliptic partial differential equations on regions with corners

    International Nuclear Information System (INIS)

    Serkh, Kirill; Rokhlin, Vladimir

    2016-01-01

    In this paper we investigate the solution of boundary value problems on polygonal domains for elliptic partial differential equations. We observe that when the problems are formulated as the boundary integral equations of classical potential theory, the solutions are representable by series of elementary functions. In addition to being analytically perspicuous, the resulting expressions lend themselves to the construction of accurate and efficient numerical algorithms. The results are illustrated by a number of numerical examples.

  18. Fourier domain image fusion for differential X-ray phase-contrast breast imaging

    International Nuclear Information System (INIS)

    Coello, Eduardo; Sperl, Jonathan I.; Bequé, Dirk; Benz, Tobias; Scherer, Kai; Herzen, Julia; Sztrókay-Gaul, Anikó; Hellerhoff, Karin; Pfeiffer, Franz; Cozzini, Cristina; Grandl, Susanne

    2017-01-01

    X-Ray Phase-Contrast (XPC) imaging is a novel technology with a great potential for applications in clinical practice, with breast imaging being of special interest. This work introduces an intuitive methodology to combine and visualize relevant diagnostic features, present in the X-ray attenuation, phase shift and scattering information retrieved in XPC imaging, using a Fourier domain fusion algorithm. The method allows to present complementary information from the three acquired signals in one single image, minimizing the noise component and maintaining visual similarity to a conventional X-ray image, but with noticeable enhancement in diagnostic features, details and resolution. Radiologists experienced in mammography applied the image fusion method to XPC measurements of mastectomy samples and evaluated the feature content of each input and the fused image. This assessment validated that the combination of all the relevant diagnostic features, contained in the XPC images, was present in the fused image as well.

  19. Fourier domain image fusion for differential X-ray phase-contrast breast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Coello, Eduardo, E-mail: eduardo.coello@tum.de [GE Global Research, Garching (Germany); Lehrstuhl für Informatikanwendungen in der Medizin & Augmented Reality, Institut für Informatik, Technische Universität München, Garching (Germany); Sperl, Jonathan I.; Bequé, Dirk [GE Global Research, Garching (Germany); Benz, Tobias [Lehrstuhl für Informatikanwendungen in der Medizin & Augmented Reality, Institut für Informatik, Technische Universität München, Garching (Germany); Scherer, Kai; Herzen, Julia [Lehrstuhl für Biomedizinische Physik, Physik-Department & Institut für Medizintechnik, Technische Universität München, Garching (Germany); Sztrókay-Gaul, Anikó; Hellerhoff, Karin [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich (Germany); Pfeiffer, Franz [Lehrstuhl für Biomedizinische Physik, Physik-Department & Institut für Medizintechnik, Technische Universität München, Garching (Germany); Cozzini, Cristina [GE Global Research, Garching (Germany); Grandl, Susanne [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich (Germany)

    2017-04-15

    X-Ray Phase-Contrast (XPC) imaging is a novel technology with a great potential for applications in clinical practice, with breast imaging being of special interest. This work introduces an intuitive methodology to combine and visualize relevant diagnostic features, present in the X-ray attenuation, phase shift and scattering information retrieved in XPC imaging, using a Fourier domain fusion algorithm. The method allows to present complementary information from the three acquired signals in one single image, minimizing the noise component and maintaining visual similarity to a conventional X-ray image, but with noticeable enhancement in diagnostic features, details and resolution. Radiologists experienced in mammography applied the image fusion method to XPC measurements of mastectomy samples and evaluated the feature content of each input and the fused image. This assessment validated that the combination of all the relevant diagnostic features, contained in the XPC images, was present in the fused image as well.

  20. Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.

    Science.gov (United States)

    Zhao, Li-Hua; Yin, Yanting; Yang, Dehua; Liu, Bo; Hou, Li; Wang, Xiaoxi; Pal, Kuntal; Jiang, Yi; Feng, Yang; Cai, Xiaoqing; Dai, Antao; Liu, Mingyao; Wang, Ming-Wei; Melcher, Karsten; Xu, H Eric

    2016-07-15

    G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Domains of pseudo-differential operators: a case for the Triebel-Lizorkin spaces

    Directory of Open Access Journals (Sweden)

    Jon Johnsen

    2005-01-01

    Full Text Available The main result is that every pseudo-differential operator of type 1, 1 and order d is continuous from the Triebel-Lizorkin space Fp,1d to Lp, 1≤p≺∞, and that this is optimal within the Besov and Triebel-Lizorkin scales. The proof also leads to the known continuity for s≻d, while for all real s the sufficiency of Hörmander's condition on the twisted diagonal is carried over to the Besov and Triebel-Lizorkin framework. To obtain this, type 1, 1-operators are extended to distributions with compact spectrum, and Fourier transformed operators of this type are on such distributions proved to satisfy a support rule, generalising the rule for convolutions. Thereby the use of reduced symbols, as introduced by Coifman and Meyer, is replaced by direct application of the paradifferential methods. A few flaws in the literature have been detected and corrected.

  2. The Receptor-Binding Domain in the VP1u Region of Parvovirus B19.

    Science.gov (United States)

    Leisi, Remo; Di Tommaso, Chiarina; Kempf, Christoph; Ros, Carlos

    2016-02-24

    Parvovirus B19 (B19V) is known as the human pathogen causing the mild childhood disease erythema infectiosum. B19V shows an extraordinary narrow tissue tropism for erythroid progenitor cells in the bone marrow, which is determined by a highly restricted uptake. We have previously shown that the specific internalization is mediated by the interaction of the viral protein 1 unique region (VP1u) with a yet unknown cellular receptor. To locate the receptor-binding domain (RBD) within the VP1u, we analyzed the effect of truncations and mutations on the internalization capacity of the recombinant protein into UT7/Epo cells. Here we report that the N-terminal amino acids 5-80 of the VP1u are necessary and sufficient for cellular binding and internalization; thus, this N-terminal region represents the RBD required for B19V uptake. Using site-directed mutagenesis, we further identified a cluster of important amino acids playing a critical role in VP1u internalization. In silico predictions and experimental results suggest that the RBD is structured as a rigid fold of three α-helices. Finally, we found that dimerization of the VP1u leads to a considerably enhanced cellular binding and internalization. Taken together, we identified the RBD that mediates B19V uptake and mapped functional and structural motifs within this sequence. The findings reveal insights into the uptake process of B19V, which contribute to understand the pathogenesis of the infection and the neutralization of the virus by the immune system.

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

    Science.gov (United States)

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

    2017-12-01

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

  4. Differential influences of local subpopulations on regional diversity and differentiation for greater sage-grouse (Centrocercus urophasianus)

    Science.gov (United States)

    Row, Jeffery R.; Oyler-McCance, Sara J.; Fedy, Brad C.

    2016-01-01

    The distribution of spatial genetic variation across a region can shape evolutionary dynamics and impact population persistence. Local population dynamics and among-population dispersal rates are strong drivers of this spatial genetic variation, yet for many species we lack a clear understanding of how these population processes interact in space to shape within-species genetic variation. Here, we used extensive genetic and demographic data from 10 subpopulations of greater sage-grouse to parameterize a simulated approximate Bayesian computation (ABC) model and (i) test for regional differences in population density and dispersal rates for greater sage-grouse subpopulations in Wyoming, and (ii) quantify how these differences impact subpopulation regional influence on genetic variation. We found a close match between observed and simulated data under our parameterized model and strong variation in density and dispersal rates across Wyoming. Sensitivity analyses suggested that changes in dispersal (via landscape resistance) had a greater influence on regional differentiation, whereas changes in density had a greater influence on mean diversity across all subpopulations. Local subpopulations, however, varied in their regional influence on genetic variation. Decreases in the size and dispersal rates of central populations with low overall and net immigration (i.e. population sources) had the greatest negative impact on genetic variation. Overall, our results provide insight into the interactions among demography, dispersal and genetic variation and highlight the potential of ABC to disentangle the complexity of regional population dynamics and project the genetic impact of changing conditions.

  5. Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

  6. Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Svendsen, Anders J; Gervin, Kristina; Lyle, Robert

    2016-01-01

    : Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6......OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated......: We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA....

  7. Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

    Science.gov (United States)

    Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol

    2013-11-01

    The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.

  8. Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women.

    Science.gov (United States)

    Travassos, Mark A; Coulibaly, Drissa; Bailey, Jason A; Niangaly, Amadou; Adams, Matthew; Nyunt, Myaing M; Ouattara, Amed; Lyke, Kirsten E; Laurens, Matthew B; Pablo, Jozelyn; Jasinskas, Algis; Nakajima, Rie; Berry, Andrea A; Takala-Harrison, Shannon; Kone, Abdoulaye K; Kouriba, Bourema; Rowe, J Alexandra; Doumbo, Ogobara K; Thera, Mahamadou A; Laufer, Miriam K; Felgner, Philip L; Plowe, Christopher V

    2015-06-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates parasite sequestration in small capillaries through tissue-specific cytoadherence. The best characterized of these proteins is VAR2CSA, which is expressed on the surface of infected erythrocytes that bind to chondroitin sulfate in the placental matrix. Antibodies to VAR2CSA prevent placental cytoadherence and protect against placental malaria. The size and complexity of the VAR2CSA protein pose challenges for vaccine development, but smaller constitutive domains may be suitable for subunit vaccine development. A protein microarray was printed to include five overlapping fragments of the 3D7 VAR2CSA extracellular region. Malian women with a history of at least one pregnancy had antibody recognition of four of these fragments and had stronger reactivity against the two distal fragments than did nulliparous women, children, and men from Mali, suggesting that the C-terminal extracellular VAR2CSA domains are a potential focus of protective immunity. With carefully chosen sera from longitudinal studies of pregnant women, this approach has the potential to identify seroreactive VAR2CSA domains associated with protective immunity against pregnancy-associated malaria. © The American Society of Tropical Medicine and Hygiene.

  9. Differential expression of a novel seven transmembrane domain protein in epididymal fat from aged and diabetic mice.

    Science.gov (United States)

    Yang, H; Egan, J M; Rodgers, B D; Bernier, M; Montrose-Rafizadeh, C

    1999-06-01

    To identify novel seven transmembrane domain proteins from 3T3-L1 adipocytes, we used PCR to amplify 3T3-L1 adipocyte complementary DNA (cDNA) with primers homologous to the N- and C-termini of pancreatic glucagon-like peptide-1 (GLP-1) receptor. We screened a cDNA library prepared from fully differentiated 3T3-L1 adipocytes using a 500-bp cDNA PCR product probe. Herein describes the isolation and characterization of a 1.6-kb cDNA clone that encodes a novel 298-amino acid protein that we termed TPRA40 (transmembrane domain protein of 40 kDa regulated in adipocytes). TPRA40 has seven putative transmembrane domains and shows little homology with the known GLP-1 receptor or with other G protein-coupled receptors. The levels of TPRA40 mRNA and protein were higher in 3T3-L1 adipocytes than in 3T3-L1 fibroblasts. TPRA40 is present in a number of mouse and human tissues. Interestingly, TPRA40 mRNA levels were significantly increased by 2- to 3-fold in epididymal fat of 24-month-old mice vs. young controls as well as in db/db and ob/ob mice vs. nondiabetic control littermates. No difference in TPRA40 mRNA levels was observed in brain, heart, skeletal muscle, liver, or kidney. Furthermore, no difference in TPRA40 expression was detected in brown fat of ob/ob mice when compared with age-matched controls. Taken together, these data suggest that TPRA40 represents a novel membrane-associated protein whose expression in white adipose tissue is altered with aging and type 2 diabetes.

  10. Frequency domain design of gain scheduling control for large wind systems in full-load region

    International Nuclear Information System (INIS)

    Burlibaşa, A.; Ceangă, E.

    2014-01-01

    Highlights: • A large wind energy system, operating under full-load regime, is considered. • According to its particularities in frequency domain, control law design is provided. • These particularities are influenced by the interactions of wind–tower–blade ensemble. • Control low, within gain scheduling strategy, is achieved imposing stability reserve. • Supplementary a criterion, aimed at reducing mechanical loads, is imposed. - Abstract: The paper presents the issue of power control law synthesis, in the case of a large wind system that operates under full-load regime, based on dynamic properties details in frequency domain. Solving this problem involves two phases: the establishment of a linearized model as faithfully as possible in various operating points of the full-load region, and synthesis of the power controller, considered with classic structure, taking into account frequency particularities of the obtained linearized model. Obtained linear model of the controlled process is of order 16 and encloses subsystems for tower fore-aft oscillations damping, and for drive-train torsion oscillations damping. The designed controller contains a PI component and a lag compensator for dynamic correction at high frequencies. It is known that the main features of wind system dynamics generated by the interaction of wind–tower–blade ensemble cause a gap in the gain characteristic of the model and complex conjugate zeros, which can move between right and left half-planes, depending on the average wind speed value. Consequently, for control law synthesis an interactive frequency solution is adopted. This is “transparent” in relation to particularities induced by wind–tower–blade interaction. This solution allows evaluation of the extent to which control law is affected by the subsystem for tower oscillations damping. Given the strong dependence between the model and the mean wind speed value, a gain scheduling control law is designed. At

  11. Differential Roles of the Glycogen-Binding Domains of β Subunits in Regulation of the Snf1 Kinase Complex▿

    Science.gov (United States)

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R.; Elbing, Karin; Schmidt, Martin C.

    2010-01-01

    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic α subunit and regulatory β and γ subunits. In this study, the role of the β subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (α), Snf4 (γ), and one of three alternative β subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three β subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the β subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation. PMID:19897735

  12. Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex.

    Science.gov (United States)

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R; Elbing, Karin; Schmidt, Martin C

    2010-01-01

    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (alpha), Snf4 (gamma), and one of three alternative beta subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three beta subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the beta subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation.

  13. Differential subcellular localization of insulin receptor substrates depends on C-terminal regions and importin β

    International Nuclear Information System (INIS)

    Kabuta, Tomohiro; Take, Kazumi; Kabuta, Chihana; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2008-01-01

    Insulin receptor substrates (IRSs) play essential roles in signal transduction of insulin and insulin-like growth factors. Previously, we showed that IRS-3 is localized to the nucleus as well as the cytosol, while IRS-1 and 2 are mainly localized to the cytoplasm. In the present study, we found that importin β directly interacts with IRS-3 and is able to mediate nuclear transport of IRS-3. Importin β interacted with the pleckstrin homology domain, the phosphotyrosine binding domain and the C-terminal region of IRS-3; indeed all of these fragments exhibited predominant nuclear localization. By contrast, almost no interaction of importin β with IRS-1 and -2 was observed, and their C-terminal regions displayed discrete spotty images in the cytosol. In addition, using chimeric proteins between IRS-1 and IRS-3, we revealed that the C-terminal regions are the main determinants of the differing subcellular localizations of IRS-1 and IRS-3.

  14. Functional analysis of SH3 domain containing ring finger 2 during the myogenic differentiation of quail myoblast cells

    Directory of Open Access Journals (Sweden)

    Si Won Kim

    2017-08-01

    Full Text Available Objective Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2 gene. Subsequently, SH3RF2 was knocked out using clustered regularly interspaced short palindromic repeat/Cas9 technology and single cell-derived SH3RF2 mutant sublines were established to study the biofunctional activity of SH3RF2 in quail myoblast (QM7 cells during muscle differentiation. Results Through a T7 endonuclease I assay and genotyping analysis, we established an SH3RF2 knockout (KO QM7#4 subline with 61 and 155 nucleotide deletion mutations in SH3RF2. After the induction of myotube differentiation, the expression profiles were analyzed and compared between regular QM7 and SH3RF2 KO QM7#4 cells by global RNA sequencing and bioinformatics analysis. Conclusion We did not detect any statistically significant role of SH3RF2 during myotube differentiation in QM7 myoblast cells. However, additional experiments are necessary to examine the biofunctional activity of SH3RF2 in cell proliferation and muscle growth.

  15. U-Pb age in zircon of intrusive granite at Acopiara complex, Crystal region, domain Central Ceara, Brazil

    International Nuclear Information System (INIS)

    Neri, T.F.O.; Hamelak, G.M.S.; Azevedo, L.R.; Mattos, I.C.; Verissimo, C.U.V.; Nogueira Neto, J.A.; Lima, M.N.

    2015-01-01

    Granitic body mineralogically composed by two micas, located at Crystal region, Ceara Central domain and intruded into lithotypes from Acopiara complex, provided an age of ∼526 Ma, indicating important period of magma generation of granitic composition associated with crustal anatexia, during Paleozoic

  16. The cysteine-rich core domain of REIC/Dkk-3 is critical for its effect on monocyte differentiation and tumor regression.

    Science.gov (United States)

    Kinoshita, Rie; Watanabe, Masami; Huang, Peng; Li, Shun-Ai; Sakaguchi, Masakiyo; Kumon, Hiromi; Futami, Junichiro

    2015-06-01

    Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor-suppressor gene and has been studied as a promising therapeutic gene for cancer gene therapy. Intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) elicits cancer cell-specific apoptosis and anticancer immune responses. The cytokine-like effect of secretory REIC/Dkk-3 on the induction of dendritic cell (DC)-like cell differentiation from monocytes plays a role in systemic anticancer immunity. In the present study, we generated recombinant full-length and N-terminally truncated REIC/Dkk-3 to characterize the biological activity of the protein. During the purification procedure, we identified a 17 kDa cysteine-rich stable product (C17-REIC) showing limited degradation. Further analysis showed that the C17-REIC domain was sufficient for the induction of DC-like cell differentiation from monocytes. Concomitant with the differentiation of DCs, the REIC/Dkk-3 protein induced the phosphorylation of glycogen synthase kinase 3β (GSK-3β) and signal transducers and activators of transcription (STAT) at a level comparable to that of granulocyte/macrophage colony-stimulating factor. In a mouse model of subcutaneous renal adenocarcinoma, intraperitoneal injection of full-length and C17-REIC proteins exerted anticancer effects in parallel with the activation of immunocompetent cells such as DCs and cytotoxic T lymphocytes in peripheral blood. Taken together, our results indicate that the stable cysteine-rich core region of REIC/Dkk-3 is responsible for the induction of anticancer immune responses. Because REIC/Dkk-3 is a naturally circulating serum protein, the upregulation REIC/Dkk-3 protein expression could be a promising option for cancer therapy.

  17. Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

    Science.gov (United States)

    Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

    2012-09-01

    For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

  18. Preliminary Experience Using Eye-Tracking Technology to Differentiate Novice and Expert Image Interpretation for Ultrasound-Guided Regional Anesthesia.

    Science.gov (United States)

    Borg, Lindsay K; Harrison, T Kyle; Kou, Alex; Mariano, Edward R; Udani, Ankeet D; Kim, T Edward; Shum, Cynthia; Howard, Steven K

    2018-02-01

    Objective measures are needed to guide the novice's pathway to expertise. Within and outside medicine, eye tracking has been used for both training and assessment. We designed this study to test the hypothesis that eye tracking may differentiate novices from experts in static image interpretation for ultrasound (US)-guided regional anesthesia. We recruited novice anesthesiology residents and regional anesthesiology experts. Participants wore eye-tracking glasses, were shown 5 sonograms of US-guided regional anesthesia, and were asked a series of anatomy-based questions related to each image while their eye movements were recorded. The answer to each question was a location on the sonogram, defined as the area of interest (AOI). The primary outcome was the total gaze time in the AOI (seconds). Secondary outcomes were the total gaze time outside the AOI (seconds), total time to answer (seconds), and time to first fixation on the AOI (seconds). Five novices and 5 experts completed the study. Although the gaze time (mean ± SD) in the AOI was not different between groups (7 ± 4 seconds for novices and 7 ± 3 seconds for experts; P = .150), the gaze time outside the AOI was greater for novices (75 ± 18 versus 44 ± 4 seconds for experts; P = .005). The total time to answer and total time to first fixation in the AOI were both shorter for experts. Experts in US-guided regional anesthesia take less time to identify sonoanatomy and spend less unfocused time away from a target compared to novices. Eye tracking is a potentially useful tool to differentiate novices from experts in the domain of US image interpretation. © 2017 by the American Institute of Ultrasound in Medicine.

  19. Contribution of glacier melt to sea-level rise since AD 1865: a regionally differentiated calculation

    NARCIS (Netherlands)

    Zuo, Z.; Oerlemans, J.

    1997-01-01

    The contribution of glacier melt, including the Greenland ice-sheet, to sea-level change since AD 1865 is estimated on the basis of modelled sensitivity of glacier mass balance to climate change and historical temperature data. Calculations are done in a regionally differentiated manner to overcome

  20. Peculiar long-range supercurrent in superconductor-ferromagnet-superconductor junction containing a noncollinear magnetic domain in the ferromagnetic region

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Hao, E-mail: menghao1982@shu.edu.cn [School of Physics and Telecommunication Engineering, Shaanxi University of Technology, Hanzhong 723001 (China); National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China); Wu, Xiuqiang [National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China); Ren, Yajie [School of Physics and Telecommunication Engineering, Shaanxi University of Technology, Hanzhong 723001 (China)

    2015-01-14

    We study the supercurrent in clean superconductor-ferromagnet-superconductor heterostructure containing a noncollinear magnetic domain in the ferromagnetic region. It is demonstrated that the magnetic domain can lead to a spin-flip scattering process, which reverses the spin orientations of the singlet Cooper pair and simultaneously changes the sign of the corresponding electronic momentum. If the ferromagnetic layers on both sides of magnetic domain have the same features, the long-range proximity effect will take place. That is because the singlet Cooper pair will create an exact phase-cancellation effect and gets an additional π phase shift as it passes through the entire ferromagnetic region. Then, the equal spin triplet pair only exists in the magnetic domain region and can not diffuse into the other two ferromagnetic layers. So, the supercurrent mostly arises from the singlet Cooper pairs, and the equal spin triplet pairs are not involved. This result can provide a approach for generating the long-range supercurrent.

  1. Emergence of differentially regulated pathways associated with the development of regional specificity in chicken skin.

    Science.gov (United States)

    Chang, Kai-Wei; Huang, Nancy A; Liu, I-Hsuan; Wang, Yi-Hui; Wu, Ping; Tseng, Yen-Tzu; Hughes, Michael W; Jiang, Ting Xin; Tsai, Mong-Hsun; Chen, Chien-Yu; Oyang, Yen-Jen; Lin, En-Chung; Chuong, Cheng-Ming; Lin, Shau-Ping

    2015-01-23

    Regional specificity allows different skin regions to exhibit different characteristics, enabling complementary functions to make effective use of the integumentary surface. Chickens exhibit a high degree of regional specificity in the skin and can serve as a good model for when and how these regional differences begin to emerge. We used developing feather and scale regions in embryonic chickens as a model to gauge the differences in their molecular pathways. We employed cosine similarity analysis to identify the differentially regulated and co-regulated genes. We applied low cell techniques for expression validation and chromatin immunoprecipitation (ChIP)-based enhancer identification to overcome limited cell availabilities from embryonic chicken skin. We identified a specific set of genes demonstrating a high correlation as being differentially expressed during feather and scale development and maturation. Some members of the WNT, TGF-beta/BMP, and Notch family known to be involved in feathering skin differentiation were found to be differentially regulated. Interestingly, we also found genes along calcium channel pathways that are differentially regulated. From the analysis of differentially regulated pathways, we used calcium signaling pathways as an example for further verification. Some voltage-gated calcium channel subunits, particularly CACNA1D, are expressed spatio-temporally in the skin epithelium. These calcium signaling pathway members may be involved in developmental decisions, morphogenesis, or epithelial maturation. We further characterized enhancers associated with histone modifications, including H3K4me1, H3K27ac, and H3K27me3, near calcium channel-related genes and identified signature intensive hotspots that may be correlated with certain voltage-gated calcium channel genes. We demonstrated the applicability of cosine similarity analysis for identifying novel regulatory pathways that are differentially regulated during development. Our study

  2. A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans.

    Directory of Open Access Journals (Sweden)

    Mariana L Coutinho

    2011-12-01

    Full Text Available The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×10(3 to 8×10(5 copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences.

  3. Towards a Differentiated and Domain-Specific View of Educational Technology: An Exploratory Study of History Teachers' Technology Use

    Science.gov (United States)

    Voet, Michiel; De Wever, Bram

    2017-01-01

    Adopting a differentiated and domain-specific view of educational technology, the present study focuses on the case of school history. It argues that, in this particular context, one of technology's main assets is its ability to support inquiry-based learning activities, during which students interpret the past through historical reasoning. As…

  4. Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.

    Science.gov (United States)

    Capes, Deborah L; Arcisio-Miranda, Manoel; Jarecki, Brian W; French, Robert J; Chanda, Baron

    2012-02-14

    Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.

  5. The finite element model for the propagation of light in scattering media: a direct method for domains with nonscattering regions.

    Science.gov (United States)

    Arridge, S R; Dehghani, H; Schweiger, M; Okada, E

    2000-01-01

    We present a method for handling nonscattering regions within diffusing domains. The method develops from an iterative radiosity-diffusion approach using Green's functions that was computationally slow. Here we present an improved implementation using a finite element method (FEM) that is direct. The fundamental idea is to introduce extra equations into the standard diffusion FEM to represent nondiffusive light propagation across a nonscattering region. By appropriate mesh node ordering the computational time is not much greater than for diffusion alone. We compare results from this method with those from a discrete ordinate transport code, and with Monte Carlo calculations. The agreement is very good, and, in addition, our scheme allows us to easily model time-dependent and frequency domain problems.

  6. GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site*

    Science.gov (United States)

    Lu, Shaoyong; Banerjee, Avik; Jang, Hyunbum; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2015-01-01

    K-Ras4B, a frequently mutated oncogene in cancer, plays an essential role in cell growth, differentiation, and survival. Its C-terminal membrane-associated hypervariable region (HVR) is required for full biological activity. In the active GTP-bound state, the HVR interacts with acidic plasma membrane (PM) headgroups, whereas the farnesyl anchors in the membrane; in the inactive GDP-bound state, the HVR may interact with both the PM and the catalytic domain at the effector binding region, obstructing signaling and nucleotide exchange. Here, using molecular dynamics simulations and NMR, we aim to figure out the effects of nucleotides (GTP and GDP) and frequent (G12C, G12D, G12V, G13D, and Q61H) and infrequent (E37K and R164Q) oncogenic mutations on full-length K-Ras4B. The mutations are away from or directly at the HVR switch I/effector binding site. Our results suggest that full-length wild-type GDP-bound K-Ras4B (K-Ras4BWT-GDP) is in an intrinsically autoinhibited state via tight HVR-catalytic domain interactions. The looser association in K-Ras4BWT-GTP may release the HVR. Some of the oncogenic mutations weaken the HVR-catalytic domain association in the K-Ras4B-GDP/-GTP bound states, which may facilitate the HVR disassociation in a nucleotide-independent manner, thereby up-regulating oncogenic Ras signaling. Thus, our results suggest that mutations can exert their effects in more than one way, abolishing GTP hydrolysis and facilitating effector binding. PMID:26453300

  7. GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site.

    Science.gov (United States)

    Lu, Shaoyong; Banerjee, Avik; Jang, Hyunbum; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2015-11-27

    K-Ras4B, a frequently mutated oncogene in cancer, plays an essential role in cell growth, differentiation, and survival. Its C-terminal membrane-associated hypervariable region (HVR) is required for full biological activity. In the active GTP-bound state, the HVR interacts with acidic plasma membrane (PM) headgroups, whereas the farnesyl anchors in the membrane; in the inactive GDP-bound state, the HVR may interact with both the PM and the catalytic domain at the effector binding region, obstructing signaling and nucleotide exchange. Here, using molecular dynamics simulations and NMR, we aim to figure out the effects of nucleotides (GTP and GDP) and frequent (G12C, G12D, G12V, G13D, and Q61H) and infrequent (E37K and R164Q) oncogenic mutations on full-length K-Ras4B. The mutations are away from or directly at the HVR switch I/effector binding site. Our results suggest that full-length wild-type GDP-bound K-Ras4B (K-Ras4B(WT)-GDP) is in an intrinsically autoinhibited state via tight HVR-catalytic domain interactions. The looser association in K-Ras4B(WT)-GTP may release the HVR. Some of the oncogenic mutations weaken the HVR-catalytic domain association in the K-Ras4B-GDP/-GTP bound states, which may facilitate the HVR disassociation in a nucleotide-independent manner, thereby up-regulating oncogenic Ras signaling. Thus, our results suggest that mutations can exert their effects in more than one way, abolishing GTP hydrolysis and facilitating effector binding. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Efficient detection of differentially methylated regions using DiMmeR

    DEFF Research Database (Denmark)

    Almeida, Diogo Marinho; Uhrenfeldt Skov, Ida; Silva, Artur

    2017-01-01

    in the programming language R, have no user interface, and do not offer all necessary steps to guide users from raw data all the way down to statistically significant differentially methylated regions (DMRs) and the associated genes. RESULTS: Here, we present DiMmeR (Discovery of Multiple Differentially Methylated...... Regions), the first free standalone software that interactively guides with a user-friendly graphical user interface (GUI) scientists the whole way through EWAS data analysis. It offers parallelized statistical methods for efficiently identifying DMRs in both Illumina 450K and 850K EPIC chip data. Di......MmeR computes empirical p-values through randomization tests, even for big data sets of hundreds of patients and thousands of permutations within a few minutes on a standard desktop PC. It is independent of any third-party libraries, computes regression coefficients, p-values and empirical p...

  9. Empirical study on regional differentiation of rural household energy use in Northwest China

    Science.gov (United States)

    Wu, Wenheng; Zhang, Xin; Guo, Xiaodong

    2018-02-01

    To better understand regional differentiation of rural household energy use, data of energy use of 232 rural households in the Linwei District located in the lower reaches of the Weihe River of Northwest China were collected by questionnaires combined with face-to-face interview. Location quotient of energy use (LQEU) method is adopted in the paper. The results show that multiple energy sources are utilized due to market orientation in the plain area, and biogas is prominent as a result of policy orientation in the loess tableland, whereas firewood is dominant due to the influence of natural environment in the Qinling mountainous area. Regional differentiation of energy use is comprehensively affected by income level, air temperature, development conditions, energy policy, etc.

  10. Transforming p21 ras protein: flexibility in the major variable region linking the catalytic and membrane-anchoring domains

    DEFF Research Database (Denmark)

    Willumsen, B M; Papageorge, A G; Hubbert, N

    1985-01-01

    or increasing it to 50 amino acids has relatively little effect on the capacity of the gene to induce morphological transformation of NIH 3T3 cells. Assays of GTP binding, GTPase and autophosphorylating activities of such mutant v-rasH-encoded proteins synthesized in bacteria indicated that the sequences...... that is required for post-translational processing, membrane localization and transforming activity of the proteins. We have now used the viral oncogene (v-rasH) of Harvey sarcoma virus to study the major variable region by deleting or duplicating parts of the gene. Reducing this region to five amino acids...... that encode these biochemical activities are located upstream from the major variable region. In the context of transformation, we propose that the region of sequence heterogeneity serves principally to connect the N-terminal catalytic domain with amino acids at the C terminus that are required to anchor...

  11. Generalization of the World Experience in Differentiation of Regions on Account of Innovation

    Directory of Open Access Journals (Sweden)

    Blahun Ivan S.

    2016-01-01

    Full Text Available One of the main strategic objectives of our State is to promote innovation, which should include development and launch of new products at the national market, development and introduction of new technologies, creation and application of new knowledge. In accordance with the said above, the article has examined the experience of European Union Member States to improve the efficiency of innovation and differentiation of regions in terms of innovation, tools for evaluation of the innovation activity status has been determined in relation to the territories of the European Union at the level of regions.

  12. Alternative splicing targeting the hTAF4-TAFH domain of TAF4 represses proliferation and accelerates chondrogenic differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Jekaterina Kazantseva

    Full Text Available Transcription factor IID (TFIID activity can be regulated by cellular signals to specifically alter transcription of particular subsets of genes. Alternative splicing of TFIID subunits is often the result of external stimulation of upstream signaling pathways. We studied tissue distribution and cellular expression of different splice variants of TFIID subunit TAF4 mRNA and biochemical properties of its isoforms in human mesenchymal stem cells (hMSCs to reveal the role of different isoforms of TAF4 in the regulation of proliferation and differentiation. Expression of TAF4 transcripts with exons VI or VII deleted, which results in a structurally modified hTAF4-TAFH domain, increases during early differentiation of hMSCs into osteoblasts, adipocytes and chondrocytes. Functional analysis data reveals that TAF4 isoforms with the deleted hTAF4-TAFH domain repress proliferation of hMSCs and preferentially promote chondrogenic differentiation at the expense of other developmental pathways. This study also provides initial data showing possible cross-talks between TAF4 and TP53 activity and switching between canonical and non-canonical WNT signaling in the processes of proliferation and differentiation of hMSCs. We propose that TAF4 isoforms generated by the alternative splicing participate in the conversion of the cellular transcriptional programs from the maintenance of stem cell state to differentiation, particularly differentiation along the chondrogenic pathway.

  13. Case Library Construction Technology of Energy Loss in Distribution Networks Considering Regional Differentiation Theory

    Directory of Open Access Journals (Sweden)

    Ze Yuan

    2017-11-01

    Full Text Available The grid structures, load levels, and running states of distribution networks in different supply regions are known as the influencing factors of energy loss. In this paper, the case library of energy loss is constructed to differentiate the crucial factors of energy loss in the different supply regions. First of all, the characteristic state values are selected as the representation of the cases based on the analysis of energy loss under various voltage classes and in different types of regions. Then, the methods of Grey Relational Analysis and the K-Nearest Neighbor are utilized to implement the critical technologies of case library construction, including case representation, processing, analysis, and retrieval. Moreover, the analysis software of the case library is designed based on the case library construction technology. Some case studies show that there are many differences and similarities concerning the factors that influence the energy loss in different types of regions. In addition, the most relevant sample case can be retrieved from the case library. Compared with the traditional techniques, constructing a case library provides a new way to find out the characteristics of energy loss in different supply regions and constitutes differentiated loss-reducing programs.

  14. Identification of regions involved in substrate binding and dimer stabilization within the central domains of yeast Hsp40 Sis1.

    Directory of Open Access Journals (Sweden)

    Júlio C Borges

    Full Text Available Protein folding, refolding and degradation are essential for cellular life and are regulated by protein homeostatic processes such those that involve the molecular chaperone DnaK/Hsp70 and its co-chaperone DnaJ. Hsp70 action is initiated when proteins from the DnaJ family bind an unfolded protein for delivery purposes. In eukaryotes, the DnaJ family can be divided into two main groups, Type I and Type II, represented by yeast cytosolic Ydj1 and Sis1, respectively. Although sharing some unique features both members of the DnaJ family, Ydj1 and Sis1 are structurally and functionally distinct as deemed by previous studies, including the observation that their central domains carry the structural and functional information even in switched chimeras. In this study, we combined several biophysical tools for evaluating the stability of Sis1 and mutants that had the central domains (named Gly/Met rich domain and C-terminal Domain I deleted or switched to those of Ydj1 to gain insight into the role of these regions in the structure and function of Sis1. The mutants retained some functions similar to full length wild-type Sis1, however they were defective in others. We found that: 1 Sis1 unfolds in at least two steps as follows: folded dimer to partially folded monomer and then to an unfolded monomer. 2 The Gly/Met rich domain had intrinsically disordered characteristics and its deletion had no effect on the conformational stability of the protein. 3 The deletion of the C-terminal Domain I perturbed the stability of the dimer. 4 Exchanging the central domains perturbed the conformational stability of the protein. Altogether, our results suggest the existence of two similar subdomains in the C-terminal domain of DnaJ that could be important for stabilizing each other in order to maintain a folded substrate-binding site as well as the dimeric state of the protein.

  15. Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.

    Science.gov (United States)

    Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Obradovic, Zoran; Uversky, Vladimir N

    2007-05-01

    Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V. N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes approximately 90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes, and coding sequence diversities possessing strong positive and negative correlation with long disordered regions.

  16. Functional Anthology of Intrinsic Disorder. II. Cellular Components, Domains, Technical Terms, Developmental Processes and Coding Sequence Diversities Correlated with Long Disordered Regions

    Science.gov (United States)

    Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

    2008-01-01

    Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions. PMID:17391015

  17. Multi-ensemble regional simulation of Indian monsoon during contrasting rainfall years: role of convective schemes and nested domain

    Science.gov (United States)

    Devanand, Anjana; Ghosh, Subimal; Paul, Supantha; Karmakar, Subhankar; Niyogi, Dev

    2018-06-01

    Regional simulations of the seasonal Indian summer monsoon rainfall (ISMR) require an understanding of the model sensitivities to physics and resolution, and its effect on the model uncertainties. It is also important to quantify the added value in the simulated sub-regional precipitation characteristics by a regional climate model (RCM), when compared to coarse resolution rainfall products. This study presents regional model simulations of ISMR at seasonal scale using the Weather Research and Forecasting (WRF) model with the synoptic scale forcing from ERA-interim reanalysis, for three contrasting monsoon seasons, 1994 (excess), 2002 (deficit) and 2010 (normal). Impact of four cumulus schemes, viz., Kain-Fritsch (KF), Betts-Janjić-Miller, Grell 3D and modified Kain-Fritsch (KFm), and two micro physical parameterization schemes, viz., WRF Single Moment Class 5 scheme and Lin et al. scheme (LIN), with eight different possible combinations are analyzed. The impact of spectral nudging on model sensitivity is also studied. In WRF simulations using spectral nudging, improvement in model rainfall appears to be consistent in regions with topographic variability such as Central Northeast and Konkan Western Ghat sub-regions. However the results are also dependent on choice of cumulus scheme used, with KF and KFm providing relatively good performance and the eight member ensemble mean showing better results for these sub-regions. There is no consistent improvement noted in Northeast and Peninsular Indian monsoon regions. Results indicate that the regional simulations using nested domains can provide some improvements on ISMR simulations. Spectral nudging is found to improve upon the model simulations in terms of reducing the intra ensemble spread and hence the uncertainty in the model simulated precipitation. The results provide important insights regarding the need for further improvements in the regional climate simulations of ISMR for various sub-regions and contribute

  18. Multi-ensemble regional simulation of Indian monsoon during contrasting rainfall years: role of convective schemes and nested domain

    Science.gov (United States)

    Devanand, Anjana; Ghosh, Subimal; Paul, Supantha; Karmakar, Subhankar; Niyogi, Dev

    2017-08-01

    Regional simulations of the seasonal Indian summer monsoon rainfall (ISMR) require an understanding of the model sensitivities to physics and resolution, and its effect on the model uncertainties. It is also important to quantify the added value in the simulated sub-regional precipitation characteristics by a regional climate model (RCM), when compared to coarse resolution rainfall products. This study presents regional model simulations of ISMR at seasonal scale using the Weather Research and Forecasting (WRF) model with the synoptic scale forcing from ERA-interim reanalysis, for three contrasting monsoon seasons, 1994 (excess), 2002 (deficit) and 2010 (normal). Impact of four cumulus schemes, viz., Kain-Fritsch (KF), Betts-Janjić-Miller, Grell 3D and modified Kain-Fritsch (KFm), and two micro physical parameterization schemes, viz., WRF Single Moment Class 5 scheme and Lin et al. scheme (LIN), with eight different possible combinations are analyzed. The impact of spectral nudging on model sensitivity is also studied. In WRF simulations using spectral nudging, improvement in model rainfall appears to be consistent in regions with topographic variability such as Central Northeast and Konkan Western Ghat sub-regions. However the results are also dependent on choice of cumulus scheme used, with KF and KFm providing relatively good performance and the eight member ensemble mean showing better results for these sub-regions. There is no consistent improvement noted in Northeast and Peninsular Indian monsoon regions. Results indicate that the regional simulations using nested domains can provide some improvements on ISMR simulations. Spectral nudging is found to improve upon the model simulations in terms of reducing the intra ensemble spread and hence the uncertainty in the model simulated precipitation. The results provide important insights regarding the need for further improvements in the regional climate simulations of ISMR for various sub-regions and contribute

  19. Differentiated responses of apple tree floral phenology to global warming in contrasting climatic regions

    Directory of Open Access Journals (Sweden)

    Jean-Michel eLegave

    2015-12-01

    Full Text Available The responses of flowering phenology to temperature increases in temperate fruit trees have rarely been investigated in contrasting climatic regions. This is an appropriate framework for highlighting varying responses to diverse warming contexts, which would potentially combine chill accumulation declines and heat accumulation increases. To examine this issue, a data set was constituted in apple tree from flowering dates collected for two phenological stages of three cultivars in seven climate-contrasting temperate regions of Western Europe and in three mild regions, one in Northern Morocco and two in Southern Brazil. Multiple change-point models were applied to flowering date series, as well as to corresponding series of mean temperature during two successive periods, respectively determining for the fulfillment of chill and heat requirements. A new overview in space and time of flowering date changes was provided in apple tree highlighting not only flowering date advances as in previous studies but also stationary flowering date series. At global scale, differentiated flowering time patterns result from varying interactions between contrasting thermal determinisms of flowering dates and contrasting warming contexts. This may explain flowering date advances in most of European regions and in Morocco vs. stationary flowering date series in the Brazilian regions. A notable exception in Europe was found in the French Mediterranean region where the flowering date series was stationary. While the flowering duration series were stationary whatever the region, the flowering durations were far longer in mild regions compared to temperate regions. Our findings suggest a new warming vulnerability in temperate Mediterranean regions, which could shift towards responding more to chill decline and consequently experience late and extended flowering under future warming scenarios.

  20. Differentiated Responses of Apple Tree Floral Phenology to Global Warming in Contrasting Climatic Regions.

    Science.gov (United States)

    Legave, Jean-Michel; Guédon, Yann; Malagi, Gustavo; El Yaacoubi, Adnane; Bonhomme, Marc

    2015-01-01

    The responses of flowering phenology to temperature increases in temperate fruit trees have rarely been investigated in contrasting climatic regions. This is an appropriate framework for highlighting varying responses to diverse warming contexts, which would potentially combine chill accumulation (CA) declines and heat accumulation (HA) increases. To examine this issue, a data set was constituted in apple tree from flowering dates collected for two phenological stages of three cultivars in seven climate-contrasting temperate regions of Western Europe and in three mild regions, one in Northern Morocco and two in Southern Brazil. Multiple change-point models were applied to flowering date series, as well as to corresponding series of mean temperature during two successive periods, respectively determining for the fulfillment of chill and heat requirements. A new overview in space and time of flowering date changes was provided in apple tree highlighting not only flowering date advances as in previous studies but also stationary flowering date series. At global scale, differentiated flowering time patterns result from varying interactions between contrasting thermal determinisms of flowering dates and contrasting warming contexts. This may explain flowering date advances in most of European regions and in Morocco vs. stationary flowering date series in the Brazilian regions. A notable exception in Europe was found in the French Mediterranean region where the flowering date series was stationary. While the flowering duration series were stationary whatever the region, the flowering durations were far longer in mild regions compared to temperate regions. Our findings suggest a new warming vulnerability in temperate Mediterranean regions, which could shift toward responding more to chill decline and consequently experience late and extended flowering under future warming scenarios.

  1. Pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions: differentiation using MRI

    International Nuclear Information System (INIS)

    Choi, S.H.; Kwon, B.J.; Na, D.G.; Kim, J.-H.; Han, M.H.; Chang, K.-H.

    2007-01-01

    Aims: To determine the differential magnetic resonance imaging (MRI) features of pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions. Materials and methods: The MRI images of 64 patients with pituitary adenoma (n = 38), craniopharyngioma (n = 13), or Rathke cleft cyst (n = 13) were retrospectively reviewed by three neuroradiologists. The following characteristics were evaluated: shape, volume, extent, component characteristics, signal intensities of solid portions on T2-weighted images, signal intensities of cystic portions on T1-weighted images, and enhancement patterns of solid portions and cyst walls of tumours. Fisher's exact test applied with Bonferroni correction was used for multiple comparison. A flowchart for differential diagnosis was constructed based on statistical analysis of the results. Results: A snowman shape, solid characteristics, and homogeneous enhancement of the solid portion were more common in pituitary adenomas (p < 0.017). A superiorly lobulated shape, third ventricle compression by superior tumour extension, mixed solid and cystic characteristics, and reticular enhancement of the solid portion were more common in craniopharyngiomas (p < 0.017). Finally, an ovoid shape, a small tumour volume, cystic characteristics, and no or thin cyst wall enhancement were more common in Rathke cleft cysts (p < 0.017). The flowchart yielded diagnostic accuracies as follows: 92.1% in pituitary adenoma; 92.3% in craniopharyngioma; 92.3% in Rathke cleft cyst; and 92.2% overall. Conclusion: A combination of MRI findings is helpful in the differential diagnosis of the three tumours involving both intrasellar and suprasellar regions

  2. Characterization of Bovine 5′-flanking Region during Differentiation of Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Hye-Jeong Jang

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs have been used as a powerful tool for research including gene manipulated animal models and the study of developmental gene regulation. Among the critical regulatory factors that maintain the pluripotency and self-renewal of undifferentiated ESCs, NANOG plays a very important role. Nevertheless, because pluripotency maintaining factors and specific markers for livestock ESCs have not yet been probed, few studies of the NANOG gene from domestic animals including bovine have been reported. Therefore, we chose mouse ESCs in order to understand and compare NANOG expression between bovine, human, and mouse during ESCs differentiation. We cloned a 600 bp (−420/+181 bovine NANOG 5′-flanking region, and tagged it with humanized recombinant green fluorescent protein (hrGFP as a tracing reporter. Very high GFP expression for bovine NANOG promoter was observed in the mouse ESC line. GFP expression was monitored upon ESC differentiation and was gradually reduced along with differentiation toward neurons and adipocyte cells. Activity of bovine NANOG (−420/+181 promoter was compared with already known mouse and human NANOG promoters in mouse ESC and they were likely to show a similar pattern of regulation. In conclusion, bovine NANOG 5-flanking region functions in mouse ES cells and has characteristics similar to those of mouse and human. These results suggest that bovine gene function studied in mouse ES cells should be evaluated and extrapolated for application to characterization of bovine ES cells.

  3. Domain wall oscillation in magnetic nanowire with a geometrically confined region

    Science.gov (United States)

    Sbiaa, R.; Bahri, M. Al; Piramanayagam, S. N.

    2018-06-01

    In conventional magnetic devices such as magnetic tunnel junctions, a steady oscillation of a soft layer magnetization could find its application in various electronic systems. However, these devices suffer from their low output signal and large spectral linewidth. A more elegant scheme based on domain wall oscillation could be a solution to these issues if DW dynamics could be controlled precisely in space and time. In fact, in DW devices, the magnetic configuration of domain wall and its position are strongly dependent on the device geometry and material properties. Here we show that in a constricted device with judiciously adjusted dimensions, a DW can be trapped within the central part and keep oscillating with a single frequency f. For 200 nm by 40 nm nanowire, f was found to vary from 2 GHz to 3 GHz for a current density between 4.8 × 1012 A/m2 and 5.6 × 1012 A/m2. More interestingly, the device fabrication is simply based on two long nanowires connected by adjusting the offset in both x and y directions. This new type of devices enables the conversion of dc-current to an ac-voltage in a controllable manner opening thus the possibility of a new nano-oscillators with better performance.

  4. Importance of Hypervariable Region 2 for Stability and Affinity of a Shark Single-Domain Antibody Specific for Ebola Virus Nucleoprotein.

    Directory of Open Access Journals (Sweden)

    George P Anderson

    Full Text Available Single-domain antibodies derived from the unique New Antigen Receptor found in sharks have numerous potential applications, ranging from diagnostic reagents to therapeutics. Shark-derived single-domain antibodies possess the same characteristic ability to refold after heat denaturation found in single-domain antibodies derived from camelid heavy-chain-only antibodies. Recently, two shark derived single-domain antibodies specific for the nucleoprotein of Ebola virus were described. Our evaluation confirmed their high affinity for the nucleoprotein, but found their melting temperatures to be low relative to most single-domain antibodies. Our first approach towards improving their stability was grafting antigen-binding regions (complementarity determining regions of one of these single-domain antibodies onto a high melting temperature shark single-domain antibody. This resulted in two variants: one that displayed excellent affinity with a low melting temperature, while the other had poor affinity but a higher melting temperature. These new proteins, however, differed in only 3 amino acids within the complementarity determining region 2 sequence. In shark single-domain antibodies, the complementarity determining region 2 is often referred to as hypervariable region 2, as this segment of the antibody domain is truncated compared to the sequence in camelid single-domain antibodies and conventional heavy chain variable domains. To elucidate which of the three amino acids or combinations thereof were responsible for the affinity and stability we made the 6 double and single point mutants that covered the intermediates between these two clones. We found a single amino acid change that achieved a 10°C higher melting temperature while maintaining sub nM affinity. This research gives insights into the impact of the shark sdAb hypervariable 2 region on both stability and affinity.

  5. Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

    Directory of Open Access Journals (Sweden)

    Yiping Fan

    Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

  6. Regional differentiation of retinoic acid-induced human pluripotent embryonic carcinoma stem cell neurons.

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    Dennis E Coyle

    Full Text Available The NTERA2 cl D1 (NT2 cell line, derived from human teratocarcinoma, exhibits similar properties as embryonic stem (ES cells or very early neuroepithelial progenitors. NT2 cells can be induced to become postmitotic central nervous system neurons (NT2N with retinoic acid. Although neurons derived from pluripotent cells, such as NT2N, have been characterized for their neurotransmitter phenotypes, their potential suitability as a donor source for neural transplantation also depends on their ability to respond to localized environmental cues from a specific region of the CNS. Therefore, our study aimed to characterize the regional transcription factors that define the rostocaudal and dorsoventral identity of NT2N derived from a monolayer differentiation paradigm using quantitative PCR (qPCR. Purified NT2N mainly expressed both GABAergic and glutamatergic phenotypes and were electrically active but did not form functional synapses. The presence of immature astrocytes and possible radial glial cells was noted. The NT2N expressed a regional transcription factor code consistent with forebrain, hindbrain and spinal cord neural progenitors but showed minimal expression of midbrain phenotypes. In the dorsoventral plane NT2N expressed both dorsal and ventral neural progenitors. Of major interest was that even under the influence of retinoic acid, a known caudalization factor, the NT2N population maintained a rostral phenotype subpopulation which expressed cortical regional transcription factors. It is proposed that understanding the regional differentiation bias of neurons derived from pluripotent stem cells will facilitate their successful integration into existing neuronal networks within the CNS.

  7. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

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    Nisha Puthiyedth

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

  8. The regional differentiation of the demographic movements in the Republic of Macedonia

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    Madjevikj Mirjanka

    2016-09-01

    Full Text Available The Republic of Macedonia covers an area of 25,713 km² and according to data from the census conducted in 2002, it has a population of 2,022,547 inhabitants. In the past, the Republic of Macedonia was characterized by some significant demographic changes, including a decline in the average annual rate of population increase. The enhanced immigration movements and sudden decline in the rates of natural population increase have led to changes in distribution of the population and to a spatial differentiation in the population. The long period of transition in the country has been reflected in the spatial development of the country and its demographic processes and to relocation of the population. The different natural-geographical characteristics, unequal regional development potentials, unequal economic development, and demographic characteristics have led to changes in the demographic situation of certain regions. The regions that continually lose part of its population clearly differ from these regions that are characterized by an increased population which is leading to a greater concentration of people in certain location. Further decades with a declining birth rate, followed by a change in the values of population increase, together with migration movements, particularly from the rural and less developed economic regions, has resulted in a decline in the population. The different zones of depopulation and concentration in a simple way express the complex relationships in the population composition.

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

    Science.gov (United States)

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

    2013-09-01

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

  10. Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

    Science.gov (United States)

    Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

    2018-01-01

    genotype. AET differentially affects the ACE C- and N-domain activities, and the N-domain activity is dependent on ACE polymorphism.

  11. Labour Market Performance Differentials and Dynamics in EU-15 Countries and Regions

    Directory of Open Access Journals (Sweden)

    Cristiano Perugini

    2007-09-01

    Full Text Available The aim of this paper is to contribute to empirical analysis of the differentials, dynamics and determinants of labour market performance in EU-15. One innovation of the paper reflects our decision not to use a single indicator of labour market performance, but to adopt three variables: employment rate, unemployment rate, and long-term unemployment rate. In addition to national data (1997-2006, the use of data at regional NUTS-2 level (1999-2005 is a key characteristic of this study. Empirical analyses are carried out by means of various comparative statistics and econometric approaches. In the latter, a large set of explicative variables is applied to examine the potential determinants of regional (unemployment levels and dynamics.

  12. Elemental Profiles of Whisk(ey Allow Differentiation by Type and Region

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    Helene Hopfer

    2017-01-01

    Full Text Available Elemental fingerprints could provide an analytical approach to product differentiation and authentication, and have been used in the past for various distilled spirits, including brandy, gin, bourbon and tequila. However, a comparison of elemental differences between different whisk(ey types, such as Bourbon and Scotch, is still missing. In this study we compare the elemental fingerprints of 68 commercial whiskies for differentiation by type (Bourbon, Tennessee, Scotch, Irish, Japanese and region. Concentrations from sub-μg/L to mid-mg/L of 53 different elements were determined with inductively-coupled plasma—mass spectrometry (ICP-MS and microwave plasma—atomic emission spectroscopy (MP-AES, and used in subsequent statistical analyses. Significant differences in several elements were found for type, and allowed a classification according to whisk(ey type. Elemental differences were also found for different production areas within Scotland, thus, providing further evidence that Scotch whiskies could be differentiated by elemental analysis. Major sources of elemental differences seem to be processing equipment (Cu, Fe, Ni, Cd, Sn, Mo, V and raw materials, such as water (Ca, Mg, Fe, Mn, Sr.

  13. Pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions: differentiation using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Choi, S.H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Kwon, B.J. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of)]. E-mail: bjkwon@radiol.snu.ac.kr; Na, D.G. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Kim, J.-H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Han, M.H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Clinical Research Institute, Seoul National University Hospital (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Chang, K.-H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Clinical Research Institute, Seoul National University Hospital (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

    2007-05-15

    Aims: To determine the differential magnetic resonance imaging (MRI) features of pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions. Materials and methods: The MRI images of 64 patients with pituitary adenoma (n = 38), craniopharyngioma (n = 13), or Rathke cleft cyst (n = 13) were retrospectively reviewed by three neuroradiologists. The following characteristics were evaluated: shape, volume, extent, component characteristics, signal intensities of solid portions on T2-weighted images, signal intensities of cystic portions on T1-weighted images, and enhancement patterns of solid portions and cyst walls of tumours. Fisher's exact test applied with Bonferroni correction was used for multiple comparison. A flowchart for differential diagnosis was constructed based on statistical analysis of the results. Results: A snowman shape, solid characteristics, and homogeneous enhancement of the solid portion were more common in pituitary adenomas (p < 0.017). A superiorly lobulated shape, third ventricle compression by superior tumour extension, mixed solid and cystic characteristics, and reticular enhancement of the solid portion were more common in craniopharyngiomas (p < 0.017). Finally, an ovoid shape, a small tumour volume, cystic characteristics, and no or thin cyst wall enhancement were more common in Rathke cleft cysts (p < 0.017). The flowchart yielded diagnostic accuracies as follows: 92.1% in pituitary adenoma; 92.3% in craniopharyngioma; 92.3% in Rathke cleft cyst; and 92.2% overall. Conclusion: A combination of MRI findings is helpful in the differential diagnosis of the three tumours involving both intrasellar and suprasellar regions.

  14. Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

    Directory of Open Access Journals (Sweden)

    Yu-Fu Hung

    2015-07-01

    Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

  15. The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.

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    Yue Ma

    Full Text Available The inverse F-BAR (IF-BAR domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA-induced neurite initiation and growth in the mouse Neuro2a cells. While ectopic- or over-expression of RhoGAP-defective mutants, srGAP1(R542A and srGAP2(R527A exert a visible inhibitory effect on neuronal differentiation. Unexpectedly, knockdown of endogenous srGAP2 fails to facilitate the neuronal differentiation induced by VPA, but promotes neurite outgrowth of differentiated cells. All three IF-BAR domains from srGAP1-3 can induce filopodia formation in Neuro2a, but the isolated IF-BAR domain from srGAP2, not from srGAP1 and srGAP3, can promote VPA-induced neurite initiation and neuronal differentiation. We identify biochemical and functional interactions of the three srGAPs family members. We propose that srGAP3-Rac1 signaling may be required for the effect of srGAP1 and srGAP2 on attenuating neuronal differentiation. Furthermore, inhibition of Slit-Robo interaction can phenocopy a loss-of-function of srGAP3, indicating that srGAP3 may be dedicated to the Slit-Robo pathway. Our results demonstrate the interplay between srGAP1, srGAP2 and srGAP3 regulates neuronal differentiation and neurite outgrowth. These findings may provide us new insights into the possible roles of srGAPs in neuronal development and a potential mechanism for neurodevelopmental diseases.

  16. Aromatic amino acids in the cellulose binding domain of Penicillium crustosum endoglucanase EGL1 differentially contribute to the cellulose affinity of the enzyme.

    Directory of Open Access Journals (Sweden)

    Jiang-Ke Yang

    Full Text Available The cellulose binding domain (CBD of cellulase binding to cellulosic materials is the initiation of a synergistic action on the enzymatic hydrolysis of the most abundant renewable biomass resources in nature. The binding of the CBD domain to cellulosic substrates generally relies on the interaction between the aromatic amino acids structurally located on the flat face of the CBD domain and the glucose rings of cellulose. In this study, we found the CBD domain of a newly cloned Penicillium crustosum endoglucanase EGL1, which was phylogenetically related to Aspergillus, Fusarium and Rhizopus, and divergent from the well-characterized Trichoderma reeseis cellulase CBD domain, contain two conserved aromatic amino acid-rich regions, Y451-Y452 and Y477-Y478-Y479, among which three amino acids Y451, Y477, and Y478 structurally sited on a flat face of this domain. Cellulose binding assays with green fluorescence protein as the marker, adsorption isotherm assays and an isothermal titration calorimetry assays revealed that although these three amino acids participated in this process, the Y451-Y452 appears to contribute more to the cellulose binding than Y477-Y478-Y479. Further glycine scanning mutagenesis and structural modelling revealed that the binding between CBD domain and cellulosic materials might be multi-amino-acids that participated in this process. The flexible poly-glucose molecule could contact Y451, Y477, and Y478 which form the contacting flat face of CBD domain as the typical model, some other amino acids in or outside the flat face might also participate in the interaction. Thus, it is possible that the conserved Y451-Y452 of CBD might have a higher chance of contacting the cellulosic substrates, contributing more to the affinity of CBD than the other amino acids.

  17. Differential gene expression in porcine SK6 cells infected with wild-type and SAP domain-mutant foot-and-mouth disease virus.

    Science.gov (United States)

    Ni, Zixin; Yang, Fan; Cao, Weijun; Zhang, Xiangle; Jin, Ye; Mao, Ruoqing; Du, Xiaoli; Li, Weiwei; Guo, Jianhong; Liu, Xiangtao; Zhu, Zixiang; Zheng, Haixue

    2016-06-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease in livestock. The viral proteinase L(pro) of FMDV is involved in pathogenicity, and mutation of the L(pro) SAP domain reduces FMDV pathogenicity in pigs. To determine the gene expression profiles associated with decreased pathogenicity in porcine cells, we performed transcriptome analysis using next-generation sequencing technology and compared differentially expressed genes in SK6 cells infected with FMDV containing L(pro) with either a wild-type or mutated version of the SAP domain. This analysis yielded 1,853 genes that exhibited a ≥ 2-fold change in expression and was validated by real-time quantitative PCR detection of several differentially expressed genes. Many of the differentially expressed genes correlated with antiviral responses corresponded to genes associated with transcription factors, immune regulation, cytokine production, inflammatory response, and apoptosis. Alterations in gene expression profiles may be responsible for the variations in pathogenicity observed between the two FMDV variants. Our results provided genes of interest for the further study of antiviral pathways and pathogenic mechanisms related to FMDV L(pro).

  18. The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine.

    Directory of Open Access Journals (Sweden)

    Hannah E Gavin

    2017-01-01

    Full Text Available Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs-a key step in V. vulnificus foodborne pathogenesis-even before onset of overt intestinal pathology.

  19. Differential diagnosis of regional cerebral hyperfixation of TC-99m HMPAO on SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shirazi, P.; Konopka, L.; Crayton, J.W. [Loyola Univ. Medical Center, Maywood, IL (United States)] [and others

    1994-05-01

    Accurate diagnostic evaluation of patients with neurologic and neuropsychiatric disease is important because early treatment may halt disease progression and prevent impairment or disability. Cerebral hyperfixation of HMPAO has been ascribed to luxury perfusion following ischemic infarction. The present study sought to identify other conditions that also display radiotracer hyperfixation in order to develop a differential diagnosis of this finding on SPECT imaging. Two hundred fifty (n=250) successive cerebral SPECT images were reviewed for evidence of HMPAO hyperfixation. Hyperfixation was defined as enhanced focal perfusion surrounded by a zone of diminished or normal cerebral perfusion. All patients were scanned after intravenous injection of 25 mCi Tc-99m HMPAO. Volume-rendered and oblique images were obtained with a Trionix triple-head SPECT system using ultra high resolution fan beam collimators. Thirteen (13/250; 5%) of the patients exhibited regions of HMPAO hyperfixation. CT or MRI abnormalities were detected in 6/13 cases. Clinical diagnoses in these patients included intractable psychosis, post-traumatic stress disorder, alcohol and narcotic dependence, major depression, acute closed-head trauma, hypothyroidism, as well as subacute ischemic infarction. A wide variety of conditions may be associated with cerebral hyperfixation of HMPAO. These conditions include neurologic and psychiatric diagnoses, and extend the consideration of hyperfixation beyond ischemic infarction. Consequently, a differential diagnosis of HMPAO hyperfixation may be broader than originally considered, and this may suggest a fundamental role for local cerebral hyperperfusion. Elucidation of the fundamental mechanism(s) for cerebral hyperperfusion requires further investigation.

  20. Terahertz time-domain spectroscopy response of amines and amino acids intercalated smectites in far-infrared region

    Energy Technology Data Exchange (ETDEWEB)

    Janek, M., E-mail: marian.janek@fns.uniba.sk [Comenius University, Faculty of Natural Sciences, Department of Physical and Theoretical Chemistry, Mlynská dolina CH1, SK-84215 Bratislava (Slovakia); Zich, D. [Comenius University, Faculty of Natural Sciences, Department of Physical and Theoretical Chemistry, Mlynská dolina CH1, SK-84215 Bratislava (Slovakia); Naftaly, M., E-mail: mira.naftaly@npl.co.uk [National Physical Laboratory, Hampton Rd, Teddington, Middlesex TW11 0LW (United Kingdom)

    2014-06-01

    Layered clay minerals from the smectite group with different chemical composition and resulting layer charge (e.g. pyrophyllite, illite, hectorite and montmorillonite) were characterised for their dielectric properties in the far-infrared region using terahertz-time domain spectroscopy (THz-TDS). Samples with distinct cation exchange capacity such as hectorite and montmorillonite were modified using cation exchange reaction with alkylamines or amino acids. The presence of these species in 2D gallery was proved by X-ray diffraction and Fourier transform infrared spectroscopy. The frequency-dependent refractive index of these minerals was determined in the experimentally accessible range of 0.1–3.0 THz (3–100 cm{sup −1}) using THz-TDS. Pristine samples revealed their refractive indices to be 1.82–2.15 at about 1 THz while the modified montmorillonite samples had their refractive indices changed by organic molecules used for their modification to 1.70–2.35 for amines and 1.97–2.36 for amino acids. The presence of organic substances in 2D gallery of clays was detectable despite the relatively high absorption of smectites with magnitude of 100 cm{sup −1}. - Graphical abstract: Display Omitted - Highlights: • “Guest” molecules in “host” layered material were investigated. • Amines and amino-acids were selected as guest molecules. • Natural and synthetic host with smectite phyllosilicate structure were used. • Dielectric properties were investigated by terahertz time domain spectroscopy. • Resonance absorption peaks of guest were detected in far infrared region.

  1. Differential Regulation of Disheveled in a Novel Vegetal Cortical Domain in Sea Urchin Eggs and Embryos: Implications for the Localized Activation of Canonical Wnt Signaling

    Science.gov (United States)

    Peng, ChiehFu Jeff; Wikramanayake, Athula H.

    2013-01-01

    Pattern formation along the animal-vegetal (AV) axis in sea urchin embryos is initiated when canonical Wnt (cWnt) signaling is activated in vegetal blastomeres. The mechanisms that restrict cWnt signaling to vegetal blastomeres are not well understood, but there is increasing evidence that the egg’s vegetal cortex plays a critical role in this process by mediating localized “activation” of Disheveled (Dsh). To investigate how Dsh activity is regulated along the AV axis, sea urchin-specific Dsh antibodies were used to examine expression, subcellular localization, and post-translational modification of Dsh during development. Dsh is broadly expressed during early sea urchin development, but immunolocalization studies revealed that this protein is enriched in a punctate pattern in a novel vegetal cortical domain (VCD) in the egg. Vegetal blastomeres inherit this VCD during embryogenesis, and at the 60-cell stage Dsh puncta are seen in all cells that display nuclear β-catenin. Analysis of Dsh post-translational modification using two-dimensional Western blot analysis revealed that compared to Dsh pools in the bulk cytoplasm, this protein is differentially modified in the VCD and in the 16-cell stage micromeres that partially inherit this domain. Dsh localization to the VCD is not directly affected by disruption of microfilaments and microtubules, but unexpectedly, microfilament disruption led to degradation of all the Dsh pools in unfertilized eggs over a period of incubation suggesting that microfilament integrity is required for maintaining Dsh stability. These results demonstrate that a pool of differentially modified Dsh in the VCD is selectively inherited by the vegetal blastomeres that activate cWnt signaling in early embryos, and suggests that this domain functions as a scaffold for localized Dsh activation. Localized cWnt activation regulates AV axis patterning in many metazoan embryos. Hence, it is possible that the VCD is an evolutionarily conserved

  2. Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Jitendra Maharana

    Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

  3. Short forms of the Utrecht-Management of Identity Commitments Scale (U-MICS) with the domains of job, romantic relationship, and region.

    Science.gov (United States)

    Schubach, Elisabeth; Zimmermann, Julia; Noack, Peter; Neyer, Franz J

    2017-01-01

    The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (n Sample1  = 95, 84% female, mean age 22.45 years; n Sample2  = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  4. Major Chromosomal Breakpoint Intervals in Breast Cancer Co-Localize with Differentially Methylated Regions

    Energy Technology Data Exchange (ETDEWEB)

    Eric Tang, Man-Hung [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Varadan, Vinay; Kamalakaran, Sitharthan [Philips Research North America, Briarcliff Manor, NY (United States); Zhang, Michael Q. [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); The University of Texas at Dallas, Richardson, TX (United States); Tsinghua University, Beijing (China); Dimitrova, Nevenka, E-mail: nevenka.dimitrova@philips.com [Philips Research North America, Briarcliff Manor, NY (United States); Hicks, James, E-mail: hicks@cshl.edu [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States)

    2012-12-27

    Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple chromosomal loci (copy number variation, or CNV), and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape, the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation, but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls (Wiedswang et al., 2003), where each sample has both high-resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions (DMR), coupled with additional genomic parameters, such as repeat elements and designated “fragile sites” in the reference genome. Through this analysis, we have identified a set of 93 regional loci called breakpoint enriched DMR (BEDMRs) characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1 Mb. BEDMR loci are further associated with local hypomethylation (66%), concentrations of the Alu SINE repeats within 3 Mb (35% of the cases), and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. Furthermore, BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors, e.g., JMJD1B, which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA

  5. Lutein Is Differentially Deposited across Brain Regions following Formula or Breast Feeding of Infant Rhesus Macaques.

    Science.gov (United States)

    Jeon, Sookyoung; Ranard, Katherine M; Neuringer, Martha; Johnson, Emily E; Renner, Lauren; Kuchan, Matthew J; Pereira, Suzette L; Johnson, Elizabeth J; Erdman, John W

    2018-01-01

    Lutein, a yellow xanthophyll, selectively accumulates in primate retina and brain. Lutein may play a critical role in neural and retinal development, but few studies have investigated the impact of dietary source on its bioaccumulation in infants. We explored the bioaccumulation of lutein in infant rhesus macaques following breastfeeding or formula-feeding. From birth to 6 mo of age, male and female rhesus macaques (Macaca mulatta) were either breastfed (BF) (n = 8), fed a formula supplemented with lutein, zeaxanthin, β-carotene, and lycopene (237, 19.0, 74.2, and 338 nmol/kg, supplemented formula-fed; SF) (n = 8), or fed a formula with low amounts of these carotenoids (38.6, 2.3, 21.5, and 0 nmol/kg, unsupplemented formula-fed; UF) (n = 7). The concentrations of carotenoids in serum and tissues were analyzed by HPLC. At 6 mo of age, the BF group exhibited significantly higher lutein concentrations in serum, all brain regions, macular and peripheral retina, adipose tissue, liver, and other tissues compared to both formula-fed groups (P Lutein concentrations were higher in the SF group than in the UF group in serum and all tissues, with the exception of macular retina. Lutein was differentially distributed across brain areas, with the highest concentrations in the occipital cortex, regardless of the diet. Zeaxanthin was present in all brain regions but only in the BF infants; it was present in both retinal regions in all groups but was significantly enhanced in BF infants compared to either formula group (P lutein concentrations compared to unsupplemented formula, concentrations were still well below those in BF infants. Regardless of diet, occipital cortex showed selectively higher lutein deposition than other brain regions, suggesting lutein's role in visual processing in early life. © 2018 American Society for Nutrition. All rights reserved.

  6. Differentiated parietal connectivity of frontal regions for "what" and "where" memory.

    Science.gov (United States)

    Rottschy, C; Caspers, S; Roski, C; Reetz, K; Dogan, I; Schulz, J B; Zilles, K; Laird, A R; Fox, P T; Eickhoff, S B

    2013-11-01

    In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann's area BA 44). As similar locations have been discussed as part of a dorsal frontal-superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related "what" and "where" processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may

  7. Annual Precipitation Fluctuation and Spatial Differentiation Characteristics of the Horqin Region

    Directory of Open Access Journals (Sweden)

    Liangxu Liu

    2017-01-01

    Full Text Available Precipitation is the main water source for vegetation survival in arid and semi-arid areas. However, previous studies always focus on the effects of precipitation in different time scales, but ignore the effects of precipitation in different spatial scales. To further study the effects of precipitation fluctuation in different spatial scales, we used the wavelet analysis method to analyze its temporal and spatial change based on data from eighteen meteorological stations during 1961–2015 in Horqin region. Results showed that: (1 from the overall tendency of precipitation changes, the precipitation inter-annual variations in Horqin region had the tendency of gradually decreasing from the southeast (District IV to the northwest; (2 the precipitation anomalies of District I–IV between 1960 and 1980 were small and approximate to the normal value; (3 in the time scale of 23–32 years, the cyclical fluctuations were very significant and the annual precipitation underwent two cyclical fluctuations from a period of low precipitation to a period of high precipitation; and (4 as results of analyzing the spatial wavelet variance of sub-region, the main cycle of precipitation in District I, District II and District III was between 10 and 11 years, while the main cycle of precipitation in District IV was 25 years. The main conclusions include the following. (1 This region tended to be arid, and the precipitation gradually decreased from the southeast (District IV to northwest (District I. (2 The influence of spatial differentiation characteristics on precipitation fluctuation in this region was cyclical fluctuation, which gradually decreased from the southeast to the northwest. The length of the cyclical change period gradually shortened. In the first main cycle, whose annual precipitation changes were most significant, the changing characteristic was District IV and District I decreased from 25 years to 10 years. (3 Predicated from the cyclical

  8. KCNK10, a Tandem Pore Domain Potassium Channel, Is a Regulator of Mitotic Clonal Expansion during the Early Stage of Adipocyte Differentiation

    Directory of Open Access Journals (Sweden)

    Makoto Nishizuka

    2014-12-01

    Full Text Available KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. We also demonstrated that KCNK10 functions as a positive regulator of mitotic clonal expansion (MCE, a necessary process for terminal differentiation. The reduction of kcnk10 expression repressed the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ and C/EBPδ as well as the phosphorylation level of Akt during the early phase of adipogenesis. In addition, knockdown of kcnk10 expression suppressed insulin-induced Akt phosphorylation. These results indicate that KCNK10 contributes to the regulation of MCE through the control of C/EBPβ and C/EBPδ expression and insulin signaling.

  9. Differential Cytotoxic Activity of Essential Oil of Lippia citriodora from Different Regions in Morocco.

    Science.gov (United States)

    Oukerrou, Moulay Ali; Tilaoui, Mounir; Mouse, Hassan Ait; Bouchmaa, Najat; Zyad, Abdelmajid

    2017-07-01

    The aim of this work was to investigate the cytotoxic effect of the essential oil of dried leaves of Lippia citriodora (H.B. & K.) harvested in different regions of Morocco. This effect was evaluated against the P815 murine mastocytoma cell line using the MTT assay. Interestingly, this work demonstrated for the first time that these essential oils exhibited a strong cytotoxic activity against the P815 cell line, with IC 50 values ranging from 7.75 to 13.25 μg/ml. This cytotoxicity began early and increased in a dose- and time-dependent manner. The chemical profile of these essential oils was analyzed by gas chromatography coupled to mass spectrometry. Importantly, the difference in terms of major components' contents was not significant suggesting probably that the differential cytotoxicity between these essential oils could be attributed to the difference in the content of these essential oils in minor compounds, which could interact with each other or with the main molecules. Finally, this study demonstrated for the first time that essential oils of L. citriodora from different regions in Morocco induced apoptosis against P815 tumor cell line. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  10. A novel method for identification and quantification of consistently differentially methylated regions.

    Directory of Open Access Journals (Sweden)

    Ching-Lin Hsiao

    Full Text Available Advances in biotechnology have resulted in large-scale studies of DNA methylation. A differentially methylated region (DMR is a genomic region with multiple adjacent CpG sites that exhibit different methylation statuses among multiple samples. Many so-called "supervised" methods have been established to identify DMRs between two or more comparison groups. Methods for the identification of DMRs without reference to phenotypic information are, however, less well studied. An alternative "unsupervised" approach was proposed, in which DMRs in studied samples were identified with consideration of nature dependence structure of methylation measurements between neighboring probes from tiling arrays. Through simulation study, we investigated effects of dependencies between neighboring probes on determining DMRs where a lot of spurious signals would be produced if the methylation data were analyzed independently of the probe. In contrast, our newly proposed method could successfully correct for this effect with a well-controlled false positive rate and a comparable sensitivity. By applying to two real datasets, we demonstrated that our method could provide a global picture of methylation variation in studied samples. R source codes to implement the proposed method were freely available at http://www.csjfann.ibms.sinica.edu.tw/eag/programlist/ICDMR/ICDMR.html.

  11. Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

    DEFF Research Database (Denmark)

    Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

    2004-01-01

    CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163...... truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...

  12. Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain.

    Science.gov (United States)

    Tiwari, Vivek; Veeraiah, Pandichelvam; Subramaniam, Vaidyanathan; Patel, Anant Bahadur

    2014-03-01

    This study investigates the effects of ethanol on neuronal and astroglial metabolism using (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of [1,6-(13)C2]/[1-(13)C]glucose or [2-(13)C]acetate, respectively. A three-compartment metabolic model was fitted to the (13)C turnover of GluC3 , GluC4, GABAC 2, GABAC 3, AspC3 , and GlnC4 from [1,6-(13)C2 ]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady-state [2-(13)C]acetate experiment and used as constraints during the metabolic model fitting. (1)H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. GlnC4 labeling was found to be unchanged from a 15 min infusion of [2-(13)C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain. Depletion of ethanol and its effect on brain functions were measured using (1)H and (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of (13)C-labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain. © 2013 International Society for Neurochemistry.

  13. A Steady Flow Model for the Differential Emission Measure in the Solar Quiet Region

    Science.gov (United States)

    Bong, S.; Chae, J.; Yun, H.; Lee, J.

    2001-05-01

    With high quality UV spectroscopy from the SoHO spacecraft, the physical structure of the solar Transition Region (TR) is of renewed interest. We have investigated the thermodynamic structure of the TR using a one dimensional magnetic tube model constrained to Raymond & Doyle's Differential Emission Measure (DEM) in the average quiet sun. We have included the effect of the expansion of magnetic flux tube and a heating which is required in addition to conductive heat, convective energy and radiative cooling. From the resulting heating and flux tube geometry, we also investigated upflows probable in the transition region. To reproduce the Doppler shift of UV lines measured using SoHO/SUMER (Chae, Yun, & Poland 1998), flux tube needs to expand rapidly above T=105 K at a rate of radius increase up to (7.4x 10-2 km-1)~ r4.1 where r4.1 is the radius at log T = 4.1. To balance the energy, an energy supply by more than (9.3x 104 erg cm-2 s-1)~π r4.12 is required at the region between 1.3x 104 K and 2.5x 104 K regardless of filling factor, suggesting a local heating in the chromosphere. As for upflows, in subsonic flow cases, a model with the same additional energy loss as in a downflow is probable. Also, supersonic flows could be easily made and, in this case, supersonic upflows could carry extra energy to corona without increasing DEM, showing the possibility that upflows play a role in corona heating. This work was supported by the Basic Science Research Institute Program, Ministry of Education (BSRI-98-5408) and by the BK21 Project of the Korean Government.

  14. Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

    Science.gov (United States)

    Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

    2017-02-01

    Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

  15. Genome-wide Anaplasma phagocytophilum AnkA-DNA interactions are enriched in intergenic regions and gene promoters and correlate with infection-induced differential gene expression.

    Directory of Open Access Journals (Sweden)

    J Stephen Dumler

    2016-09-01

    Full Text Available Anaplasma phagocytophilum, an obligate intracellular prokaryote, infects neutrophils and alters cardinal functions via reprogrammed transcription. Large contiguous regions of neutrophil chromosomes are differentially expressed during infection. Secreted A. phagocytophilum effector AnkA transits into the neutrophil or granulocyte nucleus to complex with DNA in heterochromatin across all chromosomes. AnkA binds to gene promoters to dampen cis-transcription and also has features of matrix attachment region (MAR-binding proteins that regulate three-dimensional chromatin architecture and coordinate transcriptional programs encoded in topologically-associated chromatin domains. We hypothesize that identification of additional AnkA binding sites will better delineate how A. phagocytophilum infection results in reprogramming of the neutrophil genome. Using AnkA-binding ChIP-seq, we showed that AnkA binds broadly throughout all chromosomes in a reproducible pattern, especially at: i intergenic regions predicted to be matrix attachment regions (MARs; ii within predicted lamina-associated domains; and iii at promoters ≤3,000 bp upstream of transcriptional start sites. These findings provide genome-wide support for AnkA as a regulator of cis-gene transcription. Moreover, the dominant mark of AnkA in distal intergenic regions known to be AT-enriched, coupled with frequent enrichment in the nuclear lamina, provides strong support for its role as a MAR-binding protein and genome re-organizer. AnkA must be considered a prime candidate to promote neutrophil reprogramming and subsequent functional changes that belie improved microbial fitness and pathogenicity.

  16. Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

    Science.gov (United States)

    Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J; Rick, Jacqueline; Gross, Rachel G; Nasrallah, Ilya M; Van Deerlin, Vivianna M; Trojanowski, John Q; Chen-Plotkin, Alice S; Hurtig, Howard I; Siderowf, Andrew D; Dubroff, Jacob G; Weintraub, Daniel

    2017-01-01

    Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

  17. Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

    Directory of Open Access Journals (Sweden)

    Rizwan S Akhtar

    Full Text Available Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2% were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%. Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

  18. Hypodense regions (holes) in the retinal nerve fiber layer in frequency-domain OCT scans of glaucoma patients and suspects.

    Science.gov (United States)

    Xin, Daiyan; Talamini, Christine L; Raza, Ali S; de Moraes, Carlos Gustavo V; Greenstein, Vivienne C; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

    2011-09-09

    To better understand hypodense regions (holes) that appear in the retinal nerve fiber layer (RNFL) of frequency-domain optical coherence tomography (fdOCT) scans of patients with glaucoma and glaucoma suspects. Peripapillary circle (1.7-mm radius) and cube optic disc fdOCT scans were obtained on 208 eyes from 110 patients (57.4 ± 13.2 years) with glaucomatous optic neuropathy (GON) and 45 eyes of 45 controls (48.0 ± 12.6 years) with normal results of fundus examination. Holes in the RNFL were identified independently by two observers on the circle scans. Holes were found in 33 (16%) eyes of 28 (25%) patients; they were not found in any of the control eyes. Twenty-four eyes had more than one hole. Although some holes were relatively large, others were small. In general, the holes were located adjacent to blood vessels; only three eyes had isolated holes that were not adjacent to a vessel. The holes tended to be in the regions that are thickest in healthy controls and were associated with arcuate defects in patients. Holes were not seen in the center of the temporal disc region. They were more common in the superior (25 eyes) than in the inferior (15 eyes) disc. Of the 30 eyes with holes with reliable visual fields, seven were glaucoma suspect eyes with normal visual fields. The holes in the RNFL seen in patients with GON were probably due to a local loss of RNFL fibers and can occur in the eyes of glaucoma suspects with normal visual fields.

  19. Insights into amyloid-like aggregation of H2 region of the C-terminal domain of nucleophosmin.

    Science.gov (United States)

    Russo, Anna; Diaferia, Carlo; La Manna, Sara; Giannini, Cinzia; Sibillano, Teresa; Accardo, Antonella; Morelli, Giancarlo; Novellino, Ettore; Marasco, Daniela

    2017-02-01

    Nucleophosmin (NPM1) is a multifunctional protein involved in a variety of biological processes including the pathogenesis of several human malignancies and is the most frequently mutated gene in Acute Myeloid Leukemia (AML). To deepen the role of protein regions in its biological activities, lately we reported on the structural behavior of dissected C-terminal domain (CTD) helical fragments. Unexpectedly the H2 (residues 264-277) and H3 AML-mutated regions showed a remarkable tendency to form amyloid-like assemblies with fibrillar morphology and β-sheet structure that resulted as toxic when exposed to human neuroblastoma cells. More recently NPM1 was found to be highly expressed and toxic in neurons of mouse models of Huntington's disease (HD). Here we investigate the role of each residue in the β-strand aggregation process of H2 region of NPM1 by performing a systematic alanine scan of its sequence and structural and kinetic analyses of aggregation of derived peptides by means of Circular Dichorism (CD) and Thioflavin T (Th-T) assay. These solution state investigations pointed out the crucial role exerted by the basic amyloidogenic stretch of H2 (264-271) and to shed light on the initial and main interactions involved in fibril formation we performed studies on fibrils deriving from the related Ala peptides through the analysis of fibrils with birefringence of polarized optical microscopy and wide-angle X-ray scattering (WAXS). This analysis suggested that the presence of branched Ile 269 conferred preferential packing patterns that, instead, appeared geometrically hampered by the aromatic side-chain of Phe 268 . Present investigations could be useful to deepen the knowledge of AML molecular mechanisms and the role of cytoplasmatic aggregates of NPM1c+. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions.

    Science.gov (United States)

    Wiech, K; Jbabdi, S; Lin, C S; Andersson, J; Tracey, I

    2014-10-01

    Functional neuroimaging studies suggest that the anterior, mid, and posterior division of the insula subserve different functions in the perception of pain. The anterior insula (AI) has predominantly been associated with cognitive-affective aspects of pain, while the mid and posterior divisions have been implicated in sensory-discriminative processing. We examined whether this functional segregation is paralleled by differences in (1) structural and (2) resting state connectivity and (3) in correlations with pain-relevant psychological traits. Analyses were restricted to the 3 insular subdivisions and other pain-related brain regions. Both type of analyses revealed largely overlapping results. The AI division was predominantly connected to the ventrolateral prefrontal cortex (structural and resting state connectivity) and orbitofrontal cortex (structural connectivity). In contrast, the posterior insula showed strong connections to the primary somatosensory cortex (SI; structural connectivity) and secondary somatosensory cortex (SII; structural and resting state connectivity). The mid insula displayed a hybrid connectivity pattern with strong connections with the ventrolateral prefrontal cortex, SII (structural and resting state connectivity) and SI (structural connectivity). Moreover, resting state connectivity revealed strong connectivity of all 3 subdivisions with the thalamus. On the behavioural level, AI structural connectivity was related to the individual degree of pain vigilance and awareness that showed a positive correlation with AI-amygdala connectivity and a negative correlation with AI-rostral anterior cingulate cortex connectivity. In sum, our findings show a differential structural and resting state connectivity for the anterior, mid, and posterior insula with other pain-relevant brain regions, which might at least partly explain their different functional profiles in pain processing. Copyright © 2014 The Authors. Published by Elsevier B.V. All

  1. The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

    2016-01-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  2. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  3. Temperature sensitivity of differential absorption lidar measurements of water vapor in the 720-nm region

    Science.gov (United States)

    Browell, Edward V.; Ismail, Syed; Grossmann, Benoist E.

    1991-01-01

    Recently measured properties of water vapor (H2O) absorption lines have been used in calculations to evalute the temperature sensitivity of differential absorption lidar (Dial) H2O measurements. This paper estimates the temperature sensitivity of H2O lines in the 717-733-nm region for both H2O mixing ratio and number density measurements, and discusses the influence of the H2O line ground state energies E-double-prime, the H2O absorption linewidths, the linewidth temperature dependence parameter, and the atmospheric temperature and pressure variations with altitude and location on the temperature sensitivity calculations. Line parameters and temperature sensitivity calculations for 67 H2O lines in the 720-nm band are given which can be directly used in field experiments. Water vapor lines with E-double-prime values in the 100-300/cm range were found to be optimum for Dial measurements of H2O number densities, while E-double-prime values in the 250-500/cm range were found to be optimum for H2O mixing ratio measurements.

  4. Water vapor spectroscopy in the 815-nm wavelength region for Differential Absorption Lidar measurements

    Science.gov (United States)

    Ponsardin, Patrick; Browell, Edward V.

    1995-01-01

    The differential absorption lidar (DIAL) technique was first applied to the remote measurement of atmospheric water vapor profiles from airborne platforms in 1981. The successful interpretation of the lidar profiles relies strongly on an accurate knowledge of specific water vapor absorption line parameters: line strength, pressure broadening coefficient, pressure-induced shift coefficient and the respective temperature-dependence factors. NASA Langley Research Center has developed and is currently testing an autonomous airborne water vapor lidar system: LASE (Lidar Atmospheric Sensing Experiment). This DIAL system uses a Nd:YAG-pumped Ti:Sapphire laser seeded by a diode laser as a lidar transmitter. The tunable diode has been selected to operate in the 813-818 nm wavelength region. This 5-nm spectral interval offers a large distribution of strengths for temperature-insensitive water vapor absorption lines. In support of the LASE project, a series of spectroscopic measurements were conducted for the 16 absorption lines that have been identified for use in the LASE measurements. Prior to this work, the experimental data for this water vapor absorption band were limited - to our knowledge - to the line strengths and to the line positions.

  5. Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

    International Nuclear Information System (INIS)

    Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun

    2016-01-01

    The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

  6. Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun, E-mail: tztong@bjmu.edu.cn

    2016-01-15

    The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

  7. Hard-magnetic surface layer effect on the erbium orthoferrite plate domain structure in the region of gradual spin reorientation

    International Nuclear Information System (INIS)

    Belyaeva, A.I.; Vojtsenya, S.V.; Yur'ev, V.P.

    1988-01-01

    Rearrangement of domain structures in the erbium orthoferrite plates with hard-magnetic surface layer is investigated during gradual spin reorientation. This phenomenon is explained by means of the proposed physical models. It is shown that in these plates an approach to the temperature interval of spin reorientation causes a decrease in the density of energy of domain walls separating the internal and surface domains. This decrease results in transition to the domain structure which are close to equilibrium ones inside the crystal. 30 refs.; 4 figs

  8. Primary (Poorly Differentiated Sclerosing Liposarcoma of Temporal Region. An Uncommon Tumor in a Rare Site: A Case Report

    Directory of Open Access Journals (Sweden)

    Anuradha CK Rao

    2015-02-01

    Full Text Available Liposarcoma (LS in the head and neck region is a rare tumor. The sclerosing variant of LS is a subtype of well-differentiated LS characterized by areas of conventional LS admixed with hypocellular areas of stromal sclerosis that show atypical lipomatous cells. The (poorly differentiated sclerosing LS, on the other hand, is more cellular with atypical, pleomorphic and often bizarre giant tumor cells admixed with atypical lipoblasts. We report a case of poorly differentiated sclerosing LS of temporal region in a 49-year-old man. Radiologically, the tumor was dumbbell shaped with intra and extra cranial extension. In this case, we discuss the clinico-radiological and pathological findings of an unusual tumor in a rare location. [J Interdiscipl Histopathol 2015; 3(1.000: 33-35

  9. C-terminal region of MAP7 domain containing protein 3 (MAP7D3 promotes microtubule polymerization by binding at the C-terminal tail of tubulin.

    Directory of Open Access Journals (Sweden)

    Saroj Yadav

    Full Text Available MAP7 domain containing protein 3 (MAP7D3, a newly identified microtubule associated protein, has been shown to promote microtubule assembly and stability. Its microtubule binding region has been reported to consist of two coiled coil motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus and belongs to the microtubule associated protein 7 (MAP7 family. The MAP7 domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to microtubules as well as enhanced the assembly of microtubules in vitro. Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD with the C-terminal tail (CT of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. MDCT stabilized microtubules against dilution induced disassembly. MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0 ± 0.5 µM. An immunostaining experiment showed that MDCT localized along the length of the preassembled microtubules. Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. Further, we present evidence indicating that MDCT binds to the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa cell extract. Here, we report a microtubule binding region in the C-terminal region of MAP7D3 that may have a role in regulating microtubule assembly dynamics.

  10. Insights into function of PSI domains from structure of the Met receptor PSI domain

    International Nuclear Information System (INIS)

    Kozlov, Guennadi; Perreault, Audrey; Schrag, Joseph D.; Park, Morag; Cygler, Miroslaw; Gehring, Kalle; Ekiel, Irena

    2004-01-01

    PSI domains are cysteine-rich modules found in extracellular fragments of hundreds of signaling proteins, including plexins, semaphorins, integrins, and attractins. Here, we report the solution structure of the PSI domain from the human Met receptor, a receptor tyrosine kinase critical for proliferation, motility, and differentiation. The structure represents a cysteine knot with short regions of secondary structure including a three-stranded antiparallel β-sheet and two α-helices. All eight cysteines are involved in disulfide bonds with the pattern consistent with that for the PSI domain from Sema4D. Comparison with the Sema4D structure identifies a structurally conserved core comprising the N-terminal half of the PSI domain. Interestingly, this part links adjacent SEMA and immunoglobulin domains in the Sema4D structure, suggesting that the PSI domain serves as a wedge between propeller and immunoglobulin domains and is responsible for the correct positioning of the ligand-binding site of the receptor

  11. Understanding and simulating the link between African easterly waves and Atlantic tropical cyclones using a regional climate model: the role of domain size and lateral boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Caron, Louis-Philippe [MISU, Stockholm University, Stockholm (Sweden); Universite du Quebec a Montreal, CRCMD Network, Montreal, QC (Canada); Jones, Colin G. [Swedish Meterological and Hydrological Institute, Rossby Center, Norrkoeping (Sweden)

    2012-07-15

    Using a suite of lateral boundary conditions, we investigate the impact of domain size and boundary conditions on the Atlantic tropical cyclone and african easterly Wave activity simulated by a regional climate model. Irrespective of boundary conditions, simulations closest to observed climatology are obtained using a domain covering both the entire tropical Atlantic and northern African region. There is a clear degradation when the high-resolution model domain is diminished to cover only part of the African continent or only the tropical Atlantic. This is found to be the result of biases in the boundary data, which for the smaller domains, have a large impact on TC activity. In this series of simulations, the large-scale Atlantic atmospheric environment appears to be the primary control on simulated TC activity. Weaker wave activity is usually accompanied by a shift in cyclogenesis location, from the MDR to the subtropics. All ERA40-driven integrations manage to capture the observed interannual variability and to reproduce most of the upward trend in tropical cyclone activity observed during that period. When driven by low-resolution global climate model (GCM) integrations, the regional climate model captures interannual variability (albeit with lower correlation coefficients) only if tropical cyclones form in sufficient numbers in the main development region. However, all GCM-driven integrations fail to capture the upward trend in Atlantic tropical cyclone activity. In most integrations, variations in Atlantic tropical cyclone activity appear uncorrelated with variations in African easterly wave activity. (orig.)

  12. Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

    International Nuclear Information System (INIS)

    Rumbajan, Janette Mareska; Aoki, Shigehisa; Kohashi, Kenichi; Oda, Yoshinao; Hata, Kenichiro; Saji, Tsutomu; Taguchi, Tomoaki; Tajiri, Tatsuro; Soejima, Hidenobu; Joh, Keiichiro; Maeda, Toshiyuki; Souzaki, Ryota; Mitsui, Kazumasa; Higashimoto, Ken; Nakabayashi, Kazuhiko; Yatsuki, Hitomi; Nishioka, Kenichi; Harada, Ryoko

    2013-01-01

    Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma

  13. Aerosol modelling for regional climate studies: application to anthropogenic particles and evaluation over a European/African domain

    International Nuclear Information System (INIS)

    Solmon, F.; Giorgi, F.; Liousse, C.

    2006-01-01

    A simplified anthropogenic aerosol model for use in climate studies is developed and implemented within the regional climate model RegCM. The model includes sulphur dioxide, sulphate, hydrophobic and hydrophilic black carbon (BC) and organic carbon (OC) and is run for the winter and summer seasons of 2000 over a large domain extending from northern Europe to south tropical Africa. An evaluation of the model performance is carried out in terms of surface concentrations and aerosol optical depths (AODs). For sulphur dioxide and sulphate concentration, comparison of simulated fields and experimental data collected over the EMEP European network shows that the model generally reproduces the observed spatial patterns of near-surface sulphate. Sulphate concentrations are within a factor of 2 of observations in 34% (JJA) to 57% (DJF) of cases. For OC and BC, simulated concentrations are compared to different datasets. The simulated and observed values agree within a factor of 2 in 56% (DJF) to 62% (JJA) of cases for BC and 33% (JJA) to 64% (DJF) for OC. Simulated AODs are compared with ground-based (AERONET) and satellite (MODIS, MISR, TOMS) AOD datasets. Simulated AODs are in the range of AERONET and MISR data over northern Europe, and AOD spatial patterns show consistency with MODIS and TOMS retrievals both over Europe and Africa. The main model deficiencies we find are: (i) an underestimation of surface concentrations of sulphate and OC during the summer and especially over the Mediterranean region and (ii) a general underestimation of AOD, most pronounced over the Mediterranean basin. The primary factors we identify as contributing to these biases are the lack of natural aerosols (in particular, desert dust, secondary biogenic aerosols and nitrates), uncertainties in the emission inventories and aerosol cycling by moist convection. Also, in view of the availability of better observing datasets (e.g. as part of the AMMA project), we are currently working on improving

  14. Differential neutralizing activities of a single domain camelid antibody (VHH specific for ricin toxin's binding subunit (RTB.

    Directory of Open Access Journals (Sweden)

    Cristina Herrera

    Full Text Available Ricin, a member of the A-B family of ribosome-inactivating proteins, is classified as a Select Toxin by the Centers for Disease Control and Prevention because of its potential use as a biothreat agent. In an effort to engineer therapeutics for ricin, we recently produced a collection of alpaca-derived, heavy-chain only antibody VH domains (VHH or "nanobody" specific for ricin's enzymatic (RTA and binding (RTB subunits. We reported that one particular RTB-specific VHH, RTB-B7, when covalently linked via a peptide spacer to different RTA-specific VHHs, resulted in heterodimers like VHH D10/B7 that were capable of passively protecting mice against a lethal dose challenge with ricin. However, RTB-B7 itself, when mixed with ricin at a 1 ∶ 10 toxin:antibody ratio did not afford any protection in vivo, even though it had demonstrable toxin-neutralizing activity in vitro. To better define the specific attributes of antibodies associated with ricin neutralization in vitro and in vivo, we undertook a more thorough characterization of RTB-B7. We report that RTB-B7, even at 100-fold molar excess (toxin:antibody was unable to alter the toxicity of ricin in a mouse model. On the other hand, in two well-established cytotoxicity assays, RTB-B7 neutralized ricin with a 50% inhibitory concentration (IC50 that was equivalent to that of 24B11, a well-characterized and potent RTB-specific murine monoclonal antibody. In fact, RTB-B7 and 24B11 were virtually identical when compared across a series of in vitro assays, including adherence to and neutralization of ricin after the toxin was pre-bound to cell surface receptors. RTB-B7 differed from both 24B11 and VHH D10/B7 in that it was relatively less effective at blocking ricin attachment to receptors on host cells and was not able to form high molecular weight toxin:antibody complexes in solution. Whether either of these activities is important in ricin toxin neutralizing activity in vivo remains to be determined.

  15. Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC regulates inflammasomes

    Directory of Open Access Journals (Sweden)

    Rojanasakul Yon

    2010-05-01

    Full Text Available Abstract Background The apoptotic speck-like protein containing a caspase recruitment domain (ASC is the essential adaptor protein for caspase 1 mediated interleukin (IL-1β and IL-18 processing in inflammasomes. It bridges activated Nod like receptors (NLRs, which are a family of cytosolic pattern recognition receptors of the innate immune system, with caspase 1, resulting in caspase 1 activation and subsequent processing of caspase 1 substrates. Hence, macrophages from ASC deficient mice are impaired in their ability to produce bioactive IL-1β. Furthermore, we recently showed that ASC translocates from the nucleus to the cytosol in response to inflammatory stimulation in order to promote an inflammasome response, which triggers IL-1β processing and secretion. However, the precise regulation of inflammasomes at the level of ASC is still not completely understood. In this study we identified and characterized three novel ASC isoforms for their ability to function as an inflammasome adaptor. Methods To establish the ability of ASC and ASC isoforms as functional inflammasome adaptors, IL-1β processing and secretion was investigated by ELISA in inflammasome reconstitution assays, stable expression in THP-1 and J774A1 cells, and by restoring the lack of endogenous ASC in mouse RAW264.7 macrophages. In addition, the localization of ASC and ASC isoforms was determined by immunofluorescence staining. Results The three novel ASC isoforms, ASC-b, ASC-c and ASC-d display unique and distinct capabilities to each other and to full length ASC in respect to their function as an inflammasome adaptor, with one of the isoforms even showing an inhibitory effect. Consistently, only the activating isoforms of ASC, ASC and ASC-b, co-localized with NLRP3 and caspase 1, while the inhibitory isoform ASC-c, co-localized only with caspase 1, but not with NLRP3. ASC-d did not co-localize with NLRP3 or with caspase 1 and consistently lacked the ability to function as an

  16. Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.

    Science.gov (United States)

    Runge, Steffen; Schimmer, Susann; Oschmann, Jan; Schiødt, Christine Bruun; Knudsen, Sanne Möller; Jeppesen, Claus Bekker; Madsen, Kjeld; Lau, Jesper; Thøgersen, Henning; Rudolph, Rainer

    2007-05-15

    Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.

  17. Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

    DEFF Research Database (Denmark)

    Durkin, M E; Wewer, U M; Chung, A E

    1995-01-01

    of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF......Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from lambda genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization...

  18. SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region.

    Science.gov (United States)

    Sun, Yun; Sun, Li; Xing, Ming-qing; Liu, Chun-sheng; Hu, Yong-hua

    2013-11-12

    Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence-associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post-vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to the immunoprotective mechanism

  19. Precision and accuracy in CT attenuation measurement of vascular wall using region-of-interest supported by differentiation curve

    International Nuclear Information System (INIS)

    Suzuki, Shigeru; Kidouchi, Takashi; Kuwahara, Sadatoshi; Vembar, Mani; Takei, Ryoji; Yamamoto, Asako

    2012-01-01

    Objectives: To evaluate the precision and accuracy in CT attenuation measurement of vascular wall using region-of-interest (ROI) supported by differentiation curves. Study design: We used vascular models (actual attenuation value of the wall: 87 HU) with wall thicknesses of 1.5, 1.0, or 0.5 mm, filled with contrast material of 250, 348, or 436 HU. The nine vascular models were scanned with a 64-detector CT. The wall attenuation values were measured using three sizes (diameter: 0.5, 1.0, and 1.5 mm) of ROIs without differentiation curves. Sixteen measurements were repeated for each vascular model by each of two operators. Measurements supported by differentiation curves were also performed. We used analyses of variance with repeated measures for the measured attenuations for each size of the ROI. Results: Without differentiation curves, there were significant differences in the attenuation values of the wall among the three densities of contrast material, and the attenuation values tended to be overestimated more as the contrast material density increased. Operator dependencies were also found in measurements for 0.5- and 1.5-mm thickness models. With differentiation curves, measurements were not possible for 0.5- and 1.0-mm thickness models. Using differentiation curves for 1.5-mm thickness models with a ROI of 1.0- or 1.5-mm diameter, the wall attenuations were not affected by the contrast material densities and were operator independent, measuring between 75 and 103 HU. Conclusions: The use of differentiation curves can improve the precision and accuracy in wall attenuation measurement using a ROI technique, while measurements for walls of ≤1.0 mm thickness are difficult.

  20. Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix.

    Science.gov (United States)

    Rothrauff, Benjamin B; Shimomura, Kazunori; Gottardi, Riccardo; Alexander, Peter G; Tuan, Rocky S

    2017-02-01

    Extracellular matrix (ECM) derived from decellularized tissues has been found to promote tissue neogenesis, most likely mediated by specific biochemical and physical signaling motifs that promote tissue-specific differentiation of progenitor cells. Decellularized ECM has been suggested to be efficacious for the repair of tissue injuries. However, decellularized meniscus contains a dense collagenous structure, which impedes cell seeding and infiltration and is not readily applicable for meniscus repair. In addition, the meniscus consists of two distinct anatomical regions that differ in vascularity and cellular phenotype. The purpose of this study was to explore the region-specific bioactivity of solubilized ECM derived from the inner and outer meniscal regions as determined in 2D and 3D cultures of adult mesenchymal stem cells (MSCs). When added as a medium supplement to 2D cultures of MSCs, urea-extracted fractions of the inner (imECM) and outer meniscal ECM (omECM) enhanced cell proliferation while imECM most strongly upregulated fibrochondrogenic differentiation on the basis of gene expression profiles. When added to 3D cultures of MSCs seeded in photocrosslinked methacrylated gelatin (GelMA) hydrogels, both ECM fractions upregulated chondrogenic differentiation as determined by gene expression and protein analyses, as well as elevated sulfated glycosaminoglycan sGAG content, compared to ECM-free controls. The chondrogenic effect at day 21 was most pronounced with imECM supplementation, but equivalent between ECM groups by day 42. Despite increased cartilage matrix, imECM and omECM constructs possessed compressive moduli similar to controls. In conclusion, soluble meniscal ECM may be considered for use as a tissue-specific reagent to enhance chondrogenesis for MSC-based 3D cartilage tissue engineering. The inner region of the knee meniscus is frequently injured and possesses a poor intrinsic healing capacity. Solubilized extracellular matrix (ECM) derived from

  1. ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

    International Nuclear Information System (INIS)

    Wyrwicz, Lucjan S; Koczyk, Grzegorz; Rychlewski, Leszek; Plewczynski, Dariusz

    2007-01-01

    The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

  2. Four and a half domain 2 (FHL2) scaffolding protein is a marker of connective tissues of developing digits and regulates fibrogenic differentiation of limb mesodermal progenitors.

    Science.gov (United States)

    Lorda-Diez, C I; Montero, J A; Sanchez-Fernandez, C; Garcia-Porrero, J A; Chimal-Monroy, J; Hurle, J M

    2018-04-01

    Four and a half LIM domain 2 (FHL2) is a multifunctional scaffolding protein of well-known function regulating cell signalling cascades and gene transcription in cancer tissues. However, its function in embryonic systems is poorly characterized. Here, we show that Fhl2 is involved in the differentiation of connective tissues of developing limb autopod. We show that Fhl2 exhibits spatially restricted and temporally dynamic expression around the tendons of developing digits, interphalangeal joint capsules, and fibrous peridigital tissue. Immunolabelling analysis of the skeletal progenitors identified a predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated with focal adhesions and actin cytoskeleton. In the course of chondrogenic differentiation of cultures of limb skeletal progenitors, the expression of Fhl2 is down-regulated. Furthermore, cultures of skeletal progenitors overexpressing Fhl2 take on a predominant fibrogenic appearance. Both gain-of-function and loss-of-function experiments in the micromass culture assays revealed a positive transcriptional influence of Fhl2 in the expression of fibrogenic markers including Scleraxis, Tenomodulin, Tenascin C, βig-h3, and Tgif1. We further show that the expression of Fhl2 is positively regulated by profibrogenic signals including Tgfβ2, all-trans-retinoic acid, and canonical Wnt signalling molecules and negatively regulated by prochondrogenic factors of the bone morphogenetic protein family. Expression of Fhl2 is also regulated negatively in immobilized limbs, but this influence appears to be mediated by other connective tissue markers, such as Tgfβs and Scleraxis. Copyright © 2018 John Wiley & Sons, Ltd.

  3. Rational fraction application for continuation of differential cross sections of nuclear reactions into the nonphysical region

    International Nuclear Information System (INIS)

    Borbely, I.; Nichitiu, F.

    1975-01-01

    We propose to apply rational fraction approximations instead of polynomial ones for analytic continuation of the differential cross section. On the example of p-d scattering it is demonstrated that the spectroscopic in-formation extracted in this way is more reliable

  4. Genome-wide genetic diversity and differentially selected regions among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep.

    Directory of Open Access Journals (Sweden)

    Lifan Zhang

    Full Text Available Sheep are among the major economically important livestock species worldwide because the animals produce milk, wool, skin, and meat. In the present study, the Illumina OvineSNP50 BeadChip was used to investigate genetic diversity and genome selection among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep breeds from the United States. After quality-control filtering of SNPs (single nucleotide polymorphisms, we used 48,026 SNPs, including 46,850 SNPs on autosomes that were in Hardy-Weinberg equilibrium and 1,176 SNPs on chromosome × for analysis. Phylogenetic analysis based on all 46,850 SNPs clearly separated Suffolk from Rambouillet, Columbia, Polypay, and Targhee, which was not surprising as Rambouillet contributed to the synthesis of the later three breeds. Based on pair-wise estimates of F(ST, significant genetic differentiation appeared between Suffolk and Rambouillet (F(ST = 0.1621, while Rambouillet and Targhee had the closest relationship (F(ST = 0.0681. A scan of the genome revealed 45 and 41 differentially selected regions (DSRs between Suffolk and Rambouillet and among Rambouillet-related breed populations, respectively. Our data indicated that regions 13 and 24 between Suffolk and Rambouillet might be good candidates for evaluating breed differences. Furthermore, ovine genome v3.1 assembly was used as reference to link functionally known homologous genes to economically important traits covered by these differentially selected regions. In brief, our present study provides a comprehensive genome-wide view on within- and between-breed genetic differentiation, biodiversity, and evolution among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep breeds. These results may provide new guidance for the synthesis of new breeds with different breeding objectives.

  5. SPATIAL DIFFERENTIATION OF THE REGIONS OF UKRAINE CONCERNING THE KNOWLEDGE ECONOMY

    Directory of Open Access Journals (Sweden)

    Lesia Dmytryshyn

    2017-11-01

    Full Text Available The purpose of the research is a set of theoretical and methodological, methodical and applied provisions concerning the analysis of economic development built on knowledge (KE in the regions of Ukraine and also the determination of their integral estimation of KE development level. Methodology. The research methodology is based on a systematic approach, within which analysed KAM methodology (Knowledge Assessment Methodology developed by the World Bank, identified key groups of indicators, such as the general condition of regional economies, economic stimulus and the characteristics of the institutional system, innovation, R&D sector and informational infrastructure. Considered the key factors that determine the position of knowledge in the regional development, namely: the business community, the scientific environment and the system of self-government, which forms regional policy in the light of specific conditions of areas. The possibility of this methodology’s application in the regional aspect is determined. For the research are chosen all regions of Ukraine. Exceptions are temporarily occupied territory. Accordingly, histograms of each of the key indicators’ groups are built that help to determine the level of development of a particular region. Results. Established that the symbiosis of innovative potential with the unique economic mechanisms is the catalysts that enhance the development of the regional knowledge economy. This analysis helps to see social and economic differences between the regions of Ukraine. Determined that the characteristic feature is an inadequate level of funding of science, which causes the slowdown of innovation activity in the regions because of links imbalance between industry and research industry sector. In most cases, the regions occupied similar positions in different groups of indicators. This allows us to conclude that the development of the knowledge economy components in the region is balanced

  6. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

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

  7. Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

    Science.gov (United States)

    Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

    2012-11-01

    To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both Padvanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, Padvanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, Padvanced coronary plaques. © RSNA, 2012

  8. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells.

    Science.gov (United States)

    Fernández, Agustín F; Bayón, Gustavo F; Urdinguio, Rocío G; Toraño, Estela G; García, María G; Carella, Antonella; Petrus-Reurer, Sandra; Ferrero, Cecilia; Martinez-Camblor, Pablo; Cubillo, Isabel; García-Castro, Javier; Delgado-Calle, Jesús; Pérez-Campo, Flor M; Riancho, José A; Bueno, Clara; Menéndez, Pablo; Mentink, Anouk; Mareschi, Katia; Claire, Fabian; Fagnani, Corrado; Medda, Emanuela; Toccaceli, Virgilia; Brescianini, Sonia; Moran, Sebastián; Esteller, Manel; Stolzing, Alexandra; de Boer, Jan; Nisticò, Lorenza; Stazi, Maria A; Fraga, Mario F

    2015-01-01

    In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors. © 2015 Fernández et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Regionally differentiated air pollution control regulations in the installation-related emission control law of the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Buettner, T.W.

    1992-01-01

    The volume treats an issue from the boundary zone between environmental law and environmental economics, namely the regionalization of air pollution control standards in installation-related emission control law. In order to examine the question of whether this proposal, which originates in the field of environmental economics, can be adopted and is purposeful, the author initially performs a complete inventorization of applicable norms, this covering emission control law, the law of regional planning, and the provisions of international law. This status quo is then reviewed using conformity and optimization criteria developed by the political sciences. The assessment comes to the conclusion that the introduction of regionally differentiated air pollution control standards is not desirable. The author further submits proposals for the streamlining of the law of installation-related air pollution control in the Federal Republic of Germany. (orig.) [de

  10. Differential coincidence circuit in the 10-10 second region (1960)

    International Nuclear Information System (INIS)

    Van Zurk, R.; Grenoble-1 Univ., 38; Commissariat a l'Energie Atomique, Saclay

    1960-01-01

    A coincidence circuit of low resolution time using the differential coincidence Bay principle is described. It uses three 6BN6 tubes ordered to chronotron structure. Results with Radiotechnique 56 AVP photomultipliers and for 60 Co γ-γ coincidences are 4,6.10 -10 s (full width at half maximum) if the efficiency is ε = 40 per cent and also 7,2.10 -10 s if ε = 85 per cent. (author) [fr

  11. Differential Cross-Sections for pi- p --> gamma n in the First Resonance Region

    CERN Document Server

    Guex-Le Lan, Huong; Hilscher, H; Joseph, C L; Schmitt, H; Tran, M T; Truöl, P; Vaucher, B; Winkelmann, E; Zupancic, Crtomir; Joseph, C L no 1; Tran, M T no 1; Vaucher, B no 1; Winkelmann, E no 1; Bayer, W no 2; Hilscher, H no 2; Schmitt, H no 2; Zupancic, C no 2; Truöl, P no 3; Guex, L H no 1

    1975-01-01

    Differential cross-sections for negative pion radiative capture on protons at c.m. angles of 60°, 90°, and 120° have been measured at nine incident laboratory energies between 110 and 270 MeV. Comparison with measured cross-sections for pion photoproduction and with conventional multipole analyses shows neither evidence for a violation of time reversal invariance nor for an isotensor component of the electromagnetic current of hardrons. Record added 1974-09-01, las

  12. Oxidative Unfolding of the Rubredoxin Domain and the Natively Disordered N-terminal Region Regulate the Catalytic Activity of Mycobacterium tuberculosis Protein Kinase G.

    Science.gov (United States)

    Wittwer, Matthias; Luo, Qi; Kaila, Ville R I; Dames, Sonja A

    2016-12-30

    Mycobacterium tuberculosis escapes killing in human macrophages by secreting protein kinase G (PknG). PknG intercepts host signaling to prevent fusion of the phagosome engulfing the mycobacteria with the lysosome and, thus, their degradation. The N-terminal NORS (no regulatory secondary structure) region of PknG (approximately residues 1-75) has been shown to play a role in PknG regulation by (auto)phosphorylation, whereas the following rubredoxin-like metal-binding motif (RD, residues ∼74-147) has been shown to interact tightly with the subsequent catalytic domain (approximately residues 148-420) to mediate its redox regulation. Deletions or mutations in NORS or the redox-sensitive RD significantly decrease PknG survival function. Based on combined NMR spectroscopy, in vitro kinase assay, and molecular dynamics simulation data, we provide novel insights into the regulatory roles of the N-terminal regions. The NORS region is indeed natively disordered and rather dynamic. Consistent with most earlier data, autophosphorylation occurs in our assays only when the NORS region is present and, thus, in the NORS region. Phosphorylation of it results only in local conformational changes and does not induce interactions with the subsequent RD. Although the reduced, metal-bound RD makes tight interactions with the following catalytic domain in the published crystal structures, it can also fold in its absence. Our data further suggest that oxidation-induced unfolding of the RD regulates substrate access to the catalytic domain and, thereby, PknG function under different redox conditions, e.g. when exposed to increased levels of reactive oxidative species in host macrophages. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. EU COHESION POLICY NEEDS DIFFERENTIATED POLICY MIX ADEQUATE TO SPECIFICS OF ECONOMIC REGIONS

    Directory of Open Access Journals (Sweden)

    Gheorghe ZAMAN

    2008-06-01

    Full Text Available The 2007-2013 programming period of the EU focuses on economic and social cohesion via three fundamental objectives: convergence – competitiveness and employment – European territorial co-operation. The horizontal dimension of cohesion policy refers to diminishing the regional disparities and solidarity with the lagging regions’ population. Considering the big regional disparities in the New Member States (NMS as well as the gap between their GDP per capita at national level and the EU average, these countries are the main beneficiary of the EU financial allocations, especially via convergence objective. However, two interrelated questions are entailed by this issue. One of them refers to the capacity of these countries to absorb effectively the EU funds. The other one concentrates on the impact of the absorbed EU funds, in other words to the qualitative aspects of the absorption capacity. Our paper discusses these aspects mainly from the viewpoint of regional disparities in the NMS, proposing a typology of their regions based on the main regional growth characteristics. The implications of the structural assistance on regional disparities are also addressed, taking into consideration economic and social criteria and requirements at EU, national, regional and local levels.

  14. Hypothyroidism affects differentially the cell size of epithelial cells among oviductal regions of rabbits.

    Science.gov (United States)

    Anaya-Hernández, A; Rodríguez-Castelán, J; Nicolás, L; Martínez-Gómez, M; Jiménez-Estrada, I; Castelán, F; Cuevas, E

    2015-02-01

    Oviductal regions show particular histological characteristics and functions. Tubal pathologies and hypothyroidism are related to primary and secondary infertility. The impact of hypothyroidism on the histological characteristics of oviductal regions has been scarcely studied. Our aim was to analyse the histological characteristics of oviductal regions in control and hypothyroid rabbits. Hypothyroidism was induced by oral administration of methimazole (MMI) for 30 days. For both groups, serum concentrations of thyroid and gonadal hormones were determined. Sections of oviductal regions were stained with the Masson's trichrome technique to analyse both epithelial and smooth muscle layers. The percentage of proliferative epithelial cells (anti-Ki67) in diverse oviductal regions was also quantified. Data were compared with Student t-test, Mann-Whitney U-test, or Fischer's test. In comparison with the control group, the hypothyroid group showed: (i) a low concentration of T3 and T4, but a high level of TSH; (ii) similar values of serum estradiol, progesterone and testosterone; (iii) a large size of ciliated cells in the ampulla (AMP), isthmus (IST) and utero-tubal junction (UTJ); (iv) a large size of secretory cells in the IST region; (v) a low percentage of proliferative secretory cells in the fimbria-infundibulum (FIM-INF) region; and (vi) a similar thickness of the smooth muscle layer and the cross-sectional area in the AMP and IST regions. Modifications in the size of the oviductal epithelium in hypothyroid rabbits could be related to changes in the cell metabolism that may impact on the reproductive functions achieved by oviduct. © 2014 Blackwell Verlag GmbH.

  15. ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.

    Science.gov (United States)

    Nair, Nishanth Ulhas; Sahu, Avinash Das; Bucher, Philipp; Moret, Bernard M E

    2012-01-01

    The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html.

  16. North-South differentiation and a region of high diversity in European wolves (Canis lupus.

    Directory of Open Access Journals (Sweden)

    Astrid V Stronen

    Full Text Available European wolves (Canis lupus show population genetic structure in the absence of geographic barriers, and across relatively short distances for this highly mobile species. Additional information on the location of and divergence between population clusters is required, particularly because wolves are currently recolonizing parts of Europe. We evaluated genetic structure in 177 wolves from 11 countries using over 67K single nucleotide polymorphism (SNP loci. The results supported previous findings of an isolated Italian population with lower genetic diversity than that observed across other areas of Europe. Wolves from the remaining countries were primarily structured in a north-south axis, with Croatia, Bulgaria, and Greece (Dinaric-Balkan differentiated from northcentral wolves that included individuals from Finland, Latvia, Belarus, Poland and Russia. Carpathian Mountain wolves in central Europe had genotypes intermediate between those identified in northcentral Europe and the Dinaric-Balkan cluster. Overall, individual genotypes from northcentral Europe suggested high levels of admixture. We observed high diversity within Belarus, with wolves from western and northern Belarus representing the two most differentiated groups within northcentral Europe. Our results support the presence of at least three major clusters (Italy, Carpathians, Dinaric-Balkan in southern and central Europe. Individuals from Croatia also appeared differentiated from wolves in Greece and Bulgaria. Expansion from glacial refugia, adaptation to local environments, and human-related factors such as landscape fragmentation and frequent killing of wolves in some areas may have contributed to the observed patterns. Our findings can help inform conservation management of these apex predators and the ecosystems of which they are part.

  17. Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed β-propeller domain of the HIV-1 cellular interactor EED

    Directory of Open Access Journals (Sweden)

    Gouet Patrice

    2008-02-01

    Full Text Available Abstract Background The human EED protein, a member of the superfamily of Polycomb group proteins, is involved in multiple cellular protein complexes. Its C-terminal domain, which is common to the four EED isoforms, contains seven repeats of a canonical WD-40 motif. EED is an interactor of three HIV-1 proteins, matrix (MA, integrase (IN and Nef. An antiviral activity has been found to be associated with isoforms EED3 and EED4 at the late stage of HIV-1 replication, due to a negative effect on virus assembly and genomic RNA packaging. The aim of the present study was to determine the regions of the EED C-terminal core domain which were accessible and available to protein interactions, using three-dimensional (3D protein homology modelling with a WD-40 protein of known structure, and epitope mapping of anti-EED antibodies. Results Our data suggested that the C-terminal domain of EED was folded as a seven-bladed β-propeller protein. During the completion of our work, crystallographic data of EED became available from co-crystals of the EED C-terminal core with the N-terminal domain of its cellular partner EZH2. Our 3D-model was in good congruence with the refined structural model determined from crystallographic data, except for a unique α-helix in the fourth β-blade. More importantly, the position of flexible loops and accessible β-strands on the β-propeller was consistent with our mapping of immunogenic epitopes and sites of interaction with HIV-1 MA and IN. Certain immunoreactive regions were found to overlap with the EZH2, MA and IN binding sites, confirming their accessibility and reactivity at the surface of EED. Crystal structure of EED showed that the two discrete regions of interaction with MA and IN did not overlap with each other, nor with the EZH2 binding pocket, but were contiguous, and formed a continuous binding groove running along the lateral face of the β-propeller. Conclusion Identification of antibody-, MA-, IN- and EZH2

  18. Differential erosion and the formation of layered yardangs in the Loulan region (Lop Nur), eastern Tarim Basin

    Science.gov (United States)

    Lin, Yongchong; Xu, Lishuai; Mu, Guijin

    2018-02-01

    Yardangs are a type of wind-sculpted landform which generally form in hyper-arid regions. Several factors affect the development of yardangs, and the relative importance of these factors likely varies with differences in regional environmental factors. In the Loulan region of Lop Nur, wind dynamics are the principal factor affecting the development of yardangs. However, layered yardangs, which have undergone a unique form of differential erosion, are common in the region. These erosional landforms differ from typical yardangs which are eroded solely by abrasion and deflation. We conducted field and laboratory investigations of layered yardangs to determine their origin. The results indicate that there are two types of strata comprising the yardangs: uncompacted sand-silt layers, with a lower carbonate content; and compacted clay-silt layers, with a higher carbonate content. Both types of strata are horizontal and occur in alternating layers. This type of structure enables the wind to more easily erode the less resistant sand-silt layers at different heights, leaving the more resistant compacted clay-silt layers relatively intact. Eventually the undercut remnant clay-silt layers collapse once the weight of the suspended strata exceeds their elastic resistance (more than 90% of the fallen blocks have length/thickness ratios between 1.2 and 2.5). Therefore, in addition to wind dynamics, the lithology and structure of the strata are important factors affecting the development of the layered yardangs. This type of differential erosion accelerates the development of the yardangs in the Loulan region.

  19. SU-E-J-272: Auto-Segmentation of Regions with Differentiating CT Numbers for Treatment Response Assessment

    International Nuclear Information System (INIS)

    Yang, C; Noid, G; Dalah, E; Paulson, E; Li, X; Gilat-Schmidt, T

    2015-01-01

    Purpose: It has been reported recently that the change of CT number (CTN) during and after radiation therapy (RT) may be used to assess RT response. The purpose of this work is to develop a tool to automatically segment the regions with differentiating CTN and/or with change of CTN in a series of CTs. Methods: A software tool was developed to identify regions with differentiating CTN using K-mean Cluster of CT numbers and to automatically delineate these regions using convex hull enclosing method. Pre- and Post-RT CT, PET, or MRI images acquired for sample lung and pancreatic cancer cases were used to test the software tool. K-mean cluster of CT numbers within the gross tumor volumes (GTVs) delineated based on PET SUV (standard uptake value of fludeoxyglucose) and/or MRI ADC (apparent diffusion coefficient) map was analyzed. The cluster centers with higher value were considered as active tumor volumes (ATV). The convex hull contours enclosing preset clusters were used to delineate these ATVs with color washed displays. The CTN defined ATVs were compared with the SUV- or ADC-defined ATVs. Results: CTN stability of the CT scanner used to acquire the CTs in this work is less than 1.5 Hounsfield Unit (HU) variation annually. K-mean cluster centers in the GTV have difference of ∼20 HU, much larger than variation due to CTN stability, for the lung cancer cases studied. The dice coefficient between the ATVs delineated based on convex hull enclosure of high CTN centers and the PET defined GTVs based on SUV cutoff value of 2.5 was 90(±5)%. Conclusion: A software tool was developed using K-mean cluster and convex hull contour to automatically segment high CTN regions which may not be identifiable using a simple threshold method. These CTN regions were reasonably overlapped with the PET or MRI defined GTVs

  20. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    Science.gov (United States)

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-04-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

  1. Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Rosanna Cabré

    2016-12-01

    Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

  2. A study based on trace elements of differentiated metabasic rocks from the Machado-MG region

    International Nuclear Information System (INIS)

    Choudhuri, A.; Carvalho, S.G. de.

    1983-01-01

    Large metabasic intrusive bodies occur in the Precambrian gneiss-migmatite basement around Poco Fundo - Campestre - Machado Triangle, south Minas Gerais. Separate occurrences consisting in each case of pyroxenite, metagabbro and amphibolite seem to be related to each other as is evident from their mineralogy, texture and trends of trace element concentration when plotted against their mg number (Mg/MgO + FeO mol.). Furthermore, their trace elements indicate that these rocks belong to a differentiated sequence resulting from separation of pyroxenes in situ. In spite of their high large ion lithophile element contents comparable to calc-alcaline rocks, the metabasic rocks show close resemblance to present-day mid-ocean ridge basalts when these are plotted in relevant variation diagrams. The tectonic implication of the observations is, however, not yet clear. (Author) [pt

  3. Calcium-Dependent Energetics of Calmodulin Domain Interactions with Regulatory Regions of the Ryanodine Receptor Type 1 (RyR1)

    Science.gov (United States)

    Newman, Rhonda A.; Sorensen, Brenda R.; Kilpatrick, Adina M.; Shea, Madeline A.

    2014-01-01

    Calmodulin (CaM) plays a vital role in calcium homeostasis by allosterically modulating intracellular calcium channels including the homo-tetrameric human Ryanodine Receptor Type 1 (hRyR1). Apo (calcium-free) CaM activates hRyR1 while calcium-saturated CaM inhibits it. Two CaM-binding regions (residues 1975–1999 and 3614–3643) identified in each RyR1 monomer were proposed to allow CaM to bridge adjacent RyR1 subunits. We explored the distinct roles of CaM domains by using fluorescence anisotropy to determine the affinity of CaM1–148 (full-length), CaM1–80 (N-domain) and CaM76–148 (C-domain) for peptides encompassing hRyR1 residues 1975–1999 or 3614–3643. Both CaM1–148 and CaM76–148 associated in a calcium-independent manner with similar affinities for hRyR1(3614–3643)p while CaM1–80 required calcium and bound ~250-fold more weakly. Association of CaM1–148, CaM1–80 and CaM76–148 with hRyR1(1975–1999)p was much less favorable than with hRyR1(3614–3643)p; differences between the two CaM domains were smaller. Equilibrium calcium titrations monitored by steady-state fluorescence demonstrated that both hRyR1 peptides increased the calcium-binding affinity of both CaM domains. These thermodynamic properties support a prior model in which the CaM C-domain associates with RyR1(3614–3643) at low levels of calcium, positioning CaM to rapidly respond to calcium efflux. However, the affinity of the N-domain of CaM for hRyR1(1975–1999)p is insufficient to explain a model in which CaM bridges adjacent RyR1 subunits within the tetramer. This indicates that other protein factors or properties of the tertiary or quaternary structure of hRyR1 contribute to the energetics of CaM-mediated regulation. PMID:25145833

  4. TAIL1: an isthmin-like gene, containing type 1 thrombospondin-repeat and AMOP domain, mapped to ARVD1 critical region.

    Science.gov (United States)

    Rossi, Valeria; Beffagna, Giorgia; Rampazzo, Alessandra; Bauce, Barbara; Danieli, Gian Antonio

    2004-06-23

    Isthmins represent a novel family of vertebrate secreted proteins containing one copy of the thrombospondin type 1 repeat (TSR), which in mammals is shared by several proteins with diverse biological functions, including cell adhesion, angiogenesis, and patterning of developing nervous system. We have determined the genomic organization of human TAIL1 (thrombospondin and AMOP containing isthmin-like 1), a novel isthmin-like gene encoding a protein that contains a TSR and a C-terminal AMOP domain (adhesion-associated domain in MUC4 and other proteins), characteristic of extracellular proteins involved in adhesion processes. TAIL1 gene encompasses more than 24.4 kb. Analysis of the DNA sequence surrounding the putative transcriptional start region revealed a TATA-less promoter located in a CpG island. Several consensus binding sites for the transcription factors Sp1 and MZF-1 were identified in this promoter region. In humans, TAIL1 gene is located on chromosome 14q24.3 within ARVD1 (arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 1) critical region; preliminary evidence suggests that it is expressed in several tissues, showing multiple alternative splicing.

  5. Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain.

    Science.gov (United States)

    Maliszewski-Hall, Anne M; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2017-01-01

    Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1 H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

  6. Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication

    Directory of Open Access Journals (Sweden)

    Belhumeur Pierre

    2008-11-01

    Full Text Available Abstract Background HIV-1 integrase (IN is a key viral enzymatic molecule required for the integration of the viral cDNA into the genome. Additionally, HIV-1 IN has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. Interestingly, previous studies have demonstrated that the expression of HIV-1 IN induces the lethal phenotype in some strains of Saccharomyces cerevisiae. In this study, we performed mutagenic analyses of the C-terminal region of the catalytic core domain of HIV-1 IN in order to delineate the critical amino acid(s and/or motif(s required for the induction of the lethal phenotype in the yeast strain HP16, and to further elucidate the molecular mechanism which causes this phenotype. Results Our study identified three HIV-1 IN mutants, V165A, A179P and KR186,7AA, located in the C-terminal region of the catalytic core domain of IN that do not induce the lethal phenotype in yeast. Chromatin binding assays in yeast and mammalian cells demonstrated that these IN mutants were impaired for the ability to bind chromatin. Additionally, we determined that while these IN mutants failed to interact with LEDGF/p75, they retained the ability to bind Integrase interactor 1. Furthermore, we observed that VSV-G-pseudotyped HIV-1 containing these IN mutants was unable to replicate in the C8166 T cell line and this defect was partially rescued by complementation with the catalytically inactive D64E IN mutant. Conclusion Overall, this study demonstrates that three mutations located in the C-terminal region of the catalytic core domain of HIV-1 IN inhibit the IN-induced lethal phenotype in yeast by inhibiting the binding of IN to the host chromatin. These results demonstrate that the C-terminal region of the catalytic core domain of HIV-1 IN is important for binding to host chromatin and is crucial for both viral replication and the promotion of

  7. Regional climate projection based on RCP scenarios in the CORDEX East Asia Domain Using RegCM4

    Science.gov (United States)

    Suh, M. S.; Oh, S. G.; Cha, D. H.; Kang, H. S.

    2012-04-01

    Regional climate projection data is essential to the adaptation and risk management for the expected climate change. In this stduy, we reproduced regional climate over CORDEX East Asia for 72 years from 1979 to 2050 with 50-km resolution using the latest regional climate model version 4, RegCM4, driven by HadGEM2-AO with about 135-km resolution under Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathway (RCP) 8.5/4.5. Simulation skills of RegCM4 for the present climate (1980-2005, spin up time: 1979) over CORDEX East Asia are evaluated with CRU-TS (Climate Research Unit Time-Series) 3.0 and GPCP (Global Precipitation Climatology Project). And KMA ground observation data are also used for the detailed assessment of RegCM4 over South Korea. The evaluation results showed that RegCM4 reasonalbly simulated the spatial distribution, and inter-annual and seasonal variations of surface air temperature. However, it showed a non-negligible systemartic biases in the precipitation. In particular, the rainband accompanied by the seasonal march of East Asian summer monsoon was simulated too southward, below 30° N comparing to the GPCP. As a reulst, summer precipitation over South Korea and Japan island was significantly underestimated. Under RCP8.5 (RCP4.5) scenario, annual mean temperature over the CORDEX East Asia is expected to increase by + 1.6 oC(+1.4oC) above the present level (1980-2005) by the end of the future simulation period. Most of the regions (South-Korea, South-China, North-China, India, Japan, Mongolia) show the increaseing trend of surface air temperature. On the other hand, the future changes of precipitation are not systemaic at the most of regions and seasons. More detailed results including projected regional climate change will be discussed in the presentation.

  8. Suicide and general elections in Austria: do preceding regional suicide rate differentials foreshadow subsequent voting behavior swings?

    Science.gov (United States)

    Voracek, Martin; Formann, Anton K; Fülöp, Gerhard; Sonneck, Gernot

    2003-05-01

    Suicide-epidemiological research on short-term effects of elections on national/regional suicide and parasuicide incidence has yielded contradictory evidence. Reversing the cause-effect relationship of this line of research we investigated whether preceding regional suicide rates are related to subsequent election results. For Austria's 121 districts, we regressed averaged standardized suicide rates for the preceding period (1988-1994) on political parties' subsequent electoral gains/losses (1999-to-1995) while controlling for a set of 12 domain-relevant psychosocial/economic indices. Stepwise weighted multiple regression led to a significant model. The 1999-to-1995 electoral gains/losses of two opposition parties, together with the population variation caused by migration balance and by births/deaths balance, accounted for a substantial part (30%) of the variability in preceding district-level suicide rates. Various other social indices failed to contribute further substantial increments to this model. This finding suggests that variations in preceding regional suicide incidence might be mirrored in subsequent changes in voting behavior. A speculative post hoc explanation for the finding is offered: on a community level, suicide's aftermath might produce socially and politically alienated survivors of suicide who co-shape swings towards opposition parties in subsequent general elections. The finding calls for more research on suicide's long-term aftermath. Within-country replicability and cross-national generalizability await further investigation. At present, the factor/mechanism accounting for this finding is neither well-established nor has been directly tested.

  9. Differential regional brain growth and rotation of the prenatal human tentorium cerebelli.

    Science.gov (United States)

    Jeffery, Nathan

    2002-02-01

    Folds of dura mater, the falx cerebri and tentorium cerebelli, traverse the vertebrate endocranial cavity and compartmentalize the brain. Previous studies suggest that the tentorial fold has adopted an increasingly important role in supporting the increased load of the cerebrum during human evolution, brought about by encephalization and an adaptation to bipedal posture. Ontogenetic studies of the fetal tentorium suggest that its midline profile rotates inferoposteriorly towards the foramen magnum in response to disproportionate growth of the cerebrum. This study tests the hypothesis that differential growth of the cerebral and cerebellar components of the brain underlies the inferoposterior rotation of the tentorium cerebelli during human fetal development. Brain volumes and tentorial angles were taken from high-resolution magnetic resonance images of 46 human fetuses ranging from 10 to 29 gestational weeks. Apart from the expected increases of both supratentorial and infratentorial brain volumes with age, the results confirm previous studies showing a significant relative enlargement of the supratentorial volume. Correlated with this enlargement was a rotation of the midline section of the tentorium towards the posterior cranial base. These findings support the concept that increases of supratentorial volume relative to infratentorial volume affect an inferoposterior rotation of the human fetal tentorium cerebelli. These results are discussed in the context of the role played by the tentorium cerebelli during human evolution and underline implications for phylogenetic and ontogenetic models of encephalization.

  10. Social and Spatial Continuities and Differentiations among Portuguese Ciganos: Regional Profiles

    Directory of Open Access Journals (Sweden)

    Mendes Maria Manuela

    2016-06-01

    Full Text Available The coexistence of people and societies marked by ethnic, social, cultural, religious and linguistic diversity is a subject that still generates controversies in contemporary societies. The “Ciganos’ situation” is an unavoidable issue that crosses the boundaries of different European countries, which leads to controversy and ambivalence in the so-called multicultural and/or intercultural societies characterised by the principle of universalism. In Portugal, despite the social and economic transformations that have occurred, the problems of exclusion and poverty among Ciganos persist. They are still considered the poorest ethnic group, with the worst housing conditions, lest schooling and the main target of racism and discrimination. The Portuguese Ciganos are not a homogeneous community. The diversity and plurality are not always easy to grasp by the glare generated by the adoption of interpretive perspectives that are reductively linear and deterministic of the Portuguese Ciganos. For the purpose of outlining a national picture of Portuguese Ciganos, a national study was developed that combines both qualitative and quantitative methodological approaches. The central goal of this article is to present the main results obtained through a questionnaire survey carried out to Ciganos persons and to discuss the social and spatial continuities and differentiations among Ciganos in Portugal.

  11. The pro region required for folding of carboxypeptidase Y is a partially folded domain with little regular structural core

    DEFF Research Database (Denmark)

    Sørensen, P; Winther, Jakob R.; Kaarsholm, N C

    1993-01-01

    The pro region of carboxypeptidase Y (CPY) from yeast is necessary for the correct folding of the enzyme [Winther, J. R., & Sørensen P. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9330-9334]. Using fluorescence, circular dichroism, and heteronuclear NMR analyses, it is demonstrated that the isolated...

  12. Regional-Scale Differential Time Tomography Methods: Development and Application to the Sichuan, China, Dataset

    Science.gov (United States)

    Zhang, H.; Thurber, C.; Wang, W.; Roecker, S. W.

    2008-12-01

    We extended our recent development of double-difference seismic tomography [Zhang and Thurber, BSSA, 2003] to the use of station-pair residual differences in addition to event-pair residual differences. Tomography using station- pair residual differences is somewhat akin to teleseismic tomography but with the sources contained within the model region. Synthetic tests show that the inversion using both event- and station-pair residual differences has advantages in terms of more accurately recovering higher-resolution structure in both the source and receiver regions. We used the Spherical-Earth Finite-Difference (SEFD) travel time calculation method in the tomographic system. The basic concept is the extension of a standard Cartesian FD travel time algorithm [Vidale, 1990] to the spherical case by developing a mesh in radius, co-latitude, and longitude, expressing the FD derivatives in a form appropriate to the spherical mesh, and constructing"stencil" to calculate extrapolated travel times. The SEFD travel time calculation method is more advantageous in dealing with heterogeneity and sphericity of the Earth than the simple Earth flattening transformation and the"sphere-in-a-bo" approach [Flanagan et al., 2007]. We applied this method to the Sichuan, China data set for the period of 2001 to 2004. The Vp, Vs and Vp/Vs models show that there is a clear contrast across the Longmenshan Fault, where the 2008 M8 Wenchuan earthquake initiated.

  13. Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support

    Directory of Open Access Journals (Sweden)

    Gregory Paul Marshall

    2014-07-01

    Full Text Available Microglia isolated from the neurogenic subependymal zone (SEZ and hippocampus (HC are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.

  14. Complete re-sequencing of a 2Mb topological domain encompassing the FTO/IRXB genes identifies a novel obesity-associated region upstream of IRX5

    DEFF Research Database (Denmark)

    Hunt, Lilian E; Noyvert, Boris; Bhaw-Rosun, Leena

    2015-01-01

    BACKGROUND: Association studies have identified a number of loci that contribute to an increased body mass index (BMI), the strongest of which is in the first intron of the FTO gene on human chromosome 16q12.2. However, this region is both non-coding and under strong linkage disequilibrium, making...... it recalcitrant to functional interpretation. Furthermore, the FTO gene is located within a complex cis-regulatory landscape defined by a topologically associated domain that includes the IRXB gene cluster, a trio of developmental regulators. Consequently, at least three genes in this interval have been...... implicated in the aetiology of obesity. METHODS: Here, we sequence a 2 Mb region encompassing the FTO, RPGRIP1L and IRXB cluster genes in 284 individuals from a well-characterised study group of Danish men containing extremely overweight young adults and controls. We further replicate our findings both...

  15. A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process

    Directory of Open Access Journals (Sweden)

    El Sawaf Gamal

    2009-07-01

    Full Text Available Abstract Background The E1 protein of Hepatitis C Virus (HCV can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP, and a C-terminal domain (CT comprising two segments, a pre-anchor and a trans-membrane (TM region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1. Results Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis. The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA. This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT

  16. Vector domain decomposition schemes for parabolic equations

    Science.gov (United States)

    Vabishchevich, P. N.

    2017-09-01

    A new class of domain decomposition schemes for finding approximate solutions of timedependent problems for partial differential equations is proposed and studied. A boundary value problem for a second-order parabolic equation is used as a model problem. The general approach to the construction of domain decomposition schemes is based on partition of unity. Specifically, a vector problem is set up for solving problems in individual subdomains. Stability conditions for vector regionally additive schemes of first- and second-order accuracy are obtained.

  17. Insights into the biogeographical history of the Lower Guinea Forest Domain: evidence for the role of refugia in the intraspecific differentiation of Aucoumea klaineana.

    Science.gov (United States)

    Born, Céline; Alvarez, Nadir; McKey, Doyle; Ossari, Simon; Wickings, Elisabeth Jean; Hossaert-McKey, Martine; Chevallier, Marie-Hélène

    2011-01-01

    Determining the biogeographical histories of rainforests is central to our understanding of the present distribution of tropical biodiversity. Ice age fragmentation of central African rainforests strongly influenced species distributions. Elevated areas characterized by higher species richness and endemism have been postulated to be Pleistocene forest refugia. However, it is often difficult to separate the effects of history and of present-day ecological conditions on diversity patterns at the interspecific level. Intraspecific genetic variation could yield new insights into history, because refugia hypotheses predict patterns not expected on the basis of contemporary environmental dynamics. Here, we test geographically explicit hypotheses of vicariance associated with the presence of putative refugia and provide clues about their location. We intensively sampled populations of Aucoumea klaineana, a forest tree sensitive to forest fragmentation, throughout its geographical range. Characterizing variation at 10 nuclear microsatellite loci, we were able to obtain phylogeographic data of unprecedented detail for this region. Using Bayesian clustering approaches, we demonstrated the presence of four differentiated genetic units. Their distribution matched that of forest refugia postulated from patterns of species richness and endemism. Our data also show differences in diversity dynamics at leading and trailing edges of the species' shifting distribution. Our results confirm predictions based on refugia hypotheses and cannot be explained on the basis of present-day ecological conditions. © 2010 Blackwell Publishing Ltd.

  18. Applicability of angular flux discontinuity factor preserving region-wise leakage for integro-differential transport equation

    International Nuclear Information System (INIS)

    Sakamoto, Tatsuya; Endo, Tomohiro; Yamamoto, Akio

    2014-01-01

    In the current core analysis, spatial homogenization is utilized to reduce the computational time. The discontinuity factor (DF) is one of the effective correction factors to reduce spatial homogenization error. The DF in diffusion equation is widely used; on the other hand the DF in transport equation has not been put to practical use although several efforts have been carried out. In this paper, the angular flux discontinuity factor (AFDF) as the DF for the integro-differential transport equation (e.g., the discrete-ordinate method, the method of characteristics) is theoretically described and its applicability is discussed. The AFDF is used to preserve the region-wise neutron leakage at each spatial mesh and defined as a ratio of heterogeneous and homogeneous angular fluxes at the homogenized region surface. In a homogeneous calculation with the AFDF, the angular flux is discontinuous at the region surface. In this paper the applicability of the AFDF to fuel pin cell homogenization is verified for one-dimensional slab geometry. As a result of this verification, it is confirmed that the AFDF has the capability to reduce the spatial homogenization error of fuel pin cell homogenization. (author)

  19. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.

    Science.gov (United States)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan; Stigare, Jerker; Wikström, Johan; Boldt, Henning Bünsow; Kristensen, Bjarne Winther; Pontén, Fredrik; Trouillas, Jacqueline

    2017-09-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  20. The Asia 2 specific signal peptide region and other domains in fusion protein genes characterized Asia 1 and Asia 2 canine distemper viruses

    Science.gov (United States)

    Sultan, Serageldeen; Charoenvisal, Nataya; Lan, Nguyen Thi; Yamaguchi, Ryoji; Maeda, Ken; Kai, Kazushige

    2009-01-01

    Background Although the presence of Asia 2 group of canine distemper virus (CDV) was known by the sequencing and phylogenetic analysis of hemagglutinin (H) gene, the fusion (F) protein gene sequence of Asia 2 group had not been identified. So, the sequence analysis of F gene was carried out to elucidate the genotypic varaitons among Asian isolates. Results The phylogenetic analysis of F and H gene sequences from fourteen CDV isolates obtained from diseased dogs in Japan and Thailand indicated that the F genes had a new initiation codon and extra 27 nucleotides upstream of the usual open reading frame (ORF) and the F proteins had extra 9 amino acids at the N-terminal position only in Asia 2 isolates. On the contrary, the Asia 1 isolates had three extra putative N-glycosylation sites (two sites in the signal peptide region and one site in the F1 region) except for two strains of Th12 and Ac96I (two sites in signal peptide region) adding to four putative N-glycosylation sites that were conserved among all Asian isolates and Onderstepoort strain. In addition to this difference in N-glycosylation sites, the signal peptide region had a great diversity between Asia 1 and Asia 2 isolates. Also, characteristic amino acids were detected for some strains. Conclusion Asia 2 isolates were distinguished from other CDV lineages by the extra 27 nucleotide sequence. The signal peptide region of F gene gives a remarkable differentiation between Asia 1 and Asia 2 isolates. Strains Th12 and Ac96I were differentiated from other Asia 1 strains by the F protein glycosylation sites. PMID:19807927

  1. Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.

    Science.gov (United States)

    Wang, Liwei; Wagner, Larry E; Alzayady, Kamil J; Yule, David I

    2017-07-14

    The inositol 1,4,5 trisphosphate receptor (IP 3 R) is an intracellular Ca 2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP 3 R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP 3 R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP 3 binding despite the loss of peptide continuity. In this study, we demonstrate that region-specific receptor fragmentation modifies channel regulation. Specifically, the agonist-evoked temporal Ca 2+ release profile and protein kinase A modulation of Ca 2+ release are markedly altered. Moreover, we also demonstrate that activation of fragmented IP 3 R1 can result in a distinct functional outcome. Our work suggests that proteolysis of IP 3 R1 may represent a novel form of modulation of IP 3 R1 channel function and increases the repertoire of Ca 2+ signals achievable through this channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Path Complexity in Virtual Water Maze Navigation: Differential Associations with Age, Sex, and Regional Brain Volume.

    Science.gov (United States)

    Daugherty, Ana M; Yuan, Peng; Dahle, Cheryl L; Bender, Andrew R; Yang, Yiqin; Raz, Naftali

    2015-09-01

    Studies of human navigation in virtual maze environments have consistently linked advanced age with greater distance traveled between the start and the goal and longer duration of the search. Observations of search path geometry suggest that routes taken by older adults may be unnecessarily complex and that excessive path complexity may be an indicator of cognitive difficulties experienced by older navigators. In a sample of healthy adults, we quantify search path complexity in a virtual Morris water maze with a novel method based on fractal dimensionality. In a two-level hierarchical linear model, we estimated improvement in navigation performance across trials by a decline in route length, shortening of search time, and reduction in fractal dimensionality of the path. While replicating commonly reported age and sex differences in time and distance indices, a reduction in fractal dimension of the path accounted for improvement across trials, independent of age or sex. The volumes of brain regions associated with the establishment of cognitive maps (parahippocampal gyrus and hippocampus) were related to path dimensionality, but not to the total distance and time. Thus, fractal dimensionality of a navigational path may present a useful complementary method of quantifying performance in navigation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Differential regional gray matter volumes in patients with on-line game addiction and professional gamers

    Science.gov (United States)

    Han, Doug Hyun; Lyoo, In Kyoon; Renshaw, Perry F.

    2015-01-01

    Patients with on-line game addiction (POGA) and professional video game players play video games for extended periods of time, but experience very different consequences for their on-line game play. Brain regions consisting of anterior cingulate, thalamus and occpito-temporal areas may increase the likelihood of becoming a pro-gamer or POGA. Twenty POGA, seventeen pro-gamers, and eighteen healthy comparison subjects (HC) were recruited. All magnetic resonance imaging (MRI) was performed on a 1.5 Tesla Espree MRI scanner (SIEMENS, Erlangen, Germany). Voxel-wise comparisons of gray matter volume were performed between the groups using the two-sample t-test with statistical parametric mapping (SPM5). Compared to HC, the POGA group showed increased impulsiveness and perseverative errors, and volume in left thalamus gray matter, but decreased gray matter volume in both inferior temporal gyri, right middle occipital gyrus, and left inferior occipital gyrus, compared with HC. Pro-gamers showed increased gray matter volume in left cingulate gyrus, but decreased gray matter volume in left middle occipital gyrus and right inferior temporal gyrus compared with HC. Additionally, the pro-gamer group showed increased gray matter volume in left cingulate gyrus and decreased left thalamus gray matter volume compared with the POGA group. The current study suggests that increased gray matter volumes of the left cingulate gyrus in pro-gamers and of the left thalamus in POGA may contribute to the different clinical characteristics of pro-gamers and POGA. PMID:22277302

  4. Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA

    DEFF Research Database (Denmark)

    Doritchamou, Justin; Sabbagh, Audrey; Jespersen, Jakob S

    2015-01-01

    The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses...... a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence...

  5. A local region of interest image reconstruction via filtered backprojection for fan-beam differential phase-contrast computed tomography

    International Nuclear Information System (INIS)

    Qi Zhihua; Chen Guanghong

    2007-01-01

    Recently, x-ray differential phase contrast computed tomography (DPC-CT) has been experimentally implemented using a conventional source combined with several gratings. Images were reconstructed using a parallel-beam reconstruction formula. However, parallel-beam reconstruction formulae are not directly applicable for a large image object where the parallel-beam approximation fails. In this note, we present a new image reconstruction formula for fan-beam DPC-CT. There are two major features in this algorithm: (1) it enables the reconstruction of a local region of interest (ROI) using data acquired from an angular interval shorter than 180 0 + fan angle and (2) it still preserves the filtered backprojection structure. Numerical simulations have been conducted to validate the image reconstruction algorithm. (note)

  6. Differential cross section measurements for the 6Li(n,t)alpha reaction in the few MeV region

    Energy Technology Data Exchange (ETDEWEB)

    Devlin, Matthew J [Los Alamos National Laboratory; Taddeucci, Terence N [Los Alamos National Laboratory; Hale, Gerald M [Los Alamos National Laboratory; Haight, Robert C [Los Alamos National Laboratory; O' Donnell, Johhn M [Los Alamos National Laboratory

    2008-01-01

    New measured differential cross sections of tritons and alpha particles following the {sup 6}Li(n,t){alpha} reaction are reported for incident neutron energies between 0.2 and approximately 20 MeV. The neutrons were produced by spallation at the WNR facility at the Los Alamos Neutron Science CEnter (LANSCE), with the incident neutron energy determined by the time-of-flight method. Four E-{Delta}E telescopes were used at eight laboratory angles. These data have been incorporated into a prior R-matrix fit for the compound {sup 7}Li system, and result in an (n,t) reaction cross section that is 4% to 10% higher than previous evaluations in the 1-3 MeV incident neutron energy region.

  7. Co-movement of Africa's equity markets: Regional and global analysis in the frequency-time domains

    Science.gov (United States)

    Boako, Gideon; Alagidede, Paul

    2017-02-01

    This paper examines regional and global co-movement of Africa's stock markets using the three-dimensional continuous Morlet wavelet transform methodology. The analyses which are done in segments investigate co-movements with global markets; bilateral exchange rates expressed in US dollars and euro; and four regional markets in Africa. First, we find evidence of stronger co-movements broadly narrowed to short-run fluctuations. The co-movements are time-varying and commonly non-homogeneous - with phase difference arrow vectors implying lead-lag relationships. The presence of lead-lag effects and stronger co-movements at short-run fluctuations may induce arbitrage and diversification opportunities to both local and international investors with long-term investment horizons. The findings also reveal that some African equity markets are, to a degree, segmented from volatilities of the dollar and euro exchange rates. Thus, inferring that, ceteris paribus, international investors may diversify their portfolio investments across those markets without worrying about the effects of currency price volatility.

  8. Spatial Differentiation of Landscape Values in the Murray River Region of Victoria, Australia

    Science.gov (United States)

    Zhu, Xuan; Pfueller, Sharron; Whitelaw, Paul; Winter, Caroline

    2010-05-01

    This research advances the understanding of the location of perceived landscape values through a statistically based approach to spatial analysis of value densities. Survey data were obtained from a sample of people living in and using the Murray River region, Australia, where declining environmental quality prompted a reevaluation of its conservation status. When densities of 12 perceived landscape values were mapped using geographic information systems (GIS), valued places clustered along the entire river bank and in associated National/State Parks and reserves. While simple density mapping revealed high value densities in various locations, it did not indicate what density of a landscape value could be regarded as a statistically significant hotspot or distinguish whether overlapping areas of high density for different values indicate identical or adjacent locations. A spatial statistic Getis-Ord Gi* was used to indicate statistically significant spatial clusters of high value densities or “hotspots”. Of 251 hotspots, 40% were for single non-use values, primarily spiritual, therapeutic or intrinsic. Four hotspots had 11 landscape values. Two, lacking economic value, were located in ecologically important river red gum forests and two, lacking wilderness value, were near the major towns of Echuca-Moama and Albury-Wodonga. Hotspots for eight values showed statistically significant associations with another value. There were high associations between learning and heritage values while economic and biological diversity values showed moderate associations with several other direct and indirect use values. This approach may improve confidence in the interpretation of spatial analysis of landscape values by enhancing understanding of value relationships.

  9. Differential regional gray matter volumes in patients with on-line game addiction and professional gamers.

    Science.gov (United States)

    Han, Doug Hyun; Lyoo, In Kyoon; Renshaw, Perry F

    2012-04-01

    Patients with on-line game addiction (POGA) and professional video game players play video games for extended periods of time, but experience very different consequences for their on-line game play. Brain regions consisting of anterior cingulate, thalamus and occpito-temporal areas may increase the likelihood of becoming a pro-gamer or POGA. Twenty POGA, seventeen pro-gamers, and eighteen healthy comparison subjects (HC) were recruited. All magnetic resonance imaging (MRI) was performed on a 1.5 Tesla Espree MRI scanner (SIEMENS, Erlangen, Germany). Voxel-wise comparisons of gray matter volume were performed between the groups using the two-sample t-test with statistical parametric mapping (SPM5). Compared to HC, the POGA group showed increased impulsiveness and perseverative errors, and volume in left thalamus gray matter, but decreased gray matter volume in both inferior temporal gyri, right middle occipital gyrus, and left inferior occipital gyrus, compared with HC. Pro-gamers showed increased gray matter volume in left cingulate gyrus, but decreased gray matter volume in left middle occipital gyrus and right inferior temporal gyrus compared with HC. Additionally, the pro-gamer group showed increased gray matter volume in left cingulate gyrus and decreased left thalamus gray matter volume compared with the POGA group. The current study suggests that increased gray matter volumes of the left cingulate gyrus in pro-gamers and of the left thalamus in POGA may contribute to the different clinical characteristics of pro-gamers and POGA. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Differential tolerance of two Gammarus pulex populations transplanted from different metallogenic regions to a polymetal gradient.

    Science.gov (United States)

    Khan, Farhan R; Irving, Jennifer R; Bury, Nicolas R; Hogstrand, Christer

    2011-03-01

    The River Hayle, Cornwall, UK exhibits pronounced Cu and Zn concentration gradients which were used to compare the metal handling abilities of two populations of Gammarus pulex (Crustacea: Amphipoda). One population was native to the Hayle region (Drym) and presumably has been historically impacted by elevated Cu and Zn levels, whilst naïve gammarids were collected from the River Cray, Kent, UK. Both populations were subject to a 32 day in situ exposure at four R. Hayle sites (Drym, Godolphin, Relubbus and St. Erth). Mortality (LT50), Cu and Zn accumulation and sub-cellular distribution, and oxidative stress (malondialdehyde production) increased with the expected Cu and Zn bioavailabilities at the four sites (i.e. Godolphin>Relubbus>St. Erth>Drym). The naïve population experienced greater metal induced effects in terms of Cu and Zn accumulation, oxidative stress responses and lower LT50s. Analysis of Cu and Zn sub-cellular distribution, however, revealed no significant differences in metal handling. In both populations each metal was localised predominantly to the sub-cellular fraction containing metal bound to metallothionein-like proteins (MTLP) or that holding both metal-rich granules (MRG) and exoskeleton, MTLP and MRG binding being indicative of metal detoxification. However, a greater capacity for detoxified metal storage is not a mechanism implicated in the perceived tolerance of the historically impacted gammarids. Instead our results suggest that the historically impacted population was adapted for lower uptake of Cu and Zn leading to lower bioaccumulation, stress response and ultimately mortality. These results demonstrate not only the usefulness of the in situ methodology, but also that differences in population exposure history can cause significant differences in metal responses during exposure at higher concentrations. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Hadronic cosmic ray interactions near the LHC energy region and in the UHE domain of giant EAS

    Energy Technology Data Exchange (ETDEWEB)

    Capdevielle, J.N. [AstroParticule et Cosmologie (APC), College de France, 75 - Paris (France)

    2005-07-01

    The fluctuations of ray families simulated with CORSIKA in the energy region 3.10{sup 15} - 10{sup 17} eV on the basis of standard Lns collider physics exhibits alignments of secondaries in the stratosphere and at ground level. The remarkable event recorded on the Concorde does not fit well however those cases. The possible hints of new mechanisms, especially the valence diquark breaking, are considered. Observing that the extrapolation of the original cosmic ray primary spectrum derived from the size spectrum measured in the Akeno classical EAS array coincides with the spectrum measured recently by the Hires Stereo experiment, we point out a possible overestimation of the primary energy in inclined showers of the surface arrays like AGASA. (author)

  12. Assessment of two versions of regional climate model in simulating the Indian Summer Monsoon over South Asia CORDEX domain

    Science.gov (United States)

    Pattnayak, K. C.; Panda, S. K.; Saraswat, Vaishali; Dash, S. K.

    2018-04-01

    This study assess the performance of two versions of Regional Climate Model (RegCM) in simulating the Indian summer monsoon over South Asia for the period 1998 to 2003 with an aim of conducting future climate change simulations. Two sets of experiments were carried out with two different versions of RegCM (viz. RegCM4.2 and RegCM4.3) with the lateral boundary forcings provided from European Center for Medium Range Weather Forecast Reanalysis (ERA-interim) at 50 km horizontal resolution. The major updates in RegCM4.3 in comparison to the older version RegCM4.2 are the inclusion of measured solar irradiance in place of hardcoded solar constant and additional layers in the stratosphere. The analysis shows that the Indian summer monsoon rainfall, moisture flux and surface net downward shortwave flux are better represented in RegCM4.3 than that in the RegCM4.2 simulations. Excessive moisture flux in the RegCM4.2 simulation over the northern Arabian Sea and Peninsular India resulted in an overestimation of rainfall over the Western Ghats, Peninsular region as a result of which the all India rainfall has been overestimated. RegCM4.3 has performed well over India as a whole as well as its four rainfall homogenous zones in reproducing the mean monsoon rainfall and inter-annual variation of rainfall. Further, the monsoon onset, low-level Somali Jet and the upper level tropical easterly jet are better represented in the RegCM4.3 than RegCM4.2. Thus, RegCM4.3 has performed better in simulating the mean summer monsoon circulation over the South Asia. Hence, RegCM4.3 may be used to study the future climate change over the South Asia.

  13. Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

    Science.gov (United States)

    Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

    2018-07-04

    Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

  14. A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress

    Directory of Open Access Journals (Sweden)

    Emmanuel Adu-Gyamfi

    2014-10-01

    Full Text Available Ebola virus (EBOV causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40. VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130 and find that mutations (K127A, T129A, and N130A in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress.

  15. Domain analysis

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

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

  16. Consortium for Osteogenesis Imperfecta Mutations in the Helical Domain of Type I Collagen: Regions Rich in Lethal Mutations Align With Collagen Binding Sites for Integrins and Proteoglycans

    Science.gov (United States)

    Marini, Joan C.; Forlino, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; San Antonio, James D.; Milgrom, Sarah; Hyland, James C.; Körkkö, Jarmo; Prockop, Darwin J.; De Paepe, Anne; Coucke, Paul; Symoens, Sofie; Glorieux, Francis H.; Roughley, Peter J.; Lund, Alan M.; Kuurila-Svahn, Kaija; Hartikka, Heini; Cohn, Daniel H.; Krakow, Deborah; Mottes, Monica; Schwarze, Ulrike; Chen, Diana; Yang, Kathleen; Kuslich, Christine; Troendle, James; Dalgleish, Raymond; Byers, Peter H.

    2014-01-01

    Osteogenesis imperfecta (OI) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of OI are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the proα1(I) and proα2(I) chains, respectively) that result in OI. Quantitative defects causing type I OI were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype–phenotype relationships emerge for each chain. One-third of the mutations that result in glycine substitutions in α1(I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691–823 and 910–964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibril–matrix interactions. Recurrences at the same site in α2(I) are generally concordant for outcome, unlike α1(I). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In α2(I), lethal exon skipping events are

  17. Characterization of two novel nuclear BTB/POZ domain zinc finger isoforms. Association with differentiation of hippocampal neurons, cerebellar granule cells, and macroglia

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Kjaerulff, Karen M; Pedersen, Hans C

    2002-01-01

    BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex......, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF(L) and HOF(S), that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic...

  18. Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2)

    NARCIS (Netherlands)

    C.A. Berrevoets (Cor); P. Doesburg (Paul); K. Steketee (Karine); J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractPrevious studies in yeast and mammalian cells showed a functional interaction between the amino-terminal domain and the carboxy-terminal, ligand-binding domain (LBD) of the human androgen receptor (AR). In the present study, the AR subdomains involved in

  19. The C-terminal domain of the bacteriophage T4 terminase docks on the prohead portal clip region during DNA packaging

    Science.gov (United States)

    Dixit, Aparna Banerjee; Ray, Krishanu; Thomas, Julie A.; Black, Lindsay W.

    2013-01-01

    Bacteriophage ATP-based packaging motors translocate DNA into a pre-formed prohead through a dodecameric portal ring channel to high density. We investigated portal–terminase docking interactions at specifically localized residues within a terminase-interaction region (aa279–316) in the phage T4 portal protein gp20 equated to the clip domain of the SPP1 portal crystal structure by 3D modeling. Within this region, three residues allowed A to C mutations whereas three others did not, consistent with informatics analyses showing the tolerated residues are not strongly conserved evolutionarily. About 7.5 nm was calculated by FCS-FRET studies employing maleimide Alexa488 dye labeled A316C proheads and gp17 CT-ReAsH supporting previous work docking the C-terminal end of the T4 terminase (gp17) closer to the N-terminal GFP-labeled portal (gp20) than the N-terminal end of the terminase. Such a terminase–portal orientation fits better to a proposed “DNA crunching” compression packaging motor and to portal determined DNA headful cutting. PMID:24074593

  20. Adaptor proteins intersectin 1 and 2 bind similar proline-rich ligands but are differentially recognized by SH2 domain-containing proteins.

    Directory of Open Access Journals (Sweden)

    Olga Novokhatska

    Full Text Available BACKGROUND: Scaffolding proteins of the intersectin (ITSN family, ITSN1 and ITSN2, are crucial for the initiation stage of clathrin-mediated endocytosis. These proteins are closely related but have implications in distinct pathologies. To determine how these proteins could be separated in certain cell pathways we performed a comparative study of ITSNs. METHODOLOGY/PRINCIPAL FINDINGS: We have shown that endogenous ITSN1 and ITSN2 colocalize and form a complex in cells. A structural comparison of five SH3 domains, which mediated most ITSNs protein-protein interactions, demonstrated a similarity of their ligand-binding sites. We showed that the SH3 domains of ITSN2 bound well-established interactors of ITSN1 as well as newly identified ITSNs protein partners. A search for a novel interacting interface revealed multiple tyrosines that could be phosphorylated in ITSN2. Phosphorylation of ITSN2 isoforms but not ITSN1 short isoform was observed in various cell lines. EGF stimulation of HeLa cells enhanced tyrosine phosphorylation of ITSN2 isoforms and enabled their recognition by the SH2 domains of the Fyn, Fgr and Abl1 kinases, the regulatory subunit of PI3K, the adaptor proteins Grb2 and Crk, and phospholipase C gamma. The SH2 domains mentioned were unable to bind ITSN1 short isoform. CONCLUSIONS/SIGNIFICANCE: Our results indicate that during evolution of vertebrates ITSN2 acquired a novel protein-interaction interface that allows its specific recognition by the SH2 domains of signaling proteins. We propose that these data could be important to understand the functional diversity of paralogous ITSN proteins.

  1. MR imaging findings of the corpus callosum region in the differentiation between multiple sclerosis and neuromyelitis optica

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhiye, E-mail: yyqf@hotmail.com [Department of Radiology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China); Feng, Feng, E-mail: cjr.fengfeng@vip.163.com [Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing 100730 (China); Yang, Yang, E-mail: whitean0584@sina.com.cn [Department of Neurology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China); Li, Jinfeng, E-mail: lijf_301@163.com [Department of Radiology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China); Ma, Lin, E-mail: cjr.malin@vip.163.com [Department of Radiology, PLA General Hospital, 28 Fuxing Road, Beijing 100853 (China)

    2012-11-15

    Purpose: To evaluate MR imaging findings in corpus callosum region for the discrimination between opticospinal multiple sclerosis (OSMS) and neuromyelitis optica (NMO). Materials and methods: Forty-two definite OSMS with seronegative NMO-IgG and 23 NMO with seropositive NMO-IgG, and 27 age-matched normal controls (NC) were recruited. Sagittal T2-FLAIR images with 2-mm slice thickness were obtained. Subcallosal dot-dash (SCDD) sign and subcallosal striations (SCS) sign were reviewed. Results: SCDD was more commonly detected in OSMS (28 of 42 patients) than in NMO (5 of 23 patients) (P < 0.05). SCS showed no difference between OSMS (31 of 42 patients) and NMO (12 of 23 patients) (P > 0.05). For comparing ROC analysis among SCDD, SCS, and SCDD + SCS for predicted probability through binary logistic regression analysis, SCDD + SCS had the largest area under ROC curve (0.777) than SCDD (0.725) and SCS (0.608). Conclusion: SCDD may be helpful in distinguishing OSMS from NMO. The regression equation may also be a simple and effective method of choice for the differentiation between OSMS and NMO.

  2. MR imaging findings of the corpus callosum region in the differentiation between multiple sclerosis and neuromyelitis optica

    International Nuclear Information System (INIS)

    Chen, Zhiye; Feng, Feng; Yang, Yang; Li, Jinfeng; Ma, Lin

    2012-01-01

    Purpose: To evaluate MR imaging findings in corpus callosum region for the discrimination between opticospinal multiple sclerosis (OSMS) and neuromyelitis optica (NMO). Materials and methods: Forty-two definite OSMS with seronegative NMO-IgG and 23 NMO with seropositive NMO-IgG, and 27 age-matched normal controls (NC) were recruited. Sagittal T2-FLAIR images with 2-mm slice thickness were obtained. Subcallosal dot-dash (SCDD) sign and subcallosal striations (SCS) sign were reviewed. Results: SCDD was more commonly detected in OSMS (28 of 42 patients) than in NMO (5 of 23 patients) (P 0.05). For comparing ROC analysis among SCDD, SCS, and SCDD + SCS for predicted probability through binary logistic regression analysis, SCDD + SCS had the largest area under ROC curve (0.777) than SCDD (0.725) and SCS (0.608). Conclusion: SCDD may be helpful in distinguishing OSMS from NMO. The regression equation may also be a simple and effective method of choice for the differentiation between OSMS and NMO.

  3. Niflumic acid alters gating of HCN2 pacemaker channels by interaction with the outer region of S4 voltage sensing domains.

    Science.gov (United States)

    Cheng, Lan; Sanguinetti, Michael C

    2009-05-01

    Niflumic acid, 2-[[3-(trifluoromethyl)phenyl]amino]pyridine-3-carboxylic acid (NFA), is a nonsteroidal anti-inflammatory drug that also blocks or modifies the gating of many ion channels. Here, we investigated the effects of NFA on hyperpolarization-activated cyclic nucleotide-gated cation (HCN) pacemaker channels expressed in X. laevis oocytes using site-directed mutagenesis and the two-electrode voltage-clamp technique. Extracellular NFA acted rapidly and caused a slowing of activation and deactivation and a hyperpolarizing shift in the voltage dependence of HCN2 channel activation (-24.5 +/- 1.2 mV at 1 mM). Slowed channel gating and reduction of current magnitude was marked in oocytes treated with NFA, while clamped at 0 mV but minimal in oocytes clamped at -100 mV, indicating the drug preferentially interacts with channels in the closed state. NFA at 0.1 to 3 mM shifted the half-point for channel activation in a concentration-dependent manner, with an EC(50) of 0.54 +/- 0.068 mM and a predicted maximum shift of -38 mV. NFA at 1 mM also reduced maximum HCN2 conductance by approximately 20%, presumably by direct block of the pore. The rapid onset and state-dependence of NFA-induced changes in channel gating suggests an interaction with the extracellular region of the S4 transmembrane helix, the primary voltage-sensing domain of HCN2. Neutralization (by mutation to Gln) of any three of the outer four basic charged residues in S4, but not single mutations, abrogated the NFA-induced shift in channel activation. We conclude that NFA alters HCN2 gating by interacting with the extracellular end of the S4 voltage sensor domains.

  4. Concrete domains

    OpenAIRE

    Kahn, G.; Plotkin, G.D.

    1993-01-01

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

  5. A role for chromatin topology in imprinted domain regulation.

    Science.gov (United States)

    MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

    2016-02-01

    Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

  6. Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

    DEFF Research Database (Denmark)

    Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

    2004-01-01

    binding to SRCR domain 3 exhibited effective inhibition of ligand binding. Furthermore, analysis of purified native CD163 revealed that proteolytic cleavage in SRCR domain 3 inactivates ligand binding. Calcium protects against cleavage in this domain. Analysis of the calcium sensitivity of ligand binding...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...... for the calcium-sensitive coupling of haptoglobin.hemoglobin complexes....

  7. DOES IT MATTER WHERE I LIVE IN WESTERN-EUROPE - AN ANALYSIS OF REGIONAL MORTALITY DIFFERENTIALS IN BELGIUM, GERMANY AND THE NETHERLANDS

    NARCIS (Netherlands)

    VANDERVEEN, WJ

    1994-01-01

    Regional differentials in life expectancy at birth during the 1980s in Belgium, The Netherlands and some parts of the former Federal Republic of Germany are presented and commented upon. Life expectancy at birth during the 1980s was highest in The Netherlands, and lowest in some parts of southern

  8. Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.

    Science.gov (United States)

    McDonald, Caleb B; Seldeen, Kenneth L; Deegan, Brian J; Bhat, Vikas; Farooq, Amjad

    2011-01-01

    A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3, and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 3(10) -helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. Copyright © 2010 John Wiley & Sons, Ltd.

  9. Domain Engineering

    Science.gov (United States)

    Bjørner, Dines

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

  10. Differentiation of cryptogenic lateral from mesial temporal lobe epilepsy using regional asymmetric index of F-18-FDG PET

    International Nuclear Information System (INIS)

    Song, H. C.; Lee, D. S.; Lee, S. K.; Jeong, J. M.; Jeong, Z. K.; Lee, M. C.; Ko, C. S.

    1997-01-01

    We tried to find the possibility of utilization of F-18-FDG PET to differentiate lateral (neocortical) from mesial temporal lobe epilepsy(TLE) if we adopted quantitative comparison of regional metabolic activities using asymmetric index. We studied 22 pathologically proven mesial TLE(group C in Figure), and 27 lateral TLE patients. Lateral TLE patients were normal on MR(cryptogenic: 15; group A) or had structural lesions (12: group B). Asymmetric index (AI) was calculated as (ipsilateral -contralateral) / (ipsilateral + contralateral ) x 200. AI of medial lobe of cryptogenic lateral TLE was not decreased (-4.66.2, > 0.05) and AI of medial lobe of cryptogenic lateral TLE was not decreased (-4.66.2, >0.05) and AI of lateral lobe was decreased (-13.68.9). AI of medial and lateral lobes of mesial TLE was decreased (-3.44.7 and -16.58.9, respectively). AI of medial lobe of lesional lateral TLE was -7.39.1 (p<0.05 compared with mesial TEL). It was evident that lateral lobe of lesional lateral TLE had metabolic defect or decrease (AI: -21.410.4). While we could not find difference of metabolic activity in lateral temporal lobes between cryptogenic lateral TLE and mesial TLE patients, the difference of metabolic activity was significant in medial temporal lobes which was revealed by AI quantitation. An AI value larger than -10 (cutoff: AI) predicted positively for lateral TLE(PPV:80%) and negatively for mesial TLE(NPV:77%). Asymmetry of metabolic activity in medial and not in lateral lobe of temporal lobe could give hints about whether the epileptogenic zones were mesial or lateral

  11. Differential diagnosis between aneurysm and infundibular dilatation in the IC-PC region with 3D-CTA

    International Nuclear Information System (INIS)

    Kubota, Tsukasa; Niwa, Jun; Tanigawara, Tetsuya; Chiba, Masahiko; Akiyama, Yukinori; Inamura Shigeru

    2000-01-01

    In cases of asymptomatic internal carotid-posterior communicating artery (IC-PC) protrusions, it is sometimes difficult to differentiate infundibular dilatation (ID) from aneurysm by digital subtraction angiography. We applied three-dimensional CT angiography (3D-CTA) in 32 cases of these IC-PC protrusions. SOMATOM PLUS 4 was used under such conditions as to provide images with high spatial resolution. The shaded surface display (SSD) method was adopted to reconstruct the 3D images because of its advantage in separating overlapped vasculature. We also made reference to source images and maximum intensity projection (MIP) to make sure of our diagnoses. In all cases including 4 aneurysms and 28 IDs, we were able to distinguish between ID and aneurysm. The accuracy of 3D-CTA was confirmed by 9 surgical cases. Our technique was as follows: To inject a high dose of diluted contrast medium rapidly to smaller arteries for opacification of contrast medium. To exclude neighboring useless structures except for the very close structures such as posterior clinoid process from the target image focusing on the IC-PC region. To observe the reconstructed image of MIP and SSD from various angles. The contralateral and craniocaudal view were valuable. To change the threshold level gradually and observe the configurational changes of the apex of protrusion. Poorly developed PcomA was mostly delineated at the optimum threshold level. Otherwise, the apex of protrusion remained spherical in an aneurysm and became pyramidal in shape in an ID when the threshold level was gradually decreased. In conclusion, 3D-CTA was a useful modality for IC-PC protrusions to distinguish between ID and aneurysm. (author)

  12. APPLICATION OF THE POLYGONS’ METHOD FOR THE ANALYSIS OF VOLGA FEDERAL DISTRICT’S REGIONS DIFFERENTIATION IN TERMS OF POPULATION’S SOCIAL COMFORT OF LIVING

    Directory of Open Access Journals (Sweden)

    Marina A. Skvortsova

    2014-01-01

    Full Text Available The article deals with the results of the analysis of Volga federal district’s regions differentiation in terms of population’s social comfort of living using the polygons. Constructed polygons represent a graphic image position of Volga federal district’s regions on the most important criteria of social comfort of living. Calculated indexes of social comfort of living in the regions of the Volga Federal District are an integral characteristic of the object under investigation. It suggests that there is a high degree of regions’ heterogeneity in terms of the integral indicator.

  13. Contributions of gravity and field data on the structural scheme updating of the Tellian domain and its foreland (Nefza-Bizerte region, northern Tunisia)

    Science.gov (United States)

    Essid, El Mabrouk; Kadri, Ali; Balti, Hadhemi; Gasmi, Mohamed; Zargouni, Fouad

    2018-03-01

    The Nefza-Bizerte region, eastern part of the Tunisian Alpine chain, covers the thrust sheets domain called the Tell and its Atlassic foreland. The deep structures under the Tellian thrust sheets are not enough explored. The structural interpretation of magmatic rocks, Triassic outcrops and the depressions are still a subject of discussion. In this work, we intend to investigate deep faults and their eventual role in magmatism and Triassic salt setting up and to explain the depression genesis. Analysis of the Bouguer anomaly map and its derivatives reveals the main gravity lineaments, organized in major NE- and NW-trending systems. The NE-trending system, dipping towards the NW, is the main component of the structural scheme and has controlled the tectonic evolution of this area. After the immobilization of the Tellian thrust sheets during the uppermost Langhian, the Tell and its Atlassic foreland were affected by the Tortonian compressive event with a NW-trending maximum horizontal stress. The reverse kinematics of the NE-trending deep-seated faults created at their front continental environments filled later by post-nappes Neogene deposits. After the early Pleistocene, a NNW-directed compressional stress regime deformed the post-nappes Neogene series and generated NW-trending grabens. This coexistence of compression-extension continues until present day.

  14. The cytoplasmic domain close to the transmembrane region of the glucagon-like peptide-1 receptor contains sequence elements that regulate agonist-dependent internalisation.

    Science.gov (United States)

    Vázquez, Patricia; Roncero, Isabel; Blázquez, Enrique; Alvarez, Elvira

    2005-07-01

    In order to gain better insight into the molecular events involved in the signal transduction generated through glucagon-like peptide-1 (GLP-1) receptors, we tested the effect of deletions and point mutations within the cytoplasmic tail of this receptor with a view to establishing relationships between signal transduction desensitisation and receptor internalisation. Wild-type and truncated (deletion of the last 27 amino acids (GLPR 435R) and deletion of 44 amino acids (GLPR 418R)) GLP-1 receptors bound the agonist with similar affinity. Deletion of the last 27 amino acids decreased the internalisation rate by 78%, while deletion of 44 amino acids containing all the phosphorylation sites hitherto described in this receptor decreased the internalisation rate by only 47%. Binding of the ligand to both receptors stimulated adenylyl cyclase. In contrast, deletion of the region containing amino acids 419 to 435 (GLPR 419delta435) increased the internalisation rate by 268%, and the replacement of EVQ(408-410) by alanine (GLPR A(408-410)) increased this process to 296%. In both receptors, the efficacy in stimulating adenylate cyclase was decreased. All the receptors studied were internalised by coated pits, except for the receptor with a deletion of the last 44 amino acids, which also had a faster resensitisation rate. Our findings indicate that the neighbouring trans-membrane domain of the carboxyl-terminal tail of the GLP-1 receptor contains sequence elements that regulate agonist-dependent internalisation and transmembrane signalling.

  15. Tim-4 inhibition of T-cell activation and T helper type 17 differentiation requires both the immunoglobulin V and mucin domains and occurs via the mitogen-activated protein kinase pathway

    Science.gov (United States)

    Cao, Wei; Ryan, Michelle; Buckley, Deirdre; O'Connor, Rosemary; Clarkson, Michael R

    2011-01-01

    Emerging experimental data suggest an important role for the T-cell immunoglobulin mucin 1 (Tim-1):Tim-4 pathway in autoimmune and alloimmune responses in vivo. Using a Tim-4 ectodomain human IgG Fc fusion protein we studied the role of Tim-4 in T-cell activation, signalling and differentiation responses in vitro. We demonstrate that Tim-4Fc can inhibit naive and pre-activated T-cell activation, proliferation and cytokine secretion via a Tim-1-independent pathway. Tim-4 contains immunoglobulin variable (IgV) and mucin domains; to identify which domain accounts for the inhibitory effect novel Tim-4 fusion proteins containing either the IgV or mucin domain were generated. We demonstrate that both IgV and mucin domains are required for the inhibitory effects and that they are mediated at least in part by inhibition of extracellular signal-regulated kinase pathway activity. Given the emerging interest in the role of the Tim family in T helper type 17 (Th17) cells, which play an important role in autoimmune disease and transplantation tolerance, our data show that Tim-4Fc can prevent polarization of CD4+ T cells to the Th17 phenotype. Collectively, our results highlight an inhibitory role for Tim-4Fc in vitro, which we propose is mediated by a receptor other than Tim-1. In addition, this study provides new insights into the role of Tim-4Fc in regulating Th17 immune responses and may open a new avenue for autoimmune therapy. PMID:21463297

  16. Tim-4 inhibition of T-cell activation and T helper type 17 differentiation requires both the immunoglobulin V and mucin domains and occurs via the mitogen-activated protein kinase pathway.

    LENUS (Irish Health Repository)

    Cao, Wei

    2011-06-01

    Emerging experimental data suggest an important role for the T-cell immunoglobulin mucin 1 (Tim-1):Tim-4 pathway in autoimmune and alloimmune responses in vivo. Using a Tim-4 ectodomain human IgG Fc fusion protein we studied the role of Tim-4 in T-cell activation, signalling and differentiation responses in vitro. We demonstrate that Tim-4Fc can inhibit naive and pre-activated T-cell activation, proliferation and cytokine secretion via a Tim-1-independent pathway. Tim-4 contains immunoglobulin variable (IgV) and mucin domains; to identify which domain accounts for the inhibitory effect novel Tim-4 fusion proteins containing either the IgV or mucin domain were generated. We demonstrate that both IgV and mucin domains are required for the inhibitory effects and that they are mediated at least in part by inhibition of extracellular signal-regulated kinase pathway activity. Given the emerging interest in the role of the Tim family in T helper type 17 (Th17) cells, which play an important role in autoimmune disease and transplantation tolerance, our data show that Tim-4Fc can prevent polarization of CD4(+) T cells to the Th17 phenotype. Collectively, our results highlight an inhibitory role for Tim-4Fc in vitro, which we propose is mediated by a receptor other than Tim-1. In addition, this study provides new insights into the role of Tim-4Fc in regulating Th17 immune responses and may open a new avenue for autoimmune therapy.

  17. The structure of polarization maps of skin histological sections in the Fourier domain for the tasks of benign and malignant formations differentiation

    Science.gov (United States)

    Ushenko, V. A.; Dubolazov, A. V.; Savich, V. O.; Novakovskaya, O. Y.; Olar, O. V.; Marchuk, Y. F.

    2015-02-01

    The optical model of birefringent networks of biological tissues is presented. The technique of Fourier polarimetry for selection of manifestations of linear and circular birefringence of protein fibrils is suggested. The results of investigations of statistical (statistical moments of the 1st-4th orders), correlation (dispersion and excess of autocorrelation functions) and scalar-self-similar (logarithmic dependencies of power spectra) structure of Fourier spectra of polarization azimuths distribution of laser images of skin samples are presented. The criteria of differentiation of postoperative biopsy of benign (keratoma) and malignant (adenocarcinoma) skin tumors are determined.

  18. Differentiation regional climate impact indicators at 1.5°C and 2°C warming above pre-industrial levels

    Science.gov (United States)

    Schleussner, C. F.

    2016-12-01

    Robust appraisals of climate impacts at different levels of global-mean temperature increase are vital to guide assessments of dangerous anthropogenic interference with the climate system. By establishing 1.5°C as the long term temperature limit for global average temperature increase and inviting a special report of the IPCC on the impacts of 1.5°C, the Paris Agreement has put such assessments high on the post-Paris science agenda. Here I will present recent findings of climate impacts at 1.5°C, including extreme weather events, water availability, agricultural yields, sea-level rise and risk of coral reef loss. In particular, I will present findings from a recent study that attempts to differentiate between such impacts at warming levels of 1.5°¸C and 2°C above pre-industrial (Schleussner et al., 2016). By analyzing changes in indicators for 26 world regions as applicable, the study found regional dependent differences between a 1.5°C and 2°C warming. Regional hot-spots of change emerge with tropical regions bearing the brunt of the impacts of an additional 0.5°C warming. These findings highlight the importance of regional differentiation to assess both future climate risks and different vulnerabilities to incremental increases in global-mean temperature. Building on that analysis, I will discuss limitations of existing approaches to differentiate between warming levels and outline opportunities for future work on refining our understanding of the difference between impacts at 1.5°C and 2°C warming. ReferencesSchleussner, C.-F. et al. Differential climate impacts for policy relevant limits to global warming: the case of 1.5°C and 2°C. Earth Syst. Dyn. 7, 327-351 (2016).

  19. High-resolution crystal structure reveals a HEPN domain at the C-terminal region of S. cerevisiae RNA endonuclease Swt1

    International Nuclear Information System (INIS)

    Peng, Shuxia; Zhou, Ke; Wang, Wenjia; Gao, Zengqiang; Dong, Yuhui; Liu, Quansheng

    2014-01-01

    Highlights: • Crystal structure of the C-terminal (CT) domain of Swt1 was determined at 2.3 Å. • Structure of the CT domain was identified as HEPN domain superfamily member. • Low-resolution envelope of Swt1 full-length in solution was analyzed by SAXS. • The middle and CT domains gave good fit to SAXS structural model. - Abstract: Swt1 is an RNA endonuclease that plays an important role in quality control of nuclear messenger ribonucleoprotein particles (mRNPs) in eukaryotes; however, its structural details remain to be elucidated. Here, we report the crystal structure of the C-terminal (CT) domain of Swt1 from Saccharomyces cerevisiae, which shares common characteristics of higher eukaryotes and prokaryotes nucleotide binding (HEPN) domain superfamily. To study in detail the full-length protein structure, we analyzed the low-resolution architecture of Swt1 in solution using small angle X-ray scattering (SAXS) method. Both the CT domain and middle domain exhibited a good fit upon superimposing onto the molecular envelope of Swt1. Our study provides the necessary structural information for detailed analysis of the functional role of Swt1, and its importance in the process of nuclear mRNP surveillance

  20. U-Pb age in zircon of intrusive granite at Acopiara complex, Crystal region, domain Central Ceara, Brazil; Idade U-PB em zircao de granito intrusivo no Complexo Acopiara, Regiao de Cristais, Dominio Ceara Central

    Energy Technology Data Exchange (ETDEWEB)

    Neri, T.F.O.; Hamelak, G.M.S.; Azevedo, L.R.; Mattos, I.C.; Verissimo, C.U.V.; Nogueira Neto, J.A., E-mail: neri@ufc.br [Universidade Federal do Ceara (UFC), Fortaleza (Brazil). Departamento de Geologia; Lima, M.N. [Universidade Federal de Goias (UFGO), Goiania, GO (Brazil). Curso de Geologia

    2015-07-01

    Granitic body mineralogically composed by two micas, located at Crystal region, Ceara Central domain and intruded into lithotypes from Acopiara complex, provided an age of ∼526 Ma, indicating important period of magma generation of granitic composition associated with crustal anatexia, during Paleozoic.

  1. Radiation Treatment for Malignant Small Cell Tumor of the Thoracopulmonary Region Primitive Pluripotent Histogenesis and Differential Diagnosis-A Case Report and Review of Literatures-

    International Nuclear Information System (INIS)

    Oh, Won Young; Yang, Jin Yeong; Whang, In Soon

    1991-01-01

    Malignant small round cell tumor (SRCT) of the thoracopulmonary region appears to originate in the soft tissues of the chest wall or the peripheral lung. A differential diagnosis of poorly differentiated small round cell tumors which include Ewing's sarcoma of bone and soft tissue, embryonal rhabdomyosarcoma, Askin tumor, neuroblastoma, peripheral neuroectodermal tumor, small cell osteogenic sarcoma and lymphoma are after difficult by light microscopy alone. In recent, by the extensive studies electron microscopic examination, histochemical study, immunochemical study, cytogenetics and gene analysis, these tumors may be derived from the primitive and pluripotential cells, differentiating into mesenchymal, epithelial and neural features in variable proportions. Treatment for SRCT of thoracopulmonary regin is not determined because of massive involvement of the lung, pleura or soft tissues of the chest wall resulted in a dismal outcome despite aggressive surgery, irradiation and chemotherapy

  2. Lipid domains in intact fiber-cell plasma membranes isolated from cortical and nuclear regions of human eye lenses of donors from different age groups.

    Science.gov (United States)

    Raguz, Marija; Mainali, Laxman; O'Brien, William J; Subczynski, Witold K

    2015-03-01

    The results reported here clearly document changes in the properties and the organization of fiber-cell membrane lipids that occur with age, based on electron paramagnetic resonance (EPR) analysis of lens membranes of clear lenses from donors of age groups from 0 to 20, 21 to 40, and 61 to 80 years. The physical properties, including profiles of the alkyl chain order, fluidity, hydrophobicity, and oxygen transport parameter, were investigated using EPR spin-labeling methods, which also provide an opportunity to discriminate coexisting lipid domains and to evaluate the relative amounts of lipids in these domains. Fiber-cell membranes were found to contain three distinct lipid environments: bulk lipid domain, which appears minimally affected by membrane proteins, and two domains that appear due to the presence of membrane proteins, namely boundary and trapped lipid domains. In nuclear membranes the amount of boundary and trapped phospholipids as well as the amount of cholesterol in trapped lipid domains increased with the donors' age and was greater than that in cortical membranes. The difference between the amounts of lipids in domains uniquely formed due to the presence of membrane proteins in nuclear and cortical membranes increased with the donors' age. It was also shown that cholesterol was to a large degree excluded from trapped lipid domains in cortical membranes. It is evident that the rigidity of nuclear membranes was greater than that of cortical membranes for all age groups. The amount of lipids in domains of low oxygen permeability, mainly in trapped lipid domains, were greater in nuclear than cortical membranes and increased with the age of donors. These results indicate that the nuclear fiber cell plasma membranes were less permeable to oxygen than cortical membranes and become less permeable to oxygen with age. In clear lenses, age-related changes in the lens lipid and protein composition and organization appear to occur in ways that increase fiber

  3. TWEAK-independent Fn14 self-association and NF-κB activation is mediated by the C-terminal region of the Fn14 cytoplasmic domain.

    Directory of Open Access Journals (Sweden)

    Sharron A N Brown

    Full Text Available The tumor necrosis factor (TNF superfamily member TNF-like weak inducer of apoptosis (TWEAK is a pro-inflammatory and pro-angiogenic cytokine implicated in physiological tissue regeneration and wound repair. TWEAK binds to a 102-amino acid type I transmembrane cell surface receptor named fibroblast growth factor-inducible 14 (Fn14. TWEAK:Fn14 engagement activates several intracellular signaling cascades, including the NF-κB pathway, and sustained Fn14 signaling has been implicated in the pathogenesis of chronic inflammatory diseases and cancer. Although several groups are developing TWEAK- or Fn14-targeted agents for therapeutic use, much more basic science research is required before we fully understand the TWEAK/Fn14 signaling axis. For example, we and others have proposed that TWEAK-independent Fn14 signaling may occur in cells when Fn14 levels are highly elevated, but this idea has never been tested directly. In this report, we first demonstrate TWEAK-independent Fn14 signaling by showing that an Fn14 deletion mutant that is unable to bind TWEAK can activate the NF-κB pathway in transfected cells. We then show that ectopically-expressed, cell surface-localized Fn14 can self-associate into Fn14 dimers, and we show that Fn14 self-association is mediated by an 18-aa region within the Fn14 cytoplasmic domain. Endogenously-expressed Fn14 as well as ectopically-overexpressed Fn14 could also be detected in dimeric form when cell lysates were subjected to SDS-PAGE under non-reducing conditions. Additional experiments revealed that Fn14 dimerization occurs during cell lysis via formation of an intermolecular disulfide bond at cysteine residue 122. These findings provide insight into the Fn14 signaling mechanism and may aid current studies to develop therapeutic agents targeting this small cell surface receptor.

  4. Polarization of concave domains by traveling wave pinning.

    Directory of Open Access Journals (Sweden)

    Slawomir Bialecki

    Full Text Available Pattern formation is one of the most fundamental yet puzzling phenomena in physics and biology. We propose that traveling front pinning into concave portions of the boundary of 3-dimensional domains can serve as a generic gradient-maintaining mechanism. Such a mechanism of domain polarization arises even for scalar bistable reaction-diffusion equations, and, depending on geometry, a number of stationary fronts may be formed leading to complex spatial patterns. The main advantage of the pinning mechanism, with respect to the Turing bifurcation, is that it allows for maintaining gradients in the specific regions of the domain. By linking the instant domain shape with the spatial pattern, the mechanism can be responsible for cellular polarization and differentiation.

  5. Differential distribution of proteins and lipids in detergent-resistant and detergent-soluble domains in rod outer segment plasma membranes and disks.

    Science.gov (United States)

    Elliott, Michael H; Nash, Zack A; Takemori, Nobuaki; Fliesler, Steven J; McClellan, Mark E; Naash, Muna I

    2008-01-01

    Membrane heterogeneity plays a significant role in regulating signal transduction and other cellular activities. We examined the protein and lipid components associated with the detergent-resistant membrane (DRM) fractions from retinal rod outer segment (ROS) disk and plasma membrane-enriched preparations. Proteomics and correlative western blot analysis revealed the presence of alpha and beta subunits of the rod cGMP-gated ion channel and glucose transporter type 1, among other proteins. The glucose transporter was present exclusively in ROS plasma membrane (not disks) and was highly enriched in DRMs, as was the cGMP-gated channel beta-subunit. In contrast, the majority of rod opsin and ATP-binding cassette transporter A4 was localized to detergent-soluble domains in disks. As expected, the cholesterol : fatty acid mole ratio was higher in DRMs than in the corresponding parent membranes (disk and plasma membranes, respectively) and was also higher in disks compared to plasma membranes. Furthermore, the ratio of saturated : polyunsaturated fatty acids was also higher in DRMs compared to their respective parent membranes (disk and plasma membranes). These results confirm that DRMs prepared from both disks and plasma membranes are enriched in cholesterol and in saturated fatty acids compared to their parent membranes. The dominant fatty acids in DRMs were 16 : 0 and 18 : 0; 22 : 6n3 and 18 : 1 levels were threefold higher and twofold lower, respectively, in disk-derived DRMs compared to plasma membrane-derived DRMs. We estimate, based on fatty acid recovery that DRMs account for only approximately 8% of disks and approximately 12% of ROS plasma membrane.

  6. Predicting adolescent posttraumatic stress in the aftermath of war: differential effects of coping strategies across trauma reminder, loss reminder, and family conflict domains.

    Science.gov (United States)

    Howell, Kathryn H; Kaplow, Julie B; Layne, Christopher M; Benson, Molly A; Compas, Bruce E; Katalinski, Ranka; Pasalic, Hafiza; Bosankic, Nina; Pynoos, Robert

    2015-01-01

    The vast majority of youth who lived through the Bosnian war were exposed to multiple traumatic events, including interpersonal violence, community destruction, and the loss of a loved one. This study examined factors that predict post-war psychological adjustment, specifically posttraumatic stress, in Bosnian adolescents. Regression analyses evaluated theorized differential relations between three types of post-war stressors - exposure to trauma reminders, loss reminders, and intrafamilial conflict - specific coping strategies, and posttraumatic stress symptom dimensions. We examined 555 Bosnian adolescents, aged 15-19 years, to predict their long-term posttraumatic stress reactions in the aftermath of war. Findings indicated that post-war exposure to trauma reminders, loss reminders, and family conflict, as well as engagement and disengagement coping strategies, predicted posttraumatic stress symptoms. Secondary control engagement coping responses to all three types of post-war stressors were inversely associated with posttraumatic stress symptoms, whereas primary control engagement coping responses to family conflict were inversely associated with hyperarousal symptoms. Disengagement responses to trauma reminders and family conflict were positively associated with re-experiencing symptoms. These findings shed light on ways in which trauma reminders, loss reminders, and family conflict may intersect with coping responses to influence adolescent postwar adjustment.

  7. Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen.

    Science.gov (United States)

    Terajima, Masahiko; Taga, Yuki; Chen, Yulong; Cabral, Wayne A; Hou-Fu, Guo; Srisawasdi, Sirivimol; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Kurie, Jonathan M; Marini, Joan C; Yamauchi, Mitsuo

    2016-04-29

    Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet 10, e1004465). However, the extent of decrease appears to be tissue- and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1-3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen*

    Science.gov (United States)

    Terajima, Masahiko; Taga, Yuki; Chen, Yulong; Cabral, Wayne A.; Hou-Fu, Guo; Srisawasdi, Sirivimol; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Kurie, Jonathan M.; Marini, Joan C.; Yamauchi, Mitsuo

    2016-01-01

    Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet. 10, e1004465). However, the extent of decrease appears to be tissue- and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1–3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation. PMID:26934917

  9. A Single-Domain Llama Antibody Potently Inhibits the Enzymatic Activity of Botulinum Neurotoxin by Binding to the Non-Catalytic [alpha]-Exosite Binding Region

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Jianbo; Thompson, Aaron A.; Fan, Yongfeng; Lou, Jianlong; Conrad, Fraser; Ho, Mengfei; Pires-Alves, Melissa; Wilson, Brenda A.; Stevens, Raymond C.; Marks, James D. (UIUC); (Scripps); (UCSF)

    2010-08-13

    Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically mimic substrate and bind in or around the substrate cleavage pocket. To explore the full range of binding sites for serotype A light chain (BoNT/A Lc) inhibitors, we created a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from heavy-chain-only antibody) antibodies displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K{sub d}) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of 25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K{sub d} for BoNT/A Lc of 1.47 x 10{sup -10} M and an IC{sub 50} (50% inhibitory concentration) of 4.7 x 10{sup -10} M and was resistant to heat denaturation and reducing conditions. To understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 {angstrom} resolution. The structure reveals that the Aa1 VHH binds in the {alpha}-exosite of the BoNT/A Lc, far from the active site for catalysis. The study validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and identifies the BoNT/A Lc {alpha}-exosite as a target for inhibitor development.

  10. [Spatial temporal differentiation of product-based and consumption-based CO2 emissions and balance in the Beijing-Tianjin-Hebei region: an economic input- output analysis].

    Science.gov (United States)

    Wang, Hao; Chen, Cao-cao; Pan, Tao; Liu, Chun-lan; Chen, Long; Sun, Li

    2014-09-01

    Distinguishing product-based and consumption-based CO2 emissions in the open economic region is the basis for differentiating the emission responsibility, which is attracting increasing attention of decision-makers'attention. The spatial and temporal characteristics of product-based and consumption-based CO2 emissions, as well as carbon balance, in 1997, 2002 and 2007 of JING- JIN-JI region were analyzed by the Economic Input-Output-Life Cycle Assessment model. The results revealed that both the product- based and consumption-based CO2 emissions in the region have been increased by about 4% annually. The percentage of CO2 emissions embodied in trade was 30% -83% , to which the domestic trading added the most. The territorial and consumption-based CO2 emissions in Hebei province were the predominant emission in JING-JIN-JI region, and the increasing speed and emission intensity were stronger than those of Beijing and Tianjin. JING-JIN-JI region was a net inflow region of CO2 emissions, and parts of the emission responsibility were transferred. Beijing and Tianjin were the net importers of CO2 emissions, and Hebei was a net outflow area of CO2 emissions. The key CO2 emission departments in the region were concentrated, and the similarity was great. The inter-regional mechanisms could be set up for joint prevention and control work. - Production and distribution of electricity, gas and water and smelting and pressing of metals had the highest reliability on CO2 emissions, and took on the responsibility of other departments. The EIO-LCA model could be used to analyze the product-based and consumption-based CO2 emissions, which is helpful for the delicate management of regional CO2 emissions reduction and policies making, and stimulating the reduction cooperation at regional scale.

  11. Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets.

    Science.gov (United States)

    Hou, Yixuan; Lin, Chun-Ming; Yokoyama, Masaru; Yount, Boyd L; Marthaler, Douglas; Douglas, Arianna L; Ghimire, Shristi; Qin, Yibin; Baric, Ralph S; Saif, Linda J; Wang, Qiuhong

    2017-07-15

    We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by blind serial passaging of the intestinal contents of a diarrheic piglet in Vero cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal, conventional suckling piglets with TC-PC177 or PC21A to compare their pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe clinical signs and 55% mortality. To investigate whether infection with TC-PC177 can induce cross-protection against challenge with a highly virulent PEDV strain, all the surviving piglets were challenged with PC21A at 3 weeks postinoculation. Compared with 100% protection in piglets initially inoculated with PC21A, 88% and 100% TC-PC177- and mock-inoculated piglets had diarrhea following challenge, respectively, indicating incomplete cross-protection. To investigate whether this 197-aa deletion was the determinant for the attenuation of TC-PC177, we generated a mutant (icPC22A-S1Δ197) bearing the 197-aa deletion from an infectious cDNA clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A). In neonatal gnotobiotic pigs, the icPC22A-S1Δ197 virus caused mild to moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that deletion of this 197-aa fragment in the spike protein can attenuate a highly virulent PEDV, but the virus may lose important epitopes for inducing robust protective immunity. IMPORTANCE The emerging, highly virulent PEDV strains have caused substantial economic losses worldwide. However, the virulence determinants are not established. In this study, we found that a 197-aa deletion in the N-terminal region

  12. In vivo analysis of homing pattern and differentiation potential of cells deriving from embryonic and adult haematopoietic regions

    OpenAIRE

    Petrovic, Suzana

    2004-01-01

    The experimental work of this thesis addresses the questions of whether established cell lines injected into murine blastocysts find their way back home and seed preferentially at the site of their origin. Furthermore, can they change their fate and differentiate to unrelated cell types when exposed to the embryonic environment. This survey was based on the fact that different cell lines have different potentials in developing embryos, dependent on their cellular identity. The cell lines used...

  13. Modelling of groundwater flow and flow paths for a large regional domain in northeast Uppland. A three-dimensional, mathematical modelling of groundwater flows and flow paths on a super-regional scale, for different complexity levels of the flow domain

    International Nuclear Information System (INIS)

    Holmen, Johan G.; Stigsson, Martin; Marsic, Niko; Gylling, Bjoern

    2003-12-01

    The general purpose of this study is to estimate the groundwater flow for a large regional domain by use of groundwater models; and to do that with such a resolution (degree of detail) that important local properties of the flow system studied is represented in the established models. Based on the results of the groundwater modelling, we have compared different theoretical locations of a repository for nuclear waste, considering length and breakthrough time (advective flow) for flow paths from such a repository. The area studied is located in Sweden, in the Northeast of the Uppland province. The area has a maximum horizontal extension of 90 km by 50 km, and the size of the area is approximately 2,000 km 2 . The study is based on a system analysis approach. The studied system is the groundwater flow in the rock mass of Northeast Uppland. To reach the objectives of the study, different mathematical models were devised of the studied domain; these models will, in an idealised and simplified way, reproduce the groundwater movements at the area studied. The formal models (the mathematical models) used for simulation of the groundwater flow are three dimensional mathematical descriptions of the studied hydraulic system. For establishment of the formal models we used two different numerical codes GEOAN, which is based on the finite difference method and NAMMU, which is based on the finite element method. Considering flow path lengths and breakthrough times from a theoretical repository, we have evaluated the following: Importance of the local and regional topography; Importance of cell size in the numerical model; Importance of depth of domain represented in the numerical model; Importance of regional fracture zones; Importance of local lakes; Importance of areas covered by a clay layer; Importance of a modified topography; Importance of the shore level progress. Importance of density dependent flow. The results of the study includes: Length and breakthrough time of flow

  14. Modelling of groundwater flow and flow paths for a large regional domain in northeast Uppland. A three-dimensional, mathematical modelling of groundwater flows and flow paths on a super-regional scale, for different complexity levels of the flow domain

    Energy Technology Data Exchange (ETDEWEB)

    Holmen, Johan G.; Stigsson, Martin [Golder Associates, Stockholm (Sweden); Marsic, Niko; Gylling, Bjoern [Kemakta Konsult AB, Stockholm (Sweden)

    2003-12-01

    The general purpose of this study is to estimate the groundwater flow for a large regional domain by use of groundwater models; and to do that with such a resolution (degree of detail) that important local properties of the flow system studied is represented in the established models. Based on the results of the groundwater modelling, we have compared different theoretical locations of a repository for nuclear waste, considering length and breakthrough time (advective flow) for flow paths from such a repository. The area studied is located in Sweden, in the Northeast of the Uppland province. The area has a maximum horizontal extension of 90 km by 50 km, and the size of the area is approximately 2,000 km{sup 2}. The study is based on a system analysis approach. The studied system is the groundwater flow in the rock mass of Northeast Uppland. To reach the objectives of the study, different mathematical models were devised of the studied domain; these models will, in an idealised and simplified way, reproduce the groundwater movements at the area studied. The formal models (the mathematical models) used for simulation of the groundwater flow are three dimensional mathematical descriptions of the studied hydraulic system. For establishment of the formal models we used two different numerical codes GEOAN, which is based on the finite difference method and NAMMU, which is based on the finite element method. Considering flow path lengths and breakthrough times from a theoretical repository, we have evaluated the following: Importance of the local and regional topography; Importance of cell size in the numerical model; Importance of depth of domain represented in the numerical model; Importance of regional fracture zones; Importance of local lakes; Importance of areas covered by a clay layer; Importance of a modified topography; Importance of the shore level progress. Importance of density dependent flow. The results of the study includes: Length and breakthrough time of

  15. Differences in neurogenesis differentiate between core and shell regions of auditory nuclei in the turtle (Pelodiscus sinensis): evolutionary implications.

    Science.gov (United States)

    Zeng, Shao-Ju; Xi, Chao; Zhang, Xin-Wen; Zuo, Ming-Xue

    2007-01-01

    There is a clear core-versus-shell distinction in cytoarchitecture, electrophysiological properties and neural connections in the mesencephalic and diencephalic auditory nuclei of amniotes. Determining whether the embryogenesis of auditory nuclei shows a similar organization is helpful for further understanding the constituent organization and evolution of auditory nuclei. Therefore in the present study, we injected [(3)H]-thymidine into turtle embryos (Pelodiscus sinensis) at various stages of development. Upon hatching, [(3)H]-thymidine labeling was examined in both the core and shell auditory regions in the midbrain, diencephalon and dorsal ventricular ridge. Met-enkephalin and substance P immunohistochemistry was used to distinguish the core and shell regions. In the mesencephalic auditory nucleus, the occurrence of heavily labeled neurons in the nucleus centralis of the torus semicircularis reached its peak at embryonic day 9, one day later than the surrounding shell. In the diencephalic auditory nucleus, the production of heavily labeled neurons in the central region of the reuniens (Re) was highest at embryonic day (E) 8, one day later than that in the shell region of reuniens. In the region of the dorsal ventricular ridge that received inputs from the central region of Re, the appearance of heavily labeled neurons also reached a peak one day later than that in the area receiving inputs from the shell region of reuniens. Thus, there is a core-versus-shell organization of neuronal generation in reptilian auditory areas. Copyright (c) 2007 S. Karger AG, Basel.

  16. Molecular markers for X-ray-insensitive differentiated cells in the Inner and outer regions of the mesenchymal space in planarian Dugesia japonica.

    Science.gov (United States)

    Teramoto, Machiko; Kudome-Takamatsu, Tomomi; Nishimura, Osamu; An, Yang; Kashima, Makoto; Shibata, Norito; Agata, Kiyokazu

    2016-09-01

    Planarian's strong regenerative ability is dependent on stem cells (called neoblasts) that are X-ray-sensitive and proliferative stem cells. In addition to neoblasts, another type of X-ray-sensitive cells was newly identified by recent research. Thus, planarian's X-ray-sensitive cells can be divided into at least two populations, Type 1 and Type 2, the latter corresponding to planarian's classically defined "neoblasts". Here, we show that Type 1 cells were distributed in the outer region (OR) immediately underneath the muscle layer at all axial levels from head to tail, while the Type 2 cells were distributed in a more internal region (IR) of the mesenchymal space at the axial levels from neck to tail. To elucidate the biological significance of these two regions, we searched for genes expressed in differentiated cells that were locate close to these X-ray-sensitive cell populations in the mesenchymal space, and identified six genes mainly expressed in the OR or IR, named OR1, OR2, OR3, IR1, IR2 and IR3. The predicted amino acid sequences of these genes suggested that differentiated cells expressing OR1, OR3, IR1, or IR2 provide Type 1 and Type 2 cells with specific extracellular matrix (ECM) environments. © 2016 Japanese Society of Developmental Biologists.

  17. How are the emplacement of rare-element pegmatites, regional metamorphism and magmatism interrelated in the Moldanubian domain of the Variscan Bohemian Massif, Czech Republic?

    Czech Academy of Sciences Publication Activity Database

    Melleton, J.; Gloaguen, E.; Frei, D.; Novák, M.; Breiter, Karel

    2012-01-01

    Roč. 50, č. 6 (2012), s. 1751-1773 ISSN 0008-4476 Institutional support: RVO:67985831 Keywords : LCT pegmatite * rare-element-enriched magma * columbite-tantalite * LA-SF-ICP-MS dating * Variscan orogeny * Bohemian Massif * Moldanubian domain * Bohemian Massif (Czech Republic) Subject RIV: DB - Geology ; Mineralogy Impact factor: 1.180, year: 2012

  18. Defining differentially methylated regions specific for the acquisition of pluripotency and maintenance in human pluripotent stem cells via microarray.

    Directory of Open Access Journals (Sweden)

    WenYin He

    Full Text Available Epigenetic regulation is critical for the maintenance of human pluripotent stem cells. It has been shown that pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, appear to have a hypermethylated status compared with differentiated cells. However, the epigenetic differences in genes that maintain stemness and regulate reprogramming between embryonic stem cells and induced pluripotent stem cells remain unclear. Additionally, differential methylation patterns of induced pluripotent stem cells generated using diverse methods require further study.Here, we determined the DNA methylation profiles of 10 human cell lines, including 2 ESC lines, 4 virally derived iPSC lines, 2 episomally derived iPSC lines, and the 2 parental cell lines from which the iPSCs were derived using Illumina's Infinium HumanMethylation450 BeadChip. The iPSCs exhibited a hypermethylation status similar to that of ESCs but with distinct differences from the parental cells. Genes with a common methylation pattern between iPSCs and ESCs were classified as critical factors for stemness, whereas differences between iPSCs and ESCs suggested that iPSCs partly retained the parental characteristics and gained de novo methylation aberrances during cellular reprogramming. No significant differences were identified between virally and episomally derived iPSCs. This study determined in detail the de novo differential methylation signatures of particular stem cell lines.This study describes the DNA methylation profiles of human iPSCs generated using both viral and episomal methods, the corresponding somatic cells, and hESCs. Series of ss-DMRs and ES-iPS-DMRs were defined with high resolution. Knowledge of this type of epigenetic information could be used as a signature for stemness and self-renewal and provides a potential method for selecting optimal pluripotent stem cells for human regenerative medicine.

  19. B cell lymphoma-2 (BCL-2) homology domain 3 (BH3) mimetics demonstrate differential activities dependent upon the functional repertoire of pro- and anti-apoptotic BCL-2 family proteins.

    Science.gov (United States)

    Renault, Thibaud T; Elkholi, Rana; Bharti, Archana; Chipuk, Jerry E

    2014-09-19

    The B cell lymphoma-2 (BCL-2) family is the key mediator of cellular sensitivity to apoptosis during pharmacological interventions for numerous human pathologies, including cancer. There is tremendous interest to understand how the proapoptotic BCL-2 effector members (e.g. BCL-2-associated X protein, BAX) cooperate with the BCL-2 homology domain only (BH3-only) subclass (e.g. BCL-2 interacting mediator of death, BIM; BCL-2 interacting-domain death agonist, BID) to induce mitochondrial outer membrane permeabilization (MOMP) and apoptosis and whether these mechanisms may be pharmacologically exploited to enhance the killing of cancer cells. Indeed, small molecule inhibitors of the anti-apoptotic BCL-2 family members have been designed rationally. However, the success of these "BH3 mimetics" in the clinic has been limited, likely due to an incomplete understanding of how these drugs function in the presence of multiple BCL-2 family members. To increase our mechanistic understanding of how BH3 mimetics cooperate with multiple BCL-2 family members in vitro, we directly compared the activity of several BH3-mimetic compounds (i.e. ABT-263, ABT-737, GX15-070, HA14.1, TW-37) in biochemically defined large unilamellar vesicle model systems that faithfully recapitulate BAX-dependent mitochondrial outer membrane permeabilization. Our investigations revealed that the presence of BAX, BID, and BIM differentially regulated the ability of BH3 mimetics to derepress proapoptotic molecules from anti-apoptotic proteins. Using mitochondria loaded with fluorescent BH3 peptides and cells treated with inducers of cell death, these differences were supported. Together, these data suggest that although the presence of anti-apoptotic BCL-2 proteins primarily dictates cellular sensitivity to BH3 mimetics, additional specificity is conferred by proapoptotic BCL-2 proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  1. Specific genomic regions are differentially affected by copy number alterations across distinct cancer types, in aggregated cytogenetic data.

    Science.gov (United States)

    Kumar, Nitin; Cai, Haoyang; von Mering, Christian; Baudis, Michael

    2012-01-01

    Regional genomic copy number alterations (CNA) are observed in the vast majority of cancers. Besides specifically targeting well-known, canonical oncogenes, CNAs may also play more subtle roles in terms of modulating genetic potential and broad gene expression patterns of developing tumors. Any significant differences in the overall CNA patterns between different cancer types may thus point towards specific biological mechanisms acting in those cancers. In addition, differences among CNA profiles may prove valuable for cancer classifications beyond existing annotation systems. We have analyzed molecular-cytogenetic data from 25579 tumors samples, which were classified into 160 cancer types according to the International Classification of Disease (ICD) coding system. When correcting for differences in the overall CNA frequencies between cancer types, related cancers were often found to cluster together according to similarities in their CNA profiles. Based on a randomization approach, distance measures from the cluster dendrograms were used to identify those specific genomic regions that contributed significantly to this signal. This approach identified 43 non-neutral genomic regions whose propensity for the occurrence of copy number alterations varied with the type of cancer at hand. Only a subset of these identified loci overlapped with previously implied, highly recurrent (hot-spot) cytogenetic imbalance regions. Thus, for many genomic regions, a simple null-hypothesis of independence between cancer type and relative copy number alteration frequency can be rejected. Since a subset of these regions display relatively low overall CNA frequencies, they may point towards second-tier genomic targets that are adaptively relevant but not necessarily essential for cancer development.

  2. Domain crossing

    DEFF Research Database (Denmark)

    Schraefel, M. C.; Rouncefield, Mark; Kellogg, Wendy

    2012-01-01

    In CSCW, how much do we need to know about another domain/culture before we observe, intersect and intervene with designs. What optimally would that other culture need to know about us? Is this a “how long is a piece of string” question, or an inquiry where we can consider a variety of contexts a...

  3. Distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases of Actinobacteria.

    Science.gov (United States)

    Ogawara, Hiroshi

    2016-09-01

    PASTA domains (penicillin-binding protein and serine/threonine kinase-associated domains) have been identified in penicillin-binding proteins and serine/threonine kinases of Gram-positive Firmicutes and Actinobacteria. They are believed to bind β-lactam antibiotics, and be involved in peptidoglycan metabolism, although their biological function is not definitively clarified. Actinobacteria, especially Streptomyces species, are distinct in that they undergo complex cellular differentiation and produce various antibiotics including β-lactams. This review focuses on the distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases in Actinobacteria. In Actinobacteria, PASTA domains are detectable exclusively in class A but not in class B penicillin-binding proteins, in sharp contrast to the cases in other bacteria. In penicillin-binding proteins, PASTA domains distribute independently from taxonomy with some distribution bias. Particularly interesting thing is that no Streptomyces species have penicillin-binding protein with PASTA domains. Protein kinases in Actinobacteria possess 0 to 5 PASTA domains in their molecules. Protein kinases in Streptomyces can be classified into three groups: no PASTA domain, 1 PASTA domain and 4 PASTA domain-containing groups. The 4 PASTA domain-containing groups can be further divided into two subgroups. The serine/threonine kinases in different groups may perform different functions. The pocket region in one of these subgroup is more dense and extended, thus it may be involved in binding of ligands like β-lactams more efficiently.

  4. Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene®)

    Science.gov (United States)

    Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

    1996-01-01

    Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

  5. Landscape and regional context differentially affect nest parasitism and nest predation for Wood Thrush in central Virginia, USA

    Science.gov (United States)

    Many empirical studies have shown that forest-breeding songbirds, and neotropical migrants in particular, are found in lower abundance in small patches of forest in the Eastern United States compared to similar, but larger patches in the same region. A common hypothesis for the ...

  6. MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies

    Science.gov (United States)

    Trabzuni, Daniah; Wray, Selina; Vandrovcova, Jana; Ramasamy, Adaikalavan; Walker, Robert; Smith, Colin; Luk, Connie; Gibbs, J. Raphael; Dillman, Allissa; Hernandez, Dena G.; Arepalli, Sampath; Singleton, Andrew B.; Cookson, Mark R.; Pittman, Alan M.; de Silva, Rohan; Weale, Michael E.; Hardy, John; Ryten, Mina

    2012-01-01

    The MAPT (microtubule-associated protein tau) locus is one of the most remarkable in neurogenetics due not only to its involvement in multiple neurodegenerative disorders, including progressive supranuclear palsy, corticobasal degeneration, Parksinson's disease and possibly Alzheimer's disease, but also due its genetic evolution and complex alternative splicing features which are, to some extent, linked and so all the more intriguing. Therefore, obtaining robust information regarding the expression, splicing and genetic regulation of this gene within the human brain is of immense importance. In this study, we used 2011 brain samples originating from 439 individuals to provide the most reliable and coherent information on the regional expression, splicing and regulation of MAPT available to date. We found significant regional variation in mRNA expression and splicing of MAPT within the human brain. Furthermore, at the gene level, the regional distribution of mRNA expression and total tau protein expression levels were largely in agreement, appearing to be highly correlated. Finally and most importantly, we show that while the reported H1/H2 association with gene level expression is likely to be due to a technical artefact, this polymorphism is associated with the expression of exon 3-containing isoforms in human brain. These findings would suggest that contrary to the prevailing view, genetic risk factors for neurodegenerative diseases at the MAPT locus are likely to operate by changing mRNA splicing in different brain regions, as opposed to the overall expression of the MAPT gene. PMID:22723018

  7. Differentiate responses of soil structure to natural vegetation and artificial plantation in landslide hazard region of the West Qinling Mountains, China

    Science.gov (United States)

    Wang, X.; Huang, Z.; Zhao, Y.; Hong, M.

    2017-12-01

    Natural vegetation and artificial plantation are the most important measures for ecological restoration in soil erosion and landslide hazard-prone regions of China. Previous studies have demonstrated that both measures can significantly change the soil structure and decrease soil and water erosion. Few reports have compared the effects of the two contrasting measures on mechanical and hydrological properties and further tested the differentiate responses of soil structure. In the study areas, two vegetation restoration measures-natural vegetation restoration (NVR) and artificial plantation restoration (APR) compared with control site, with similar topographical and geological backgrounds were selected to investigate the different effects on soil structure based on eight-year ecological restoration projects. The results showed that the surface vegetation played an important role in releasing soil erosion and enhance soil structure stability through change the soil aggregates (SA) and total soil porosity (TSP). The SArestoration and conservation in geological hazard-prone regions.

  8. Histogram analysis of apparent diffusion coefficient maps for the differentiation between lymphoma and metastatic lymph nodes of squamous cell carcinoma in head and neck region.

    Science.gov (United States)

    Wang, Yan-Jun; Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Shen, Jie; Shi, Hai-Bin; Wu, Fei-Yun

    2018-06-01

    Background To clarify the nature of cervical malignant lymphadenopathy is highly important for the diagnosis and differential diagnosis of head and neck tumors. Purpose To investigate the role of first-order apparent diffusion coefficient (ADC) histogram analysis for differentiating lymphoma from metastatic lymph nodes of squamous cell carcinoma (SCC) in the head and neck region. Material and Methods Diffusion-weighted imaging (DWI) data of 67 patients (lymphoma, n = 20; SCC, n = 47) with malignant lymphadenopathy were retrospectively analyzed. The SCC group was divided into nasopharyngeal SCC and non-nasopharyngeal SCC groups. The ADC histogram features (ADC 10 , ADC 25 , ADC mean , ADC median , ADC 75 , ADC 90 , skewness, and kurtosis) were derived and then compared by independent-samples t-test and one-way analysis of variance test, respectively. Receiver operating characteristic curve analyses were employed to investigate diagnostic performance of the significant parameters. Results Lymphoma showed significantly lower ADC mean , ADC median , ADC 75 , and ADC 90 than SCC (all P  0.05). Lymphoma showed significantly lower ADC 25 , ADC mean , ADC median , ADC 75 , and ADC 90 than non-nasopharyngeal SCC (all P histogram analysis is capable of differentiating lymphoma from metastatic lymph nodes of SCC, especially those of non-nasopharyngeal SCC.

  9. Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A-like inhibitor of differentiation 1 (EID1

    Directory of Open Access Journals (Sweden)

    Diana Vargas

    2008-01-01

    Full Text Available Transcriptional activation (TA mediated by the effect of thyroid hormones on target genes requires co-activator proteins such as the early region 1A (E1A associated 300 kDa binding protein (p300 and the cAMP response element binding protein (CREB binding protein (CBP, known as the p300/CBP complex, which acetylate histones 3 and 4 to allow transcriptional machinery access to the target gene promoter. Little is known on the role of p300 in thyroid hormone receptor (TR mediated TA but the E1A-like inhibitor of differentiation 1 (EID1, an inhibitor of p300 histone acetyltransferase (HAT, is a functional homolog of E1A and may inhibit myogenic differentiation factor D (MyoD transcriptional activity and reduces muscle cell differentiation. We evaluated the influence of EID1 on TR-mediated transcriptional activity using transfection and mammalian two-hybrid studies to show that EID1 may partially reduces TA activity of the TR receptor, probably due to p300 blockage since EID1 mutants cannot reduce TR-mediated TA. The EID1 does not affect the function of p160 co-activator proteins (160 kDa proteins of steroid receptor co-activators and is functionally independent of co-repressor proteins or TR binding. Summarizing, EID1 reduces TR-mediated transcriptional activity by blocking p300 and may play an important role in thyroid receptor activity in muscle and other tissues.

  10. Strong and stable geographic differentiation of swamp buffalo maternal and paternal lineages indicates domestication in the China/Indochina border region.

    Science.gov (United States)

    Zhang, Yi; Lu, Yongfang; Yindee, Marnoch; Li, Kuan-Yi; Kuo, Hsiao-Yun; Ju, Yu-Ten; Ye, Shaohui; Faruque, Md Omar; Li, Qiang; Wang, Yachun; Cuong, Vu Chi; Pham, Lan Doan; Bouahom, Bounthong; Yang, Bingzhuang; Liang, Xianwei; Cai, Zhihua; Vankan, Dianne; Manatchaiworakul, Wallaya; Kowlim, Nonglid; Duangchantrasiri, Somphot; Wajjwalku, Worawidh; Colenbrander, Ben; Zhang, Yuan; Beerli, Peter; Lenstra, Johannes A; Barker, J Stuart F

    2016-04-01

    The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y-chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y-chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock. © 2015 John Wiley & Sons Ltd.

  11. SH2 Domain Histochemistry.

    Science.gov (United States)

    Buhs, Sophia; Nollau, Peter

    2017-01-01

    Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.

  12. Small-scale structure and chemical differentiation in the central region of the Sagittarius B2 molecular cloud

    International Nuclear Information System (INIS)

    Goldsmith, P.F.; Snell, R.L.; Hasegawa, T.; Ukita, N.; Nobeyama Radio Observatory, Minamimaki, Japan)

    1987-01-01

    Fifteen arcsec angular resolution observations of a number of molecular species in the center of the Sgr B2 molecular cloud, including HC3N in the ground and v7 = 1 vibrational states, SO, OCS,l and HNCO, have been performed. Emission from HC3N is fairly uniformly distributed over the region studied; SO and OCS have a spatially extended component but are strongly centrally peaked. HNCO and vibrationally excited HC 3 N emission are essentially restricted to a very small region around the center of activity in the north. The difference between the spatial distributions are attributed to variation in the chemical abundances of the various clumps. The excitation requirements of the vibrationally excited HC 3 N imply the presence of dust and gas at high temperatures. The results further heighten the apparent contradiction presented by the lack of infrared emission from this source. 53 references

  13. Hydrological differentiation and spatial distribution of high altitude wetlands in a semi-arid Andean region derived from satellite data

    Science.gov (United States)

    Otto, M.; Scherer, D.; Richters, J.

    2011-05-01

    High Altitude Wetlands of the Andes (HAWA) belong to a unique type of wetland within the semi-arid high Andean region. Knowledge about HAWA has been derived mainly from studies at single sites within different parts of the Andes at only small time scales. On the one hand, HAWA depend on water provided by glacier streams, snow melt or precipitation. On the other hand, they are suspected to influence hydrology through water retention and vegetation growth altering stream flow velocity. We derived HAWA land cover from satellite data at regional scale and analysed changes in connection with precipitation over the last decade. Perennial and temporal HAWA subtypes can be distinguished by seasonal changes of photosynthetically active vegetation (PAV) indicating the perennial or temporal availability of water during the year. HAWA have been delineated within a region of 12 800 km2 situated in the Northwest of Lake Titicaca. The multi-temporal classification method used Normalized Differenced Vegetation Index (NDVI) and Normalized Differenced Infrared Index (NDII) data derived from two Landsat ETM+ scenes at the end of austral winter (September 2000) and at the end of austral summer (May 2001). The mapping result indicates an unexpected high abundance of HAWA covering about 800 km2 of the study region (6 %). Annual HAWA mapping was computed using NDVI 16-day composites of Moderate Resolution Imaging Spectroradiometer (MODIS). Analyses on the relation between HAWA and precipitation was based on monthly precipitation data of the Tropical Rain Measurement Mission (TRMM 3B43) and MODIS Eight Day Maximum Snow Extent data (MOD10A2) from 2000 to 2010. We found HAWA subtype specific dependencies on precipitation conditions. A strong relation exists between perennial HAWA and snow fall (r2: 0.82) in dry austral winter months (June to August) and between temporal HAWA and precipitation (r2: 0.75) during austral summer (March to May). Annual changes in spatial extend of perennial HAWA

  14. Trends in child immunization across geographical regions in India: focus on urban-rural and gender differentials.

    Directory of Open Access Journals (Sweden)

    Prashant Kumar Singh

    Full Text Available Although child immunization is regarded as a highly cost-effective lifesaver, about fifty percent of the eligible children aged 12-23 months in India are without essential immunization coverage. Despite several programmatic initiatives, urban-rural and gender difference in child immunization pose an intimidating challenge to India's public health agenda. This study assesses the urban-rural and gender difference in child immunization coverage during 1992-2006 across six major geographical regions in India.Three rounds of the National Family Health Survey (NFHS conducted during 1992-93, 1998-99 and 2005-06 were analyzed. Bivariate analyses, urban-rural and gender inequality ratios, and the multivariate-pooled logistic regression model were applied to examine the trends and patterns of inequalities over time.The analysis of change over one and half decades (1992-2006 shows considerable variations in child immunization coverage across six geographical regions in India. Despite a decline in urban-rural and gender differences over time, children residing in rural areas and girls remained disadvantaged. Moreover, northeast, west and south regions, which had the lowest gender inequality in 1992 observed an increase in gender difference over time. Similarly, urban-rural inequality increased in the west region during 1992-2006.This study suggests periodic evaluation of the health care system is vital to assess the between and within group difference beyond average improvement. It is essential to integrate strong immunization systems with broad health systems and coordinate with other primary health care delivery programs to augment immunization coverage.

  15. Trends in child immunization across geographical regions in India: focus on urban-rural and gender differentials.

    Science.gov (United States)

    Singh, Prashant Kumar

    2013-01-01

    Although child immunization is regarded as a highly cost-effective lifesaver, about fifty percent of the eligible children aged 12-23 months in India are without essential immunization coverage. Despite several programmatic initiatives, urban-rural and gender difference in child immunization pose an intimidating challenge to India's public health agenda. This study assesses the urban-rural and gender difference in child immunization coverage during 1992-2006 across six major geographical regions in India. Three rounds of the National Family Health Survey (NFHS) conducted during 1992-93, 1998-99 and 2005-06 were analyzed. Bivariate analyses, urban-rural and gender inequality ratios, and the multivariate-pooled logistic regression model were applied to examine the trends and patterns of inequalities over time. The analysis of change over one and half decades (1992-2006) shows considerable variations in child immunization coverage across six geographical regions in India. Despite a decline in urban-rural and gender differences over time, children residing in rural areas and girls remained disadvantaged. Moreover, northeast, west and south regions, which had the lowest gender inequality in 1992 observed an increase in gender difference over time. Similarly, urban-rural inequality increased in the west region during 1992-2006. This study suggests periodic evaluation of the health care system is vital to assess the between and within group difference beyond average improvement. It is essential to integrate strong immunization systems with broad health systems and coordinate with other primary health care delivery programs to augment immunization coverage.

  16. Regional differentiation and post-glacial expansion of the Atlantic silverside, Menidia menidia, an annual fish with high dispersal potential

    OpenAIRE

    Mach, Megan E.; Sbrocco, Elizabeth J.; Hice, Lyndie A.; Duffy, Tara A.; Conover, David O.; Barber, Paul H.

    2010-01-01

    The coastal marine environment of the Northwest Atlantic contains strong environmental gradients that create distinct marine biogeographic provinces by limiting dispersal, recruitment, and survival. This region has also been subjected to numerous Pleistocene glacial cycles, resulting in repeated extirpations and recolonizations in northern populations of marine organisms. In this study, we examined patterns of genetic structure and historical demography in the Atlantic silverside, Menidia men...

  17. The Rock Art of Upper Tibet and Ladakh: Inner Asian cultural adaptation, regional differentiation and the Western Tibetan Plateau Style

    OpenAIRE

    Bruneau , Laurianne; Bellezza , John V.

    2013-01-01

    International audience; This paper examines common thematic and esthetic features discernable in the rock art of the western portion of the Tibetan plateau. This rock art is international in scope; it includes Ladakh (La-dwags) (under Indian jurisdiction), Tö (Stod) and the Changthang (Byang-thang) (under Chinese administration) hereinafter called Upper Tibet. This work sets out the relationship of this art to other regions of Inner Asia and defines what we call the 'Western Tibetan Plateau S...

  18. Enterovirus Exposure Uniquely Discriminates Type 1 Diabetes Patients with a Homozygous from a Heterozygous Melanoma Differentiation-Associated Protein 5/Interferon Induced with Helicase C Domain 1 A946T Genotype.

    Science.gov (United States)

    Schulte, Barbara M; Gielen, Paul R; Kers-Rebel, Esther D; Prosser, Amy C; Lind, Katharina; Flodström-Tullberg, Malin; Tack, Cees J; Elving, Lammy D; Adema, Gosse J

    2016-09-01

    In children at risk for type 1 diabetes, innate immune activity is detected before seroconversion. Enterovirus infections have been linked to diabetes development, and a polymorphism (A946T) in the innate immune sensor recognizing enterovirus RNA, interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5, predisposes to disease. We hypothesized that the strength of innate antienteroviral responses is affected in autoimmune type 1 diabetes patients and linked to the A946T polymorphism. We compared induction of interferon-stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in healthy individuals and diabetes patients upon stimulation with enterovirus, enterovirus-antibody complexes, or ligands mimicking infection in relation to the A946T polymorphism. Overall, PBMCs of diabetes patients and healthy donors showed comparable ISG induction upon stimulation. No differences were observed in DCs. Interestingly, the data imply that the magnitude of responses to enterovirus and enterovirus-antibody complexes in PBMCs is critically influenced by the A946T polymorphism and elevated in heterozygotes compared to TT homozygous individuals in autoimmune diabetes patients, but not healthy controls. These data imply an intrinsic difference in the responses to enterovirus and enterovirus-antibody complexes in diabetes patients carrying a TT risk genotype compared to heterozygotes that may influence control of enterovirus clearance.

  19. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    remote access via IP-based devices such as smartphones. The Trusted Domain platform fits existing legacy technologies by managing their interoperability and access controls, and it seeks to avoid the security issues of relying on third-party servers outside the home. It is a distributed system...... of wireless standards, limited resources of embedded systems, etc. Taking these challenges into account, we present a Trusted Domain home automation platform, which dynamically and securely connects heterogeneous networks of Short-Range Wireless devices via simple non-expert user. interactions, and allows......In the digital age of home automation and with the proliferation of mobile Internet access, the intelligent home and its devices should be accessible at any time from anywhere. There are many challenges such as security, privacy, ease of configuration, incompatible legacy devices, a wealth...

  20. Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio (Devario aequipinnatus) and Zebrafish (Danio rerio) Hearts

    Science.gov (United States)

    Manalo, Trina; May, Adam; Quinn, Joshua; Lafontant, Dominique S.; Shifatu, Olubusola; He, Wei; Gonzalez-Rosa, Juan M.; Burns, Geoffrey C.; Burns, Caroline E.; Burns, Alan R.; Lafontant, Pascal J.

    2016-01-01

    Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish (Danio rerio) and giant danio (Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins—wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)—in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins’ ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID:27680670

  1. Identification of new polymorphic regions and differentiation of cultivated olives (Olea europaea L.) through plastome sequence comparison

    Science.gov (United States)

    2010-01-01

    Background The cultivated olive (Olea europaea L.) is the most agriculturally important species of the Oleaceae family. Although many studies have been performed on plastid polymorphisms to evaluate taxonomy, phylogeny and phylogeography of Olea subspecies, only few polymorphic regions discriminating among the agronomically and economically important olive cultivars have been identified. The objective of this study was to sequence the entire plastome of olive and analyze many potential polymorphic regions to develop new inter-cultivar genetic markers. Results The complete plastid genome of the olive cultivar Frantoio was determined by direct sequence analysis using universal and novel PCR primers designed to amplify all overlapping regions. The chloroplast genome of the olive has an organisation and gene order that is conserved among numerous Angiosperm species and do not contain any of the inversions, gene duplications, insertions, inverted repeat expansions and gene/intron losses that have been found in the chloroplast genomes of the genera Jasminum and Menodora, from the same family as Olea. The annotated sequence was used to evaluate the content of coding genes, the extent, and distribution of repeated and long dispersed sequences and the nucleotide composition pattern. These analyses provided essential information for structural, functional and comparative genomic studies in olive plastids. Furthermore, the alignment of the olive plastome sequence to those of other varieties and species identified 30 new organellar polymorphisms within the cultivated olive. Conclusions In addition to identifying mutations that may play a functional role in modifying the metabolism and adaptation of olive cultivars, the new chloroplast markers represent a valuable tool to assess the level of olive intercultivar plastome variation for use in population genetic analysis, phylogenesis, cultivar characterisation and DNA food tracking. PMID:20868482

  2. Hydrological differentiation and spatial distribution of high altitude wetlands in a semi-arid Andean region derived from satellite data

    Directory of Open Access Journals (Sweden)

    M. Otto

    2011-05-01

    Full Text Available High Altitude Wetlands of the Andes (HAWA belong to a unique type of wetland within the semi-arid high Andean region. Knowledge about HAWA has been derived mainly from studies at single sites within different parts of the Andes at only small time scales. On the one hand, HAWA depend on water provided by glacier streams, snow melt or precipitation. On the other hand, they are suspected to influence hydrology through water retention and vegetation growth altering stream flow velocity. We derived HAWA land cover from satellite data at regional scale and analysed changes in connection with precipitation over the last decade. Perennial and temporal HAWA subtypes can be distinguished by seasonal changes of photosynthetically active vegetation (PAV indicating the perennial or temporal availability of water during the year. HAWA have been delineated within a region of 12 800 km2 situated in the Northwest of Lake Titicaca. The multi-temporal classification method used Normalized Differenced Vegetation Index (NDVI and Normalized Differenced Infrared Index (NDII data derived from two Landsat ETM+ scenes at the end of austral winter (September 2000 and at the end of austral summer (May 2001. The mapping result indicates an unexpected high abundance of HAWA covering about 800 km2 of the study region (6 %. Annual HAWA mapping was computed using NDVI 16-day composites of Moderate Resolution Imaging Spectroradiometer (MODIS. Analyses on the relation between HAWA and precipitation was based on monthly precipitation data of the Tropical Rain Measurement Mission (TRMM 3B43 and MODIS Eight Day Maximum Snow Extent data (MOD10A2 from 2000 to 2010. We found HAWA subtype specific dependencies on precipitation conditions. A strong relation exists between perennial HAWA and snow fall (r2: 0.82 in dry austral winter months (June to August and between temporal HAWA and precipitation (r2: 0.75 during austral summer

  3. Added diagnostic benefit of 16-row whole-body spiral CT in patients with multiple trauma differentiated by region and injury severity according to the ATLS registered concept

    International Nuclear Information System (INIS)

    Maurer, M.H.; Knopke, S.; Schroeder, R.J.

    2008-01-01

    Purpose: to determine the added diagnostic benefit of using MS-CT in multiple trauma patients differentiated by severity of injury and affected body region. Materials and methods: a retrospective analysis was performed of the 16-row whole-body spiral CT findings in 275 multiple trauma patients (73% men, 27% women; age 39.6 ± 18.9 years) with regard to additional findings and new findings obtained with CT compared to the findings obtained by conventional projection radiography and abdominal ultrasound in the emergency room. The additional and new findings were differentiated by body region (head, face, chest, pelvis, abdomen, spine) and the degree of severity according to the three classes of injuries distinguished by the ATLS registered concept (class 1: simple injury, class 2: potentially life threatening, class 3: immediately life threatening). Results: a total of 921 additional findings (findings potentially relevant for further diagnosis and therapy in addition to the findings obtained by conventional radiography or ultrasound) were obtained by MS-CT in all patients. The distribution by number of patients and body region was as follows: 22 neck, 76 face, 125 chest, 112 abdomen, 50 pelvis, and 91 spine. Most additional findings were categorized as potentially life threatening (ATLS class 2). In addition, there were 439 completely new findings, involving the head in 128 patients (mostly ATLS class 3), the face in 18, the chest in 47, the abdomen in 26, and the spine in 9 patients. Most new findings involving the face, abdomen, and spine were ATLS class 2 injuries. (orig.)

  4. Differentiating local and regional sources of Chinese urban air pollution based on the effect of the Spring Festival

    Science.gov (United States)

    Wang, Chuan; Huang, Xiao-Feng; Zhu, Qiao; Cao, Li-Ming; Zhang, Bin; He, Ling-Yan

    2017-07-01

    The emission of pollutants is extremely reduced during the annual Chinese Spring Festival (SF) in Shenzhen, China. During the SF, traffic flow drops by ˜ 50 % and the industrial plants are almost entirely shut down in Shenzhen. To characterize the variation in ambient air pollutants due to the Spring Festival effect, various gaseous and particulate pollutants were measured in real time in urban Shenzhen over three consecutive winters (2014-2016). The results indicate that the concentrations of NOx, volatile organic compounds (VOCs), black carbon (BC), primary organic aerosols, chloride, and nitrate in submicron aerosols decrease by 50-80 % during SF periods relative to non-Spring Festival periods, regardless of meteorological conditions. This decrease suggests that these pollutants are mostly emitted or secondarily formed from urban local emissions. The concentration variation in species mostly from regional or natural sources, however, is found to be much less, such as for bulk fine particulate matter (PM2. 5). More detailed analysis of the Spring Festival effect reveals an urgent need to reduce emissions of SO2 and VOCs on a regional scale rather than on an urban scale to reduce urban PM2. 5 in Shenzhen, which can also be useful as a reference for other megacities in China.

  5. Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.

    Science.gov (United States)

    Pan, Bo; Huang, Xu-Feng; Deng, Chao

    2016-03-28

    Aripiprazole, a dopamine D₂ receptor (D₂R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D₂R antagonist) and bifeprunox (a D₂R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D₂Rs.

  6. Rare RNF213 variants in the C-terminal region encompassing the RING-finger domain are associated with moyamoya angiopathy in Caucasians.

    Science.gov (United States)

    Guey, Stéphanie; Kraemer, Markus; Hervé, Dominique; Ludwig, Thomas; Kossorotoff, Manoëlle; Bergametti, Françoise; Schwitalla, Jan Claudius; Choi, Simone; Broseus, Lucile; Callebaut, Isabelle; Genin, Emmanuelle; Tournier-Lasserve, Elisabeth

    2017-08-01

    Moyamoya angiopathy (MMA) is a cerebral angiopathy affecting the terminal part of internal carotid arteries. Its prevalence is 10 times higher in Japan and Korea than in Europe. In East Asian countries, moyamoya is strongly associated to the R4810K variant in the RNF213 gene that encodes for a protein containing a RING-finger and two AAA+ domains. This variant has never been detected in Caucasian MMA patients, but several rare RNF213 variants have been reported in Caucasian cases. Using a collapsing test based on exome data from 68 European MMA probands and 573 ethnically matched controls, we showed a significant association between rare missense RNF213 variants and MMA in European patients (odds ratio (OR)=2.24, 95% confidence interval (CI)=(1.19-4.11), P=0.01). Variants specific to cases had higher pathogenicity predictive scores (median of 24.2 in cases versus 9.4 in controls, P=0.029) and preferentially clustered in a C-terminal hotspot encompassing the RING-finger domain of RNF213 (P<10 -3 ). This association was even stronger when restricting the analysis to childhood-onset and familial cases (OR=4.54, 95% CI=(1.80-11.34), P=1.1 × 10 -3 ). All clinically affected relatives who were genotyped were carriers. However, the need for additional factors to develop MMA is strongly suggested by the fact that only 25% of mutation carrier relatives were clinically affected.

  7. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

    Directory of Open Access Journals (Sweden)

    Paula A Gajewski

    Full Text Available Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC and hippocampus (HPC of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc. Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.

  8. Sorghum Landrace Collections from Cooler Regions of the World Exhibit Magnificent Genetic Differentiation and Early Season Cold Tolerance

    Directory of Open Access Journals (Sweden)

    Frank Maulana

    2017-05-01

    Full Text Available Cold temperature is an important abiotic stress affecting sorghum production in temperate regions. It reduces seed germination, seedling emergence and seedling vigor thus limiting the production of the crop both temporally and spatially. The objectives of this study were (1 to assess early season cold temperature stress response of sorghum germplasm from cooler environments and identify sources of tolerance for use in breeding programs, (2 to determine population structure and marker-trait association among these germplasms for eventual development of marker tools for improving cold tolerance. A total of 136 sorghum accessions from cooler regions of the world were phenotyped for seedling growth characteristics under cold temperature imposed through early planting. The accessions were genotyped using 67 simple sequence repeats markers spanning all ten linkage groups of sorghum, of which 50 highly polymorphic markers were used in the analysis. Genetic diversity and population structure analyses sorted the population into four subpopulations. Several accessions distributed in all subpopulations showed either better or comparable level of tolerance to the standard cold tolerance source, Shan qui red. Association analysis between the markers and seedling traits identified markers Xtxp34, Xtxp88, and Xtxp319 as associated with seedling emergence, Xtxp211 and Xtxp304 with seedling dry weight, and Xtxp20 with seedling height. The markers were detected on chromosomes previously found to harbor QTLs associated with cold tolerance in sorghum. Once validated these may serve as genomic tools in marker-assisted breeding or for screening larger pool of genotypes to identify additional sources of cold tolerance.

  9. Cercospora zeina from Maize in South Africa Exhibits High Genetic Diversity and Lack of Regional Population Differentiation.

    Science.gov (United States)

    Muller, Mischa F; Barnes, Irene; Kunene, Ncobile T; Crampton, Bridget G; Bluhm, Burton H; Phillips, Sonia M; Olivier, Nicholas A; Berger, Dave K

    2016-10-01

    South Africa is one of the leading maize-producing countries in sub-Saharan Africa. Since the 1980s, Cercospora zeina, a causal agent of gray leaf spot of maize, has become endemic in South Africa, and is responsible for substantial yield reductions. To assess genetic diversity and population structure of C. zeina in South Africa, 369 isolates were collected from commercial maize farms in three provinces (KwaZulu-Natal, Mpumalanga, and North West). These isolates were evaluated with 14 microsatellite markers and species-specific mating type markers that were designed from draft genome sequences of C. zeina isolates from Africa (CMW 25467) and the United States (USPA-4). Sixty alleles were identified across 14 loci, and gene diversity values within each province ranged from 0.18 to 0.35. High levels of gene flow were observed (Nm = 5.51), and in a few cases, identical multilocus haplotypes were found in different provinces. Overall, 242 unique multilocus haplotypes were identified with a low clonal fraction of 34%. No distinct population clusters were identified using STRUCTURE, principal coordinate analysis, or Weir's theta θ statistic. The lack of population differentiation was supported by analysis of molecular variance tests, which indicated that only 2% of the variation was attributed to variability between populations from each province. Mating type ratios of MAT1-1 and MAT1-2 idiomorphs from 335 isolates were not significantly different from a 1:1 ratio in all provinces, which provided evidence for sexual reproduction. The draft genome of C. zeina CMW 25467 exhibited a complete genomic copy of the MAT1-1 idiomorph as well as exonic fragments of MAT genes from both idiomorphs. The high level of gene diversity, shared haplotypes at different geographical locations within South Africa, and presence of both MAT idiomorphs at all sites indicates widespread dispersal of C. zeina between maize fields in the country as well as evidence for sexual recombination. The

  10. Assessment of genetic mutations in the XRCC2 coding region by high resolution melting curve analysis and the risk of differentiated thyroid carcinoma in Iran

    Directory of Open Access Journals (Sweden)

    Shima Fayaz

    2012-01-01

    Full Text Available Homologous recombination (HR is the major pathway for repairing double strand breaks (DSBs in eukaryotes and XRCC2 is an essential component of the HR repair machinery. To evaluate the potential role of mutations in gene repair by HR in individuals susceptible to differentiated thyroid carcinoma (DTC we used high resolution melting (HRM analysis, a recently introduced method for detecting mutations, to examine the entire XRCC2 coding region in an Iranian population. HRM analysis was used to screen for mutations in three XRCC2 coding regions in 50 patients and 50 controls. There was no variation in the HRM curves obtained from the analysis of exons 1 and 2 in the case and control groups. In exon 3, an Arg188His polymorphism (rs3218536 was detected as a new melting curve group (OR: 1.46; 95%CI: 0.432-4.969; p = 0.38 compared with the normal melting curve. We also found a new Ser150Arg polymorphism in exon 3 of the control group. These findings suggest that genetic variations in the XRCC2 coding region have no potential effects on susceptibility to DTC. However, further studies with larger populations are required to confirm this conclusion.

  11. Localization of Daucus carota NMCP1 to the nuclear periphery: the role of the N-terminal region and an NLS-linked sequence motif, RYNLRR, in the tail domain

    Directory of Open Access Journals (Sweden)

    Yuta eKimura

    2014-02-01

    Full Text Available Recent ultrastructural studies revealed that a structure similar to the vertebrate nuclear lamina exists in the nuclei of higher plants. However, plant genomes lack genes for lamins and intermediate-type filament proteins, and this suggests that plant-specific nuclear coiled-coil proteins make up the lamina-like structure in plants. NMCP1 is a protein, first identified in Daucus carota cells, that localizes exclusively to the nuclear periphery in interphase cells. It has a tripartite structure comprised of head, rod, and tail domains, and includes putative nuclear localization signal (NLS motifs. We identified the functional NLS of DcNMCP1 (carrot NMCP1 and determined the protein regions required for localizing to the nuclear periphery using EGFP-fused constructs transiently expressed in Apium graveolens epidermal cells. Transcription was driven under a CaMV35S promoter, and the genes were introduced into the epidermal cells by a DNA-coated microprojectile delivery system. Of the NLS motifs, KRRRK and RRHK in the tail domain were highly functional for nuclear localization. Addition of the N-terminal 141 amino acids from DcNMCP1 shifted the localization of a region including these NLSs from the entire nucleus to the nuclear periphery. Using this same construct, the replacement of amino acids in RRHK or its preceding sequence, YNL, with alanine residues abolished localization to the nuclear periphery, while replacement of KRRRK did not affect localization. The sequence R/Q/HYNLRR/H, including YNL and the first part of the sequence of RRHK, is evolutionarily conserved in a subclass of NMCP1 sequences from many plant species. These results show that NMCP1 localizes to the nuclear periphery by a combined action of a sequence composed of R/Q/HYNLRR/H, NLS, and the N-terminal region including the head and a portion of the rod domain, suggesting that more than one binding site is implicated in localization of NMCP1.

  12. Domain-to-domain coupling in voltage-sensing phosphatase.

    Science.gov (United States)

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

  13. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Jensen, Tanja B; Meuleman, Philip

    2011-01-01

    Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma...... genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(ΔHVR1), 1b(ΔHVR1), 2b(ΔHVR1), and 3a(ΔHVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA...... density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ∼1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles...

  14. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization

    DEFF Research Database (Denmark)

    Prentø, Jannick Cornelius; Jensen, Tanja Bertelsen; Meuleman, Philip

    2011-01-01

    Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma...... genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(¿HVR1), 1b(¿HVR1), 2b(¿HVR1), and 3a(¿HVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA...... density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ~1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles...

  15. Regional inequalities of child mortality in peninsular Malaysia with special reference to the differentials between Perlis and Kuala Terengganu.

    Science.gov (United States)

    Brehm, U

    1993-05-01

    In Peninsular Malaysia child mortality rates (5q0) vary from 13 to 63 per thousand at district level. The spatial pattern is closely associated with the regional distribution of socio-economic factors. But due to multicollinearity it is difficult to isolate the influence of socio-economic variables from other variables by employing aggregated data. However, individual data collected in a case-control-study that was conducted in Perlis and Kuala Terengganu confirm the important role of socio-economic factors. So it should be possible to achieve a further reduction of child mortality by raising the income and educational level of the under-privileged groups. Apart from that, as the case of Perlis shows, the provision of family planning and preventive medical services may also contribute to lower child mortality independent from socio-economic changes. But, as the comparison with Kuala Terengganu shows, the utilization of family planning and preventive medical services is not only influenced by the accessibility to, but also by the socio-culturally determined acceptability of such services.

  16. Regional up-regulation of NOX2 contributes to the differential vulnerability of outer hair cells to neomycin.

    Science.gov (United States)

    Qi, Meihao; Qiu, Yang; Zhou, Xueying; Tian, Keyong; Zhou, Ke; Sun, Fei; Yue, Bo; Chen, Fuquan; Zha, Dingjun; Qiu, Jianhua

    2018-06-02

    In hearing loss induced by aminoglycoside antibiotics, the outer hair cells (OHCs) in the basal turn are always more susceptible than OHCs in the apical turn, while the underlying mechanisms remain unknown. In this study, we reported that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs among different turns, at a relatively low level. However, after neomycin treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in vitro studies demonstrated that inhibition of NOX2 significantly alleviated neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our study shows that regional up-expression of NOX2 and subsequent increase of ROS in OHCs of the basal turn is an important factor contributing to the vulnerability of OHCs there, which should shed light on the prevention of hearing loss induced by aminoglycoside antibiotics. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex

    Directory of Open Access Journals (Sweden)

    Pavlos eRigas

    2015-10-01

    Full Text Available Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models.

  18. Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex.

    Science.gov (United States)

    Rigas, Pavlos; Adamos, Dimitrios A; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A; Skaliora, Irini

    2015-01-01

    Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models.

  19. Differential cross section measurements of the π-p elastic scattering in the Coulomb interference region between 30 and 140 GeV

    International Nuclear Information System (INIS)

    Ille, B.

    1979-01-01

    The differential cross section of elastic π - -p scattering in the Coulomb interference region from 30 GeV to 140 GeV has been measured at the CERN SPS using in conjunction an ionization chamber recoil spectrometer and a forward multiwire proportional chamber-magnet spectrometer. The phase of the π - -p forward hadronic amplitude was found to go four negative value (at 30 GeV) to positive value (at 140 GeV), passing through zero at about 60 GeV. The logarithmic slope at small /t/ (/t/ approximately 0.03 (GeV/c) 2 ) has also been measured and was found to be higher by about 3 (GeV/c) -2 than the values determined at higher /t/ (/t/ = 0.2 (GeV/c) 2 ) [fr

  20. Circular intensity differential scattering (CIDS) measurements in the soft x-ray region of the spectrum (∼16 eV to 500 eV)

    International Nuclear Information System (INIS)

    Maestre, M.F.; Bustamante, C.; Snyder, P.; Rowe, E.; Hansen, R.

    1991-03-01

    We propose the use of recently developed techniques of circular intensity differential scattering (CIDS), as extended to the soft x-ray region of the spectrum (16 eV to 500 eV), to study the higher order organization of the eukaryotic chromosome. CIDS is the difference in scattering power of an object when illuminated by right circularly polarized vs. left circularly polarized electromagnetic radiation of arbitrary wavelength. CIDS has been shown to be a very sensitive measure of the helical organization of the scattering object eg. the eukaryotic chromosome. Preliminary results of measurements of samples of bacteriophages and octopus sperm done at SRC, Wisconsin, show the technique to be very sensitive to the dimensional parameters of the particles interrogated by circularly polarized light. 7 refs., 5 figs

  1. Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice

    Science.gov (United States)

    Tajerian, Maral; Leu, David; Yang, Phillip; Huang, Ting Ting; Kingery, Wade S; Clark, J David

    2015-01-01

    Background Complex regional pain syndrome (CRPS) is a painful, disabling and often chronic condition, where many patients transition from an acute phase with prominent peripheral neurogenic inflammation to a chronic phase with evident central nervous system (CNS) changes. Ketamine is a centrally-acting agent believed to work through blockade of N-methyl-D-aspartate (NMDA) receptors and is being increasingly used for the treatment of refractory CRPS, although the basis for the drug’s effects and efficacy at different stages of the syndrome remain unclear. Methods We used a mouse model of CRPS (n=8–12/group) involving tibia fracture/cast immobilization to test the efficacy of ketamine (2 mg/kg/day; 7 days) or vehicle infusion during acute (3weeks [3w] post-fracture) and chronic (7w post-fracture) stages. Results Acute phase fracture mice displayed elevated limb temperature, edema and nociceptive sensitization that were not reduced by ketamine. Fracture mice treated with ketamine during the chronic phase showed reduced nociceptive sensitization that persisted beyond completion of the infusion. During this chronic phase, ketamine also reduced latent nociceptive sensitization and improved motor function at 18 weeks post-fracture. No side effects of the infusions were identified. These behavioral changes were associated with altered spinal astrocyte activation and expression of pain-related proteins including NMDA receptor 2b (NR2b), Ca2+/calmodulin-dependent protein kinase ii (CaMK2), and brain-derived neurotrophic factor (BNDF). Conclusions Collectively, these results demonstrate that ketamine is efficacious in the chronic, but not acute stages of CRPS, suggesting that the centrally-acting drug is relatively ineffective in early CRPS when peripheral mechanisms are more critical for supporting nociceptive sensitization. PMID:26492479

  2. Conservation and genetic characterisation of common bean landraces from Cilento region (southern Italy): high differentiation in spite of low genetic diversity.

    Science.gov (United States)

    De Luca, Daniele; Cennamo, Paola; Del Guacchio, Emanuele; Di Novella, Riccardo; Caputo, Paolo

    2018-02-01

    Since its introduction from Central-South America to Italy almost 500 years ago, the common bean (Phaseolus vulgaris L.) was largely cultivated across the peninsula in hundreds of different landraces. However, globalisation and technological modernisation of agricultural practices in the last decades promoted the cultivation of few varieties at the expense of traditional and local agro-ecotypes, which have been confined to local markets or have completely disappeared. The aim of this study was to evaluate the genetic diversity and differentiation in 12 common bean landraces once largely cultivated in the Cilento region (Campania region, southern Italy), and now the object of a recovery program to save them from extinction. The analysis conducted using 13 nuclear microsatellite loci in 140 individuals revealed a high degree of homozygosity within each landrace and a strong genetic differentiation that was reflected in the success in assigning individuals to the source landrace. On the contrary, internal transcribed spacers 1 and 2, analysed in one individual per landrace, were highly similar among common bean landraces but allowed the identification of a cowpea variety (Vigna unguiculata Walp.), a crop largely cultivated in the Old World before the arrival of common bean from Americas. In conclusion, our study highlighted that conservation of landraces is important not only for the cultural and socio-economic value that they have for local communities, but also because the time and conditions in which they have been selected have led to that genetic distinctiveness that is at the basis of many potential agronomical applications and dietary benefits.

  3. Eco-environment Restoration and Regional Differentiation Characteristics Based on “Building Terrace and Returning Slope Farmland to Forests and Grass”

    Institute of Scientific and Technical Information of China (English)

    Yanhua; LIU; Yong; XU

    2013-01-01

    Based on the scientific and technological achievements in the past decade in the Loess Hilly-gully Region and the successful demonstration experience in Yan’an Yangou watershed, we summarize the characteristics of eco-environment restoration pattern based on "building terrace and returning slope farmland to forests and grass". According to the data on land use, slope farmland and the agricultural population in 1999, we calculate the area of new terrace that needs to be built, the area of garden plot that needs to be extended, vegetation restoration area and investment demand in counties (cities, districts). Establishing and using some indicators, such as basic farmland extension indicator, garden plot extension indicator, vegetation restoration index and investment demand density, we conduct type classification and analysis of regional differentiation characteristics in 55 counties (cities, districts). The results show that in the Loess Hilly-gully Region, 691 600 hm2 of new terrace needs to be built, 792 000 hm2 of economic forests and orchards need to be extended, 5 410 200 hm2 of vegetation needs to be restored, and the total investment demand is 15.82 billion yuan; in terms of geographical distribution, obviously there are two key areas for eco-environment restoration (one is located in the border area between northern Shaanxi and northwestern Shanxi, and the other is located in the eastern Gansu and southern Ningxia area); the classified regional guidance policies should be formulated as soon as possible, and the limited funds should be concentrated in the key areas.

  4. Sex Differences in Medium Spiny Neuron Excitability and Glutamatergic Synaptic Input: Heterogeneity Across Striatal Regions and Evidence for Estradiol-Dependent Sexual Differentiation

    Directory of Open Access Journals (Sweden)

    Jinyan Cao

    2018-04-01

    Full Text Available Steroid sex hormones and biological sex influence how the brain regulates motivated behavior, reward, and sensorimotor function in both normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the caudate–putamen, nucleus accumbens core (AcbC, and shell. These brain regions are of particular interest to neuroendocrinologists given that they express membrane-associated but not nuclear estrogen receptors, and also the well-established role of the sex steroid hormone 17β-estradiol (estradiol in modulating striatal dopamine systems. Indeed, output neurons of the striatum, the medium spiny neurons (MSNs, exhibit estradiol sensitivity and sex differences in electrophysiological properties. Here, we review sex differences in rat MSN glutamatergic synaptic input and intrinsic excitability across striatal regions, including evidence for estradiol-mediated sexual differentiation in the nucleus AcbC. In prepubertal animals, female MSNs in the caudate–putamen exhibit a greater intrinsic excitability relative to male MSNs, but no sex differences are detected in excitatory synaptic input. Alternatively, female MSNs in the nucleus AcbC exhibit increased excitatory synaptic input relative to male MSNs, but no sex differences in intrinsic excitability were detected. Increased excitatory synaptic input onto female MSNs in the nucleus AcbC is abolished after masculinizing estradiol or testosterone exposure during the neonatal critical period. No sex differences are detected in MSNs in prepubertal nucleus accumbens shell. Thus, despite possessing the same neuron type, striatal regions exhibit heterogeneity in sex differences in MSN electrophysiological properties, which likely contribute to the sex differences observed in striatal function.

  5. The Regional Earth System Model (RegESM) using RegCM4 coupled with the MITgcm ocean model: First assessments over the MED-CORDEX domain

    Science.gov (United States)

    Mariotti, Laura; Utku Turunçoǧlu, Ufuk; Farneti, Riccardo; Sannino, Gianmaria; Vittoria Struglia, Maria; Carillo, Adriana; Giorgi, Filippo

    2016-04-01

    In the framework of global climate studies, there is an increasingly growing concern about the vulnerability of the Mediterranean region, where high population density and intense exploitation activities pose severe questions on the sustainability of terrestrial water management, both for the present and the future. Ocean modeling studies suggest that the Mediterranean thermohaline circulation could be weakened in conditions of global greenhouse warming, an event which would undoubtedly affect regional climate, possibly triggering global feedback processes. Experiments with the atmosphere-ocean coupled system confirmed that a good comprehension of Mediterranean processes requires the explicit inclusion of the feedbacks between the atmospheric and the oceanic components, thus achieving a complete, fully coupled description of the Mediterranean hydrological cycle, at the same time gaining new insights in our current ability to reproduce the atmospheric hydrological processes and to close the hydrological balance. These issues are addressed by the upgraded PROTHEUS system which was jointly developed by ENEA and ICTP. Here we present a first evaluation of the performances of the new PROTHEUS system (called PROTHEUS 2.0) composed by the regional climate model RegCM4 (Giorgi et al. 2012) coupled with both the ocean model MITgcm (Marshall J. et al. 1997a,b) and the HD river model (Max-Planck's HD model; Hagemann and Dümenil, 1998) using RegESM (Regional Earth System Model) as a driver. The three-component (atmosphere, ocean and river routing) fully coupled model exchanges sea surface temperature (SST) from the ocean to the atmospheric model, surface wind stress, energy and freshwater fluxes from the atmosphere to the ocean model, surface and sub-surface runoff from the atmospheric component to the river routing model (Max-Planck's HD model; Hagemann and Dümenil, 1998). In order to have water conservation within the system, the river routing component sends the

  6. Atomic structure of the sweet-tasting protein thaumatin I at pH 8.0 reveals the large disulfide-rich region in domain II to be sensitive to a pH change

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, Tetsuya, E-mail: t2masuda@kais.kyoto-u.ac.jp [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Ohta, Keisuke [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Mikami, Bunzo [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Kitabatake, Naofumi [Department of Foods and Human Nutrition, Notre Dame Seishin University, Okayama 700-8516 (Japan); Tani, Fumito [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Structure of a recombinant thaumatin at pH 8.0 determined at a resolution of 1.0 A. Black-Right-Pointing-Pointer Substantial fluctuations of a loop in domain II was found in the structure at pH 8.0. Black-Right-Pointing-Pointer B-factors for Lys137, Lys163, and Lys187 were significantly affected by pH change. Black-Right-Pointing-Pointer An increase in mobility might play an important role in the heat-induced aggregation. -- Abstract: Thaumatin, an intensely sweet-tasting plant protein, elicits a sweet taste at 50 nM. Although the sweetness remains when thaumatin is heated at 80 Degree-Sign C for 4 h under acid conditions, it rapidly declines when heating at a pH above 6.5. To clarify the structural difference at high pH, the atomic structure of a recombinant thaumatin I at pH 8.0 was determined at a resolution of 1.0 A. Comparison to the crystal structure of thaumatin at pH 7.3 and 7.0 revealed the root-mean square deviation value of a C{alpha} atom to be substantially greater in the large disulfide-rich region of domain II, especially residues 154-164, suggesting that a loop region in domain II to be affected by solvent conditions. Furthermore, B-factors of Lys137, Lys163, and Lys187 were significantly affected by pH change, suggesting that a striking increase in the mobility of these lysine residues, which could facilitate a reaction with a free sulfhydryl residue produced via the {beta}-elimination of disulfide bonds by heating at a pH above 7.0. The increase in mobility of lysine residues as well as a loop region in domain II might play an important role in the heat-induced aggregation of thaumatin above pH 7.0.

  7. Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates

    Directory of Open Access Journals (Sweden)

    Wang Jinkai

    2012-08-01

    Full Text Available Abstract Background The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. Results To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Conclusions Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

  8. Topological domain walls in helimagnets

    Science.gov (United States)

    Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.

    2018-05-01

    Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.

  9. Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

    Science.gov (United States)

    Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

    2018-02-01

    The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

  10. Late Quaternary developments of Mediterranean oaks in the Atlantic domain of the Iberian Peninsula: The case of the Cantabrian region (N Spain)

    Science.gov (United States)

    Uzquiano, P.; Ruiz-Zapata, MaB.; Gil-Garcia, MaJ.; Fernández, S.; Carrión, J. S.

    2016-12-01

    A synthesis of the occurrence of the evergreen oak (Quercus ilex-type) in the Cantabrian region (northern Spain) is presented on the basis of integrated charcoal and pollen analyses. Archaeological charcoal comes largely from sites along the littoral and pre-littoral territories of the Basque Country, Cantabria and Asturias dated from 45 to 3.7 Kyr cal BP, and culturally ranging from Mousterian to Iron Age. Pollen information is produced from a few archaeological sites but mainly from peats and lake sediments. Q. ilex-type is observed as early as at 45-30 Kyr cal BP, with sporadic occurrences in vegetation contexts dominated by Pinus sylvestris-type, which was widely exploited by Mousterian and Aurignacian inhabitants. Afterwards, during the Upper Palaeolithic, there is an important decline, and Q. ilex-type is hardly present between 29 and 15 Kyr cal BP, with open environments dominated by heathland shrubs. From Late Magdalenian onwards, Q. ilex-type expanded again, remaining in the landscape of the Cantabrian region throughout the Holocene, although subordinated in deciduous oak forests under the influence of oceanic climate conditions. Q. ilex-type had a more favourable position than deciduous Quercus across the Cantabrian southern slopes and northwest of the adjacent Iberian Cordillera, where oceanic influences have become attenuated by summer drought and continentality.

  11. .Gov Domains API

    Data.gov (United States)

    General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

  12. AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: implications for myocardial differentiation and regional identity.

    Science.gov (United States)

    Thomas, Penny S; Rajderkar, Sudha; Lane, Jamie; Mishina, Yuji; Kaartinen, Vesa

    2014-06-15

    BMP signaling plays an essential role in second heart field-derived heart and arterial trunk development, including myocardial differentiation, right ventricular growth, and interventricular, outflow tract and aortico-pulmonary septation. It is mediated by a number of different BMP ligands, and receptors, many of which are present simultaneously. The mechanisms by which they regulate morphogenetic events and degree of redundancy amongst them have still to be elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in anterior second heart field-derived cell development, and compared it with that of BmpR1a. By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1 plays an essential role in arterial pole morphogenesis, identifying defects in outflow tract wall and cushion morphology that preceded a spectrum of septation defects from double outlet right ventricle to common arterial trunk in mutants. Its absence caused dysregulation in gene expression important for myocardial differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2). Although these defects resemble to some degree those in the equivalent Bmpr1a mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1 locus only partially restored septation in Acvr1 mutants. These data show that both BmpR1a and AcvR1 are needed for normal heart development, in which they play some non-redundant roles, and refine our understanding of the genetic and morphogenetic processes underlying Bmp-mediated heart development important in human congenital heart disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. S-type granite generation and emplacement during a regional switch from extensional to contractional deformation (Central Iberian Zone, Iberian autochthonous domain, Variscan Orogeny)

    Science.gov (United States)

    Pereira, M. F.; Díez Fernández, R.; Gama, C.; Hofmann, M.; Gärtner, A.; Linnemann, U.

    2018-01-01

    Zircon grains extracted from S-type granites of the Mêda-Escalhão-Penedono Massif (Central Iberian Zone, Variscan Orogen) constrain the timing of emplacement and provide information about potential magma sources. Simple and composite zircon grains from three samples of S-type granite were analyzed by LA-ICP-MS. New U-Pb data indicate that granites crystallized in the Bashkirian (318.7 ± 4.8 Ma) overlapping the proposed age range of ca. 321-317 Ma of the nearby S-type granitic rocks of the Carrazeda de Anciães, Lamego and Ucanha-Vilar massifs. The timing of emplacement of such S-type granites seems to coincide with the waning stages of activity of a D2 extensional shear zone (i.e. Pinhel shear zone) developed in metamorphic conditions that reached partial melting and anatexis (ca. 321-317 Ma). Dykes of two-mica granites (resembling diatexite migmatite) are concordant and discordant to the compositional layering and S2 (main) foliation of the high-grade metamorphic rocks of the Pinhel shear zone. Much of the planar fabric in these dykes was formed during magmatic crystallization and subsequent solid-state deformation. Field relationships suggest contemporaneity between the ca. 319-317 Ma old magmatism of the study area and the switch from late D2 extensional deformation to early D3 contractional deformation. Inherited zircon cores are well preserved in these late D2-early D3 S-type granite plutons. U-Pb ages of inherited zircon cores range from ca. 2576 to ca. 421 Ma. The spectra of inherited cores overlap closely the range of detrital and magmatic zircon grains displayed by the Ediacaran to Silurian metasedimentary and metaigneous rocks of the Iberian autochthonous and parautochthonous domains. This is evidence of a genetic relationship between S-type granites and the host metamorphic rocks. There is no substantial evidence for the addition of mantle-derived material in the genesis of these late D2-early D3 S-type granitic rocks. The ɛNd arrays of heterogeneous

  14. Diffusion weighted imaging for differentiating benign from malignant orbital tumors: Diagnostic performance of the apparent diffusion coefficient based on region of interest selection method

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiao Quan; Hu, Hao Hu; Su, Guo Yi; Liu, Hu; Shi, Hai Bin; Wu, Fei Yun [First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2016-09-15

    To evaluate the differences in the apparent diffusion coefficient (ADC) measurements based on three different region of interest (ROI) selection methods, and compare their diagnostic performance in differentiating benign from malignant orbital tumors. Diffusion-weighted imaging data of sixty-four patients with orbital tumors (33 benign and 31 malignant) were retrospectively analyzed. Two readers independently measured the ADC values using three different ROIs selection methods including whole-tumor (WT), single-slice (SS), and reader-defined small sample (RDSS). The differences of ADC values (ADC-ROI{sub WT}, ADC-ROI{sub SS}, and ADC-ROI{sub RDSS}) between benign and malignant group were compared using unpaired t test. Receiver operating characteristic curve was used to determine and compare their diagnostic ability. The ADC measurement time was compared using ANOVA analysis and the measurement reproducibility was assessed using Bland-Altman method and intra-class correlation coefficient (ICC). Malignant group showed significantly lower ADC-ROI{sub WT}, ADC-ROI{sub SS}, and ADC-ROI{sub RDSS} than benign group (all p < 0.05). The areas under the curve showed no significant difference when using ADC-ROI{sub WT}, ADC-ROI{sub SS}, and ADC-ROI{sub RDSS} as differentiating index, respectively (all p > 0.05). The ROI{sub SS} and ROI{sub RDSS} required comparable measurement time (p > 0.05), while significantly shorter than ROI{sub WT} (p < 0.05). The ROI{sub SS} showed the best reproducibility (mean difference ± limits of agreement between two readers were 0.022 [-0.080–0.123] × 10{sup -3} mm{sup 2}/s; ICC, 0.997) among three ROI method. Apparent diffusion coefficient values based on the three different ROI selection methods can help to differentiate benign from malignant orbital tumors. The results of measurement time, reproducibility and diagnostic ability suggest that the ROI{sub SS} method are potentially useful for clinical practice.

  15. An experimental and petrologic investigation of the source regions of lunar magmatism in the context of the primordial differentiation of the moon

    Science.gov (United States)

    Elardo, Stephen M.

    The primordial differentiation of the Moon via a global magma ocean has become the paradigm under which all lunar data are interpreted. The success of this model in explaining multiple geochemical, petrologic, and isotopic characteristics lunar geology has led to magma oceans becoming the preferred model for the differentiation of Earth, Mars, Mercury, Vesta, and other large terrestrial bodies. The goal of this work is to combine petrologic analyses of lunar samples with high pressure, high temperature petrologic experiments to place new and detailed constraints the petrogenetic processes that operated during different stages of lunar magmatism, the processes that have acted upon these magmas to obscure their relationship to their mantle source regions, and how those source regions fit into the context of the lunar magma ocean model. This work focuses on two important phases of lunar magmatism: the ancient crust-building plutonic lithologies of the Mg-suite dating to ~4.3 Ga, and the most recent known mare basaltic magmas dating to ~3 Ga. These samples provide insight into the petrogenesis of magmas and interior thermal state when the Moon was a hot, juvenile planet, and also during the last gasps of magmatism from a cooling planet. Chapter 1, focusing on Mg-suite troctolite 76535, presents data on chromite symplectites, olivine-hosted melt inclusions, intercumulus mineral assemblages, and cumulus mineral chemistry to argue that the 76535 was altered by metasomatism by a migrating basaltic melt. This process could effectively raise radioisotope systems above their mineral-specific blocking temperatures and help explain some of the Mg-suite-FAN age overlap. Chapter 2 focuses on lunar meteorites NWA 4734, 032, and LAP 02205, which are 3 of the 5 youngest igneous samples from the Moon. Using geochemical and isotopic data combined with partial melting models, it is shown that these basalts do not have a link to the KREEP reservoir, and a model is presented for low

  16. Study of the galactic centre region in the soft γ ray domain from the observations performed by the space telescope SIGMA

    International Nuclear Information System (INIS)

    Cordier, Bertrand

    1992-01-01

    This research thesis reports the detailed presentation of the SIGMA telescope, and its use for the observation of the galactic centre region. The SIGMA (gamma imagery system with random mask) telescope is based on an imagery technique using a coded aperture mask, and comprises three main components: the code-mask which modulates information and defines the experiment angular resolution, a position detector which provides the coordinates of the point of interaction of photons and their energy, and allows images to be built up, and active and passive shielding to reduce the background noise. The telescope operating modes and performance (space resolution, angular resolution, camera energy response, sensitivity) are presented. The data reduction procedure is described. Then, the author presents the Galaxy centre, discusses previous observations, and reports and comments new observations performed by using SIGMA [fr

  17. Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues

    Directory of Open Access Journals (Sweden)

    Graziela de Sá Machado Araújo

    2018-03-01

    Full Text Available A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5mC of alleles at CpG islands (CGIs in their promoter regions. This 5mCpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs. iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion. iDMRs function as regulatory platforms, built through the recruitment of chemical modifications to histones to achieve differential, parent-of-origin-dependent chromatin segmentation states. Here, we used a comparative computational data mining approach to identify 125 novel constitutive candidate iDMRs that integrate the maximal number of allele-specific methylation region records overlapping CGIs in human methylomes. Twenty-nine candidate iDMRs display gametic 5mCpG asymmetry, and another 96 are candidate secondary iDMRs. We established the maternal origin of the 5mCpG imprints of one gametic (PARD6G-AS1 and one secondary (GCSAML iDMRs. We also found a constitutively hemimethylated, nonimprinted domain at the PWWP2AP1 promoter CGI with oocyte-derived methylation asymmetry. Given that the 5mCpG level at the iDMRs is not a sufficient criterion to predict active or silent locus states and that iDMRs can regulate genes from a distance of more than 1 Mb, we used RNA-Seq experiments from the Genotype-Tissue Expression project and public archives to assess the transcriptional expression profiles of SNPs across 4.6 Mb spans around the novel maternal iDMRs. We showed that PARD6G-AS1 and GCSAML are expressed biallelically in multiple tissues. We found evidence of tissue-specific monoallelic expression of ZNF124 and OR2L13, located 363 kb upstream and 419 kb downstream, respectively, of the GCSAML iDMR. We hypothesize that the GCSAML

  18. May functional imaging be helpful for behavioral assessment in children? Regions of motor and associative cortico-subcortical circuits can be differentiated by laterality and rostrality

    Directory of Open Access Journals (Sweden)

    Julia M. August

    2015-06-01

    Full Text Available Background: Cortico-subcortical circuits are organized into the sensorimotor, associative and limbic loop. These neuronal preconditions play an important role regarding the understanding and treatment of behavioral problems in children. Differencing evidence argues for a lateralized organization of the sensorimotor loop and a bilateral (i.e. non-lateralized organization of the associative loop. However, a firm behavioral-neurobiological distinction of these circuits has been difficult, specifically in children. Objectives: Thus, the aim was a comprehensive functional visualization and differentiation of the sensorimotor and the associative circuit during childhood. As a new approach, laterality and rostrality features were used to distinguish between the two circuits within one single motor task. Methods: 24 healthy boys performed self-paced index finger tapping with each hand separately during functional magnetic resonance imaging at 3 Tesla. Results: A contrast analysis for left against right hand movement revealed lateralized activation in typical sensorimotor regions such as primary sensorimotor cortex, caudal supplementary motor area (SMA, caudal putamen and thalamus. A conjunction analysis confirmed bilateral involvement of known associative regions including pre-SMA, rostral SMA and rostral putamen. Conclusion: A functional visualization of two distinct corticostriatal circuits is provided in childhood. Both, the sensorimotor and associative circuit may be discriminated by their laterality characteristics already in minors. Additionally, the results support the concept of a modified functional subdivision of the SMA in a rostral (associative and caudal (motor part. A further development of this approach might help to nurture behavioral assessment and neurofeedback training in child mental health.

  19. Airborne differential absorption lidar for water vapour measurements in the upper troposphere and lower stratosphere in the spectral region around 940 nm

    Energy Technology Data Exchange (ETDEWEB)

    Poberaj, G.

    2000-07-01

    Two all-solid-state laser systems were developed and studied in detail to optimise their performance for an airborne water vapour differential absorption lidar (DIAL). Their special features are high average output powers and excellent spectral properties in the 940-nm spectral region relevant for monitoring very low water vapour contents in the upper troposphere and lower stratosphere. One system is an injection-seeded pulsed Ti:sapphire ring laser with a spectral bandwidth of 105 MHz and an average power of 1.1 W. The other system is an injection-seeded optical parametric oscillator (OPO) in a ring configuration. Using KTP as nonlinear crystal, a signal output with a spectral bandwidth of 140 MHz and an average power of 1.2 W was achieved. Both systems, the Ti:sapphire ring laser and the KTP OPO, possess spectral purity values higher than 99%. The pump source for these systems is a frequency doubled diode-pumped Nd:YAG laser operating at a repetition rate of 100 Hz. The KTP OPO system has been used as a transmitter in a new airborne water vapour DIAL instrument. For the first time, measurements of two-dimensional water vapour distributions with a high vertical (500 m) and horizontal (20 km) resolution across several potential vorticity streamers were performed. Very low water vapour mixing ratios (10-50 ppmv) and strong gradients were observed in the tropopause region. The sensitivity of the DIAL instrument in the centre of a stratospheric intrusion ranges from 3% in the near field to 12% in the far field (4 km). The first comparison experiments with in situ measuring instruments show a good agreement. Considerable differences are found between DIAL measurements and data obtained from the ECMWF operational analyses and a mesoscale numerical model. (orig.)

  20. Drug detection by terahertz time-domain spectroscopy

    International Nuclear Information System (INIS)

    Duan Ruixin; Zhu Yiming; Zhao Hongwei

    2013-01-01

    Due to unique spectral region, functional imaging ability, excellent penetration and safety characteristics of terahertz radiation, the terahertz technology rapidly becomes a vital method to detect and analyze drugs. In this paper, firstly, we identify the functional groups of anti-diabetic drugs by density functional theory (DFT), HIPHOP models and experimental results from terahertz time-domain spectroscopy measurements. Secondly, we identify four kinds of herbs of radix curcumae by using the support vector machine (SVM) analysis. Besides, we analyze the absorption of anhydrous and hydrous glucose, and determine the state of water in the crystalized D-glucose·H 2 O through the results of differential scanning calorimetry measurement. Finally, we summarize the advantages and disadvantages of terahertz time-domain spectroscopy method in drug detection and analyzing. (authors)

  1. Polar Domain Discovery with Sparkler

    Science.gov (United States)

    Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

    2017-12-01

    The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

  2. Building Measures of Instructional Differentiation from Teacher Checklists

    Science.gov (United States)

    Williams, Ryan; Swanlund, Andrew; Miller, Shazia; Konstantopoulos, Spyros; van der Ploeg, Arie

    2012-01-01

    Differentiated instruction is commonly believed to be critical to improving the quality and efficiency of teachers' instructional repertoires (Fischer & Rose, 2001; Tomlinson, 2004). Tomlinson (2000) describes differentiation in four domains: content, process, product, and learning environment. Content differentiation involves varying…

  3. Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic Regions in Late-Onset Severe Preeclampsia: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Lisha Zhu

    Full Text Available Preeclampsia (PE is a leading cause of perinatal morbidity and mortality. However, as a common form of PE, the etiology of late-onset PE is elusive. We analyzed 5-methylcytosine (5mC and 5-hydroxymethylcytosine (5hmC levels in the placentas of late-onset severe PE patients (n = 4 and normal controls (n = 4 using a (hydroxymethylated DNA immunoprecipitation approach combined with deep sequencing ([h]MeDIP-seq, and the results were verified by (hMeDIP-qPCR. The most significant differentially methylated regions (DMRs were verified by MassARRAY EppiTYPER in an enlarged sample size (n = 20. Bioinformatics analysis identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of 5hmC that were associated with 61 genes, thus showing significant differences between the PE patients and the controls (>2-fold, p<0.05. Further, only one gene, PTPRN2, had both 5mC and 5hmC changes in patients. The ErbB signaling pathway was enriched in those 403 genes that had significantly different 5mC level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic roles in the regulation of the disease, but work independently. We reveal the genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset PE placentas for the first time, and the identified ErbB signaling pathway and the gene PTPRN2 may be relevant to the epigenetic pathogenesis of late-onset PE.

  4. Recall versus familiarity when recall fails for words and scenes: the differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions.

    Science.gov (United States)

    Ryals, Anthony J; Cleary, Anne M; Seger, Carol A

    2013-01-25

    This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Differential gene expression patterns in developing sexually dimorphic rat brain regions exposed to antiandrogenic, estrogenic, or complex endocrine disruptor mixtures: glutamatergic synapses as target.

    Science.gov (United States)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver; Axelstad, Marta; Boberg, Julie; Christiansen, Sofie; Rehrauer, Hubert; Georgijevic, Jelena Kühn; Hass, Ulla; Kortenkamp, Andreas; Schlumpf, Margret

    2015-04-01

    The study addressed the question whether gene expression patterns induced by different mixtures of endocrine disrupting chemicals (EDCs) administered in a higher dose range, corresponding to 450×, 200×, and 100× high-end human exposure levels, could be characterized in developing brain with respect to endocrine activity of mixture components, and which developmental processes were preferentially targeted. Three EDC mixtures, A-Mix (anti-androgenic mixture) with 8 antiandrogenic chemicals (di-n-butylphthalate, diethylhexylphthalate, vinclozolin, prochloraz, procymidone, linuron, epoxiconazole, and DDE), E-Mix (estrogenic mixture) with 4 estrogenic chemicals (bisphenol A, 4-methylbenzylidene camphor, 2-ethylhexyl 4-methoxycinnamate, and butylparaben), a complex mixture, AEP-Mix, containing the components of A-Mix and E-Mix plus paracetamol, and paracetamol alone, were administered by oral gavage to rat dams from gestation day 7 until weaning. General developmental endpoints were not affected by EDC mixtures or paracetamol. Gene expression was analyzed on postnatal day 6, during sexual brain differentiation, by exon microarray in medial preoptic area in the high-dose group, and by real-time RT-PCR in medial preoptic area and ventromedial hypothalamus in all dose groups. Expression patterns were mixture, sex, and region specific. Effects of the analgesic drug paracetamol, which exhibits antiandrogenic activity in peripheral systems, differed from those of A-Mix. All mixtures had a strong, mixture-specific impact on genes encoding for components of excitatory glutamatergic synapses and genes controlling migration and pathfinding of glutamatergic and GABAergic neurons, as well as genes linked with increased risk of autism spectrum disorders. Because development of glutamatergic synapses is regulated by sex steroids also in hippocampus, this may represent a general target of ECD mixtures.

  6. Generational comparisons (F1 versus F3) of vinclozolin induced epigenetic transgenerational inheritance of sperm differential DNA methylation regions (epimutations) using MeDIP-Seq.

    Science.gov (United States)

    Beck, Daniel; Sadler-Riggleman, Ingrid; Skinner, Michael K

    2017-07-01

    Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation has been shown to involve DNA methylation alterations in the germline (e.g. sperm). These differential DNA methylation regions (DMRs) are termed epimutations and in part transmit the transgenerational phenotypes. The agricultural fungicide vinclozolin exposure of a gestating female rat has previously been shown to promote transgenerational disease and epimutations in F3 generation (great-grand-offspring) animals. The current study was designed to investigate the actions of direct fetal exposure on the F1 generation rat sperm DMRs compared to the F3 transgenerational sperm DMRs. A protocol involving methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (Seq) was used in the current study. Bioinformatics analysis of the MeDIP-Seq data was developed and several different variations in the bioinformatic analysis were evaluated. Observations indicate needs to be considered. Interestingly, the F1 generation DMRs were found to be fewer in number and for the most part distinct from the F3 generation epimutations. Observations suggest the direct exposure induced F1 generation sperm DMRs appear to promote in subsequent generations alterations in the germ cell developmental programming that leads to the distinct epimutations in the F3 generation. This may help explain the differences in disease and phenotypes between the direct exposure F1 generation and transgenerational F3 generation. Observations demonstrate a distinction between the direct exposure versus transgenerational epigenetic programming induced by environmental exposures and provide insights into the molecular mechanisms involved in the epigenetic transgenerational inheritance phenomenon.

  7. Enterovirus Exposure Uniquely Discriminates Type 1 Diabetes Patients with a Homozygous from a Heterozygous Melanoma Differentiation-Associated Protein 5/Interferon Induced with Helicase C Domain 1 A946T Genotype

    NARCIS (Netherlands)

    Schulte, B.M.; Gielen, P.R.; Kers-Rebel, E.D.; Prosser, A.C.; Lind, K.; Flodstrom-Tullberg, M.; Tack, C.J.J.; Elving, L.D.; Adema, G.J.

    2016-01-01

    In children at risk for type 1 diabetes, innate immune activity is detected before seroconversion. Enterovirus infections have been linked to diabetes development, and a polymorphism (A946T) in the innate immune sensor recognizing enterovirus RNA, interferon-induced with helicase C domain 1/melanoma

  8. Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease

    NARCIS (Netherlands)

    Tjernberg, Pernilla; Vos, Hans L.; Spaargaren-van Riel, Caroline C.; Luken, Brenda M.; Voorberg, Jan; Bertina, Rogier M.; Eikenboom, Jeroen C. J.

    2006-01-01

    Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 von Willebrand disease (VWD). Our objective

  9. Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing.

    Science.gov (United States)

    Olivares, Ela I; Lage-Castellanos, Agustín; Bobes, María A; Iglesias, Jaime

    2018-01-01

    We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called "Fusiform Face Area", "FFA" and "Occipital Face Area", "OFA", respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

  10. Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing

    Directory of Open Access Journals (Sweden)

    Ela I. Olivares

    2018-03-01

    Full Text Available We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs in both intra-domain (face-feature and cross-domain (face-occupation matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called “Fusiform Face Area”, “FFA” and “Occipital Face Area”, “OFA”, respectively, the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

  11. The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor.

    Science.gov (United States)

    Harms, Frederike L; Alawi, Malik; Amor, David J; Tan, Tiong Y; Cuturilo, Goran; Lissewski, Christina; Brinkmann, Julia; Schanze, Denny; Kutsche, Kerstin; Zenker, Martin

    2018-02-01

    Noonan syndrome is characterized by typical craniofacial dysmorphism, postnatal growth retardation, congenital heart defect, and learning difficulties and belongs to the RASopathies, a group of neurodevelopmental disorders caused by germline mutations in genes encoding components of the RAS-MAPK pathway. Mutations in the RAF1 gene are associated with Noonan syndrome, with a high prevalence of hypertrophic cardiomyopathy (HCM). RAF1 mutations cluster in exons encoding the conserved region 2 (CR2), the kinase activation segment of the CR3 domain, and the C-terminus. We present two boys with Noonan syndrome and the identical de novo RAF1 missense variant c.1082G>C/p.(Gly361Ala) affecting the CR3, but located outside the kinase activation segment. The p.(Gly361Ala) mutation has been identified as a RAF1 allele conferring resistance to RAF inhibitors. This amino acid change favors a RAF1 conformation that allows for enhanced RAF dimerization and increased intrinsic kinase activity. Both patients with Noonan syndrome showed typical craniofacial dysmorphism, macrocephaly, and short stature. One individual developed HCM and was diagnosed with a disseminated oligodendroglial-like leptomeningeal tumor (DOLT) of childhood at the age of 9 years. While there is a well-established association of NS with malignant tumors, especially childhood hemato-oncological diseases, brain tumors have rarely been reported in Noonan syndrome. Our data demonstrate that mutation scanning of the entire coding region of genes associated with Noonan syndrome is mandatory not to miss rare variants located outside the known mutational hotspots. © 2017 Wiley Periodicals, Inc.

  12. Novel Bacteriocinogenic Lactobacillus plantarum Strains and Their Differentiation by Sequence Analysis of 16S rDNA, 16S-23S and 23S-5S Intergenic Spacer Regions and Randomly Amplified Polymorphic DNA Analysis

    Directory of Open Access Journals (Sweden)

    Morteza Shojaei Moghadam

    2010-01-01

    Full Text Available Six strains of bacteriocinogenic Lactobacillus plantarum (TL1, RG11, RS5, UL4, RG14 and RI11 isolated from Malaysian foods were investigated for their structural bacteriocin genes. A new combination of plantaricin EF and plantaricin W bacteriocin structural genes was successfully amplified from all studied strains, suggesting that they were novel bacteriocin-producing L. plantarum strains. A four-base pair variable region was detected in the short 16S-23S intergenic spacer regions of the studied strains by a comparative analysis with 17 L. plantarum strains deposited in the GenBank, implying they were new genotypes. The studied L. plantarum strains were subsequently differentiated into four groups on the basis of the detected four-base pair variable region of the short 16S-23S intergenic spacer region. Further analysis of the DNA sequence of 23S-5S intergenic spacer region revealed only one type of 23S-5S intergenic spacer region present in the studied strains, indicating it was highly conserved among the studied L. plantarum strains. Three randomly amplified polymorphic DNA experiments using three different combinations of arbitrary primers successfully differentiated the studied L. plantarum strains from each other, confirming they were different strains. In conclusion, the studied L. plantarum strains were shown to be novel bacteriocin producers and high level of strain discrimination could be achieved with a combination of randomly amplified polymorphic DNA analysis and the analysis of the variable region of short 16S-23S intergenic spacer region present in L. plantarum strains.

  13. Diferenciais regionais de mortalidade por câncer no Estado do Rio de Janeiro, Brasil, 1979-1981 Regional differentials in cancer mortality in a region of, Brazil, 1979-1981

    Directory of Open Access Journals (Sweden)

    Cynthia Boschi

    1991-08-01

    Full Text Available A partir do fato de que os neoplasmas malignos foram a terceira causa de morte no Estado do Rio de Janeiro, Brasil, no ano de 1980, apresentando taxa bruta igual a 89,8 por 100.000 habitantes, foi analisada a mortalidade por câncer segundo suas principais localizações anatômicas, no período 1979-1981. Dividiu-se o Estado em três regiões distintas: Capital, Cinturão Metropolitano e Interior. Foram calculados coeficientes de mortalidade trienais, posteriormente padronizados pelo método direto utilizando-se, para tal, a população mundial. Para cumprir o objetivo de comparar diferentes regiões geográficas foram calculadas razões padronizadas de mortalidade. Observou-se que as principais localizações anatômicas foram pulmão, estômago, próstata, esôfago e fígado, nos homens; e mama, estômago, pulmão, cérvix uterino e útero (não especificado, nas mulheres. Encontrou-se que as maiores taxas para o total de tumores ocorreram na Capital e as menores no Interior, sendo as maiores razões padronizadas de mortalidade aquelas para mama (1,88, cólon (1,71 e pulmão (1,70. A mortalidade por neoplasmas malignos de esôfago e de fígado foi maior no Interior do que nas demais regiões, em ambos os sexos. Concluiu-se que existe comportamento distinto da mortalidade por câncer entre as diferentes regiões, apontando, mais uma vez, na direção da determinação ambiental de grande parte dos neoplasmas malignos.In 1980, malignant neoplasms ranked 3rd as a cause of death in the State of Rio de Janeiro, Brazil, with a crude mortality rate of 89.8 per 100,000. Cancer mortality data for 1979-1981 are presented for the State, with the objective of analyzing regional differentials. For the purpose of comparing mortality from the most important cancers, the State was divided into three regions: Capital, Metropolitan Belt and Interior, on the basis of the geographical structure of the State - which gave rise to the present urbanization patterns

  14. "In vivo" toxicity of a truncated version of the Drosophila Rst-IrreC protein is dependent on the presence of a glutamine-rich region in its intracellular domain

    Directory of Open Access Journals (Sweden)

    RICARDO C. MACHADO

    2002-06-01

    Full Text Available The roughest-irregular chiasm C ( rst-irreC gene of Drosophila melanogaster encodes a transmembrane glycoprotein containing five immunoglobulin-like domains in its extracellular portion and an intracytoplasmic tail rich in serine and threonine as well some conserved motifs suggesting signal transduction activity. In the compound eye, loss-of-function rst-irreC mutants lack the characteristic wave of programmed cell death happening in early pupa and which is essential for the elimination of the surplus interommatidial cells. Here we report an investigation on the role played by the Rst-irreC molecule in triggering programmed cell death. "In vivo" transient expression assays showed that deletion of the last 80 amino acids of the carboxyl terminus produces a form of the protein that is highly toxic to larvae. This toxicity is suppressed if an additional 47 amino acid long, glutamine-rich region ("opa-like domain", is also removed from the protein. The results suggest the possibility that the opa-like domain and the carboxyl terminus act in concert to modulate rst-irreC function in apoptosis, and we discuss this implication in the context of the general mechanisms causing glutamine-rich neurodegenerative diseases in humans.O gene roughest-irregular chiasm C ( rst-irreC de Drosophila melanogaster, codifica uma glicoproteína transmembranar contendo cinco domínios semelhantes a imunoglobulina em sua porção extracelular e uma cauda intracitoplasmática rica em serina e treonina, assim como alguns sequências conservadas que sugerem atividade transdutora de sinais. No olho composto, mutantes rst-irreC de perda de função não apresentam uma característica "onda" de morte celular programada que ocorre no início do período pupal e que é essencial para a eliminação de células interomatidiais em excesso. Aqui descrevemos uma investigação sobre o papel desempenhado pela molécula Rst-IrreC no disparo da morte celular programada. Ensaios de

  15. Dynamical downscaling with the fifth-generation Canadian regional climate model (CRCM5) over the CORDEX Arctic domain: effect of large-scale spectral nudging and of empirical correction of sea-surface temperature

    Science.gov (United States)

    Takhsha, Maryam; Nikiéma, Oumarou; Lucas-Picher, Philippe; Laprise, René; Hernández-Díaz, Leticia; Winger, Katja

    2017-10-01

    As part of the CORDEX project, the fifth-generation Canadian Regional Climate Model (CRCM5) is used over the Arctic for climate simulations driven by reanalyses and by the MPI-ESM-MR coupled global climate model (CGCM) under the RCP8.5 scenario. The CRCM5 shows adequate skills capturing general features of mean sea level pressure (MSLP) for all seasons. Evaluating 2-m temperature (T2m) and precipitation is more problematic, because of inconsistencies between observational reference datasets over the Arctic that suffer of a sparse distribution of weather stations. In our study, we additionally investigated the effect of large-scale spectral nudging (SN) on the hindcast simulation driven by reanalyses. The analysis shows that SN is effective in reducing the spring MSLP bias, but otherwise it has little impact. We have also conducted another experiment in which the CGCM-simulated sea-surface temperature (SST) is empirically corrected and used as lower boundary conditions over the ocean for an atmosphere-only global simulation (AGCM), which in turn provides the atmospheric lateral boundary conditions to drive the CRCM5 simulation. This approach, so-called 3-step approach of dynamical downscaling (CGCM-AGCM-RCM), which had considerably improved the CRCM5 historical simulations over Africa, exhibits reduced impact over the Arctic domain. The most notable positive effect over the Arctic is a reduction of the T2m bias over the North Pacific Ocean and the North Atlantic Ocean in all seasons. Future projections using this method are compared with the results obtained with the traditional 2-step dynamical downscaling (CGCM-RCM) to assess the impact of correcting systematic biases of SST upon future-climate projections. The future projections are mostly similar for the two methods, except for precipitation.

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

    International Nuclear Information System (INIS)

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

    2005-10-01

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

  17. Tlx controls proliferation and patterning of lateral telencephalic progenitor domains.

    Science.gov (United States)

    Stenman, Jan M; Wang, Bei; Campbell, Kenneth

    2003-11-19

    We showed previously that the orphan nuclear receptor Tlx is required for the correct establishment of the pallio-subpallial boundary. Loss of Tlx results in a dorsal expansion of ventral markers (e.g., the homeodomain protein GSH2) into the ventralmost pallial region, i.e., the ventral pallium. We also observed a disproportionate reduction in the size of the Tlx mutant lateral ganglionic eminence (LGE) from embryonic day 14.5 onward. Here we show that this reduction is caused, at least in large part, by a proliferation defect. Interestingly, in Tlx mutants, the LGE derivatives are differentially affected. Although the development of the Tlx mutant striatum is compromised, an apparently normal number of olfactory bulb interneurons are observed. Consistent with this observation, we found that Tlx is required for the normal establishment of the ventral LGE that gives rise to striatal projection neurons. This domain is reduced by the dorsal and ventral expansion of molecular markers normally confined to progenitor domains flanking the ventral LGE. Finally, we investigated possible genetic interactions between Gsh2 and Tlx in lateral telencephalic development. Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity.

  18. Differential branching fraction and angular moments analysis of the decay $B^0 \\to K^+ \\pi^- \\mu^+ \\mu^-$ in the $K^*_{0,2}(1430)^0$ region

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Archilli, Flavio; d'Argent, Philippe; Arnau Romeu, Joan; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Babuschkin, Igor; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Baszczyk, Mateusz; Batozskaya, Varvara; Batsukh, Baasansuren; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bezshyiko, Iaroslava; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bitadze, Alexander; Bizzeti, Andrea; Blake, Thomas; Blanc, Frederic; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Boettcher, Thomas; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Bossu, Francesco; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Camboni, Alessandro; Campana, Pierluigi; Campora Perez, Daniel; Campora Perez, Daniel Hugo; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chobanova, Veronika; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Costa Sobral, Cayo Mar; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Serio, Marilisa; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Déléage, Nicolas; Easo, Sajan; Ebert, Marcus; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Farley, Nathanael; Farry, Stephen; Fay, Robert; Fazzini, Davide; Ferguson, Dianne; Fernandez Albor, Victor; Fernandez Prieto, Antonio; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fini, Rosa Anna; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Franco Lima, Vinicius; Frank, Markus; Frei, Christoph; Fu, Jinlin; Furfaro, Emiliano; Färber, Christian; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; Garcia Martin, Luis Miguel; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gizdov, Konstantin; Gligorov, V.V.; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gorelov, Igor Vladimirovich; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Gruberg Cazon, Barak Raimond; Grünberg, Oliver; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Göbel, Carla; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; Hatch, Mark; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hombach, Christoph; Hopchev, P H; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Kariuki, James Mwangi; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Koliiev, Serhii; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozachuk, Anastasiia; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Leflat, Alexander; Lefrançois, Jacques; Lefèvre, Regis; Lemaitre, Florian; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Maltsev, Timofei; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Mogini, Andrea; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Mulder, Mick; Mussini, Manuel; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Oldeman, Rudolf; Onderwater, Gerco; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Pais, Preema Rennee; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Pastore, Alessandra; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petrov, Aleksandr; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Pomery, Gabriela Johanna; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Poslavskii, Stanislav; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Remon Alepuz, Clara; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vicente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Romanovskiy, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rudolph, Matthew Scott; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sadykhov, Elnur; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schellenberg, Margarete; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubert, Konstantin; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Simone, Saverio; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefko, Pavol; Stefkova, Slavorima; Steinkamp, Olaf; Stemmle, Simon; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Toriello, Francis; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tully, Alison; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valassi, Andrea; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Venkateswaran, Aravindhan; Vernet, Maxime; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voneki, Balazs; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Vázquez Sierra, Carlos; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Wark, Heather Mckenzie; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zarebski, Kristian Alexander; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhang, Yu; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhu, Xianglei; Zhukov, Valery; Zucchelli, Stefano

    2016-12-15

    Measurements of the differential branching fraction and angular moments of the decay $B^0 \\to K^+ \\pi^- \\mu^+ \\mu^-$ in the $K^*_{0,2}(1430)^0$ in the $K^+\\pi^-$ invariant mass range $1330 < m (K^+ \\pi^-) <1530~ \\text{MeV}/c^2$ are presented. Proton-proton collision data are used, corresponding to an integrated luminosity of 3 fb$^{-1}$ collected by the LHCb experiment. Differential branching fraction measurements are reported in five bins of the invariant mass squared of the dimuon system, $q^2$, between 0.1 and 8.0 $\\text{GeV}^2/c^4$. For the first time, an angular analysis sensitive to the S-, P- and D-wave contributions of this rare decay is performed. The set of 40 normalised angular moments describing the decay is presented for the $q^2$ range $1.1-6.0 \\text{GeV}^2/c^4$.

  19. Generalized vector calculus on convex domain

    Science.gov (United States)

    Agrawal, Om P.; Xu, Yufeng

    2015-06-01

    In this paper, we apply recently proposed generalized integral and differential operators to develop generalized vector calculus and generalized variational calculus for problems defined over a convex domain. In particular, we present some generalization of Green's and Gauss divergence theorems involving some new operators, and apply these theorems to generalized variational calculus. For fractional power kernels, the formulation leads to fractional vector calculus and fractional variational calculus for problems defined over a convex domain. In special cases, when certain parameters take integer values, we obtain formulations for integer order problems. Two examples are presented to demonstrate applications of the generalized variational calculus which utilize the generalized vector calculus developed in the paper. The first example leads to a generalized partial differential equation and the second example leads to a generalized eigenvalue problem, both in two dimensional convex domains. We solve the generalized partial differential equation by using polynomial approximation. A special case of the second example is a generalized isoperimetric problem. We find an approximate solution to this problem. Many physical problems containing integer order integrals and derivatives are defined over arbitrary domains. We speculate that future problems containing fractional and generalized integrals and derivatives in fractional mechanics will be defined over arbitrary domains, and therefore, a general variational calculus incorporating a general vector calculus will be needed for these problems. This research is our first attempt in that direction.

  20. Matriptase and prostasin are expressed in human skin in an inverse trend over the course of differentiation and are targeted to different regions of the plasma membrane

    Directory of Open Access Journals (Sweden)

    Chih-Hsin Lai

    2016-10-01

    Full Text Available Matriptase and prostasin, acting as a tightly coupled proteolytic cascade, were reported to be required for epidermal barrier formation in mouse skin. Here we show that, in human skin, matriptase and prostasin are expressed with an inverse pattern over the course of differentiation. Matriptase was detected primarily in epidermal basal keratinocytes and the basaloid cells in the outer root sheath of hair follicles and the sebaceous gland, where prostasin was not detected. In contrast, prostasin was detected primarily in differentiated cells in the epidermal granular layer, the inner root sheath of hair follicles, and the sebaceous gland, where matriptase expression is negligible. While co-expressed in the middle stage of differentiation, prostasin was detected as polarized patches, and matriptase at intercellular junctions. Targeting to different subcellular localizations is also observed in HaCaT human keratinocytes, in which matriptase was detected primarily at intercellular junctions, and prostasin primarily on membrane protrusion. Furthermore, upon induction of zymogen activation, free active prostasin remains cell-associated and free active matriptase is rapidly shed into the extracellular milieu. Our data suggest that matriptase and prostasin likely function as independent entities in human skin rather than as a tightly coupled proteolytic cascade as observed in mouse skin.

  1. Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

    Science.gov (United States)

    Marchbank, Tania; Mandir, Nikki; Calnan, Denis; Goodlad, Robert A; Podas, Theo; Playford, Raymond J

    2018-01-24

    Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed. Effects on regional gut growth and intraluminal growth factor activity were then determined. Despite calorie intake being similar in all groups, soya rich feed caused 20% extra total body weight gain. Stomach weight was highest on soya and casein diets. Soya enhanced diet caused greatest increase in small intestinal weight and preserved luminal growth factor activity at levels sufficient to increase proliferation in vitro. Regional small intestinal proliferation was highest in proximal segment in ED fed animals whereas distal small intestine proliferation was greater in soya fed animals. Colonic weight and proliferation throughout the colon was higher in animals receiving soya or whey supplemented feeds. We conclude that specific protein supplementation with either soya, casein or whey may be beneficial to rest or increase growth in different regions of the bowel through mechanisms that include differentially affecting luminal growth factor bioactivity. These results have implications for targeting specific regions of the bowel for conditions such as Crohn's disease and chemotherapy.

  2. Domain decomposition methods and deflated Krylov subspace iterations

    NARCIS (Netherlands)

    Nabben, R.; Vuik, C.

    2006-01-01

    The balancing Neumann-Neumann (BNN) and the additive coarse grid correction (BPS) preconditioner are fast and successful preconditioners within domain decomposition methods for solving partial differential equations. For certain elliptic problems these preconditioners lead to condition numbers which

  3. Differential activation of brain regions involved with error-feedback and imitation based motor simulation when observing self and an expert's actions in pilots and non-pilots on a complex glider landing task.

    Science.gov (United States)

    Callan, Daniel E; Terzibas, Cengiz; Cassel, Daniel B; Callan, Akiko; Kawato, Mitsuo; Sato, Masa-Aki

    2013-05-15

    In this fMRI study we investigate neural processes related to the action observation network using a complex perceptual-motor task in pilots and non-pilots. The task involved landing a glider (using aileron, elevator, rudder, and dive brake) as close to a target as possible, passively observing a replay of one's own previous trial, passively observing a replay of an expert's trial, and a baseline do nothing condition. The objective of this study is to investigate two types of motor simulation processes used during observation of action: imitation based motor simulation and error-feedback based motor simulation. It has been proposed that the computational neurocircuitry of the cortex is well suited for unsupervised imitation based learning, whereas, the cerebellum is well suited for error-feedback based learning. Consistent with predictions, pilots (to a greater extent than non-pilots) showed significant differential activity when observing an expert landing the glider in brain regions involved with imitation based motor simulation (including premotor cortex PMC, inferior frontal gyrus IFG, anterior insula, parietal cortex, superior temporal gyrus, and middle temporal MT area) than when observing one's own previous trial which showed significant differential activity in the cerebellum (only for pilots) thought to be concerned with error-feedback based motor simulation. While there was some differential brain activity for pilots in regions involved with both Execution and Observation of the flying task (potential Mirror System sites including IFG, PMC, superior parietal lobule) the majority was adjacent to these areas (Observation Only Sites) (predominantly in PMC, IFG, and inferior parietal loblule). These regions showing greater activity for observation than for action may be involved with processes related to motor-based representational transforms that are not necessary when actually carrying out the task. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Timing of metamorphism and exhumation in the Nordøyane ultra-high-pressure domain, Western Gneiss Region, Norway: New constraints from complementary CA-ID-TIMS and LA-MC-ICP-MS geochronology

    Science.gov (United States)

    Butler, J. P.; Jamieson, R. A.; Dunning, G. R.; Pecha, M. E.; Robinson, P.; Steenkamp, H. M.

    2018-06-01

    We present the results of a combined CA-ID-TIMS and LA-MC-ICP-MS U-Pb geochronology study of zircon and associated rutile and titanite from the Nordøyane ultra-high-pressure (UHP) domain in the Western Gneiss Region (WGR) of Norway. The dated samples include 4 eclogite bodies, 2 host-rock migmatites, and 2 cross-cutting pegmatites and leucosomes, all from the island of Harøya. Zircon from a coesite eclogite yielded an age of ca. 413 Ma, interpreted as the time of UHP metamorphism in this sample. Zircon data from the other eclogite bodies yielded metamorphic ages of ca. 413 Ma, 407 Ma, and 406 Ma; zircon trace-element data associated with 413 Ma and 407 Ma ages are consistent with eclogite-facies crystallization. In all of the eclogites, U-Pb dates from zircon cores, interpreted as the times of protolith crystallization, range from ca. 1680-1586 Ma, consistent with Gothian ages from orthogneisses in Nordøyane and elsewhere in the WGR. A zircon core age of ca. 943 Ma from one sample agrees with Sveconorwegian ages of felsic gneisses and pegmatites in the western part of the area. Migmatites hosting the eclogite bodies yielded zircon core ages of ca. 1657-1591 Ma and rim ages of ca. 395-392 Ma, interpreted as the times of Gothian protolith formation and Scandian partial melt crystallization, respectively. Pegmatite in an eclogite boudin neck yielded a crystallization age of ca. 388 Ma, interpreted as the time of melt crystallization. Rutile and titanite from 3 samples (an eclogite and two migmatites) yielded concordant ID-TIMS ages of 378-376 Ma. The results are similar to existing U-Pb data from other Nordøyane eclogites (415-405 Ma). In combination with previous pressure-temperature data from the coesite eclogite, these ages indicate that peak metamorphic conditions of 3 GPa/760 °C were reached ca. 413 Ma, followed by decompression to 1 GPa/810 °C by ca. 397 Ma and cooling below ca. 600 °C by ca. 375 Ma. The results are compatible with protracted UHP

  5. Advanced differential quadrature methods

    CERN Document Server

    Zong, Zhi

    2009-01-01

    Modern Tools to Perform Numerical DifferentiationThe original direct differential quadrature (DQ) method has been known to fail for problems with strong nonlinearity and material discontinuity as well as for problems involving singularity, irregularity, and multiple scales. But now researchers in applied mathematics, computational mechanics, and engineering have developed a range of innovative DQ-based methods to overcome these shortcomings. Advanced Differential Quadrature Methods explores new DQ methods and uses these methods to solve problems beyond the capabilities of the direct DQ method.After a basic introduction to the direct DQ method, the book presents a number of DQ methods, including complex DQ, triangular DQ, multi-scale DQ, variable order DQ, multi-domain DQ, and localized DQ. It also provides a mathematical compendium that summarizes Gauss elimination, the Runge-Kutta method, complex analysis, and more. The final chapter contains three codes written in the FORTRAN language, enabling readers to q...

  6. A modulated differential scanning calorimetry and small-angle x-ray scattering study of the interfacial region in structured latices

    Directory of Open Access Journals (Sweden)

    Hourston Douglas J.

    2001-01-01

    Full Text Available The interfacial structure of poly(styrene (PS-poly(methyl acrylate (PMA structured latices has been investigated by means of modulated-temperature differential scanning calorimetry (M-TDSC and small-angle x-ray scattering (SAXS. The differential of heat capacity, dCp/dT, signal from M-TDSC was used to quantify the weight fraction of interface in these latices. For PS-PMA (50:50 by weight structured latices in which the PS component had different crosslink densities (0, 1, 3, 5 and 10 mol% of crosslinking agent, the weight fraction of interface was about 13%. With increasing crosslink density, the fraction of interface increased only slightly. A core-shell model has been used to analyse SAXS data for these PS-PMA latices. M-TDSC can only provide information about the weight fraction of interface, but the combination of M-TDSC and SAXS can provide much more information on the morphology of such structured latices.

  7. Differential patterns of human immunoglobulin G subclass responses to distinct regions of a single protein, the merozoite surface protein 1 of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Cavanagh, D R; Dobaño, C; Elhassan, I M

    2001-01-01

    Comparisons of immunoglobulin G (IgG) subclass responses to the major polymorphic region and to a conserved region of MSP-1 in three cohorts of African villagers exposed to Plasmodium falciparum revealed that responses to Block 2 are predominantly IgG3 whereas antibodies to MSP-1(19) are mainly IgG......1. The striking dominance of IgG3 to Block 2 may explain the short duration of this response and also the requirement for continuous stimulation by malaria infection to maintain clinical immunity....

  8. A mixed finite element domain decomposition method for nearly elastic wave equations in the frequency domain

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Xiaobing [Univ. of Tennessee, Knoxville, TN (United States)

    1996-12-31

    A non-overlapping domain decomposition iterative method is proposed and analyzed for mixed finite element methods for a sequence of noncoercive elliptic systems with radiation boundary conditions. These differential systems describe the motion of a nearly elastic solid in the frequency domain. The convergence of the iterative procedure is demonstrated and the rate of convergence is derived for the case when the domain is decomposed into subdomains in which each subdomain consists of an individual element associated with the mixed finite elements. The hybridization of mixed finite element methods plays a important role in the construction of the discrete procedure.

  9. Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family

    DEFF Research Database (Denmark)

    Silvestri, B; Calderazzo, F; Coppola, V

    1998-01-01

    We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non-specific ......We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non......-specific mitogens such as phytohaemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced, probably due to the lectin-binding properties of gp90/Mac-2BP, the response to T cell receptor (TCR) agonists such as superantigens and allogeneic cells was potentiated. When...... lymphocytes were stimulated with different anti-TCR:CD3 MoAbs, both in soluble and solid-phase form, gp90/Mac-2BP was able to down-regulate the proliferative response to anti-CD3 MoAb, whereas the response to anti-TCR alphabeta MoAb was enhanced. A similar differential effect was observed when a MoAb against...

  10. Differential Accumulation of Retroelements and Diversification of NB-LRR Disease Resistance Genes in Duplicated Regions Following Polyploidy in the Ancestor of Soybean

    Science.gov (United States)

    The genomes of most flowering plants have undergone polyploidization at some point in their evolution. How such polyploidization events have impacted the subsequent evolution of genome structure is poorly understood. We sequenced two homoeologous regions in soybean (Glycine max), which underwent a...

  11. Differential effects of high atmospheric N and S deposition on bog plant/lichen tissue and porewater chemistry across the Athabasca Oil Sands Region

    Science.gov (United States)

    R. Kelman Wieder; Melanie A. Vile; Kimberli D. Scott; Cara M. Albright; Kelly J. McMillen; Dale H. Vitt; Mark E. Fenn

    2016-01-01

    Oil extraction and development activities in the Athabasca Oil Sands Region of northern Alberta, Canada, release NOx, SOx, and NHy to the atmosphere, ultimately resulting in increasing N and S inputs to surrounding ecosystems through atmospheric deposition. Peatlands are a major feature of the northern Alberta landscape, with bogs covering 6-10% of the land area, and...

  12. Study of domain structure in segmented polyether polyurethaneureas by PAT

    International Nuclear Information System (INIS)

    Yin Chuanyuan; Xu Weizheng; Gu Qingchao

    1990-01-01

    The domain structure of segmented polyether polyurethaneureas is investigated by means of positron annihilation technique, small angle X-ray scattering and differential scanning calorimetry. The experimental results show that the decrease of domain volume and free volume results from the increase of hard segment contents, and that the increase of domain volume and free volume results from the increase of molecular weight of soft segments

  13. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    Science.gov (United States)

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  14. Measurement of the differential and total cross sections of the γ d →K0Λ (p ) reaction within the resonance region

    Science.gov (United States)

    Compton, N.; Taylor, C. E.; Hicks, K.; Cole, P.; Zachariou, N.; Ilieva, Y.; Nadel-Turonski, P.; Klempt, E.; Nikonov, V. A.; Sarantsev, A. V.; Adhikari, K. P.; Adhikari, S.; Akbar, Z.; Anefalos Pereira, S.; Avakian, H.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A. S.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Camp, M.; Cao, Frank Thanh; Cao, T.; Carman, D. S.; Celentano, A.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fedotov, G.; Filippi, A.; Fleming, J. A.; Fradi, A.; Gavalian, G.; Ghandilyan, Y.; Giovanetti, K. L.; Girod, F. X.; Glazier, D. I.; Gleason, C.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Heddle, D.; Holtrop, M.; Hughes, S. M.; Hyde, C. E.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jo, H. S.; Joo, K.; Joosten, S.; Keller, D.; Khachatryan, G.; Khachatryan, M.; Khandaker, M.; Kim, W.; Klein, A.; Klein, F. J.; Kubarovsky, V.; Kuleshov, S. V.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; McKinnon, B.; Meyer, C. A.; Mineeva, T.; Mirazita, M.; Mokeev, V.; Montgomery, R. A.; Movsisyan, A.; Munevar, E.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Prok, Y.; Protopopescu, D.; Raue, B. A.; Ripani, M.; Ritchie, B. G.; Rizzo, A.; Rosner, G.; Sabatié, F.; Salgado, C.; Schumacher, R. A.; Sharabian, Y. G.; Simonyan, A.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Stepanyan, S.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Torayev, B.; Trivedi, A.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Wood, M. H.; Zachariou, N.; Zhang, J.; CLAS Collaboration

    2017-12-01

    We report the first measurement of differential and total cross sections for the γ d →K0Λ (p ) reaction, using data from the CLAS detector at the Thomas Jefferson National Accelerator Facility. Data collected during two separate experimental runs were studied with photon-energy coverage 0.8-3.6 GeV and 0.5- 2.6 GeV, respectively. The two measurements are consistent giving confidence in the method and determination of systematic uncertainties. The cross sections are compared with predictions from the KAON-MAID theoretical model (without kaon exchange), which deviate from the data at higher W and at forward kaon angles. These data, along with previously published cross sections for K+Λ photoproduction, provide essential constraints on the nucleon resonance spectrum. A first partial wave analysis was performed that describes the data without the introduction of new resonances.

  15. Differentiation of Toxocara canis and Toxocara cati based on PCR-RFLP analyses of rDNA-ITS and mitochondrial cox1 and nad1 regions.

    Science.gov (United States)

    Mikaeili, Fattaneh; Mathis, Alexander; Deplazes, Peter; Mirhendi, Hossein; Barazesh, Afshin; Ebrahimi, Sepideh; Kia, Eshrat Beigom

    2017-09-26

    The definitive genetic identification of Toxocara species is currently based on PCR/sequencing. The objectives of the present study were to design and conduct an in silico polymerase chain reaction-restriction fragment length polymorphism method for identification of Toxocara species. In silico analyses using the DNASIS and NEBcutter softwares were performed with rDNA internal transcribed spacers, and mitochondrial cox1 and nad1 sequences obtained in our previous studies along with relevant sequences deposited in GenBank. Consequently, RFLP profiles were designed and all isolates of T. canis and T. cati collected from dogs and cats in different geographical areas of Iran were investigated with the RFLP method using some of the identified suitable enzymes. The findings of in silico analyses predicted that on the cox1 gene only the MboII enzyme is appropriate for PCR-RFLP to reliably distinguish the two species. No suitable enzyme for PCR-RFLP on the nad1 gene was identified that yields the same pattern for all isolates of a species. DNASIS software showed that there are 241 suitable restriction enzymes for the differentiation of T. canis from T. cati based on ITS sequences. RsaI, MvaI and SalI enzymes were selected to evaluate the reliability of the in silico PCR-RFLP. The sizes of restriction fragments obtained by PCR-RFLP of all samples consistently matched the expected RFLP patterns. The ITS sequences are usually conserved and the PCR-RFLP approach targeting the ITS sequence is recommended for the molecular differentiation of Toxocara species and can provide a reliable tool for identification purposes particularly at the larval and egg stages.

  16. A Stochastic Climate Generator for Agriculture in Southeast Asian Domains

    Science.gov (United States)

    Greene, A. M.; Allis, E. C.

    2014-12-01

    We extend a previously-described method for generating future climate scenarios, suitable for driving agricultural models, to selected domains in Lao PDR, Bangladesh and Indonesia. There are notable differences in climatology among the study regions, most importantly the inverse seasonal relationship of southeast Asian and Australian monsoons. These differences necessitate a partially-differentiated modeling approach, utilizing common features for better estimation while allowing independent modeling of divergent attributes. The method attempts to constrain uncertainty due to both anthropogenic and natural influences, providing a measure of how these effects may combine during specified future decades. Seasonal climate fields are downscaled to the daily time step by resampling the AgMERRA dataset, providing a full suite of agriculturally relevant variables and enabling the propagation of climate uncertainty to agricultural outputs. The role of this research in a broader project, conducted under the auspices of the International Fund for Agricultural Development (IFAD), is discussed.

  17. [Population genetic differentiation of Phrynocephalus axillaris in east of Xinjiang Uygur Autonomous Region based on sequence variation of mitochondrial ND4-tRNALeu gene].

    Science.gov (United States)

    Li, Jun; Guo, Xian-Guang; Wang, Yue-Zhao

    2010-08-01

    A 838 bp fragment of mtDNA ND4-tRNALeu gene was sequenced for 66 individuals from five populations (DB: Dabancheng, TU: Turpan, SS: Shanshan, HL: Liushuquan, HD: East district of Hami) of Phrynocephalus axillaris distributed in east of Xinjiang Uygur Autonomous Region. Seventeen haplotypes were identified from 29 nucleotide polymorphic sites in the aligned 838 bp sequence. Excluding DB, there were relatively high haplotype diversity [(0.600+/-0.113)oscillation since Pleistocene and genetic drift.

  18. Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

    OpenAIRE

    Barber, Bridget E; William, Timothy; Grigg, Matthew J; Yeo, Tsin W; Anstey, Nicholas M

    2013-01-01

    Abstract Background In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy perfor...

  19. Computational models of Bitemporal, Bifrontal and Right Unilateral ECT predict differential stimulation of brain regions associated with efficacy and cognitive side effects.

    Science.gov (United States)

    Bai, S; Gálvez, V; Dokos, S; Martin, D; Bikson, M; Loo, C

    2017-03-01

    Extensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes placed bilaterally in the frontotemporal region) is the form of ECT with relatively potent clinical and cognitive side effects. However, the reasons for this are poorly understood. This study used computational modelling to examine regional differences in brain excitation between BT, Bifrontal (BF) and Right Unilateral (RUL) ECT, currently the most clinically-used ECT placements. Specifically, by comparing similarities and differences in current distribution patterns between BT ECT and the other two placements, the study aimed to create an explanatory model of critical brain sites that mediate antidepressant efficacy and sites associated with cognitive, particularly memory, adverse effects. High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare differences in activation between the three ECT placements, using subtraction maps. In this exploratory study on three realistic head models, Bitemporal ECT resulted in greater direct stimulation of deep midline structures and also left temporal and inferior frontal regions. Interpreted in light of existing knowledge on depressive pathophysiology and cognitive neuroanatomy, it is suggested that the former sites are related to efficacy and the latter to cognitive deficits. We hereby propose an approach using binarised subtraction models that can be used to optimise, and even individualise, ECT therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Supersymmetric domain walls

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Kleinschmidt, Axel; Riccioni, Fabio

    2012-01-01

    We classify the half-supersymmetric "domain walls," i.e., branes of codimension one, in toroidally compactified IIA/IIB string theory and show to which gauged supergravity theory each of these domain walls belong. We use as input the requirement of supersymmetric Wess-Zumino terms, the properties of

  1. A systemic domain model for ambient pervasive persuasive games

    OpenAIRE

    Eglin, Roger; Eyles, Mark; Dansey, Neil

    2008-01-01

    By the development of the system domain model it is hoped that a greater conceptual and theoretical clarity may be brought to understanding the complex and multifaceted nature of pervasive and ambient computer games. This paper presents a conceptual model, the system domain model, to illustrate domain areas that exist in a console, pervasive or ambient game. It is implicit that the regions that the systemic domain model describes are contextually dependent. By developing this model it is poss...

  2. A Highly Accurate Regular Domain Collocation Method for Solving Potential Problems in the Irregular Doubly Connected Domains

    Directory of Open Access Journals (Sweden)

    Zhao-Qing Wang

    2014-01-01

    Full Text Available Embedding the irregular doubly connected domain into an annular regular region, the unknown functions can be approximated by the barycentric Lagrange interpolation in the regular region. A highly accurate regular domain collocation method is proposed for solving potential problems on the irregular doubly connected domain in polar coordinate system. The formulations of regular domain collocation method are constructed by using barycentric Lagrange interpolation collocation method on the regular domain in polar coordinate system. The boundary conditions are discretized by barycentric Lagrange interpolation within the regular domain. An additional method is used to impose the boundary conditions. The least square method can be used to solve the overconstrained equations. The function values of points in the irregular doubly connected domain can be calculated by barycentric Lagrange interpolation within the regular domain. Some numerical examples demonstrate the effectiveness and accuracy of the presented method.

  3. Constraint Differentiation

    DEFF Research Database (Denmark)

    Mödersheim, Sebastian Alexander; Basin, David; Viganò, Luca

    2010-01-01

    We introduce constraint differentiation, a powerful technique for reducing search when model-checking security protocols using constraint-based methods. Constraint differentiation works by eliminating certain kinds of redundancies that arise in the search space when using constraints to represent...... results show that constraint differentiation substantially reduces search and considerably improves the performance of OFMC, enabling its application to a wider class of problems....

  4. Differential manifolds

    CERN Document Server

    Kosinski, Antoni A

    2007-01-01

    The concepts of differential topology form the center of many mathematical disciplines such as differential geometry and Lie group theory. Differential Manifolds presents to advanced undergraduates and graduate students the systematic study of the topological structure of smooth manifolds. Author Antoni A. Kosinski, Professor Emeritus of Mathematics at Rutgers University, offers an accessible approach to both the h-cobordism theorem and the classification of differential structures on spheres.""How useful it is,"" noted the Bulletin of the American Mathematical Society, ""to have a single, sho

  5. Differential response of vegetation in Hulun Lake region at the northern margin of Asian summer monsoon to extreme cold events of the last deglaciation

    Science.gov (United States)

    Zhang, Shengrui; Xiao, Jule; Xu, Qinghai; Wen, Ruilin; Fan, Jiawei; Huang, Yun; Yamagata, Hideki

    2018-06-01

    The response of vegetation to extreme cold events during the last deglaciation is important for assessing the impact of possible extreme climatic events on terrestrial ecosystems under future global warming scenarios. Here, we present a detailed record of the development of regional vegetation in the northern margin of Asian summer monsoon during the last deglaciation (16,500-11,000 cal yr BP) based on a radiocarbon-dated high-resolution pollen record from Hulun Lake, northeast China. The results show that the regional vegetation changed from subalpine meadow-desert steppe to mixed coniferous and deciduous forest-typical steppe during the last deglaciation. However, its responses to the Heinrich event 1 (H1) and the Younger Dryas event (YD) were significantly different: during the H1 event, scattered sparse forest was present in the surrounding mountains, while within the lake catchment the vegetation cover was poor and was dominated by desert steppe. In contrast, during the YD event, deciduous forest developed and the proportion of coniferous forest increased in the mountains, the lake catchment was occupied by typical steppe. We suggest that changes in Northern Hemisphere summer insolation and land surface conditions (ice sheets and sea level) caused temperature and monsoonal precipitation variations that contributed to the contrasting vegetation response during the two cold events. We conclude that under future global warming scenarios, extreme climatic events may cause a deterioration of the ecological environment of the Hulun Lake region, resulting in increased coniferous forest and decreased total forest cover in the surrounding mountains, and a reduction in typical steppe in the lake catchment.

  6. Physical and chemical differentiation of the luminous star-forming region W49A. Results from the JCMT Spectral Legacy Survey

    Science.gov (United States)

    Nagy, Z.; van der Tak, F. F. S.; Fuller, G. A.; Plume, R.

    2015-05-01

    Context. The massive and luminous star-forming region W49A is a well-known Galactic candidate to probe the physical conditions and chemistry similar to those expected in external starburst galaxies. Aims: We aim to probe the physical and chemical structure of W49A on a spatial scale of ~0.8 pc based on the JCMT Spectral Legacy Survey, which covers the frequency range between 330 and 373 GHz. Methods: The wide 2 × 2 arcmin field and the high spectral resolution of the HARP instrument on JCMT provides information on the spatial structure and kinematics of the cloud traced by the observed molecular lines. For species where multiple transitions are available, we estimate excitation temperatures and column densities using a population diagram method that takes beam dilution and optical depth corrections into account. Results: We detected 255 transitions corresponding to 63 species in the 330-373 GHz range at the center position of W49A. Excitation conditions can be probed for 14 molecules, including the complex organic molecules CH3CCH, CH3CN, and CH3OH. The chemical composition suggests the importance of shock, photon-dominated region (PDR), and hot core chemistry. Many molecular lines show a significant spatial extent across the maps including CO and its isotopologues, high density tracers (e.g., HCN, HNC, CS, HCO+), and tracers of UV irradiation (e.g., CN and C2H). The spatially extended species reveal a complex velocity-structure of W49A with possible infall and outflow motions. Large variations are seen between the subregions with mostly blue-shifted emission toward the eastern tail, mostly red-shifted emission toward the northern clump, and emission peaking around the expected source velocity toward the southwest clump. Conclusions: A comparison of column density ratios of characteristic species observed toward W49A to Galactic PDRs suggests that while the chemistry toward the W49A center is driven by a combination of UV irradiation and shocks, UV irradiation

  7. Domain wall engineering through exchange bias

    International Nuclear Information System (INIS)

    Albisetti, E.; Petti, D.

    2016-01-01

    The control of the structure and position of magnetic domain walls is at the basis of the development of different magnetic devices and architectures. Several nanofabrication techniques have been proposed to geometrically confine and shape domain wall structures; however, a fine tuning of the position and micromagnetic configuration is hardly achieved, especially in continuous films. This work shows that, by controlling the unidirectional anisotropy of a continuous ferromagnetic film through exchange bias, domain walls whose spin arrangement is generally not favored by dipolar and exchange interactions can be created. Micromagnetic simulations reveal that the domain wall width, position and profile can be tuned by establishing an abrupt change in the direction and magnitude of the exchange bias field set in the system. - Highlights: • Micromagnetic simulations study domain walls in exchange biased thin films. • Novel domain wall configurations can be stabilized via exchange bias. • Domain walls nucleate at the boundary of regions with different exchange bias. • Domain wall width and spin profile are controlled by tuning the exchange bias.

  8. U.S. EPA Environmental Quality Index - Air Domain

    Science.gov (United States)

    This is an invited presentation by Region 5, Air Office, who asked me to provide an overview of the Air Domain and health results associated with the Air Domain of the Environmental Quality Index. Region 5 is hosting an Air Toxics meeting for its member states (Ohio, Michigan, I...

  9. Differential Effects of Inactivation of Discrete Regions of Medial Prefrontal Cortex on Memory Consolidation of Moderate and Intense Inhibitory Avoidance Training

    Directory of Open Access Journals (Sweden)

    María E. Torres-García

    2017-11-01

    Full Text Available It has been found that the medial prefrontal cortex (mPFC is involved in memory encoding of aversive events, such as inhibitory avoidance (IA training. Dissociable roles have been described for different mPFC subregions regarding various memory processes, wherein the anterior cingulate cortex (ACC, prelimbic cortex (PL, and infralimbic cortex (IL are involved in acquisition, retrieval, and extinction of aversive events, respectively. On the other hand, it has been demonstrated that intense training impedes the effects on memory of treatments that typically interfere with memory consolidation. The aim of this work was to determine if there are differential effects on memory induced by reversible inactivation of neural activity of ACC, PL, or IL produced by tetrodotoxin (TTX in rats trained in IA using moderate (1.0 mA and intense (3.0 mA foot-shocks. We found that inactivation of ACC has no effects on memory consolidation, regardless of intensity of training. PL inactivation impairs memory consolidation in the 1.0 mA group, while no effect on consolidation was produced in the 3.0 mA group. In the case of IL, a remarkable amnestic effect in LTM was observed in both training conditions. However, state-dependency can explain the amnestic effect of TTX found in the 3.0 mA IL group. In order to circumvent this effect, TTX was injected into IL immediately after training (thus avoiding state-dependency. The behavioral results are equivalent to those found after PL inactivation. Therefore, these findings provide evidence that PL and IL, but not ACC, mediate LTM of IA only in moderate training.

  10. Ordinary differential equations with applications in molecular biology.

    Science.gov (United States)

    Ilea, M; Turnea, M; Rotariu, M

    2012-01-01

    Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances

  11. Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*

    Science.gov (United States)

    Caplan, Steve; Sorgen, Paul L.

    2013-01-01

    The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701

  12. Differential equations

    CERN Document Server

    Barbu, Viorel

    2016-01-01

    This textbook is a comprehensive treatment of ordinary differential equations, concisely presenting basic and essential results in a rigorous manner. Including various examples from physics, mechanics, natural sciences, engineering and automatic theory, Differential Equations is a bridge between the abstract theory of differential equations and applied systems theory. Particular attention is given to the existence and uniqueness of the Cauchy problem, linear differential systems, stability theory and applications to first-order partial differential equations. Upper undergraduate students and researchers in applied mathematics and systems theory with a background in advanced calculus will find this book particularly useful. Supplementary topics are covered in an appendix enabling the book to be completely self-contained.

  13. An approach to regional wetland digital elevation model development using a differential global positioning system and a custom-built helicopter-based surveying system

    Science.gov (United States)

    Jones, J.W.; Desmond, G.B.; Henkle, C.; Glover, R.

    2012-01-01

    Accurate topographic data are critical to restoration science and planning for the Everglades region of South Florida, USA. They are needed to monitor and simulate water level, water depth and hydroperiod and are used in scientific research on hydrologic and biologic processes. Because large wetland environments and data acquisition challenge conventional ground-based and remotely sensed data collection methods, the United States Geological Survey (USGS) adapted a classical data collection instrument to global positioning system (GPS) and geographic information system (GIS) technologies. Data acquired with this instrument were processed using geostatistics to yield sub-water level elevation values with centimetre accuracy (??15 cm). The developed database framework, modelling philosophy and metadata protocol allow for continued, collaborative model revision and expansion, given additional elevation or other ancillary data. ?? 2012 Taylor & Francis.

  14. Optimization of Region of Interest Drawing for Quantitative Analysis: Differentiation Between Benign and Malignant Breast Lesions on Contrast-Enhanced Sonography.

    Science.gov (United States)

    Nakata, Norio; Ohta, Tomoyuki; Nishioka, Makiko; Takeyama, Hiroshi; Toriumi, Yasuo; Kato, Kumiko; Nogi, Hiroko; Kamio, Makiko; Fukuda, Kunihiko

    2015-11-01

    This study was performed to evaluate the diagnostic utility of quantitative analysis of benign and malignant breast lesions using contrast-enhanced sonography. Contrast-enhanced sonography using the perflubutane-based contrast agent Sonazoid (Daiichi Sankyo, Tokyo, Japan) was performed in 94 pathologically proven palpable breast mass lesions, which could be depicted with B-mode sonography. Quantitative analyses using the time-intensity curve on contrast-enhanced sonography were performed in 5 region of interest (ROI) types (manually traced ROI and circular ROIs of 5, 10, 15, and 20 mm in diameter). The peak signal intensity, initial slope, time to peak, positive enhancement integral, and wash-out ratio were investigated in each ROI. There were significant differences between benign and malignant lesions in the time to peak (P benign and malignant lesions in the time to peak (P benign and malignant breast lesions. © 2015 by the American Institute of Ultrasound in Medicine.

  15. Differential environmental impacts on small and medium size rivers from center of São Paulo State, Brazil, and regional management perspectives

    Directory of Open Access Journals (Sweden)

    Paula Caroline dos Reis Oliveira

    2014-12-01

    Full Text Available AIM: This study aimed to evaluate, comparatively, the influence of distinct environmental impacts in the watershed on the rivers Capivara, Lavapés, Araquá and Pardo and the transference of effects downstream. METHODS: The limnological/water quality study was carried out in rainy (March/2007 and dry (September/2007 seasons, considering 17 sampling stations. RESULTS: Variables such as channel width and depth, water velocity and temperature increased towards the river's mouth; water transparency, velocity and dissolved oxygen were higher in the upstream regions. Light penetration was total at most sampling stations and pH was predominantly acid. The sampling stations impacted by pollution sources, Lavapés and Araquá Rivers, exhibited higher values of electric conductivity, suspended solids, total nitrogen, nitrate, nitrite, ammonium, total dissolved phosphorus, BOD, and thermotolerant coliforms. Higher values of electric conductivity, turbidity and suspended solids were observed in the rainy season, whereas higher chlorophyll concentrations occurred in the dry season. The Lavapés River exhibits the worst environmental condition, while Capivara River is under better state of conservation. This study shows that it is urgent the implementation of measures for preservation and restoration of these regional aquatic ecosystems. All studied rivers were influenced by seasonal variation, sewage discharges and by watershed use and occupation. The TSI is a good analysis tool. The studied rivers export organic matter and TN, TP and SS loads to Tietê and Paranapanema rivers. CONCLUSIONS: This study show the importance of river management and that the accelerated degradation of the river systems indicates the little progress of the Brazilian legislation in terms of preservation and good management practices and that the interface between science, law, management and conservation need to be improved.

  16. Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.

    Science.gov (United States)

    Bimpisidis, Zisis; Öberg, Carl M; Maslava, Natallia; Cenci, M Angela; Lundblad, Cornelia

    2017-06-01

    Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [ 14 C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [ 14 C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Image-domain full waveform inversion

    KAUST Repository

    Zhang, Sanzong

    2013-08-20

    The main difficulty with the data-domain full waveform inversion (FWI) is that it tends to get stuck in the local minima associated with the waveform misfit function. This is because the waveform misfit function is highly nonlinear with respect to changes in velocity model. To reduce this nonlinearity, we define the image-domain objective function to minimize the difference of the suboffset-domain common image gathers (CIGs) obtained by migrating the observed data and the calculated data. The derivation shows that the gradient of this new objective function is the combination of the gradient of the conventional FWI and the image-domain differential semblance optimization (DSO). Compared to the conventional FWI, the imagedomain FWI is immune to cycle skipping problems by smearing the nonzero suboffset images along wavepath. It also can avoid the edge effects and the gradient artifacts that are inherent in DSO due to the falsely over-penalized focused images. This is achieved by subtracting the focused image associated with the calculated data from the unfocused image associated with the observed data in the image-domain misfit function. The numerical results of the Marmousi model show that image-domain FWI is less sensitive the initial model than the conventional FWI. © 2013 SEG.

  18. Image-domain full waveform inversion

    KAUST Repository

    Zhang, Sanzong; Schuster, Gerard T.

    2013-01-01

    The main difficulty with the data-domain full waveform inversion (FWI) is that it tends to get stuck in the local minima associated with the waveform misfit function. This is because the waveform misfit function is highly nonlinear with respect to changes in velocity model. To reduce this nonlinearity, we define the image-domain objective function to minimize the difference of the suboffset-domain common image gathers (CIGs) obtained by migrating the observed data and the calculated data. The derivation shows that the gradient of this new objective function is the combination of the gradient of the conventional FWI and the image-domain differential semblance optimization (DSO). Compared to the conventional FWI, the imagedomain FWI is immune to cycle skipping problems by smearing the nonzero suboffset images along wavepath. It also can avoid the edge effects and the gradient artifacts that are inherent in DSO due to the falsely over-penalized focused images. This is achieved by subtracting the focused image associated with the calculated data from the unfocused image associated with the observed data in the image-domain misfit function. The numerical results of the Marmousi model show that image-domain FWI is less sensitive the initial model than the conventional FWI. © 2013 SEG.

  19. Surveillance for Secure Differentiation

    DEFF Research Database (Denmark)

    Hamilton, William B; Brickman, Joshua M

    2017-01-01

    The precise place and time where embryonic differentiation begins is regulated by regionalized signaling. In this issue of Cell Stem Cell, Wang et al. (2017) investigate how converging Wnt and Nodal signals promote mesendoderm through a p53, Wnt3 feed-forward loop, pointing to a mechanism by which...

  20. Differential impact of parental region of birth on negative parenting behavior and its effects on child mental health: Results from a large sample of 6 to 11 year old school children in France.

    Science.gov (United States)

    Kovess-Masfety, Viviane; Husky, Mathilde; Pitrou, Isabelle; Fermanian, Christophe; Shojaei, Taraneh; Chee, Christine Chan; Siddiqi, Arjumand; Beiser, Morton

    2016-05-04

    In France, one in 10 residents has immigrated mainly from North Africa, West Africa or the Caribbean including the French West Indies. However little is known about how parents from these regions behave when they migrate to countries that have different cultural norms. It is therefore important to determine how ethno-cultural background affects parental behavior and subsequent child mental health in the context of immigration. The objectives are: 1) to compare negative parenting behaviors of French residents from diverse ethno-cultural backgrounds 2) to examine the relationship between parental region of origin and child mental health, and 3) to investigate the extent to which ethno-cultural context moderates the effect of parenting styles on child mental health. A cross-sectional study was conducted in 2005 in 100 schools in South-East France. The Dominic Interactive and the parent-reported Strengths and Difficulties Questionnaire were used to assess child psychopathology. The Parent Behavior and Attitude Questionnaire was used to assess parenting styles. The final sample included data on 1,106 mother and child dyads. Caring and punitive attitudes were significantly different across mothers as a function of region of origin. This association was stronger for punitive attitudes with the highest prevalence in the Caribbean/African group, while mothers from Maghreb were more similar to French natives. Differences in caring behaviors were similar though less pronounced. Among children of Maghrebian descent, punitive parenting was associated with an increased risk of internalizing disorders while this association was weaker among children of African and Afro-Caribbean descent. Parental region of origin is an important component of both parenting styles and their effect on child mental health. Interventions on parenting should consider both the region of origin and the differential impact of origin on the effect of parenting styles, thus allowing for a finer

  1. Multimedia applications in differential services

    International Nuclear Information System (INIS)

    Mahfooz, S.; Merabti, M.; Pereira, R.

    2003-01-01

    In this paper we present a mechanism to provide Quality of Service (QoS) guarantees to different multimedia applications that share link bandwidth in IP-based differential services domain. In this mechanism weights are associated with each and to individual users according to their priorities. In order to evaluate the performance of our scheme we conducted simulations. The test data used portray different multimedia applications i.e. MPEG-2, IP telephony. The simulation results obtained show the effectiveness of our scheme for multimedia applications by allocating link share to each multimedia application and minimising end-to-end transmission delay 9Y bringing them in line with the recommended standard acceptable transmission delay for multimedia applications. This paper also presents extension to our proposed Relative Bandwidth Sharing (RES) scheme for differential services. We have identified and highlighted the role of border routers and core routers in differential services domain. Exploring features of Internet Protocol IPv6 in our architecture. (author)

  2. Conserved Domain Database (CDD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins.

  3. Regionalism, Regionalization and Regional Development

    Directory of Open Access Journals (Sweden)

    Liviu C. Andrei

    2016-03-01

    Full Text Available Sustained development is a concept associating other concepts, in its turn, in the EU practice, e.g. regionalism, regionalizing and afferent policies, here including structural policies. This below text, dedicated to integration concepts, will limit on the other hand to regionalizing, otherwise an aspect typical to Europe and to the EU. On the other hand, two aspects come up to strengthen this field of ideas, i.e. the region (al-regionalism-(regional development triplet has either its own history or precise individual outline of terms.

  4. Age-related functional changes in domain-specific medial temporal lobe pathways.

    Science.gov (United States)

    Berron, David; Neumann, Katja; Maass, Anne; Schütze, Hartmut; Fliessbach, Klaus; Kiven, Verena; Jessen, Frank; Sauvage, Magdalena; Kumaran, Dharshan; Düzel, Emrah

    2018-05-01

    There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this

  5. Modelling biochemical reaction systems by stochastic differential equations with reflection.

    Science.gov (United States)

    Niu, Yuanling; Burrage, Kevin; Chen, Luonan

    2016-05-07

    In this paper, we gave a new framework for modelling and simulating biochemical reaction systems by stochastic differential equations with reflection not in a heuristic way but in a mathematical way. The model is computationally efficient compared with the discrete-state Markov chain approach, and it ensures that both analytic and numerical solutions remain in a biologically plausible region. Specifically, our model mathematically ensures that species numbers lie in the domain D, which is a physical constraint for biochemical reactions, in contrast to the previous models. The domain D is actually obtained according to the structure of the corresponding chemical Langevin equations, i.e., the boundary is inherent in the biochemical reaction system. A variant of projection method was employed to solve the reflected stochastic differential equation model, and it includes three simple steps, i.e., Euler-Maruyama method was applied to the equations first, and then check whether or not the point lies within the domain D, and if not perform an orthogonal projection. It is found that the projection onto the closure D¯ is the solution to a convex quadratic programming problem. Thus, existing methods for the convex quadratic programming problem can be employed for the orthogonal projection map. Numerical tests on several important problems in biological systems confirmed the efficiency and accuracy of this approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Echothymia: environmental dependency in the affective domain.

    Science.gov (United States)

    Marin, Robert S; Gorovoy, Ian R

    2014-01-01

    Echothymia is stimulus-bound affective behavior, an echophenomenon in the domain of affect. Like echolalia and echopraxia, it is a concomitant of the environmental dependency associated with dysfunction of the frontal-striatal systems that mediate so-called frontal lobe functions. The authors introduce the definition and phenomenology of echothymia, overview its differential diagnosis and clinical significance, and suggest ways in which understanding echothymia may contribute to clinical management.

  7. Strategic Leadership Development: An Operation Domain Application

    Science.gov (United States)

    1997-03-01

    effectiveness. The Stratified Systems Theory Model is used to identify skills and attributes for the three leadership domains of Direct, Operation, and...tools they need to help the organization achieve its goals. In discussing leadership , it is important to distinguish between management and leadership ...Peter Drucker and Warren Bennis, two noted authors on leadership , offered the following differentiation: “ Management is doing things right

  8. Individual globular domains and domain unfolding visualized in overstretched titin molecules with atomic force microscopy.

    Directory of Open Access Journals (Sweden)

    Zsolt Mártonfalvi

    Full Text Available Titin is a giant elastomeric protein responsible for the generation of passive muscle force. Mechanical force unfolds titin's globular domains, but the exact structure of the overstretched titin molecule is not known. Here we analyzed, by using high-resolution atomic force microscopy, the structure of titin molecules overstretched with receding meniscus. The axial contour of the molecules was interrupted by topographical gaps with a mean width of 27.7 nm that corresponds well to the length of an unfolded globular (immunoglobulin and fibronectin domain. The wide gap-width distribution suggests, however, that additional mechanisms such as partial domain unfolding and the unfolding of neighboring domain multimers may also be present. In the folded regions we resolved globules with an average spacing of 5.9 nm, which is consistent with a titin chain composed globular domains with extended interdomain linker regions. Topographical analysis allowed us to allocate the most distal unfolded titin region to the kinase domain, suggesting that this domain systematically unfolds when the molecule is exposed to overstretching forces. The observations support the prediction that upon the action of stretching forces the N-terminal ß-sheet of the titin kinase unfolds, thus exposing the enzyme's ATP-binding site and hence contributing to the molecule's mechanosensory function.

  9. Differential games

    CERN Document Server

    Friedman, Avner

    2006-01-01

    This volume lays the mathematical foundations for the theory of differential games, developing a rigorous mathematical framework with existence theorems. It begins with a precise definition of a differential game and advances to considerations of games of fixed duration, games of pursuit and evasion, the computation of saddle points, games of survival, and games with restricted phase coordinates. Final chapters cover selected topics (including capturability and games with delayed information) and N-person games.Geared toward graduate students, Differential Games will be of particular interest

  10. Detection and differentiation of pollution in urban surface soils using magnetic properties in arid and semi-arid regions of northwestern China.

    Science.gov (United States)

    Wang, Bo; Xia, Dunsheng; Yu, Ye; Jia, Jia; Xu, Shujing

    2014-01-01

    Increasing urbanization and industrialization over the world has caused many social and environmental problems, one of which drawing particular concern is the soil pollution and its ecological degradation. In this study, the efficiency of magnetic methods for detecting and discriminating contaminates in the arid and semi-arid regions of northwestern China was investigated. Topsoil samples from six typical cities (i.e. Karamay, Urumqi, Lanzhou, Yinchuan, Shizuishan and Wuhai) were collected and a systematic analysis of their magnetic properties was conducted. Results indicate that the topsoil samples from the six cities were all dominated by coarse low-coercivity magnetite. In addition, the average magnetite contents in the soils from Urumqi and Lanzhou were shown to be much higher than those from Karamay, Yinchuan, Shizuishan and Wuhai, and they also have relatively higher χlf and χfd% when compared with cities in eastern China. Moreover, specific and distinctive soil pollution signals were identified at each sampling site using the combined various magnetic data, reflecting distinct sources. Industrial and traffic-derived pollution was dominant in Urumqi and Lanzhou, in Yinchuan industrial progress was observed to be important with some places affected by vehicle emission, while Karamay, Shizuishan and Wuhai were relatively clean. The magnetic properties of these latter three cities are significantly affected by both anthropogenic pollution and local parent materials from the nearby Gobi desert. The differences in magnetic properties of topsoil samples affected by mixed industrial and simplex traffic emissions are not obvious, but significant differences exist in samples affected by simplex industrial/vehicle emissions and domestic pollution. The combined magnetic analyses thus provide a sensitive and powerful tool for classifying samples according to likely sources, and may even provide a valuable diagnostic tool for discriminating among different cities

  11. Differential equilibration and intergranular diffusion of trace elements during rapid regional metamorphism: constraints from LA-ICP-MS mapping of a garnet population

    Science.gov (United States)

    George, F. R.; Gaidies, F.

    2017-12-01

    Trace element zoning contained within a metapelitic garnet population yields information pertaining to a more complex prograde reaction history than is evident in major element zoning patterns and other conventional analyses. In particular, while trace elements may not act as a rate-limiting component for garnet crystallization, their incorporation into garnet growth surfaces provides a nuanced insight into the crystallization history of the population, and the extent of equilibration of trace elements in the matrix. In this study, we present LA-ICP-MS raster maps of trace element concentrations from several population-representative, centrally sectioned garnets from a garnet-grade metapelite of the Sikkim Himalaya, India. Equilibrium forward modeling of garnet crystallization and simulation of diffusional modification indicates that the garnet population crystallized rapidly over <1 Myr between 515 °C/4.5 kbar and 565 °C/5.5 kbar, as a consequence of high heating rates during regional amphibolite-facies metamorphism. While the rate of diffusional homogenization of major divalent cations is interpreted to have exceeded the rate of interfacial advance (yielding simple prograde growth zoning), trace element distributions record a more complex transport history. In particular, yttrium and the heavy rare earth elements (HREE) document a transition from an overprinted sigmoidal core to concentric repeated HREE and yttrium annuli in all crystals. This suggests that there was a discrete increase in the length scale of equilibration along the advancing garnet interface at some point in the growth history. However, there is no evidence for a coeval change in HREE transport thorough the intergranular network. Conversely, spiral core-to-rim zoning of chromium indicates the element remains almost completely immobile in the matrix over the duration of garnet growth.

  12. Differential Geometry

    CERN Document Server

    Stoker, J J

    2011-01-01

    This classic work is now available in an unabridged paperback edition. Stoker makes this fertile branch of mathematics accessible to the nonspecialist by the use of three different notations: vector algebra and calculus, tensor calculus, and the notation devised by Cartan, which employs invariant differential forms as elements in an algebra due to Grassman, combined with an operation called exterior differentiation. Assumed are a passing acquaintance with linear algebra and the basic elements of analysis.

  13. Detection and differentiation of pollution in urban surface soils using magnetic properties in arid and semi-arid regions of northwestern China

    International Nuclear Information System (INIS)

    Wang, Bo; Xia, Dunsheng; Yu, Ye; Jia, Jia; Xu, Shujing

    2014-01-01

    Increasing urbanization and industrialization over the world has caused many social and environmental problems, one of which drawing particular concern is the soil pollution and its ecological degradation. In this study, the efficiency of magnetic methods for detecting and discriminating contaminates in the arid and semi-arid regions of northwestern China was investigated. Topsoil samples from six typical cities (i.e. Karamay, Urumqi, Lanzhou, Yinchuan, Shizuishan and Wuhai) were collected and a systematic analysis of their magnetic properties was conducted. Results indicate that the topsoil samples from the six cities were all dominated by coarse low-coercivity magnetite. In addition, the average magnetite contents in the soils from Urumqi and Lanzhou were shown to be much higher than those from Karamay, Yinchuan, Shizuishan and Wuhai, and they also have relatively higher χ lf and χ fd % when compared with cities in eastern China. Moreover, specific and distinctive soil pollution signals were identified at each sampling site using the combined various magnetic data, reflecting distinct sources. Industrial and traffic-derived pollution was dominant in Urumqi and Lanzhou, in Yinchuan industrial progress was observed to be important with some places affected by vehicle emission, while Karamay, Shizuishan and Wuhai were relatively clean. The magnetic properties of these latter three cities are significantly affected by both anthropogenic pollution and local parent materials from the nearby Gobi desert. The differences in magnetic properties of topsoil samples affected by mixed industrial and simplex traffic emissions are not obvious, but significant differences exist in samples affected by simplex industrial/vehicle emissions and domestic pollution. The combined magnetic analyses thus provide a sensitive and powerful tool for classifying samples according to likely sources, and may even provide a valuable diagnostic tool for discriminating among different cities

  14. Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.

    Science.gov (United States)

    Paliwal, Anupam; Temkin, Alexis M; Kerkel, Kristi; Yale, Alexander; Yotova, Iveta; Drost, Natalia; Lax, Simon; Nhan-Chang, Chia-Ling; Powell, Charles; Borczuk, Alain; Aviv, Abraham; Wapner, Ronald; Chen, Xiaowei; Nagy, Peter L; Schork, Nicholas; Do, Catherine; Torkamani, Ali; Tycko, Benjamin

    2013-08-01

    Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM.

  15. The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

    Science.gov (United States)

    Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

    2017-07-15

    Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

  16. Context-specific requirements of functional domains of the Spectraplakin Short stop in vivo.

    Science.gov (United States)

    Bottenberg, Wolfgang; Sanchez-Soriano, Natalia; Alves-Silva, Juliana; Hahn, Ines; Mende, Michael; Prokop, Andreas

    2009-07-01

    Spectraplakins are large multifunctional cytoskeletal interacting molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. It has been speculated that the various functional domains and regions found in Spectraplakins are used in context-specific manners, a model which would provide a crucial explanation for the multifunctional nature of Spectraplakins. Here we tested this possibility by studying domain requirements of the Drosophila Spectraplakin Short stop (Shot) in three different cellular contexts in vivo: (1) neuronal growth, which requires dynamic actin-microtubule interaction; (2) formation and maintenance of tendon cells, which depends on highly stabilised arrays of actin filaments and microtubules, and (3) compartmentalisation in neurons, which is likely to involve cortical F-actin networks. Using these cellular contexts for rescue experiments with Shot deletion constructs in shot mutant background, a number of differential domain requirements were uncovered. First, binding of Shot to F-actin through the first Calponin domain is essential in neuronal contexts but dispensable in tendon cells. This finding is supported by our analyses of shot(kakP2) mutant embryos, which produce only endogenous isoforms lacking the first Calponin domain. Thus, our data demonstrate a functional relevance for these isoforms in vivo. Second, we provide the first functional role for the Plakin domain of Shot, which has a strong requirement for compartmentalisation in neurons and axonal growth, demonstrating that Plakin domains of long Spectraplakin isoforms are of functional relevance. Like the Calponin domain, also the Plakin domain is dispensable in tendon cells, and the currently assumed role of Shot as a linker of microtubules to the tendon cell surface may have to be reconsidered. Third, we demonstrate a function of Shot as an actin-microtubule linker in dendritic growth, thus shedding new light into

  17. Interfacial Dynamics of Abelian Domains: Differential Geometric Methods

    International Nuclear Information System (INIS)

    Owczarek, Robert M.; Makaruk, Hanna E.

    1997-11-01

    The equation: ReF'(T,Z)ZF'(T,Z) = 1 for conformal maps f(t,z) is important in interfacial dynamics. We extend the results by Gustafsson on existence and uniqueness of solutions of this equation from the case when f(t,z) is a rational function of z to the case when the spatial derivative f'(t,z) is rational

  18. Effects of sub-domain structure on initial magnetization curve and domain size distribution of stacked media

    International Nuclear Information System (INIS)

    Sato, S.; Kumagai, S.; Sugita, R.

    2015-01-01

    In this paper, in order to confirm the sub-domain structure in stacked media demagnetized with in-plane field, initial magnetization curves and magnetic domain size distribution were investigated. Both experimental and simulation results showed that an initial magnetization curve for the medium demagnetized with in-plane field (MDI) initially rose faster than that for the medium demagnetized with perpendicular field (MDP). It is inferred that this is because the MDI has a larger number of domain walls than the MDP due to the existence of the sub-domains, resulting in an increase in the probability of domain wall motion. Dispersion of domain size for the MDI was larger than that for the MDP. This is because sub-domains are formed not only inside the domain but also at the domain boundary region, and they change the position of the domain boundary to affect the domain size. - Highlights: • An initial magnetization curve for MDI initially rose faster than that for MDP. • Dispersion of domain size for the MDI was larger than that for the MDP. • Experimental and simulation results can be explained by existence of sub-domains

  19. Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

    International Nuclear Information System (INIS)

    Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

    2011-01-01

    Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

  20. Constructing Regional advantage

    DEFF Research Database (Denmark)

    Asheim, Bjørn T.; Boschma, Ron; Cooke, Phil

    2011-01-01

    This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related variety, knowledge bases and policy platforms. Related variety attaches importance to knowledge spillovers across complementary...... economic development within and between regions in action lines appropriate to incorporate the basic principles behind related variety and differentiated knowledge bases....

  1. Identification of highly deformed even–even nuclei in the neutron- and proton-rich regions of the nuclear chart from the B(E2)↑ and E2 predictions in the generalized differential equation model

    International Nuclear Information System (INIS)

    Nayak, R.C.; Pattnaik, S.

    2015-01-01

    We identify here the possible occurrence of large deformations in the neutron- and proton-rich (n-rich and p-rich) regions of the nuclear chart from extensive predictions of the values of the reduced quadrupole transition probability B(E2)↑ for the transition from the ground state to the first 2 + state and the corresponding excitation energy E2 of even–even nuclei in the recently developed generalized differential equation (GDE) model exclusively meant for these physical quantities. This is made possible from our analysis of the predicted values of these two physical quantities and the corresponding deformation parameters derived from them such as the quadrupole deformation β 2 , the ratio of β- 2 to the Weisskopf single-particle β 2(sp) and the intrinsic electric quadrupole moment Q 0 , calculated for a large number of both known as well as hitherto unknown even–even isotopes of oxygen to fermium (0 to FM; Z = 8 – 100). Our critical analysis of the resulting data convincingly support possible existence of large collectivity for the nuclides 30,32 Ne, 34 Mg, 60 Ti, 42,62,64 Cr, 50,68 Fe, 52,72 Ni, 72,70,96 Kr, 74,76 Sr, 78,80,106,108 Zr, 82,84,110,112 Mo, 140 Te, 144 Xe, 148 Ba, 122 Ce, 128,156 Nd, 130,132,158,160 Sm and 138,162,164,166 Gd, whose values of β 2 are found to exceed 0.3 and even 0.4 in some cases. Our findings of large deformations in the exotic n-rich regions support the existence of another “island of inversion” in the heavy-mass region possibly caused by breaking of the N = 70 subshell closure. (author)

  2. Domain: Labour market

    NARCIS (Netherlands)

    Oude Mulders, J.; Wadensjö, E.; Hasselhorn, H.M.; Apt, W.

    This domain chapter is dedicated to summarize research on the effects of labour market contextual factors on labour market participation of older workers (aged 50+) and identify research gaps. While employment participation and the timing of (early) retirement is often modelled as an individual

  3. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  4. Domain-Specific Multimodeling

    DEFF Research Database (Denmark)

    Hessellund, Anders

    the overall level of abstraction. It does, however, also introduce a new problem of coordinating multiple different languages in a single system. We call this problem the coordination problem. In this thesis, we present the coordination method for domain-specific multimodeling that explicitly targets...

  5. GlycoDomainViewer

    DEFF Research Database (Denmark)

    Joshi, Hiren J; Jørgensen, Anja; Schjoldager, Katrine T

    2018-01-01

    features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated. The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body...

  6. A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain.

    Science.gov (United States)

    Wu, R; Wilton, R; Cuff, M E; Endres, M; Babnigg, G; Edirisinghe, J N; Henry, C S; Joachimiak, A; Schiffer, M; Pokkuluri, P R

    2017-04-01

    We report the structural and biochemical characterization of a novel periplasmic ligand-binding protein, Dret_0059, from Desulfohalobium retbaense DSM 5692, an organism isolated from Lake Retba, in Senegal. The structure of the protein consists of a unique combination of a periplasmic solute binding protein (SBP) domain at the N-terminal and a tandem PAS-like sensor domain at the C-terminal region. SBP domains are found ubiquitously, and their best known function is in solute transport across membranes. PAS-like sensor domains are commonly found in signal transduction proteins. These domains are widely observed as parts of many protein architectures and complexes but have not been observed previously within the same polypeptide chain. In the structure of Dret_0059, a ketoleucine moiety is bound to the SBP, whereas a cytosine molecule is bound in the distal PAS-like domain of the tandem PAS-like domain. Differential scanning flourimetry support the binding of ligands observed in the crystal structure. There is significant interaction between the SBP and tandem PAS-like domains, and it is possible that the binding of one ligand could have an effect on the binding of the other. We uncovered three other proteins with this structural architecture in the non-redundant sequence data base, and predict that they too bind the same substrates. The genomic context of this protein did not offer any clues for its function. We did not find any biological process in which the two observed ligands are coupled. The protein Dret_0059 could be involved in either signal transduction or solute transport. © 2017 The Protein Society.

  7. The framing of scientific domains

    DEFF Research Database (Denmark)

    Dam Christensen, Hans

    2014-01-01

    domains, and UNISIST helps understanding this navigation. Design/methodology/approach The UNISIST models are tentatively applied to the domain of art history at three stages, respectively two modern, partially overlapping domains, as well as an outline of an art historical domain anno c1820...

  8. Faraday instability in deformable domains

    International Nuclear Information System (INIS)

    Pucci, G.

    2013-01-01

    Hydrodynamical instabilities are usually studied either in bounded regions or free to grow in space. In this article we review the experimental results of an intermediate situation, in which an instability develops in deformable domains. The Faraday instability, which consists in the formation of surface waves on a liquid experiencing a vertical forcing, is triggered in floating liquid lenses playing the role of deformable domains. Faraday waves deform the lenses from the initial circular shape and the mutual adaptation of instability patterns with the lens boundary is observed. Two archetypes of behaviour have been found. In the first archetype a stable elongated shape is reached, the wave vector being parallel to the direction of elongation. In the second archetype the waves exceed the response of the lens border and no equilibrium shape is reached. The lens stretches and eventually breaks into fragments that have a complex dynamics. The difference between the two archetypes is explained by the competition between the radiation pressure the waves exert on the lens border and its response due to surface tension.

  9. Measuring regional authority

    NARCIS (Netherlands)

    Marks, G.W.; Hooghe, E.A.E.B.; Schakel, A.H.

    2008-01-01

    This article sets out a conceptual basis for measuring regional authority and engages basic measurement issues. Regional authority is disaggregated into two domains (self-rule and shared rule) and these are operationalised in eight dimensions. The article concludes by examining the robustness of

  10. Non-dense domain operator matrices and Cauchy problems

    International Nuclear Information System (INIS)

    Lalaoui Rhali, S.

    2002-12-01

    In this work, we study Cauchy problems with non-dense domain operator matrices. By assuming that the entries of an unbounded operator matrix are Hille-Yosida operators, we give a necessary and sufficient condition ensuring that the part of this operator matrix generates a semigroup in the closure of its domain. This allows us to prove the well-posedness of the corresponding Cauchy problem. Our results are applied to delay and neutral differential equations. (author)

  11. Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C 2 A