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Sample records for prs expressing rhodopsin

  1. Light-promoted rhodopsin expression and starvation survival in the marine dinoflagellate Oxyrrhis marina.

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    Zhiling Guo

    Full Text Available The discovery of microbial rhodopsins in marine proteobacteria changed the dogma that photosynthesis is the only pathway to use the solar energy for biological utilization in the marine environment. Although homologs of these rhodopsins have been identified in dinoflagellates, the diversity of the encoding genes and their physiological roles remain unexplored. As an initial step toward addressing the gap, we conducted high-throughput transcriptome sequencing on Oxyrrhis marina to retrieve rhodopsin transcripts, rapid amplification of cDNA ends to isolate full-length cDNAs of dominant representatives, and quantitative reverse-transcription PCR to investigate their expression under varying conditions. Our phylogenetic analyses showed that O. marina contained both the proton-pumping type (PR and sensory type (SR rhodopsins, and the transcriptome data showed that the PR type dominated over the SR type. We compared rhodopsin gene expression for cultures kept under light: dark cycle and continuous darkness in a time course of 24 days without feeding. Although both types of rhodopsin were expressed under the two conditions, the expression levels of PR were much higher than SR, consistent with the transcriptomic data. Furthermore, relative to cultures kept in the dark, rhodopsin expression levels and cell survival rate were both higher in cultures grown in the light. This is the first report of light-dependent promotion of starvation survival and concomitant promotion of PR expression in a eukaryote. While direct evidence needs to come from functional test on rhodopsins in vitro or gene knockout/knockdown experiments, our results suggest that the proton-pumping rhodopsin might be responsible for the light-enhanced survival of O. marina, as previously demonstrated in bacteria.

  2. Proton-pumping rhodopsins are abundantly expressed by microbial eukaryotes in a high-Arctic fjord.

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    Vader, Anna; Laughinghouse, Haywood D; Griffiths, Colin; Jakobsen, Kjetill S; Gabrielsen, Tove M

    2018-02-01

    Proton-pumping rhodopsins provide an alternative pathway to photosynthesis by which solar energy can enter the marine food web. Rhodopsin genes are widely found in marine bacteria, also in the Arctic, and were recently reported from several eukaryotic lineages. So far, little is known about rhodopsin expression in Arctic eukaryotes. In this study, we used metatranscriptomics and 18S rDNA tag sequencing to examine the mid-summer function and composition of marine protists (size 0.45-10 µm) in the high-Arctic Billefjorden (Spitsbergen), especially focussing on the expression of microbial proton-pumping rhodopsins. Rhodopsin transcripts were highly abundant, at a level similar to that of genes involved in photosynthesis. Phylogenetic analyses placed the environmental rhodopsins within disparate eukaryotic lineages, including dinoflagellates, stramenopiles, haptophytes and cryptophytes. Sequence comparison indicated the presence of several functional types, including xanthorhodopsins and a eukaryotic clade of proteorhodopsin. Transcripts belonging to the proteorhodopsin clade were also abundant in published metatranscriptomes from other oceanic regions, suggesting a global distribution. The diversity and abundance of rhodopsins show that these light-driven proton pumps play an important role in Arctic microbial eukaryotes. Understanding this role is imperative to predicting the future of the Arctic marine ecosystem faced by a changing light climate due to diminishing sea-ice. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Variation in rhodopsin kinase expression alters the dim flash response shut off and the light adaptation in rod photoreceptors.

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    Sakurai, Keisuke; Young, Joyce E; Kefalov, Vladimir J; Khani, Shahrokh C

    2011-08-29

    Rod photoreceptors are exquisitely sensitive light detectors that function in dim light. The timely inactivation of their light responses is critical for the ability of rods to reliably detect and count photons. A key step in the inactivation of the rod transduction is the phosphorylation of the rod visual pigment, rhodopsin, catalyzed by G-protein-dependent receptor kinase 1 (GRK1). Absence of GRK1 greatly prolongs the photoreceptors' light response and enhances their susceptibility to degeneration. This study examined the light responses from mouse rods expressing various levels of GRK1 to evaluate how their function is modulated by rhodopsin inactivation. Transretinal and single-cell rod electrophysiological recordings were obtained from several strains of mice expressing GRK1 at 0.3- to 3-fold the wild-type levels. The effect of GRK1 expression level on the function of mouse rods was examined in darkness and during background adaptation. Altering the expression of GRK1 from 0.3- to 3-fold that in wild-type rods had little effect on the single photon response amplitude. Notably, increasing the expression level of GRK1 accelerated the dim flash response shut off but had no effect on the saturated response shut off. Additionally, GRK1 excess abolished the acceleration of saturated responses shut off during light adaptation. These results demonstrate that rhodopsin inactivation can modulate the kinetics of recovery from dim light stimulation. More importantly, the ratio of rhodopsin kinase to its modulator recoverin appears critical for the proper adaptation of rods and the acceleration of their response shut off in background light.

  4. Modulation of rhodopsin gene expression and signaling mechanisms evoked by endothelins in goldfish and murine pigment cell lines

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    G.J.D. Lopes

    2010-09-01

    Full Text Available Endothelins (ETs and sarafotoxins (SRTXs belong to a family of vasoconstrictor peptides, which regulate pigment migration and/or production in vertebrate pigment cells. The teleost Carassius auratus erythrophoroma cell line, GEM-81, and Mus musculus B16 melanocytes express rhodopsin, as well as the ET receptors, ETB and ETA, respectively. Both cell lines are photoresponsive, and respond to light with a decreased proliferation rate. For B16, the doubling time of cells kept in 14-h light (14L:10-h darkness (10D was higher compared to 10L:14D, or to DD. The doubling time of cells kept in 10L:14D was also higher compared to DD. Using real-time PCR, we demonstrated that SRTX S6c (12-h treatment, 100 pM and 1 nM; 24-h treatment, 1 nM and ET-1 (12-h treatment, 10 and 100 pM; 24- and 48-h treatments, 100 pM increased rhodopsin mRNA levels in GEM-81 and B16 cells, respectively. This modulation involves protein kinase C (PKC and the mitogen-activated protein kinase cascade in GEM-81 cells, and phospholipase C, Ca2+, calmodulin, a Ca2+/calmodulin-dependent kinase, and PKC in B16 cells. Cells were kept under constant darkness throughout the gene expression experiments. These results show that rhodopsin mRNA levels can be modulated by SRTXs/ETs in vertebrate pigment cells. It is possible that SRTX S6c binding to the ETB receptors in GEM-81 cells, and ET-1 binding to ETA receptors in B16 melanocytes, although activating diverse intracellular signaling mechanisms, mobilize transcription factors such as c-Fos, c-Jun, c-Myc, and neural retina leucine zipper protein. These activated transcription factors may be involved in the positive regulation of rhodopsin mRNA levels in these cell lines.

  5. Wild-type phosphoribosylpyrophosphate synthase (PRS from Mycobacterium tuberculosis: a bacterial class II PRS?

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    Ardala Breda

    Full Text Available The 5-phospho-α-D-ribose 1-diphosphate (PRPP metabolite plays essential roles in several biosynthetic pathways, including histidine, tryptophan, nucleotides, and, in mycobacteria, cell wall precursors. PRPP is synthesized from α-D-ribose 5-phosphate (R5P and ATP by the Mycobacterium tuberculosis prsA gene product, phosphoribosylpyrophosphate synthase (MtPRS. Here, we report amplification, cloning, expression and purification of wild-type MtPRS. Glutaraldehyde cross-linking results suggest that MtPRS predominates as a hexamer, presenting varied oligomeric states due to distinct ligand binding. MtPRS activity measurements were carried out by a novel coupled continuous spectrophotometric assay. MtPRS enzyme activity could be detected in the absence of P(i. ADP, GDP and UMP inhibit MtPRS activity. Steady-state kinetics results indicate that MtPRS has broad substrate specificity, being able to accept ATP, GTP, CTP, and UTP as diphosphoryl group donors. Fluorescence spectroscopy data suggest that the enzyme mechanism for purine diphosphoryl donors follows a random order of substrate addition, and for pyrimidine diphosphoryl donors follows an ordered mechanism of substrate addition in which R5P binds first to free enzyme. An ordered mechanism for product dissociation is followed by MtPRS, in which PRPP is the first product to be released followed by the nucleoside monophosphate products to yield free enzyme for the next round of catalysis. The broad specificity for diphosphoryl group donors and detection of enzyme activity in the absence of P(i would suggest that MtPRS belongs to Class II PRS proteins. On the other hand, the hexameric quaternary structure and allosteric ADP inhibition would place MtPRS in Class I PRSs. Further data are needed to classify MtPRS as belonging to a particular family of PRS proteins. The data here presented should help augment our understanding of MtPRS mode of action. Current efforts are toward experimental structure

  6. Wild-Type Phosphoribosylpyrophosphate Synthase (PRS) from Mycobacterium tuberculosis: A Bacterial Class II PRS?

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    Breda, Ardala; Martinelli, Leonardo K. B.; Bizarro, Cristiano V.; Rosado, Leonardo A.; Borges, Caroline B.; Santos, Diógenes S.; Basso, Luiz A.

    2012-01-01

    The 5-phospho-α-D-ribose 1-diphosphate (PRPP) metabolite plays essential roles in several biosynthetic pathways, including histidine, tryptophan, nucleotides, and, in mycobacteria, cell wall precursors. PRPP is synthesized from α-D-ribose 5-phosphate (R5P) and ATP by the Mycobacterium tuberculosis prsA gene product, phosphoribosylpyrophosphate synthase (MtPRS). Here, we report amplification, cloning, expression and purification of wild-type MtPRS. Glutaraldehyde cross-linking results suggest that MtPRS predominates as a hexamer, presenting varied oligomeric states due to distinct ligand binding. MtPRS activity measurements were carried out by a novel coupled continuous spectrophotometric assay. MtPRS enzyme activity could be detected in the absence of Pi. ADP, GDP and UMP inhibit MtPRS activity. Steady-state kinetics results indicate that MtPRS has broad substrate specificity, being able to accept ATP, GTP, CTP, and UTP as diphosphoryl group donors. Fluorescence spectroscopy data suggest that the enzyme mechanism for purine diphosphoryl donors follows a random order of substrate addition, and for pyrimidine diphosphoryl donors follows an ordered mechanism of substrate addition in which R5P binds first to free enzyme. An ordered mechanism for product dissociation is followed by MtPRS, in which PRPP is the first product to be released followed by the nucleoside monophosphate products to yield free enzyme for the next round of catalysis. The broad specificity for diphosphoryl group donors and detection of enzyme activity in the absence of Pi would suggest that MtPRS belongs to Class II PRS proteins. On the other hand, the hexameric quaternary structure and allosteric ADP inhibition would place MtPRS in Class I PRSs. Further data are needed to classify MtPRS as belonging to a particular family of PRS proteins. The data here presented should help augment our understanding of MtPRS mode of action. Current efforts are toward experimental structure determination of MtPRS

  7. Evolution of rhodopsin ion pumps in haloarchaea

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    Ford Doolittle W

    2007-05-01

    Full Text Available Abstract Background The type 1 (microbial rhodopsins are a diverse group of photochemically reactive proteins that display a broad yet patchy distribution among the three domains of life. Recent work indicates that this pattern is likely the result of lateral gene transfer (LGT of rhodopsin genes between major lineages, and even across domain boundaries. Within the lineage in which the microbial rhodopsins were initially discovered, the haloarchaea, a similar patchy distribution is observed. In this initial study, we assess the roles of LGT and gene loss in the evolution of haloarchaeal rhodopsin ion pump genes, using phylogenetics and comparative genomics approaches. Results Mapping presence/absence of rhodopsins onto the phylogeny of the RNA polymerase B' subunit (RpoB' of the haloarchaea supports previous notions that rhodopsins are patchily distributed. The phylogeny for the bacteriorhodopsin (BR protein revealed two discrepancies in comparison to the RpoB' marker, while the halorhodopsin (HR tree showed incongruence to both markers. Comparative analyses of bacteriorhodopsin-linked regions of five haloarchaeal genomes supported relationships observed in the BR tree, and also identified two open reading frames (ORFs that were more frequently linked to the bacteriorhodopsin gene than those genes previously shown to be important to the function and expression of BR. Conclusion The evidence presented here reveals a complex evolutionary history for the haloarchaeal rhodopsins, with both LGT and gene loss contributing to the patchy distribution of rhodopsins within this group. Similarities between the BR and RpoB' phylogenies provide supportive evidence for the presence of bacteriorhodopsin in the last common ancestor of haloarchaea. Furthermore, two loci that we have designated bacterio-opsin associated chaperone (bac and bacterio-opsin associated protein (bap are inferred to have important roles in BR biogenesis based on frequent linkage and co

  8. PRS and POS/PRS coupling experiments on Hawk

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    Peterson, G G; Apruzese, J P; Commisso, R J [Naval Research Laboratory, Washington, DC (United States). Plasma Physics Div.; and others

    1997-12-31

    Experiments are being conducted on Hawk to investigate the electrical coupling of a plasma opening switch (POS) to a neon plasma radiation source (PRS) and to evaluate the K SHELL x-ray yield scaling of implosions with different initial radii, mass, and implosion times. Understanding the coupling and scaling is important for optimizing the performance of more powerful inductive-storage generators that rely on POS technology. (author). 1 tab., 5 figs., 7 refs.

  9. Evidence of microbial rhodopsins in Antarctic Dry Valley edaphic systems.

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    Guerrero, Leandro D; Vikram, Surendra; Makhalanyane, Thulani P; Cowan, Don A

    2017-09-01

    Microorganisms able to synthesize rhodopsins have the capacity to translocate ions through their membranes, using solar energy to generate a proton motive force. Rhodopsins are the most abundant phototrophic proteins in oceanic surface waters and are key constituents in marine bacterial ecology. However, it remains unclear how rhodopsins are used in most microorganisms. Despite their abundance in marine and fresh-water systems, the presence of functional rhodopsin systems in edaphic habitats has never been reported. Here, we show the presence of several new putative H + , Na + and Cl + pumping rhodopsins identified by metagenomic analysis of Antarctic desert hypolithic communities. Reconstruction of two Proteobacteria genomes harboring xanthorhodopsin-like proteins and one Bacteroidetes genome with a Na-pumping-like rhodopsin indicated that these bacteria were aerobic heterotrophs possessing the apparent capacity for the functional expression of rhodopsins. The existence of these protein systems in hypolithic bacteria expands the known role of rhodopsins to include terrestrial environments and suggests a possible predominant function as heterotrophic energy supply proteins, a feasible microbial adaptation to the harsh conditions prevalent in Antarctic edaphic systems. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Tricistronic operon expression of the genes gcaD (tms), which encodes N-acetylglucosamine 1-phosphate uridyltransferase, prs, which encodes phosphoribosyl diphosphate synthetase, and ctc in vegetative cells of Bacillus subtilis

    DEFF Research Database (Denmark)

    Hilden, Ida; Krath, Britta N.; Hove-Jensen, Bjarne

    1995-01-01

    The gcaD, prs, and ctc genes were shown to be organized as a tricistronic operon. The transcription of the prs gene, measured as phosphoribosyl diphosphate synthetase activity, and of the ctc gene, measured as β-galactosidase activity specified by a ctc-lacZ protein fusion, were dependent...

  11. Bacillus caldolyticus prs gene encoding phosphoribosyldiphosphate synthase

    DEFF Research Database (Denmark)

    Krath, Britta N.; Hove-Jensen, Bjarne

    1996-01-01

    The prs gene, encoding phosphoribosyl-diphosphate (PRPP) synthase, as well as the flanking DNA sequences were cloned and sequenced from the Gram-positive thermophile, Bacillus caldolyticus. Comparison with the homologous sequences from the mesophile, Bacillus subtilis, revealed a gene (gca......D) encoding N-acetylglucosamine-l-phosphate uridyltransferase upstream of prs, and a gene homologous to ctc downstream of prs. cDNA synthesis with a B. caldolyticus gcaD-prs-ctc-specified mRNA as template, followed by amplification utilising the polymerase chain reaction indicated that the three genes are co......-transcribed. Comparison of amino acid sequences revealed a high similarity among PRPP synthases across a wide phylogenetic range. An E. coli strain harbouring the B. caldolyticus prs gene in a multicopy plasmid produced PRPP synthase activity 33-fold over the activity of a haploid B. caldolyticus strain. B. caldolyticus...

  12. Management of nuclear PRs activity with optimal conditions

    International Nuclear Information System (INIS)

    Ohnishi, Teruaki

    1997-01-01

    A methodology is proposed to derive optimal conditions for the activity of nuclear public relations (PRs). With the use of data-bases available at present, expressions were derived which connect the budget allocated for the PRs activity with the intensity of stimulus for four types of activity of the advertisement in the press, the exclusive publicity, the pamphlet and the advertisement on television. Optimal conditions for the activity were determined by introducing a model describing a relation between the intensity of stimulus and the extent of the change of public's attitude to nuclear energy, namely the effect of PRs activity, and also by giving the optimal ratio of allocation of the budget among the four types of activity as a function of cost versus effectiveness of each type. Those optimal conditions, being for the ratio of allocation of the budget, the execution time and the intensity of each type of activity at that time, vary depending on the number of household in a target region, the target class of demography, the duration time of activity, and the amount of budget for the activity. It becomes clear from numerical calculation that the optimal conditions and the effect of activity show quite strong non-linearity with respect to the variation of those variables, and that the effect of PRs activity averaged over all public in the target region becomes to be maximum, in Japan, when the activity is executed with the optimal conditions determined for the target class of middle- and advanced-aged women. The management of nuclear PRs activity becomes possible by introducing such a method of fixation of optimal conditions for the activity as described here. (author)

  13. Characterization of the hemA-prs region of the Escherichia coli and Salmonella typhimurium chromosomes

    DEFF Research Database (Denmark)

    Post, David A.; Hove-Jensen, Bjarne; Switzer, Robert L.

    1993-01-01

    The prs gene, encoding phosphoribosylpyrophosphate synthetase, is preceded by a leader, which is 302 bp long in Escherichia coli and 417 bp in Salmonella typhimurium. A potential open reading frame (ORF) extends across the prs promoter and into the leader. The region between the prs coding region...... two promoters, the first promoter (P1) originating upstream of ORF 1, and expressing the prs gene in a tricistronic operon and a second promoter (P2), located within the ORF 2 coding frame, which transcribes the prs gene only. The transcripts encoding prs only were 20 times as abundant...... in the amount of message originating from the promoter P2....

  14. Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

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    Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

    2016-10-01

    Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations--F45L, V209M and F220C--yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.

  15. Development and characterization of membrane surface display system using molecular chaperon, prsA, of Bacillus subtilis

    International Nuclear Information System (INIS)

    Kim, June-Hyung; Park, In-Suk; Kim, Byung-Gee

    2005-01-01

    We report a new membrane surface display system based on molecular chaperon, prsA, of Bacillus subtilis. Clostridium thermocellum cellulase, celA, was fused to C-terminal end of PrsA. Cellulase activity of B. subtilis protoplast, which expressed PrsA-CelA was 15 times higher compared to control strain. More than 85% of total cellulase activity was observed in surface displayed format and less than 15% of total cellulase activity was found in supernatant. Flow cytometric analysis of protoplast of PrsA-CelA fusion expressing bacteria provided another proof of uniform expression of fusion protein onto cytoplasmic membrane of B. subtilis. Without lysozyme treatment, only part of cellulase activity (10%) was observed in whole cell fraction

  16. The Activation Pathway of Human Rhodopsin in Comparison to Bovine Rhodopsin*

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    Kazmin, Roman; Rose, Alexander; Szczepek, Michal; Elgeti, Matthias; Ritter, Eglof; Piechnick, Ronny; Hofmann, Klaus Peter; Scheerer, Patrick; Hildebrand, Peter W.; Bartl, Franz J.

    2015-01-01

    Rhodopsin, the photoreceptor of rod cells, absorbs light to mediate the first step of vision by activating the G protein transducin (Gt). Several human diseases, such as retinitis pigmentosa or congenital night blindness, are linked to rhodopsin malfunctions. Most of the corresponding in vivo studies and structure-function analyses (e.g. based on protein x-ray crystallography or spectroscopy) have been carried out on murine or bovine rhodopsin. Because these rhodopsins differ at several amino acid positions from human rhodopsin, we conducted a comprehensive spectroscopic characterization of human rhodopsin in combination with molecular dynamics simulations. We show by FTIR and UV-visible difference spectroscopy that the light-induced transformations of the early photointermediates are very similar. Significant differences between the pigments appear with formation of the still inactive Meta I state and the transition to active Meta II. However, the conformation of Meta II and its activity toward the G protein are essentially the same, presumably reflecting the evolutionary pressure under which the active state has developed. Altogether, our results show that although the basic activation pathways of human and bovine rhodopsin are similar, structural deviations exist in the inactive conformation and during receptor activation, even between closely related rhodopsins. These differences between the well studied bovine or murine rhodopsins and human rhodopsin have to be taken into account when the influence of point mutations on the activation pathway of human rhodopsin are investigated using the bovine or murine rhodopsin template sequences. PMID:26105054

  17. Identification of the key determinant of the transport promiscuity in Na+-translocating rhodopsins.

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    Mamedov, Adalyat M; Bertsova, Yulia V; Anashkin, Viktor A; Mamedov, Mahir D; Baykov, Alexander A; Bogachev, Alexander V

    2018-05-15

    Bacterial Na + -transporting rhodopsins convert solar energy into transmembrane ion potential difference. Typically, they are strictly specific for Na + , but some can additionally transport H + . To determine the structural basis of cation promiscuity in Na + -rhodopsins, we compared their primary structures and found a single position that harbors a cysteine in strictly specific Na + -rhodopsins and a serine in the promiscuous Krokinobacter eikastus Na + -rhodopsin (Kr2). A Cys253Ser variant of the strictly specific Dokdonia sp. PRO95 Na + -rhodopsin (NaR) was indeed found to transport both Na + and H + in a light-dependent manner when expressed in retinal-producing Escherichia coli cells. The dual specificity of the NaR variant was confirmed by analysis of its photocycle, which revealed an acceleration of the cation-capture step by comparison with the wild-type NaR in a Na + -deficient medium. The structural basis for the dependence of the Na + /H + specificity in Na + -rhodopsin on residue 253 remains to be determined. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. data sets Simulations in articulating light-weight PRS

    NARCIS (Netherlands)

    Van den Berg, Bert

    2008-01-01

    The data sets are output of 3 different steps in the development a simulations of a PRS as described in chapter 3.3: Simulations in articulating light-weight PRS A case for Pedagogy-oriented and Rating-based Hybrid Recommendation Strategies Rob Nadolski, Bert van den Berg, Adriana Berlanga, Hans

  19. Digoxin-induced retinal degeneration depends on rhodopsin.

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    Landfried, Britta; Samardzija, Marijana; Barben, Maya; Schori, Christian; Klee, Katrin; Storti, Federica; Grimm, Christian

    2017-03-16

    Na,K-ATPases are energy consuming ion pumps that are required for maintaining ion homeostasis in most cells. In the retina, Na,K-ATPases are especially important to sustain the dark current in photoreceptor cells needed for rapid hyperpolarization of rods and cones in light. Cardiac glycosides like digoxin inhibit the activity of Na,K-ATPases by targeting their catalytic alpha subunits. This leads to a disturbed ion balance, which can affect cellular function and survival. Here we show that the treatment of wild-type mice with digoxin leads to severe retinal degeneration and loss of vision. Digoxin induced cell death specifically in photoreceptor cells with no or only minor effects in other retinal cell types. Photoreceptor-specific cytotoxicity depended on the presence of bleachable rhodopsin. Photoreceptors of Rpe65 knockouts, which have no measurable rhodopsin and photoreceptors of Rpe65 R91W mice that have treatment. Similarly, cones in the all-cone retina of Nrl knockout mice were also not affected. Digoxin induced expression of several genes involved in stress signaling and inflammation. It also activated proteins such as ERK1/2, AKT, STAT1, STAT3 and CASP1 during a period of up to 10 days after treatment. Activation of signaling genes and proteins, as well as the dependency on bleachable rhodopsin resembles mechanisms of light-induced photoreceptor degeneration. Digoxin-mediated photoreceptor cell death may thus be used as an inducible model system to study molecular mechanisms of retinal degeneration.

  20. The rhodopsin-transducin complex houses two distinct rhodopsin molecules.

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    Jastrzebska, Beata; Ringler, Philippe; Palczewski, Krzysztof; Engel, Andreas

    2013-05-01

    Upon illumination the visual receptor rhodopsin (Rho) transitions to the activated form Rho(∗), which binds the heterotrimeric G protein, transducin (Gt) causing GDP to GTP exchange and Gt dissociation. Using succinylated concanavalin A (sConA) as a probe, we visualized native Rho dimers solubilized in 1mM n-dodecyl-β-d-maltoside (DDM) and Rho monomers in 5mM DDM. By nucleotide depletion and affinity chromatography together with crosslinking and size exclusion chromatography, we trapped and purified nucleotide-free Rho(∗)·Gt and sConA-Rho(∗)·Gt complexes kept in solution by either DDM or lauryl-maltose-neopentyl-glycol (LMNG). The 3 D envelope calculated from projections of negatively stained Rho(∗)·Gt-LMNG complexes accommodated two Rho molecules, one Gt heterotrimer and a detergent belt. Visualization of triple sConA-Rho(∗)·Gt complexes unequivocally demonstrated a pentameric assembly of the Rho(∗)·Gt complex in which the photoactivated Rho(∗) dimer serves as a platform for binding the Gt heterotrimer. Importantly, individual monomers of the Rho(∗) dimer in the heteropentameric complex exhibited different capabilities for regeneration with either 11-cis or 9-cis-retinal. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Nanoparticle-mediated rhodopsin cDNA but not intron-containing DNA delivery causes transgene silencing in a rhodopsin knockout model.

    Science.gov (United States)

    Zheng, Min; Mitra, Rajendra N; Filonov, Nazar A; Han, Zongchao

    2016-03-01

    Previously, we compared the efficacy of nanoparticle (NP)-mediated intron-containing rhodopsin (sgRho) vs. intronless cDNA in ameliorating retinal disease phenotypes in a rhodopsin knockout (RKO) mouse model of retinitis pigmentosa. We showed that NP-mediated sgRho delivery achieved long-term expression and phenotypic improvement in RKO mice, but not NP housing cDNA. However, the protein level of the NP-sgRho construct was only 5-10% of wild-type at 8 mo postinjection. To have a better understanding of the reduced levels of long-term expression of the vectors, in the present study, we evaluated the epigenetic changes of subretinal delivering NP-cDNA vs. NP-sgRho in the RKO mouse eyes. Following the administration, DNA methylation and histone status of specific regions (bacteria plasmid backbone, promoter, rhodopsin gene, and scaffold/matrix attachment region) of the vectors were evaluated at various time points. We documented that epigenetic transgene silencing occurred in vector-mediated gene transfer, which were caused by the plasmid backbone and the cDNA of the transgene, but not the intron-containing transgene. No toxicity or inflammation was found in the treated eyes. Our results suggest that cDNA of the rhodopsin transgene and bacteria backbone interfered with the host defense mechanism of DNA methylation-mediated transgene silencing through heterochromatin-associated modifications. © FASEB.

  2. Genomic makeup of the marine flavobacterium Nonlabens (Donghaeana) dokdonensis and identification of a novel class of rhodopsins.

    Science.gov (United States)

    Kwon, Soon-Kyeong; Kim, Byung Kwon; Song, Ju Yeon; Kwak, Min-Jung; Lee, Choong Hoon; Yoon, Jung-Hoon; Oh, Tae Kwang; Kim, Jihyun F

    2013-01-01

    Rhodopsin-containing marine microbes such as those in the class Flavobacteriia play a pivotal role in the biogeochemical cycle of the euphotic zone (Fuhrman JA, Schwalbach MS, Stingl U. 2008. Proteorhodopsins: an array of physiological roles? Nat Rev Microbiol. 6:488-494). Deciphering the genome information of flavobacteria and accessing the diversity and ecological impact of microbial rhodopsins are important in understanding and preserving the global ecosystems. The genome sequence of the orange-pigmented marine flavobacterium Nonlabens dokdonensis (basonym: Donghaeana dokdonensis) DSW-6 was determined. As a marine photoheterotroph, DSW-6 has written in its genome physiological features that allow survival in the oligotrophic environments. The sequence analysis also uncovered a gene encoding an unexpected type of microbial rhodopsin containing a unique motif in addition to a proteorhodopsin gene and a number of photolyase or cryptochrome genes. Homologs of the novel rhodopsin gene were found in other flavobacteria, alphaproteobacteria, a species of Cytophagia, a deinococcus, and even a eukaryote diatom. They all contain the characteristic NQ motif and form a phylogenetically distinct group. Expression analysis of this rhodopsin gene in DSW-6 indicated that it is induced at high NaCl concentrations, as well as in the presence of light and the absence of nutrients. Genomic and metagenomic surveys demonstrate the diversity of the NQ rhodopsins in nature and the prevalent occurrence of the encoding genes among microbial communities inhabiting hypersaline niches, suggesting its involvement in sodium metabolism and the sodium-adapted lifestyle.

  3. Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

    Science.gov (United States)

    Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

    2014-01-01

    G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599

  4. Rhodopsin-lipid interactions studied by NMR.

    Science.gov (United States)

    Soubias, Olivier; Gawrisch, Klaus

    2013-01-01

    The biophysical properties of the lipid matrix are known to influence function of integral membrane proteins. We report on a sample preparation method for reconstitution of membrane proteins which uses porous anodic aluminum oxide (AAO) filters with 200-nm-wide pores of high density. The substrate permits formation of tubular, single membranes that line the inner surface of pores. One square centimeter of filter with a thickness of 60μm yields on the order of 500cm(2) of solid-supported single bilayer surface, sufficient for NMR studies. The tubular bilayers are free of detergent, fully hydrated, and accessible for ligands from one side of the membrane. The use of AAO filters greatly improves reproducibility of the reconstitution process such that the influence of protein on lipid order parameters can be studied with high resolution. As an example, results for the G protein-coupled receptor of class A, bovine rhodopsin, are shown. By (2)H NMR order parameter measurements, it is detected that rhodopsin insertion elastically deforms membranes near the protein. Furthermore, by (1)H saturation-transfer NMR under conditions of magic angle spinning, we demonstrate detection of preferences in interactions of rhodopsin with particular lipid species. It is assumed that function of integral membrane proteins depends on both protein-induced elastic deformations of the lipid matrix and preferences for interaction of the protein with particular lipid species in the first layer of lipids surrounding the protein. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. First cytoplasmic loop of glucagon-like peptide-1 receptor can function at the third cytoplasmic loop position of rhodopsin.

    Science.gov (United States)

    Yamashita, Takahiro; Tose, Koji; Shichida, Yoshinori

    2008-01-01

    G protein-coupled receptors (GPCRs) are classified into several families based on their amino acid sequences. In family 1, GPCRs such as rhodopsin and adrenergic receptor, the structure-function relationship has been extensively investigated to demonstrate that exposure of the third cytoplasmic loop is essential for selective G protein activation. In contrast, much less is known about other families. Here we prepared chimeric mutants between Gt-coupled rhodopsin and Gi/Go- and Gs-coupled glucagon-like peptide-1 (GLP-1) receptor of family 2 and tried to identify the loop region that functions at the third cytoplasmic loop position of rhodopsin. We succeeded in expressing a mutant having the first cytoplasmic loop of GLP-1 receptor and found that this mutant activated Gi and Go efficiently but did not activate Gt. Moreover, the rhodopsin mutant having the first loop of Gs-coupled secretin receptor of family 2 decreased the Gi and Go activation efficiencies. Therefore, the first loop of GLP-1 receptor would share a similar role to the third loop of rhodopsin in G protein activation. This result strongly suggested that different families of GPCRs have maintained molecular architectures of their ancestral types to generate a common mechanism, namely exposure of the cytoplasmic loop, to activate peripheral G protein.

  6. Wavelength Discrimination in Drosophila Suggests a Role of Rhodopsin 1 in Color Vision

    OpenAIRE

    Garbers, Christian; Wachtler, Thomas

    2016-01-01

    Among the five photoreceptor opsins in the eye of Drosophila, Rhodopsin 1 (Rh1) is expressed in the six outer photoreceptors. In a previous study that combined behavioral genetics with computational modeling, we demonstrated that flies can use the signals from Rh1 for color vision. Here, we provide an in-depth computational analysis of wildtype Drosophila wavelength discrimination specifically considering the consequences of different choices of computations in the preprocessing of the behavi...

  7. Thermal Stability of Rhodopsin and Progression of Retinitis Pigmentosa

    Science.gov (United States)

    Liu, Monica Yun; Liu, Jian; Mehrotra, Devi; Liu, Yuting; Guo, Ying; Baldera-Aguayo, Pedro A.; Mooney, Victoria L.; Nour, Adel M.; Yan, Elsa C. Y.

    2013-01-01

    Over 100 point mutations in the rhodopsin gene have been associated with retinitis pigmentosa (RP), a family of inherited visual disorders. Among these, we focused on characterizing the S186W mutation. We compared the thermal properties of the S186W mutant with another RP-causing mutant, D190N, and with WT rhodopsin. To assess thermal stability, we measured the rate of two thermal reactions contributing to the thermal decay of rhodopsin as follows: thermal isomerization of 11-cis-retinal and hydrolysis of the protonated Schiff base linkage between the 11-cis-retinal chromophore and opsin protein. We used UV-visible spectroscopy and HPLC to examine the kinetics of these reactions at 37 and 55 °C for WT and mutant rhodopsin purified from HEK293 cells. Compared with WT rhodopsin and the D190N mutant, the S186W mutation dramatically increases the rates of both thermal isomerization and dark state hydrolysis of the Schiff base by 1–2 orders of magnitude. The results suggest that the S186W mutant thermally destabilizes rhodopsin by disrupting a hydrogen bond network at the receptor's active site. The decrease in the thermal stability of dark state rhodopsin is likely to be associated with higher levels of dark noise that undermine the sensitivity of rhodopsin, potentially accounting for night blindness in the early stages of RP. Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients. PMID:23625926

  8. Kinematic Analysis and Performance Evaluation of Novel PRS Parallel Mechanism

    Science.gov (United States)

    Balaji, K.; Khan, B. Shahul Hamid

    2018-02-01

    In this paper, a 3 DoF (Degree of Freedom) novel PRS (Prismatic-Revolute- Spherical) type parallel mechanisms has been designed and presented. The combination of striaght and arc type linkages for 3 DOF parallel mechanism is introduced for the first time. The performances of the mechanisms are evaluated based on the indices such as Minimum Singular Value (MSV), Condition Number (CN), Local Conditioning Index (LCI), Kinematic Configuration Index (KCI) and Global Conditioning Index (GCI). The overall reachable workspace of all mechanisms are presented. The kinematic measure, dexterity measure and workspace analysis for all the mechanism have been evaluated and compared.

  9. highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models

    Directory of Open Access Journals (Sweden)

    Huai-Wei Huang

    2018-02-01

    Full Text Available Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highroad, which is required for photoreceptors to clear folding-defective mutant Rhodopsin-1 proteins. Specifically, knockdown or genetic deletion of highroad blocks the degradation of folding-defective Rhodopsin-1 mutant, ninaEG69D. Moreover, loss of highroad accelerates the age-related retinal degeneration phenotype of ninaEG69D mutants. Elevated highroad transcript levels are detected in ninaEG69D flies, and interestingly, deprivation of retinoids in the fly diet blocks this effect. Consistently, mutations in the retinoid transporter, santa maria, impairs the induction of highroad in ninaEG69D flies. In cultured S2 cells, highroad expression is induced by retinoic acid treatment. These results indicate that cellular quality-control mechanisms against misfolded Rhodopsin-1 involve regulation of gene expression by retinoids.

  10. Chimeric microbial rhodopsins for optical activation of Gs-proteins

    Science.gov (United States)

    Yoshida, Kazuho; Yamashita, Takahiro; Sasaki, Kengo; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

    2017-01-01

    We previously showed that the chimeric proteins of microbial rhodopsins, such as light-driven proton pump bacteriorhodopsin (BR) and Gloeobacter rhodopsin (GR) that contain cytoplasmic loops of bovine rhodopsin, are able to activate Gt protein upon light absorption. These facts suggest similar protein structural changes in both the light-driven proton pump and animal rhodopsin. Here we report two trials to engineer chimeric rhodopsins, one for the inserted loop, and another for the microbial rhodopsin template. For the former, we successfully activated Gs protein by light through the incorporation of the cytoplasmic loop of β2-adrenergic receptor (β2AR). For the latter, we did not observe any G-protein activation for the light-driven sodium pump from Indibacter alkaliphilus (IndiR2) or a light-driven chloride pump halorhodopsin from Natronomonas pharaonis (NpHR), whereas the light-driven proton pump GR showed light-dependent G-protein activation. This fact suggests that a helix opening motion is common to G protein coupled receptor (GPCR) and GR, but not to IndiR2 and NpHR. Light-induced difference FTIR spectroscopy revealed similar structural changes between WT and the third loop chimera for each light-driven pump. A helical structural perturbation, which was largest for GR, was further enhanced in the chimera. We conclude that similar structural dynamics that occur on the cytoplasmic side of GPCR are needed to design chimeric microbial rhodopsins. PMID:29362703

  11. Altered phosphorylation of rhodopsin in retinal dystrophic Irish Setters

    International Nuclear Information System (INIS)

    Cunnick, J.; Takemoto, D.J.; Takemoto, L.J.

    1986-01-01

    The carboxyl-terminus of rhodopsin in retinal dystrophic (rd) Irish Setters is altered near a possible phosphorylation site. To determine if this alteration affects ATP-mediated phosphorylation they compared the phosphorylation of rhodopsin from rd affected Irish Setters and normal unaffected dogs. Retinas from 8-week-old Irish Setters were phosphorylated with γ- 32 P-ATP and separated on SDS-PAGE. Compared to unaffected normal retinas, equalized for rhodopsin content, phosphorylation of rd rhodopsin was drastically reduced. When rd retinas were mixed with normal dog retinas, phosphorylation of the latter was inhibited. Inhibition also occurred when bovine retinas were mixed with rd retinas. The rd-mediated inhibition of phosphorylation was prevented by including 1mM NaF in the reaction mixture. Likewise, 1mM NaF restored phosphorylation of rd rhodopsin to normal levels. Phosphopeptide maps of rd and normal rhodopsin were identical and indicated 5 phosphopeptides present in each. Results suggest that one cause of the depressed rd rhodopsin phosphorylation is an increased phosphatase activity

  12. Phosphoribosylpyrophosphate synthetase of Bacillus subtilis. Cloning, characterization and chromosomal mapping of the prs gene

    DEFF Research Database (Denmark)

    Nilsson, Dan; Hove-Jensen, Bjarne

    1987-01-01

    The gene (prs) encoding phosphoribosylpyrophosphate (PRPP) synthetase has been cloned from a library of Bacillus subtilis DNA by complementation of an Escherichia coli prs mutation. Flanking DNA sequences were pruned away by restriction endonuclease and exonuclease BAL 31 digestions, resulting...... in a DNA fragment of approx. 1.8 kb complementing the E. coli prs mutation. Minicell experiments revealed that this DNA fragment coded for a polypeptide, shown to be the PRPP synthetase subunit, with an Mr of approx. 40,000. B. subtilis strains harbouring the prs gene in a multicopy plasmid contained up...... to nine-fold increased PRPP synthetase activity. The prs gene was cloned in an integration vector and the resulting hybrid plasmid inserted into the B. subtilis chromosome by homologous recombination. The integration site was mapped by transduction and the gene order established as purA-guaA-prs-cysA....

  13. Primary processes in photolysis of octopus rhodopsin.

    Science.gov (United States)

    Ohtani, H; Kobayashi, T; Tsuda, M; Ebrey, T G

    1988-01-01

    The photolysis of octopus rhodopsin was studied by picosecond time-resolved spectroscopy at physiological temperature (8 degrees C) and by steady-state spectroscopy at very low temperature (10 K). Both hypsorhodopsin and bathorhodopsin were formed from a bathorhodopsin-like red-shifted intermediate "primerhodopsin," which was the primary photoproduct with our time resolution (36 ps). Though it was proposed that hypsorhodopsin is formed solely by a multiphoton process, the present results obtained by using blue light pulses (461 nm) of low intensity showed that hypsorhodopsin is formed by a single photon mechanism via thermal decay from primerhodopsin. When the excitation intensity is increased, a channel for the photochemical formation of hypsorhodopsin from primerhodopsin is opened. There are two thermal pathways leading from primerhodopsin. One process is the formation of hypsorhodopsin, which is later thermally converted to bathorhodopsin, and the other is the direct formation of bathorhodopsin from primerhodopsin. The formation efficiencies at room temperature of hypsorhodopsin and bathorhodopsin at very low excitation intensity were estimated to be larger than 0.6 and smaller than 0.4, respectively. The formation of hypsorhodopsin was also found in the early stages of the irradiation of octopus rhodopsin with weak continuous light at 10 K. However bathorhodopsin is formed three times more efficiently than hypsorhodopsin at 10 K.At physiological temperatures the formation of hypsorhodopsin in D(2)O takes place more slowly than in H(2)O. This indicates that the lifetime of primerhodopsin is decreased by H(2)O/D(2)O exchange. The rate constant for the primerhodopsin --> bathorhodopsin conversion is more sensitive than that for the primerhodopsin --> hypsorhodopsin conversion. The transformation of hypsorhodopsin to bathorhodopsin shows no deuterium effect at low temperature.

  14. File list: Oth.Prs.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  3. File list: ALL.Prs.05.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: ALL.Prs.20.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: InP.Prs.50.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: His.Prs.10.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: His.Prs.20.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: ALL.Prs.50.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: ALL.Prs.10.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: InP.Prs.10.AllAg.Prostate [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Pol.Prs.10.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.Prs.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: InP.Prs.50.AllAg.PC-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Oth.Prs.20.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Oth.Prs.50.GABPA.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Oth.Prs.10.GABPA.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: DNS.Prs.05.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: Unc.Prs.50.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: ALL.Prs.10.AllAg.Prostate_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: InP.Prs.50.AllAg.Prostate_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: InP.Prs.05.AllAg.Prostate_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: InP.Prs.20.AllAg.Prostate_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  4. File list: InP.Prs.10.AllAg.Prostate_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: His.Prs.20.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Prs.20.AllAg.Prostate_cancer_cells hg19 Histone Prostate Prostate cancer cells ...SRX022579,SRX022581,SRX022580 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Prs.20.AllAg.Prostate_cancer_cells.bed ...

  6. File list: Pol.Prs.05.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Pol.Prs.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Prs.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Prs.05.RNA_polymerase_III.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Prs.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: InP.Prs.20.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Prs.20.Input_control.AllCell hg19 Input control Input control Prostate SRX53966...X306505,SRX475374,SRX540851,SRX475375,SRX1098753,SRX334229,SRX176071,SRX315154 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Prs.20.Input_control.AllCell.bed ...

  12. File list: DNS.Prs.20.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Prs.20.AllAg.Prostate_cancer_cells hg19 DNase-seq Prostate Prostate cancer cell...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Prs.20.AllAg.Prostate_cancer_cells.bed ...

  13. Assessing Primary Representational System (PRS) Preference for Neurolinguistic Programming (NLP) Using Three Methods.

    Science.gov (United States)

    Dorn, Fred J.

    1983-01-01

    Considered three methods of identifying Primary Representational System (PRS)--an interview, a word list, and a self-report--in a study of 120 college students. Results suggested the three methods offer little to counselors either collectively or individually. Results did not validate the PRS construct, suggesting the need for further research.…

  14. Primary structure of the tms and prs genes of Bacillus subtilis

    DEFF Research Database (Denmark)

    Nilsson, Dan; Hove-Jensen, Bjarne; Arnvig, Kirsten

    1989-01-01

    The nucleotide sequence was determined of a 3211 nucleotide pair EcoRI-PvuII DNA fragment containing the tms and prs genes as well as a part of the ctc gene of Bacillus subtilis. The prs gene encodes phosphoribosylpyrophosphate (PRPP) synthetase, whereas the functioning of the tms and ctc gene...... products remains to be established. The prs gene contains an open reading frame of 317 codons resulting in a subunit Mr of 34828. An open reading frame comprising the tms gene contained 456 codons resulting in a putative translation product with an Mr of 49,554. Comparison of the deduced B. subtilis PRPP...

  15. Molecular genetics of rhodopsin and phototrans duction in the visual system of Drosophila

    International Nuclear Information System (INIS)

    Zuker, C.; Cowman, A.; Montell, C.; Rubin, G.

    1987-01-01

    The authors have isolated the genes encoding four Drosophila visual pigments. Each of these opsins is expressed in a set of functionally and anatomically distinct photoreceptor cells of the eye. One is expressed in the six outer photoreceptor cells (R1-R6), the second in the central R8 photoreceptor cell, and the other two in the UV sensitive R7 photoreceptor cells. They have determined the structure and nucleotide sequence of each of these genes. They have used P element-mediated gene transfer to introduce the cloned structural gene for the R1-R6 opsin in the Drosophila germline and restored the ninaE mutant phenotype to wild-type. In an attempt to study the contribution of the various opsins to the specific functional properties of the different photoreceptor cell types, they have genetically engineered Drosophila lines that express R8 opsin in the R1-R6 photoreceptor cells. In collaboration with Drs. Ozaki and Pak at Purdue University, they have used oligonucleotide site-directed mutagenesis to mutate selected amino acids and regions of the rhodopsin molecule and reintroduced the mutated genes into Drosophila to analyze structure-function relationships in the rhodopsin molecule

  16. On the origins of arrestin and rhodopsin

    Directory of Open Access Journals (Sweden)

    Alvarez Carlos E

    2008-07-01

    Full Text Available Abstract Background G protein coupled receptors (GPCRs are the most numerous proteins in mammalian genomes, and the most common targets of clinical drugs. However, their evolution remains enigmatic. GPCRs are intimately associated with trimeric G proteins, G protein receptor kinases, and arrestins. We conducted phylogenetic studies to reconstruct the history of arrestins. Those findings, in turn, led us to investigate the origin of the photosensory GPCR rhodopsin. Results We found that the arrestin clan is comprised of the Spo0M protein family in archaea and bacteria, and the arrestin and Vps26 families in eukaryotes. The previously known animal arrestins are members of the visual/beta subfamily, which branched from the founding "alpha" arrestins relatively recently. Curiously, we identified both the oldest visual/beta arrestin and opsin genes in Cnidaria (but not in sponges. The arrestin clan has 14 human members: 6 alphas, 4 visual/betas, and 4 Vps26 genes. Others recently showed that the 3D structure of mammalian Vps26 and the biochemical function of the yeast alpha arrestin PalF are similar to those of beta arrestins. We note that only alpha arrestins have PY motifs (known to bind WW domains in their C-terminal tails, and only visual/betas have helix I in the Arrestin N domain. Conclusion We identified ciliary opsins in Cnidaria and propose this subfamily is ancestral to all previously known animal opsins. That finding is consistent with Darwin's theory that eyes evolved once, and lends some support to Parker's hypothesis that vision triggered the Cambrian explosion of life forms. Our arrestin findings have implications on the evolution of GPCR signaling, and on the biological roles of human alpha arrestins.

  17. Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

    Science.gov (United States)

    Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

    2005-03-01

    Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

  18. Flash photolysis of rhodopsin in the cat retina

    International Nuclear Information System (INIS)

    Ripps, H.; Mehaffey, L.; Siegel, I.M.; Ernst, W.; Kemp, C.M.

    1981-01-01

    The bleaching of rhodopsin by short-duration flashes of a xenon discharge lamp was studied in vivo in the cat retina with the aid of a rapid, spectral-scan fundus reflectometer. Difference spectra recorded over a broad range of intensities showed that the bleaching efficacy of high-intensity flashes was less than that of longer duration, steady lights delivering the same amount of energy. Both the empirical results and those derived from a theoretical analysis of flash photolysis indicate that, under the conditions of these experiments, the upper limit of the flash bleaching of rhodopsin in cat is approximately 90%. Although the fact that a full bleach could not be attained is attributable to photoreversal, i.e., the photic regeneration of rhodopsin from its light-sensitive intermediates, the 90% limit is considerably higher than the 50% (or lower) value obtained under other experimental circumstances. Thus, it appears that the duration (approximately 1 ms) and spectral composition of the flash, coupled with the kinetic parameters of the thermal and photic reactions in the cat retina, reduce the light-induced regeneration of rhodopsin to approximately 10%

  19. Resonance raman spectroscopy of an ultraviolet-sensitive insect rhodopsin

    International Nuclear Information System (INIS)

    Pande, C.; Deng, H.; Rath, P.; Callender, R.H.; Schwemer, J.

    1987-01-01

    The authors present the first visual pigment resonance Raman spectra from the UV-sensitive eyes of an insect, Ascalaphus macaronius (owlfly). This pigment contains 11-cis-retinal as the chromophore. Raman data have been obtained for the acid metarhodopsin at 10 0 C in both H 2 O and D 2 O. The C=N stretching mode at 1660 cm -1 in H 2 O shifts to 1631 cm -1 upon deuteriation of the sample, clearly showing a protonated Schiff base linkage between the chromophore and the protein. The structure-sensitive fingerprint region shows similarities to the all-trans-protonated Schiff base of model retinal chromophores, as well as to the octopus acid metarhodopsin and bovine metarhodopsin I. Although spectra measured at -100 0 C with 406.7-nm excitation, to enhance scattering from rhodopsin (λ/sub max/ 345 nm), contain a significant contribution from a small amount of contaminants [cytochrome(s) and/or accessory pigment] in the sample, the C=N stretch at 1664 cm -1 suggests a protonated Schiff base linkage between the chromophore and the protein in rhodopsin as well. For comparison, this mode also appears at ∼ 1660 cm -1 in both the vertebrate (bovine) and the invertebrate (octopus) rhodopsins. These data are particularly interesting since the absorption maximum of 345 nm for rhodopsin might be expected to originate from an unprotonated Schiff base linkage. That the Schiff base linkage in the owlfly rhodopsin, like in bovine and in octopus, is protonated suggests that a charged chromophore is essential to visual transduction

  20. Voltage imaging in vivo with a new class of rhodopsin-based indicators

    Science.gov (United States)

    Douglass, Adam

    2013-03-01

    Reliable, optical detection of single action potentials in an intact brain is one of the longest-standing challenges in neuroscience. We have recently shown that a number of microbial rhodopsins exhibit intrinsic fluorescence that is sensitive to transmembrane potential. One class of indicator, derived from Archaerhodopsin-3 (Arch), responds to voltage transients with a speed and sensitivity that enable near-perfect identification of single action potentials in cultured neurons [Nat Methods. (2011). 9:90-5]. We have extended the use of these indicators to an in vivo context through the application of advanced imaging techniques to the larval zebrafish. Using planar-illumination, spinning-disk confocal, and epifluorescence imaging modalities, we have successfully recorded electrical activity in a variety of fish structures, including the brain and heart, in a completely noninvasive manner. Transgenic lines expressing Arch variants in defined cells enable comprehensive measurements to be made from specific target populations. In parallel, we have also extended the capabilities of our indicators by improving their multiphoton excitability and overall brightness. Microbial rhodopsin-based voltage indicators now enable optical interrogation of complex neural circuits, and electrophysiology in systems for which electrode-based techniques are challenging.

  1. Rhodopsin Forms Nanodomains in Rod Outer Segment Disc Membranes of the Cold-Blooded Xenopus laevis.

    Directory of Open Access Journals (Sweden)

    Tatini Rakshit

    Full Text Available Rhodopsin forms nanoscale domains (i.e., nanodomains in rod outer segment disc membranes from mammalian species. It is unclear whether rhodopsin arranges in a similar manner in amphibian species, which are often used as a model system to investigate the function of rhodopsin and the structure of photoreceptor cells. Moreover, since samples are routinely prepared at low temperatures, it is unclear whether lipid phase separation effects in the membrane promote the observed nanodomain organization of rhodopsin from mammalian species. Rod outer segment disc membranes prepared from the cold-blooded frog Xenopus laevis were investigated by atomic force microscopy to visualize the organization of rhodopsin in the absence of lipid phase separation effects. Atomic force microscopy revealed that rhodopsin nanodomains form similarly as that observed previously in mammalian membranes. Formation of nanodomains in ROS disc membranes is independent of lipid phase separation and conserved among vertebrates.

  2. Studies on light transduction by bacteriorhodopsin and rhodopsin

    International Nuclear Information System (INIS)

    Braiman, M.; Bubis, J.; Doi, T.; Chen, H.B.; Flitsch, S.L.; Franke, R.R.; Gilles-Gonzalez, M.A.; Graham, R.M.; Karnik, S.S.; Khorana, H.G.; Knox, B.E.; Krebs, M.P.; Marti, T.; Mogi, T.; Nakayama, T.; Oprian, D.D.; Puckett, K.L.; Sakmar, T.P.; Stern, L.J.; Subramaniam, S.; Thompson, D.A.

    1988-01-01

    The visual photoreceptor pigments in vertebrates and invertebrates all use retinal (vitamin A aldehyde) as the light-absorbing molecule. Recently, Stoeckenius et al. discovered bacteriorhodopsin (bR) in the purple membrane of the extreme halophile, Halobacterium halobium, which also contains all-trans retinal as the chromophore, bR carries out light-dependent proton translocation from the inside to the outside of the H. halobium cell. Since the discovery of bR, H. halobium has been found to elaborate three more retinal-based light-transducing proteins. These are halorhodopsin, a chloride ion pump, and sensory rhodopsins I and II. The authors are carrying out structure-function studies of bacteriorhodopsin, bovine rhodopsin, and related proteins primarily by the technique of recombinant DNA; they summarize below the results they have obtained recently

  3. Microbial rhodopsins on leaf surfaces of terrestrial plants

    OpenAIRE

    Atamna-Ismaeel, Nof; Finkel, Omri M.; Glaser, Fabian; Sharon, Itai; Schneider, Ron; Post, Anton F.; Spudich, John L.; von Mering, Christian; Vorholt, Julia A.; Iluz, David; Béjà, Oded; Belkin, Shimshon

    2011-01-01

    The above-ground surfaces of terrestrial plants, the phyllosphere, comprise the main interface between the terrestrial biosphere and solar radiation. It is estimated to host up to 1026 microbial cells that may intercept part of the photon flux impinging on the leaves. Based on 454-pyrosequencing-generated metagenome data, we report on the existence of diverse microbial rhodopsins in five distinct phyllospheres from tamarisk (Tamarix nilotica), soybean (Glycine max), Arabidopsis (Arabidopsis t...

  4. File list: InP.Prs.50.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Prs.50.AllAg.Prostate_cancer_cells hg19 Input control Prostate Prostate cancer ...cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Prs.50.AllAg.Prostate_cancer_cells.bed ...

  5. File list: NoD.Prs.05.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: InP.Prs.10.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Prs.10.AllAg.Prostate_cancer_cells hg19 Input control Prostate Prostate cancer ...cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Prs.10.AllAg.Prostate_cancer_cells.bed ...

  7. Scanning Laser Ophthalmoscope Measurement of Local Fundus Reflectance and Autofluorescence Changes Arising from Rhodopsin Bleaching and Regeneration

    OpenAIRE

    Morgan, Jessica I. W.; Pugh, Edward N.

    2013-01-01

    Rhodopsin was measured locally in the retina with a widely available, dual wavelength scanning laser ophthalmoscope that does not require pupil dilation. Increased autofluorescence attendant bleaching arises largely from transient removal of rhodopsin's screening of autofluorescent fluorochromes.

  8. Structure of the gene encoding phosphoribosylpyrophosphate synthetase (prsA) in Salmonella typhimurium

    DEFF Research Database (Denmark)

    Bower, Stanley G.; Hove-Jensen, Bjarne; Switzer, Robert L.

    1988-01-01

    in a 416-base-pair 5' untranslated leader in the prsA transcript, which was shown by deletion to be necessary for maximal synthesis of phosphoribosylpyrophosphate synthetase. The S. typhimurium leader contains a 115-base-pair insert relative to the E. coli leader. The insert appears to have no functional...

  9. Functional reconstitution of rhodopsin into tubular lipid bilayers supported by nanoporous media.

    Science.gov (United States)

    Soubias, Olivier; Polozov, Ivan V; Teague, Walter E; Yeliseev, Alexei A; Gawrisch, Klaus

    2006-12-26

    We report on a novel reconstitution method for G-protein-coupled receptors (GPCRs) that yields detergent-free, single, tubular membranes in porous anodic aluminum oxide (AAO) filters at concentrations sufficient for structural studies by solid-state NMR. The tubular membranes line the inner surface of pores that traverse the filters, permitting easy removal of detergents during sample preparation as well as delivery of ligands for functional studies. Reconstitution of bovine rhodopsin into AAO filters did not interfere with rhodopsin function. Photoactivation of rhodopsin in AAO pores, monitored by UV-vis spectrophotometry, was indistinguishable from rhodopsin in unsupported unilamellar liposomes. The rhodopsin in AAO pores is G-protein binding competent as shown by a [35S]GTPgammaS binding assay. The lipid-rhodopsin interaction was investigated by 2H NMR on sn-1- or sn-2-chain perdeuterated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phospholine as a matrix lipid. Rhodopsin incorporation increased mosaic spread of bilayer orientations and contributed to spectral density of motions with correlation times in the range of nano- to microseconds, detected as a significant reduction in spin-spin relaxation times. The change in lipid chain order parameters due to interaction with rhodopsin was insignificant.

  10. Bias in phylogenetic reconstruction of vertebrate rhodopsin sequences.

    Science.gov (United States)

    Chang, B S; Campbell, D L

    2000-08-01

    Two spurious nodes were found in phylogenetic analyses of vertebrate rhodopsin sequences in comparison with well-established vertebrate relationships. These spurious reconstructions were well supported in bootstrap analyses and occurred independently of the method of phylogenetic analysis used (parsimony, distance, or likelihood). Use of this data set of vertebrate rhodopsin sequences allowed us to exploit established vertebrate relationships, as well as the considerable amount known about the molecular evolution of this gene, in order to identify important factors contributing to the spurious reconstructions. Simulation studies using parametric bootstrapping indicate that it is unlikely that the spurious nodes in the parsimony analyses are due to long branches or other topological effects. Rather, they appear to be due to base compositional bias at third positions, codon bias, and convergent evolution at nucleotide positions encoding the hydrophobic residues isoleucine, leucine, and valine. LogDet distance methods, as well as maximum-likelihood methods which allow for nonstationary changes in base composition, reduce but do not entirely eliminate support for the spurious resolutions. Inclusion of five additional rhodopsin sequences in the phylogenetic analyses largely corrected one of the spurious reconstructions while leaving the other unaffected. The additional sequences not only were more proximal to the corrected node, but were also found to have intermediate levels of base composition and codon bias as compared with neighboring sequences on the tree. This study shows that the spurious reconstructions can be corrected either by excluding third positions, as well as those encoding the amino acids Ile, Val, and Leu (which may not be ideal, as these sites can contain useful phylogenetic signal for other parts of the tree), or by the addition of sequences that reduce problems associated with convergent evolution.

  11. Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities

    Science.gov (United States)

    Di Pierdomenico, Johnny; García-Ayuso, Diego; Pinilla, Isabel; Cuenca, Nicolás; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Villegas-Pérez, María P.

    2017-01-01

    To study the course of photoreceptor cell death and macro and microglial reactivity in two rat models of retinal degeneration with different etiologies. Retinas from P23H-1 (rhodopsin mutation) and Royal College of Surgeon (RCS, pigment epithelium malfunction) rats and age-matched control animals (Sprague-Dawley and Pievald Viro Glaxo, respectively) were cross-sectioned at different postnatal ages (from P10 to P60) and rhodopsin, L/M- and S-opsin, ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acid protein (GFAP), and proliferating cell nuclear antigen (PCNA) proteins were immunodetected. Photoreceptor nuclei rows and microglial cells in the different retinal layers were quantified. Photoreceptor degeneration starts earlier and progresses quicker in P23H-1 than in RCS rats. In both models, microglial cell activation occurs simultaneously with the initiation of photoreceptor death while GFAP over-expression starts later. As degeneration progresses, the numbers of microglial cells increase in the retina, but decreasing in the inner retina and increasing in the outer retina, more markedly in RCS rats. Interestingly, and in contrast with healthy animals, microglial cells reach the outer nuclei and outer segment layers. The higher number of microglial cells in dystrophic retinas cannot be fully accounted by intraretinal migration and PCNA immunodetection revealed microglial proliferation in both models but more importantly in RCS rats. The etiology of retinal degeneration determines the initiation and pattern of photoreceptor cell death and simultaneously there is microglial activation and migration, while the macroglial response is delayed. The actions of microglial cells in the degeneration cannot be explained only in the basis of photoreceptor death because they participate more actively in the RCS model. Thus, the retinal degeneration caused by pigment epithelium malfunction is more inflammatory and would probably respond better to interventions

  12. Mutational Analysis of the Rhodopsin Gene in Sector Retinitis Pigmentosa.

    Science.gov (United States)

    Napier, Maria L; Durga, Dash; Wolsley, Clive J; Chamney, Sarah; Alexander, Sharon; Brennan, Rosie; Simpson, David A; Silvestri, Giuliana; Willoughby, Colin E

    2015-01-01

    To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland. A case series of sector RP in a tertiary ocular genetics clinic. Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent. The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced. Rhodopsin mutational status. A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO. The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.

  13. Prospects for octopus rhodopsin utilization in optical and quantum computation

    International Nuclear Information System (INIS)

    Sivozhelezov, V.; Nicolini, A.

    2007-01-01

    Visual membranes of octopus, whose main component is the light-sensitive signal transducer octopus rhodopsin (octR), are extremely highly ordered, easily capture single photons, and are sensitive to light polarization, which shows their high potential for use as a QC detector. However, artificial membranes made of octR are neither highly enough ordered nor stable, while the bacterial homolog of octR, bacteriorhodopsin (bR), having the same topology as octR, forms both stable and ordered artificial membranes but lacks the optical properties important for optical QC. In this study, we investigate the structural basis for ordering of the two proteins in membranes in terms of crystallization behavior. We compare atomic resolution 3D structures of octR and bR and show the possibility for structural bR/octR interconversion by mutagenesis. We also show that the use of (nano)biotechnology can allow (1) high-precision manipulation of the light acceptor, retinal, including converting its surrounding into that of bacterial rhodopsin, the protein already used in optical-computation devices and (2) development of multicomponent and highly regular 2D structures with a high potential for being efficient optical QC detectors

  14. Allosteric behavior in the activation of transducin mediated by rhodopsin

    International Nuclear Information System (INIS)

    Wessling-Resnick, M.; Johnson, G.I.

    1986-01-01

    Transducin is a member of the family of regulatory GTP-binding proteins which provide a signal transduction mechanism for many cell surface receptors. These receptors act in a catalytic manner to displace GDP bound to the G protein in exchange for GTP during a process referred to as activation. The authors have studied the steady-state kinetics of the activation of transducin mediated by rhodopsin by employing the non-hydrolyzable GTP analog, [ 35 S]-GTPγS. The substrate-velocity curves display remarkable allosteric behavior with a Hill coefficient, n/sub H/ = 2. Lineweaver-Burke plots with respect to reciprocal [transducin] show curvilinearity indicative of positive cooperativity. However, a series of parallel lines are generated by plotting the linear transformation as [transducin] -2 . The double reciprocal plots with respect to [GTPγS] are a series of parallel lines. The initial rate analysis supports a double displacement catalytic mechanism for the molecular interactions between the photon receptor, G protein, and guanine nucleotides. It remains to be determined whether the positive cooperative behavior the authors observe can be assigned to the interaction of multiple transducins with rhodopsin, the presence of an allosteric effector, or hysteresis in the receptor's activity. These unique observations also provide insight into the molecular interactions of members of the family of G protein-coupled receptors

  15. Conceptual design of Decade Half, a 15-MA, 300-ns PRS driver

    International Nuclear Information System (INIS)

    Spence, Phil; Corcoran, Pat; Douglas, John; Tucker, Terry; Altes, Bob; Childers, Kendall; Sincerny, Peter; Whitehead, Lavell; Kenyon, Van; Babineau, Marc; Cotter, Tim; Kurucz, Pete; Davis, R.

    2002-01-01

    The Decade radiation effects simulator is located at AEDC and presently consists of four modules capable of operation as either a large area bremsstrahlung source (Decade Quad LAB) or a plasma radiation source (Decade Quad PRS). During 2001 we investigated several conceptual system architectures for connecting the current of eight Decade modules to a single PRS load. This Decade Half radiation source will be used in combination with other synchronized radiation effects simulators to offer a combined-effects testing capability at AEDC. We describe and compare the projected performance, risk, and relative cost of several rough conceptual designs, and discuss in more detail the 'water bridge' concept that was selected for more complete conceptual design development. We present a self-consistent electrical and mechanical conceptual design for Decade Half, including an equivalent circuit model, details of the mechanical architecture (including operation, maintenance, and turnaround considerations), and electrical performance estimates of approximately 15 MA peak current delivered to a representative large radius, ∼ 300 ns implosion time PRS load

  16. [Thermal stability of rhodopsins and opsins in warm- and cold-blooded vertebrates].

    Science.gov (United States)

    Berman, A L; Suvorov, S A; Parnova, R G; Gracheva, O A; Rychkova, M P

    1981-01-01

    Thermal stability of rhodopsins and opsins has been studied in endothermic (sheep, cattle, pig, rat) and ectothermic (frog) animals under two different conditions -- in the intact photoreceptor membranes (PM) and after substitution of the lipid surrounding of rhodopsins by molecules of a detergent Triton X-100. Lipid composition of PM in these animals was also studied, as well as the effect of proteases (pronase and papaine) upon thermal stability of rhodopsins in PM and in 1% Triton X-100 solutions. The thermal resistance of rhodopsins in PM was found to vary in the animals used to a great extent. The maximal differences in thermal stability of rhodopsins in ecto- and endothermic animals were due to the properties of photoreceptor protein itself, whereas in ectothermic animals they resulted mainly from differences in the lipid composition of PM. PM of endothermic animals differ from those of ectothermic ones by a lower content of polyenoic fatty acids and by a higher amount of phosphatidyl ethanolamine. The thermal stability of rhodopsins is not due to rhodopsin molecule as a whole, and depends mainly on its part which is directly bound to 11-cis retinal, located in hydrophobic region of PM and inaccessible to protease attack.

  17. 76 FR 34122 - 30-Day Notice of Proposed Information Collection: NEA/PI Online Performance Reporting System (PRS)

    Science.gov (United States)

    2011-06-10

    ... political, economic, education and women's rights reform in 20 countries of the Middle East and North Africa... PRS streamlines communication with implementers and allows for rapid identification of information...

  18. Programme Reporting Standards (PRS for improving the reporting of sexual, reproductive, maternal, newborn, child and adolescent health programmes

    Directory of Open Access Journals (Sweden)

    Anna E. Kågesten

    2017-08-01

    Full Text Available Abstract Background Information about design, implementation, monitoring and evaluation is central to understand the impact of programmes within the field of sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH. Existing reporting guidelines do not orient on reporting of contextual and implementation issues in sufficient detail. We therefore developed Programme Reporting Standards (PRS to be used by SRMNCAH programme implementers and researchers. Methods Building on the first step of the PRS development (a systematic review to identify reporting items, we conducted a three-round online Delphi consensus survey with experts. Consensus was defined a-priori as 80% agreement of items as essential. This was followed by a technical consultation with a group of experts to refine the items, definitions and their structuring. The revised PRS was piloted to assess its relevance to current SRMNCAH programme reports and identify key issues regarding the use of the PRS. Results Of the 81 participants invited to the Delphi survey, 20 responded to all three rounds. In the final round, 27 items received consensus as essential; three items were ranked as “borderline” essential; 20 items as supplementary. The items were subsequently revised, followed by a technical consultation with 29 experts to further review and refine the PRS. The feedback resulted in substantial changes to the structure and content of the PRS into 24 items across five domains: Programme overview; Programme components and implementation; Monitoring of Implementation; Evaluation and Results; and Synthesis. This version was used in a piloting exercise, where questions regarding how much information to report and how to comment on the quality of the information reported were addressed. All items were kept in the PRS following the pilot although minor changes were made to the flow and description of items. Conclusions The PRS 1.0 is the result of a structured

  19. Phosphoribosylpyrophosphate synthetase of Escherichia coli. Properties of the purified enzyme and primary structure of the prs gene

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne; Harlow, Kenneth W.; King, Cheryl J.

    1986-01-01

    of ADP. The nucleotide sequence of the E. coli prs gene has been determined and the coding segment established. The deduced amino acid sequence of P-Rib-PP synthetase contained 314 amino acid residues and the molecular weight was calculated as 34,060. The initiation site of transcription was determined......Phosphoribosylpyrophosphate (P-Rib-PP) synthetase of Escherichia coli has been purified to near homogeneity from a strain harboring the prs gene, encoding P-Rib-PP synthetase, on a multicopy plasmid. Analysis of the enzyme showed that it required inorganic phosphate for activity and for stability...

  20. Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

    International Nuclear Information System (INIS)

    Tomasello, Gaia; Altoe, Piero; Stenta, Marco; Olaso-Gonzalez, Gloria; Garavelli, Marco; Orlandi, Giorgio

    2007-01-01

    Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the β-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutral GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, β-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data

  1. Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

    Science.gov (United States)

    Khan, Muhammad Zahid; He, Ling

    2017-04-01

    In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

  2. Combined solid state and solution NMR studies of α,ε-15N labeled bovine rhodopsin

    International Nuclear Information System (INIS)

    Werner, Karla; Lehner, Ines; Dhiman, Harpreet Kaur; Richter, Christian; Glaubitz, Clemens; Schwalbe, Harald; Klein-Seetharaman, Judith; Khorana, H. Gobind

    2007-01-01

    Rhodopsin is the visual pigment of the vertebrate rod photoreceptor cell and is the only member of the G protein coupled receptor family for which a crystal structure is available. Towards the study of dynamics in rhodopsin, we report NMR-spectroscopic investigations of α,ε- 15 N-tryptophan labeled rhodopsin in detergent micelles and reconstituted in phospholipids. Using a combination of solid state 13 C, 15 N-REDOR and HETCOR experiments of all possible 13 C' i-1 carbonyl/ 15 N i -tryptophan isotope labeled amide pairs, and H/D exchange 1 H, 15 N-HSQC experiments conducted in solution, we assigned chemical shifts to all five rhodopsin tryptophan backbone 15 N nuclei and partially to their bound protons. 1 H, 15 N chemical shift assignment was achieved for indole side chains of Trp35 1.30 and Trp175 4.65 . 15 N chemical shifts were found to be similar when comparing those obtained in the native like reconstituted lipid environment and those obtained in detergent micelles for all tryptophans except Trp175 4.65 at the membrane interface. The results suggest that the integrated solution and solid state NMR approach presented provides highly complementary information in the study of structure and dynamics of large membrane proteins like rhodopsin

  3. Study of the orientation of retinal in bovine rhodopsin: the use of a photoactivatable retinal analog

    International Nuclear Information System (INIS)

    Nakayama, T.

    1987-01-01

    Rhodopsin is the major transmembrane protein in the photoreceptor cells of vertebrate and invertebrate retina. Bovine rhodopsin consists of a polypeptide chain of 348 amino acids of known sequence in which the chromophore, 11-cis-retinal, is linked to Lys-296 as a Schiff base. To investigate the orientation of retinal in the protein and to study the interactions between retinal and the protein, the authors have developed a crosslinking approach using a 3 H-labeled photoactivatable analog of retinal. Bleached rhodopsin in rod outer segments was reconstituted with the analog to give a pigment with λ/sub max/ at 460nm. Reduction of the Schiff base with borane dimenthylamine, followed by degradation with CNBr and sequencing of the radioactive fragment showed that the analog is attached to Lys-296, as in the native rhodopsin. Further, the reconstitute protein after photolysis was phosphorylated by rhodopsin kinase. Photolysis of the reconstituted pigment at -15 0 C resulted in crosslinking of the analog to the opsin to the extent of 30% as analyzed by SDS electrophoresis. The site(s) of crosslinking in the protein are under investigation

  4. Scanning laser ophthalmoscope measurement of local fundus reflectance and autofluorescence changes arising from rhodopsin bleaching and regeneration.

    Science.gov (United States)

    Morgan, Jessica I W; Pugh, Edward N

    2013-03-01

    We measured the bleaching and regeneration kinetics of rhodopsin in the living human eye with two-wavelength, wide-field scanning laser ophthalmoscopy (SLO), and investigated the effect of rhodopsin bleaching on autofluorescence intensity. The retina was imaged with an Optos P200C SLO by its reflectance of 532 and 633 nm light, and its autofluorescence excited by 532 nm light, before and after exposure to lights calibrated to bleach rhodopsin substantially. Bleaching was confined to circular retinal regions of 4.8° visual angle located approximately 16° superotemporal and superonasal to fixation. Images were captured as 12-bit tiff files and postprocessed to extract changes in reflectance and autofluorescence. At the locus of bleaching transient increases in reflectance of the 532 nm, but not the 633 nm beam were observed readily and quantified. A transient increase in autofluorescence also occurred. The action spectrum, absolute sensitivity, and recovery of the 532 nm reflectance increase were consistent with previous measurements of human rhodopsin's spectral sensitivity, photosensitivity, and regeneration kinetics. The autofluorescence changes closely tracked the changes in rhodopsin density. The bleaching and regeneration kinetics of rhodopsin can be measured locally in the human retina with a widely available SLO. The increased autofluorescence excited by 532 nm light upon bleaching appears primarily due to transient elimination of rhodopsin's screening of autofluorescent fluorochromes in the RPE. The spatially localized measurement with a widely available SLO of rhodopsin, the most abundant protein in the retina, could be a valuable adjunct to retinal health assessment.

  5. Modelo analítico del efecto de PRS sobre satélites GPS

    Science.gov (United States)

    Meza, A.; Brunini, C.; Usandivaras, J. C.

    El sistema GPS (Global Position System) es, hoy en día, la herramienta de navegación y posicionamiento más potente y lo será sin duda en la próxima década. Gran parte de su valiosa utilidad se debe a la alta precisión que permite lograr y ésta, a su vez, depende, entre otras causas, de la precisión con que se conocen las órbitas de los satélites. La presión de radiación solar (PRS) fija el límite de la precisión con que pueden calcularse en la actualidad las efemérides satelitarias. El objetivo de este trabajo es proponer una mejor resolución de este fenómeno. El modelo analítico aquí presentado, se basa en el análisis del comportamiento de los residuos de un ajuste por mínimos cuadrados en el que se utiliza el modelo de PRS propuesto por Beutler. El mismo consiste en un modelo determinista del fenómeno con dos parámetros libres. Los resultados obtenidos ponen de manifiesto que, aún después de aplicar dichos parámetros, prevalecen en los residuos efectos semidiurnos en las componentes radial,tangencial y normal. Estos resultados obtenidos se comparan con los de un trabajo desarrollado por el Instituto de Berne (Beutler et al., 1994), en el que se utilizaron como pseudo-observaciones las órbitas precisas del IGS (CODE). El intervalo de integración escogido por este centro fueron las semanas 680 y 681. En resumen se tienen arcos de 14 días para todos los satélites, donde las efemérides precisas de los mismos para los 14 días fueron utilizados como pseudo-observaciones. El modelo de fuerza que empleó dicho centro fue básicamente el tradicional en lo que respecta al modelo de las fuerzas gravitacionales, y para la PRS utilizo el modelo standard de Beutler. Los parámetros de este modelo junto con las 6 condiciones iniciales (posición y velocidad) fueron ajustados por el método general de mínimos cuadrados. Los residuos en la componente radial, tangencial y normal, para los satélites con un buen comportamiento, presentan una

  6. Bacillus subtilis PrsA is required in vivo as an extracytoplasmic chaperone for secretion of active enzymes synthesized either with or without pro-sequences

    DEFF Research Database (Denmark)

    Jabobs, Myra F; Andersen, Jens Bo; Kontinen, Vesa P.

    1993-01-01

    In prsA (protein secretion) mutants of Bacillus subtilis, decreased levels of exoproteins, including alpha-amylase and subtilisins, are found extracellularly. The effect of prsA on subtilisin secretion is elaborated here. Extracytoplasmic folding and secretion of active subtilisin is assisted...

  7. FTIR study of the photoreaction of bovine rhodopsin in the presence of hydroxylamine.

    Science.gov (United States)

    Katayama, Kota; Furutani, Yuji; Kandori, Hideki

    2010-07-15

    In bovine rhodopsin, 11-cis-retinal forms a Schiff base linkage with Lys296. The Schiff base is not reactive to hydroxylamine in the dark, which is consistent with the well-protected retinal binding site. In contrast, under illumination it easily forms all-trans retinal oxime, resulting in the loss of color. This suggests that activation of rhodopsin creates a specific reaction channel for hydroxylamine or loosens the chromophore binding pocket. In the present study, to extract structural information on the Schiff base vicinity and to understand the changes upon activation of rhodopsin, we compared light-induced FTIR difference spectra of bovine rhodopsin in the presence and absence of hydroxylamine under physiological pH (approximately 7). Although the previous FTIR study did not observe the complex formation between rhodopsin and G-protein transducin in hydrated films, the present study clearly shows that hydrated films can be used for studies of the interaction between rhodopsin and hydroxylamine. Hydroxylamine does not react with the Schiff base of Meta-I intermediate trapped at 240 K, possibly because of decreased conformational motions under the frozen environment, while FTIR spectroscopy showed that hydroxylamine affects the hydrogen bonds of the Schiff base and water molecules in Meta-I. In contrast, formation of the retinal oxime was clearly observed at 280 K, the characteristic temperature of Meta-II accumulation in the absence of hydroxylamine, and time-dependent formation of retinal oxime was observed from Meta-II at 265 K as well. The obtained difference FTIR spectra of retinal oxime and opsin are different from that of Meta-II. It is likely that the antiparallel beta-sheet constituting a part of the retinal binding pocket at the extracellular surface is structurally disrupted in the presence of hydroxylamine, which allows the hydrolysis of the Schiff base into retinal oxime.

  8. Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa

    Science.gov (United States)

    Kim, Kwang Joong; Kim, Cinoo; Bok, Jeong; Kim, Kyung-Seon; Lee, Eun-Ju; Park, Sung Pyo; Chung, Hum; Han, Bok-Ghee; Kim, Hyung-Lae; Kimm, Kuchan; Yu, Hyeong Gon

    2011-01-01

    Purpose To determine the spectrum and frequency of rhodopsin gene (RHO) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype–phenotype correlations in patients with mutations. Methods The RHO mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing. Results Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (c.893C>A, p.A298D) and four known mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T, p.P347L). The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M. Conclusions The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype–phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy. PMID:21677794

  9. Microbial and viral-like rhodopsins present in coastal marine sediments from four polar and subpolar regions

    Energy Technology Data Exchange (ETDEWEB)

    López, José L.; Golemba, Marcelo; Hernández, Edgardo; Lozada, Mariana; Dionisi, Hebe; Jansson, Janet K.; Carroll, Jolynn; Lundgren, Leif; Sjöling, Sara; Mac Cormack, Walter P.; Sobecky, Patricia

    2016-11-03

    Rhodopsins are broadly distributed. In this work, we analyzed 23 metagenomes corresponding to marine sediment samples from four regions that share cold climate conditions (Norway; Sweden; Argentina and Antarctica). In order to investigate the genes evolution of viral rhodopsins, an initial set of 6224 bacterial rhodopsin sequences according to COG5524 were retrieved from the 23 metagenomes. After selection by the presence of transmembrane domains and alignment, 123 viral (51) and non-viral (72) sequences (>50 amino acids) were finally included in further analysis. Viral rhodopsin genes were homologs of Phaeocystis globosa virus and Organic lake Phycodnavirus. Non-viral microbial rhodopsin genes were ascribed to Bacteroidetes, Planctomycetes, Firmicutes, Actinobacteria, Cyanobacteria, Proteobacteria, Deinococcus-Thermus and Cryptophyta and Fungi. A rescreening using Blastp, using as queries the viral sequences previously described, retrieved 30 sequences (>100 amino acids). Phylogeographic analysis revealed a geographical clustering of the sequences affiliated to the viral group. This clustering was not observed for the microbial non-viral sequences. The phylogenetic reconstruction allowed us to propose the existence of a putative ancestor of viral rhodopsin genes related to Actinobacteria and Chloroflexi. This is the first report about the existence of a phylogeographic association of the viral rhodopsin sequences from marine sediments.

  10. A distance measurement between specific sites on the cytoplasmic surface of bovine rhodopsin in rod outer segment disk membranes.

    Science.gov (United States)

    Albert, A D; Watts, A; Spooner, P; Groebner, G; Young, J; Yeagle, P L

    1997-08-14

    Structural information on mammalian integral membrane proteins is scarce. As part of work on an alternative approach to the structure of bovine rhodopsin, a method was devised to obtain an intramolecular distance between two specific sites on rhodopsin while in the rod outer segment disk membrane. In this report, the distance between the rhodopsin kinase phosphorylation site(s) on the carboxyl terminal and the top of the third transmembrane helix was measured on native rhodopsin. Rhodopsin was labeled with a nuclear spin label (31P) by limited phosphorylation with rhodopsin kinase. Major phosphorylation occurs at serines 343 and 338 on the carboxyl terminal. The phosphorylated rhodopsin was then specifically labeled on cysteine 140 with an electron spin label. Magic angle spinning 31P-nuclear magnetic resonance revealed the resonance arising from the phosphorylated protein. The enhancement of the transverse relaxation of this resonance by the paramagnetic spin label was observed. The strength of this perturbation was used to determine the through-space distance between the phosphorylation site(s) and the spin label position. A distance of 18 +/- 3 A was obtained.

  11. Batch crystallization of rhodopsin for structural dynamics using an X-ray free-electron laser

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Wenting; Nogly, Przemyslaw; Rheinberger, Jan; Kick, Leonhard M.; Gati, Cornelius; Nelson, Garrett; Deupi, Xavier; Standfuss, Jörg; Schertler, Gebhard; Panneels, Valérie, E-mail: valerie.panneels@psi.ch [Paul Scherrer Institute, OFLC/103, 5232 Villigen-PSI (Switzerland)

    2015-06-27

    A new batch preparation method is presented for high-density micrometre-sized crystals of the G protein-coupled receptor rhodopsin for use in time-resolved serial femtosecond crystallography at an X-ray free-electron laser using a liquid jet. Rhodopsin is a membrane protein from the G protein-coupled receptor family. Together with its ligand retinal, it forms the visual pigment responsible for night vision. In order to perform ultrafast dynamics studies, a time-resolved serial femtosecond crystallography method is required owing to the nonreversible activation of rhodopsin. In such an approach, microcrystals in suspension are delivered into the X-ray pulses of an X-ray free-electron laser (XFEL) after a precise photoactivation delay. Here, a millilitre batch production of high-density microcrystals was developed by four methodical conversion steps starting from known vapour-diffusion crystallization protocols: (i) screening the low-salt crystallization conditions preferred for serial crystallography by vapour diffusion, (ii) optimization of batch crystallization, (iii) testing the crystal size and quality using second-harmonic generation (SHG) imaging and X-ray powder diffraction and (iv) production of millilitres of rhodopsin crystal suspension in batches for serial crystallography tests; these crystals diffracted at an XFEL at the Linac Coherent Light Source using a liquid-jet setup.

  12. The two parallel photocycles of the Chlamydomonas sensory photoreceptor histidine kinase rhodopsin 1.

    Science.gov (United States)

    Luck, Meike; Hegemann, Peter

    2017-10-01

    Histidine kinase rhodopsins (HKRs) belong to a class of unexplored sensory photoreceptors that share a similar modular architecture. The light sensing rhodopsin domain is covalently linked to signal-transducing modules and in some cases to a C-terminal guanylyl-cyclase effector. In spite of their wide distribution in unicellular organisms, very little is known about their physiological role and mechanistic functioning. We investigated the photochemical properties of the recombinant rhodopsin-fragment of Cr-HKR1 originating from Chlamydomonas reinhardtii. Our spectroscopic studies revealed an unusual thermal stability of the photoproducts with the deprotonated retinal Schiff base (RSB). Upon UV-irradiation these Rh-UV states with maximal absorbance in the UVA-region (Rh-UV) photochemically convert to stable blue light absorbing rhodopsin (Rh-Bl) with protonated chromophore. The heterogeneity of the sample is based on two parallel photocycles with the chromophore in C 15 =N-syn- or -anti-configuration. This report represents an attempt to decipher the underlying reaction schemes and interconversions of the two coexisting photocycles. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Water permeation through the internal water pathway in activated GPCR rhodopsin.

    Directory of Open Access Journals (Sweden)

    Katsufumi Tomobe

    Full Text Available Rhodopsin is a light-driven G-protein-coupled receptor that mediates signal transduction in eyes. Internal water molecules mediate activation of the receptor in a rhodopsin cascade reaction and contribute to conformational stability of the receptor. However, it remains unclear how internal water molecules exchange between the bulk and protein inside, in particular through a putative solvent pore on the cytoplasmic. Using all-atom molecular dynamics simulations, we identified the solvent pore on cytoplasmic side in both the Meta II state and the Opsin. On the other hand, the solvent pore does not exist in the dark-adapted rhodopsin. We revealed two characteristic narrow regions located within the solvent pore in the Meta II state. The narrow regions distinguish bulk and the internal hydration sites, one of which is adjacent to the conserved structural motif "NPxxY". Water molecules in the solvent pore diffuse by pushing or sometimes jumping a preceding water molecule due to the geometry of the solvent pore. These findings revealed a total water flux between the bulk and the protein inside in the Meta II state, and suggested that these pathways provide water molecules to the crucial sites of the activated rhodopsin.

  14. Rhodopsin in plasma from patients with diabetic retinopathy - development and validation of digital ELISA by Single Molecule Array (Simoa) technology

    DEFF Research Database (Denmark)

    Petersen, Eva Rabing Brix; Olsen, Dorte Aalund; Christensen, Henry

    2017-01-01

    BACKGROUND: Diabetic retinopathy (DR) is the most frequent cause of blindness among younger adults in the western world. No blood biomarkers exist to detect DR. Hypothetically, Rhodopsin concentrations in blood has been suggested as an early marker for retinal damage. The aim of this study...... was therefore to develop and validate a Rhodopsin assay by employing digital ELISA technology, and to investigate whether Rhodopsin concentrations in diabetes patients with DR are elevated compared with diabetes patients without DR. METHODS: A digital ELISA assay using a Simoa HD-1 Analyzer (Quanterix......©, Lexington, MA 02421, USA) was developed and validated and applied on a cohort of diabetes patients characterised with (n=466) and without (n=144) DR. RESULTS: The Rhodopsin assay demonstrated a LOD of 0.26ng/l, a LLOQ of 3ng/l and a linear measuring range from 3 to 2500ng/l. Total CV% was 32%, 23%, 19...

  15. PRS: PERSONNEL RECOMMENDATION SYSTEM FOR HUGE DATA ANALYSIS USING PORTER STEMMER

    Directory of Open Access Journals (Sweden)

    T N Chiranjeevi

    2016-04-01

    Full Text Available Personal recommendation system is one which gives better and preferential recommendation to the users to satisfy their personalized requirements such as practical applications like Webpage Preferences, Sport Videos preferences, Stock selection based on price, TV preferences, Hotel preferences, books, Mobile phones, CDs and various other products now use recommender systems. The existing Pearson Correlation Coefficient (PCC and item-based algorithm using PCC, are called as UPCC and IPCC respectively. These systems are mainly based on only the rating services and does not consider the user personal preferences, they simply just give the result based on the ratings. As the size of data increases it will give the recommendations based on the top rated services and it will miss out most of user preferences. These are main drawbacks in the existing system which will give same results to the users based on some evaluations and rankings or rating service, they will neglect the user preferences and necessities. To address this problem we propose a new approach called, Personnel Recommendation System (PRS for huge data analysis using Porter Stemmer to solve the above challenges. In the proposed system it provides a personalized service recommendation list to the users and recommends the most useful services to the users which will increase the accuracy and efficiency in searching better services. Particularly, a set of suggestions or keywords are provided to indicate user preferences and we used Collaborative Filtering and Porter Stemmer algorithm which gives a suitable recommendations to the users. In real, the broad experiments are conducted on the huge database which is available in real world, and outcome shows that our proposed personal recommender method extensively improves the precision and efficiency of service recommender system over the KASR method. In our approach mainly consider the user preferences so it will not miss out the any of the data

  16. High-temperature and high-humidity response of the Eberline Model PRS-2 and the Eberline Model NRD neutron detector

    International Nuclear Information System (INIS)

    McAtee, J.L.

    1981-03-01

    The high-humidity and high-temperature response of the Eberline Model PRS-2 portable scaler-ratemeter and the Eberline Model NRD neutron detector was studied in an environmental chamber. The BF 3 probe used in the NRD detector was found to produce count rate surges at temperatures > 50 0 C and at relative humidity > 50%. The PRS-2 scaler-ratemeter was found to be relatively insensitive to high temperatures and high humidity

  17. Feeding and the rhodopsin family G-Protein Coupled Receptors (GPCRs in nematodes and arthropods

    Directory of Open Access Journals (Sweden)

    Joao Carlos dos Reis Cardoso

    2012-12-01

    Full Text Available In vertebrates, receptors of the rhodopsin G-protein coupled superfamily (GPCRs play an important role in the regulation of feeding and energy homeostasis and are activated by peptide hormones produced in the brain-gut axis. These peptides regulate appetite and energy expenditure by promoting or inhibiting food intake. Sequence and function homologues of human GPCRs involved in feeding exist in the nematode roundworm, Caenorhabditis elegans (C. elegans and the arthropod fruit fly, Drosophila melanogaster (D. melanogaster, suggesting that the mechanisms that regulate food intake emerged early and have been conserved during metazoan radiation. Nematodes and arthropods are the most diverse and successful animal phyla on Earth. They can survive in a vast diversity of environments and have acquired distinct life styles and feeding strategies. The aim of the present review is to investigate if this diversity has affected the evolution of invertebrate GPCRs. Homologues of the C. elegans and D. melanogaster rhodopsin receptors were characterized in the genome of other nematodes and arthropods and receptor evolution compared. With the exception of bombesin receptors (BBR that are absent from nematodes, a similar gene complement was found. In arthropods, rhodopsin GPCR evolution is characterized by species-specific gene duplications and deletions and in nematodes by gene expansions in species with a free-living stage and gene deletions in representatives of obligate parasitic taxa. Based upon variation in GPCR gene number and potentially divergent functions within phyla we hypothesize that life style and feeding diversity practiced by nematodes and arthropods was one factor that contributed to rhodopsin GPCR gene evolution. Understanding how the regulation of food intake has evolved in invertebrates will contribute to the development of novel drugs to control nematodes and arthropods and the pests and diseases that use them as vectors.

  18. Feeding and the rhodopsin family g-protein coupled receptors in nematodes and arthropods.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Fonseca, Vera G; Power, Deborah M

    2012-01-01

    In vertebrates, receptors of the rhodopsin G-protein coupled superfamily (GPCRs) play an important role in the regulation of feeding and energy homeostasis and are activated by peptide hormones produced in the brain-gut axis. These peptides regulate appetite and energy expenditure by promoting or inhibiting food intake. Sequence and function homologs of human GPCRs involved in feeding exist in the nematode roundworm, Caenorhabditis elegans (C. elegans), and the arthropod fruit fly, Drosophila melanogaster (D. melanogaster), suggesting that the mechanisms that regulate food intake emerged early and have been conserved during metazoan radiation. Nematodes and arthropods are the most diverse and successful animal phyla on Earth. They can survive in a vast diversity of environments and have acquired distinct life styles and feeding strategies. The aim of the present review is to investigate if this diversity has affected the evolution of invertebrate GPCRs. Homologs of the C. elegans and D. melanogaster rhodopsin receptors were characterized in the genome of other nematodes and arthropods and receptor evolution compared. With the exception of bombesin receptors (BBR) that are absent from nematodes, a similar gene complement was found. In arthropods, rhodopsin GPCR evolution is characterized by species-specific gene duplications and deletions and in nematodes by gene expansions in species with a free-living stage and gene deletions in representatives of obligate parasitic taxa. Based upon variation in GPCR gene number and potentially divergent functions within phyla we hypothesize that life style and feeding diversity practiced by nematodes and arthropods was one factor that contributed to rhodopsin GPCR gene evolution. Understanding how the regulation of food intake has evolved in invertebrates will contribute to the development of novel drugs to control nematodes and arthropods and the pests and diseases that use them as vectors.

  19. Studying of Phototransformation of Light Signal by Photoreceptor Pigments - Rhodopsin, Iodopsin and Bacteriorhodopsin

    OpenAIRE

    Ignat Ignatov; Oleg Mosin

    2014-01-01

    This review article views predominately the structure and function of animal and bacterial photoreceptor pigments (rhodopsin, iodopsin, bacteriorhodopsin) and their aspects of nano- and biotechnological usage. On an example of bacteriorhodopsin is described the method of its isolation from purple membranes of photo-organotrophic halobacterium Halobacterium halobium by cellular autolysis by distilled water, processing of bacterial biomass by ultrasound at 22 KHz, alcohol extraction of low and ...

  20. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa

    International Nuclear Information System (INIS)

    Dryja, T.P.; Han, L.B.; Cowley, G.S.; McGee, T.L.; Berson, E.L.

    1991-01-01

    The authors searched for point mutations in every exon of the rhodopsin gene in 150 patients from separate families with autosomal dominant retinitis pigmentosa. Including the 4 mutations the authors reported previously, they found a total of 17 different mutations that correlate with the disease. Each of these mutations is a single-base substitution corresponding to a single amino acid substitution. Based on current models for the structure of rhodopsin, 3 of the 17 mutant amino acids are normally located on the cytoplasmic side of the protein, 6 in transmembrane domains, and 8 on the intradiscal side. Forty-three of the 150 patients (29%) carry 1 of these mutations, and no patient has more than 1 mutation. In every family with a mutation so far analyzed, the mutation cosegregates with the disease. They found one instance of a mutation in an affected patient that was absent in both unaffected parents (i.e., a new germ-line mutation), indicating that some isolate cases of retinitis pigmentosa carry a mutation of the rhodopsin gene

  1. Retinal Ligand Mobility Explains Internal Hydration and Reconciles Active Rhodopsin Structures

    Science.gov (United States)

    Leioatts, Nicholas; Mertz, Blake; Martínez-Mayorga, Karina; Romo, Tod D.; Pitman, Michael C.; Feller, Scott E.; Grossfield, Alan; Brown, Michael F.

    2014-01-01

    Rhodopsin, the mammalian dim-light receptor, is one of the best-characterized G-protein-coupled receptors, a pharmaceutically important class of membrane proteins that has garnered a great deal of attention because of the recent availability of structural information. Yet the mechanism of rhodopsin activation is not fully understood. Here, we use microsecond-scale all-atom molecular dynamics simulations, validated by solid-state 2H nuclear magnetic resonance spectroscopy, to understand the transition between the dark and metarhodopsin I (Meta I) states. Our analysis of these simulations reveals striking differences in ligand flexibility between the two states. Retinal is much more dynamic in Meta I, adopting an elongated conformation similar to that seen in the recent activelike crystal structures. Surprisingly, this elongation corresponds to both a dramatic influx of bulk water into the hydrophobic core of the protein and a concerted transition in the highly conserved Trp2656.48 residue. In addition, enhanced ligand flexibility upon light activation provides an explanation for the different retinal orientations observed in X-ray crystal structures of active rhodopsin. PMID:24328554

  2. The Anabaena sensory rhodopsin transducer defines a novel superfamily of prokaryotic small-molecule binding domains

    Directory of Open Access Journals (Sweden)

    De Souza Robson F

    2009-08-01

    Full Text Available Abstract The Anabaena sensory rhodopsin transducer (ASRT is a small protein that has been claimed to function as a signaling molecule downstream of the cyanobacterial sensory rhodopsin. However, orthologs of ASRT have been detected in several bacteria that lack rhodopsin, raising questions about the generality of this function. Using sequence profile searches we show that ASRT defines a novel superfamily of β-sandwich fold domains. Through contextual inference based on domain architectures and predicted operons and structural analysis we present strong evidence that these domains bind small molecules, most probably sugars. We propose that the intracellular versions like ASRT probably participate as sensors that regulate a diverse range of sugar metabolism operons or even the light sensory behavior in Anabaena by binding sugars or related metabolites. We also show that one of the extracellular versions define a predicted sugar-binding structure in a novel cell-surface lipoprotein found across actinobacteria, including several pathogens such as Tropheryma, Actinomyces and Thermobifida. The analysis of this superfamily also provides new data to investigate the evolution of carbohydrate binding modes in β-sandwich domains with very different topologies. Reviewers: This article was reviewed by M. Madan Babu and Mark A. Ragan.

  3. Solution structure of the parvulin-type PPIase domain of Staphylococcus aureus PrsA – Implications for the catalytic mechanism of parvulins

    Directory of Open Access Journals (Sweden)

    Koskela Harri

    2009-03-01

    Full Text Available Abstract Background Staphylococcus aureus is a Gram-positive pathogenic bacterium causing many kinds of infections from mild respiratory tract infections to life-threatening states as sepsis. Recent emergence of S. aureus strains resistant to numerous antibiotics has created a need for new antimicrobial agents and novel drug targets. S. aureus PrsA is a membrane associated extra-cytoplasmic lipoprotein which contains a parvulin-type peptidyl-prolyl cis-trans isomerase domain. PrsA is known to act as an essential folding factor for secreted proteins in Gram-positive bacteria and thus it is a potential target for antimicrobial drugs against S. aureus. Results We have solved a high-resolution solution structure of the parvulin-type peptidyl-prolyl cis-trans isomerase domain of S. aureus PrsA (PrsA-PPIase. The results of substrate peptide titrations pinpoint the active site and demonstrate the substrate preference of the enzyme. With detailed NMR spectroscopic investigation of the orientation and tautomeric state of the active site histidines we are able to give further insight into the structure of the catalytic site. NMR relaxation analysis gives information on the dynamic behaviour of PrsA-PPIase. Conclusion Detailed structural description of the S. aureus PrsA-PPIase lays the foundation for structure-based design of enzyme inhibitors. The structure resembles hPin1-type parvulins both structurally and regarding substrate preference. Even though a wealth of structural data is available on parvulins, the catalytic mechanism has yet to be resolved. The structure of S. aureus PrsA-PPIase and our findings on the role of the conserved active site histidines help in designing further experiments to solve the detailed catalytic mechanism.

  4. Combined solid state and solution NMR studies of {alpha},{epsilon}-{sup 15}N labeled bovine rhodopsin

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Karla; Lehner, Ines [Johann Wolfgang Goethe-Universitaet Frankfurt, Center for Biomolecular Magnetic Resonance (Germany); Dhiman, Harpreet Kaur [University of Pittsburgh School of Medicine, Department of Structural Biology (United States); Richter, Christian; Glaubitz, Clemens; Schwalbe, Harald, E-mail: schwalbe@nmr.uni-frankfurt.de; Klein-Seetharaman, Judith [Johann Wolfgang Goethe-Universitaet Frankfurt, Center for Biomolecular Magnetic Resonance (Germany); Khorana, H. Gobind [Massachusetts Institute of Technology, Departments of Biology and Chemistry (United States)], E-mail: khorana@mit.edu

    2007-04-15

    Rhodopsin is the visual pigment of the vertebrate rod photoreceptor cell and is the only member of the G protein coupled receptor family for which a crystal structure is available. Towards the study of dynamics in rhodopsin, we report NMR-spectroscopic investigations of {alpha},{epsilon}-{sup 15}N-tryptophan labeled rhodopsin in detergent micelles and reconstituted in phospholipids. Using a combination of solid state {sup 13}C,{sup 15}N-REDOR and HETCOR experiments of all possible {sup 13}C'{sub i-1} carbonyl/{sup 15}N{sub i}-tryptophan isotope labeled amide pairs, and H/D exchange {sup 1}H,{sup 15}N-HSQC experiments conducted in solution, we assigned chemical shifts to all five rhodopsin tryptophan backbone {sup 15}N nuclei and partially to their bound protons. {sup 1}H,{sup 15}N chemical shift assignment was achieved for indole side chains of Trp35{sup 1.30} and Trp175{sup 4.65}. {sup 15}N chemical shifts were found to be similar when comparing those obtained in the native like reconstituted lipid environment and those obtained in detergent micelles for all tryptophans except Trp175{sup 4.65} at the membrane interface. The results suggest that the integrated solution and solid state NMR approach presented provides highly complementary information in the study of structure and dynamics of large membrane proteins like rhodopsin.

  5. Alkylated hydroxylamine derivatives eliminate peripheral retinylidene Schiff bases but cannot enter the retinal binding pocket of light-activated rhodopsin.

    Science.gov (United States)

    Piechnick, Ronny; Heck, Martin; Sommer, Martha E

    2011-08-23

    Besides Lys-296 in the binding pocket of opsin, all-trans-retinal forms adducts with peripheral lysine residues and phospholipids, thereby mimicking the spectral and chemical properties of metarhodopsin species. These pseudophotoproducts composed of nonspecific retinylidene Schiff bases have long plagued the investigation of rhodopsin deactivation and identification of decay products. We discovered that, while hydroxylamine can enter the retinal binding pocket of light-activated rhodopsin, the modified hydroxylamine compounds o-methylhydroxylamine (mHA), o-ethylhydroxylamine (eHA), o-tert-butylhydroxylamine (t-bHA), and o-(carboxymethyl)hydroxylamine (cmHA) are excluded. However, the alkylated hydroxylamines react quickly and efficiently with exposed retinylidene Schiff bases to form their respective retinal oximes. We further investigated how t-bHA affects light-activated rhodopsin and its interaction with binding partners. We found that both metarhodopsin II (Meta II) and Meta III are resistant to t-bHA, and neither arrestin nor transducin binding is affected by t-bHA. This discovery suggests that the hypothetical solvent channel that opens in light-activated rhodopsin is extremely stringent with regard to size and/or polarity. We believe that alkylated hydroxylamines will prove to be extremely useful reagents for the investigation of rhodopsin activation and decay mechanisms. Furthermore, the use of alkylated hydroxylamines should not be limited to in vitro studies and could help elucidate visual signal transduction mechanisms in the living cells of the retina. © 2011 American Chemical Society

  6. Rhodopsin in the Dark Hot Sea: Molecular Analysis of Rhodopsin in a Snailfish, Careproctus rhodomelas, Living near the Deep-Sea Hydrothermal Vent.

    Directory of Open Access Journals (Sweden)

    Rie Sakata

    Full Text Available Visual systems in deep-sea fishes have been previously studied from a photobiological aspect; however, those of deep-sea fish inhabiting the hydrothermal vents are far less understood due to sampling difficulties. In this study, we analyzed the visual pigment of a deep-sea snailfish, Careproctus rhodomelas, discovered and collected only near the hydrothermal vents of oceans around Japan. Proteins were solubilized from the C. rhodomelas eyeball and subjected to spectroscopic analysis, which revealed the presence of a pigment characterized by an absorption maximum (λmax at 480 nm. Immunoblot analysis of the ocular protein showed a rhodopsin-like immunoreactivity. We also isolated a retinal cDNA encoding the entire coding sequence of putative C. rhodomelas rhodopsin (CrRh. HEK293EBNA cells were transfected with the CrRh cDNA and the proteins extracted from the cells were subjected to spectroscopic analysis. The recombinant CrRh showed the absorption maximum at 480 nm in the presence of 11-cis retinal. Comparison of the results from the eyeball extract and the recombinant CrRh strongly suggests that CrRh has an A1-based 11-cis-retinal chromophore and works as a photoreceptor in the C. rhodomelas retina, and hence that C. rhodomelas responds to dim blue light much the same as other deep-sea fishes. Because hydrothermal vent is a huge supply of viable food, C. rhodomelas likely do not need to participate diel vertical migration and may recognize the bioluminescence produced by aquatic animals living near the hydrothermal vents.

  7. Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod Rhodopsin in the Human Retina.

    Directory of Open Access Journals (Sweden)

    Martin Ehler

    Full Text Available We introduce and describe a novel non-invasive in-vivo method for mapping local rod rhodopsin distribution in the human retina over a 30-degree field. Our approach is based on analyzing the brightening of detected lipofuscin autofluorescence within small pixel clusters in registered imaging sequences taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO over a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying variational optimization techniques from applied mathematics. The physical model and the numerical analysis with its implementation are outlined in detail. This new technique enables the creation of spatial maps of the retinal rhodopsin and retinal pigment epithelium (RPE bisretinoid distribution with an ≈ 50μm resolution.

  8. Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod Rhodopsin in the Human Retina

    Science.gov (United States)

    Ehler, Martin; Dobrosotskaya, Julia; Cunningham, Denise; Wong, Wai T.; Chew, Emily Y.; Czaja, Wojtek; Bonner, Robert F.

    2015-01-01

    We introduce and describe a novel non-invasive in-vivo method for mapping local rod rhodopsin distribution in the human retina over a 30-degree field. Our approach is based on analyzing the brightening of detected lipofuscin autofluorescence within small pixel clusters in registered imaging sequences taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO) over a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying variational optimization techniques from applied mathematics. The physical model and the numerical analysis with its implementation are outlined in detail. This new technique enables the creation of spatial maps of the retinal rhodopsin and retinal pigment epithelium (RPE) bisretinoid distribution with an ≈ 50μm resolution. PMID:26196397

  9. Opsin cDNA sequences of a UV and green rhodopsin of the satyrine butterfly Bicyclus anynana.

    Science.gov (United States)

    Vanhoutte, K J A; Eggen, B J L; Janssen, J J M; Stavenga, D G

    2002-11-01

    The cDNAs of an ultraviolet (UV) and long-wavelength (LW) (green) absorbing rhodopsin of the bush brown Bicyclus anynana were partially identified. The UV sequence, encoding 377 amino acids, is 76-79% identical to the UV sequences of the papilionids Papilio glaucus and Papilio xuthus and the moth Manduca sexta. A dendrogram derived from aligning the amino acid sequences reveals an equidistant position of Bicyclus between Papilio and Manduca. The sequence of the green opsin cDNA fragment, which encodes 242 amino acids, represents six of the seven transmembrane regions. At the amino acid level, this fragment is more than 80% identical to the corresponding LW opsin sequences of Dryas, Heliconius, Papilio (rhodopsin 2) and Manduca. Whereas three LW absorbing rhodopsins were identified in the papilionid butterflies, only one green opsin was found in B. anynana.

  10. Requests for post-registration studies (PRS), patients follow-up in actual practice: Changes in the role of databases.

    Science.gov (United States)

    Berdaï, Driss; Thomas-Delecourt, Florence; Szwarcensztein, Karine; d'Andon, Anne; Collignon, Cécile; Comet, Denis; Déal, Cécile; Dervaux, Benoît; Gaudin, Anne-Françoise; Lamarque-Garnier, Véronique; Lechat, Philippe; Marque, Sébastien; Maugendre, Philippe; Méchin, Hubert; Moore, Nicholas; Nachbaur, Gaëlle; Robain, Mathieu; Roussel, Christophe; Tanti, André; Thiessard, Frantz

    2018-02-01

    Early market access of health products is associated with a larger number of requests for information by the health authorities. Compared with these expectations, the growing expansion of health databases represents an opportunity for responding to questions raised by the authorities. The computerised nature of the health system provides numerous sources of data, and first and foremost medical/administrative databases such as the French National Inter-Scheme Health Insurance Information System (SNIIRAM) database. These databases, although developed for other purposes, have already been used for many years with regard to post-registration studies (PRS). The use thereof will continue to increase with the recent creation of the French National Health Data System (SNDS [2016 health system reform law]). At the same time, other databases are available in France, offering an illustration of "product use under actual practice conditions" by patients and health professionals (cohorts, specific registries, data warehouses, etc.). Based on a preliminary analysis of requests for PRS, approximately two-thirds appeared to have found at least a partial response in existing databases. Using these databases has a number of disadvantages, but also numerous advantages, which are listed. In order to facilitate access and optimise their use, it seemed important to draw up recommendations aiming to facilitate these developments and guarantee the conditions for their technical validity. The recommendations drawn up notably include the need for measures aiming to promote the visibility of research conducted on databases in the field of PRS. Moreover, it seemed worthwhile to promote the interoperability of health data warehouses, to make it possible to match information originating from field studies with information originating from databases, and to develop and share algorithms aiming to identify criteria of interest (proxies). Methodological documents, such as the French National

  11. Spectral methods for study of the G-protein-coupled receptor rhodopsin. II. Magnetic resonance methods

    Science.gov (United States)

    Struts, A. V.; Barmasov, A. V.; Brown, M. F.

    2016-02-01

    This article continues our review of spectroscopic studies of G-protein-coupled receptors. Magnetic resonance methods including electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) provide specific structural and dynamical data for the protein in conjunction with optical methods (vibrational, electronic spectroscopy) as discussed in the accompanying article. An additional advantage is the opportunity to explore the receptor proteins in the natural membrane lipid environment. Solid-state 2H and 13C NMR methods yield information about both the local structure and dynamics of the cofactor bound to the protein and its light-induced changes. Complementary site-directed spin-labeling studies monitor the structural alterations over larger distances and correspondingly longer time scales. A multiscale reaction mechanism describes how local changes of the retinal cofactor unlock the receptor to initiate large-scale conformational changes of rhodopsin. Activation of the G-protein-coupled receptor involves an ensemble of conformational substates within the rhodopsin manifold that characterize the dynamically active receptor.

  12. Protective role of grape seed extract against the effect of electromagnetic radiation on retinal rhodopsin

    International Nuclear Information System (INIS)

    Naglaa Mohamed Samir Mohamed El hansi

    2013-01-01

    In recent time, people exposure to blue light has increased. Much of the world of commercial display and industry is lit with cool white fluorescent tubes which emit a strong spike of light in the blue and ultraviolet ranges. Indeed many homes and offices are lit with cool white fluorescent tubes. No doubts, more people are spending more time in front of Video Display Terminals which produce blue light. This study aimed to investigate the effect of blue light and the combined effect of blue light and gamma radiation on retinal rhodopsin. Also, the possible protective role of grape seed extract (GSE) to retinal rhodopsin was tested. New zealand albino rabbits were used in this study. The rabbits were classified into five groups I, II, III, IV and V according to the following: Group I: used as control group. Group II: subdivided into four subgroups subgroups were exposed to blue light of intensity 3.9 lux and decapitated after 48 hours, one week, two weeks and 3 weeks respectively. Group III: subdivided into four subgroups. All rabbits were supplemented with 10 mg/Kg body weight Grape seed extract (GSE) two weeks before exposure to 3.9 lux blue light. GSE supplementation was continued till decapitation. Rabbits were decapitated after 48 hours, one week, two weeks and 3 weeks of exposure to blue light respectively. Group IV: subdivided into two subgroups. The two subgroups were exposed to blue light of 3.9 lux for one week and two weeks, then irradiated with 5 Gy gamma rays and decapitated. Group V: subdivided into two subgroups. The rabbits were supplemented with 10 mg/Kg body weight Grape seed extract (GSE) two weeks before exposure to 3.9 lux blue light for one week and two weeks respectively. After these periods, the rabbits were irradiated with 5 Gy gamma rays then decapitated. GSE supplementation was continued till decapitation. At the end of each period, the electroretinogram (ERG) was recorded. After the decapitation, the rhodopsin was extracted and the

  13. Detection of rhodopsin dimerization in situ by PIE-FCCS, a time-resolved fluorescence spectroscopy.

    Science.gov (United States)

    Smith, Adam W

    2015-01-01

    Rhodopsin self-associates in the plasma membrane. At low concentrations, the interactions are consistent with a monomer-dimer equilibrium (Comar et al., J Am Chem Soc 136(23):8342-8349, 2014). At high concentrations in native tissue, higher-order clusters have been observed (Fotiadis et al., Nature 421:127-128, 2003). The physiological role of rhodopsin dimerization is still being investigated, but it is clear that a quantitative assessment is essential to determining the function of rhodopsin clusters in vision. To quantify rhodopsin interactions, I will outline the theory and methodology of a specialized time-resolved fluorescence spectroscopy for measuring membrane protein-protein interactions called pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). The strength of this technique is its ability to quantify rhodopsin interactions in situ (i.e., a live cell plasma membrane). There are two reasons for restricting the scope to live cell membranes. First, the compositional heterogeneity of the plasma membrane creates a complex milieu with thousands of lipid, protein, and carbohydrate species. This makes it difficult to infer quaternary interactions from detergent solubilized samples or construct a model phospholipid bilayer that recapitulates all of the interactions present in native membranes. Second, organizational structure and dynamics is a key feature of the plasma membrane, and fixation techniques like formaldehyde cross-linking and vitrification will modulate the interactions. PIE-FCCS is based on two-color fluorescence imaging with time-correlated single-photon counting (TCSPC) (Becker et al., Rev Sci Instrum 70:1835-1841, 1999). By time-tagging every detected photon, the data can be analyzed as a fluorescence intensity distribution, fluorescence lifetime histogram, or fluorescence (cross-)correlation spectra (FCS/FCCS) (Becker, Advanced time-correlated single-photon counting techniques, Springer, Berlin, 2005). These

  14. Thermal decay of rhodopsin: role of hydrogen bonds in thermal isomerization of 11-cis retinal in the binding site and hydrolysis of protonated Schiff base.

    Science.gov (United States)

    Liu, Jian; Liu, Monica Yun; Nguyen, Jennifer B; Bhagat, Aditi; Mooney, Victoria; Yan, Elsa C Y

    2009-07-01

    Although thermal stability of the G protein-coupled receptor rhodopsin is directly related to its extremely low dark noise level and has recently generated considerable interest, the chemistry behind the thermal decay process of rhodopsin has remained unclear. Using UV-vis spectroscopy and HPLC analysis, we have demonstrated that the thermal decay of rhodopsin involves both hydrolysis of the protonated Schiff base and thermal isomerization of 11-cis to all-trans retinal. Examining the unfolding of rhodopsin by circular dichroism spectroscopy and measuring the rate of thermal isomerization of 11-cis retinal in solution, we conclude that the observed thermal isomerization of 11-cis to all-trans retinal happens when 11-cis retinal is in the binding pocket of rhodopsin. Furthermore, we demonstrate that solvent deuterium isotope effects are involved in the thermal decay process by decreasing the rates of thermal isomerization and hydrolysis, suggesting that the rate-determining step of these processes involves breaking hydrogen bonds. These results provide insight into understanding the critical role of an extensive hydrogen-bonding network on stabilizing the inactive state of rhodopsin and contribute to our current understanding of the low dark noise level of rhodopsin, which enables this specialized protein to function as an extremely sensitive biological light detector. Because similar hydrogen-bonding networks have also been suggested by structural analysis of two other GPCRs, beta1 and beta2 adrenergic receptors, our results could reveal a general role of hydrogen bonds in facilitating GPCR function.

  15. HAA1 and PRS3 overexpression boosts yeast tolerance towards acetic acid improving xylose or glucose consumption: unravelling the underlying mechanisms.

    Science.gov (United States)

    Cunha, Joana T; Costa, Carlos E; Ferraz, Luís; Romaní, Aloia; Johansson, Björn; Sá-Correia, Isabel; Domingues, Lucília

    2018-04-02

    Acetic acid tolerance and xylose consumption are desirable traits for yeast strains used in industrial biotechnological processes. In this work, overexpression of a weak acid stress transcriptional activator encoded by the gene HAA1 and a phosphoribosyl pyrophosphate synthetase encoded by PRS3 in a recombinant industrial Saccharomyces cerevisiae strain containing a xylose metabolic pathway was evaluated in the presence of acetic acid in xylose- or glucose-containing media. HAA1 or PRS3 overexpression resulted in superior yeast growth and higher sugar consumption capacities in the presence of 4 g/L acetic acid, and a positive synergistic effect resulted from the simultaneous overexpression of both genes. Overexpressing these genes also improved yeast adaptation to a non-detoxified hardwood hydrolysate with a high acetic acid content. Furthermore, the overexpression of HAA1 and/or PRS3 was found to increase the robustness of yeast cell wall when challenged with acetic acid stress, suggesting the involvement of the modulation of the cell wall integrity pathway. This study clearly shows HAA1 and/or, for the first time, PRS3 overexpression to play an important role in the improvement of industrial yeast tolerance towards acetic acid. The results expand the molecular toolbox and add to the current understanding of the mechanisms involved in higher acetic acid tolerance, paving the way for the further development of more efficient industrial processes.

  16. Influence of GDP on interaction of transducin with cyclic nucleotide phosphodiesterase and rhodopsin from bovine retinal rods

    International Nuclear Information System (INIS)

    Rybin, V.O.

    1986-01-01

    In the presence of guanine nucleotides and rhodopsin-containing membranes from bovine retinal rod outer segments transducin stimulates light-sensitive cyclic nucleotide phosphodiesterase 5.5- to 7-fold. The activation constant (K/sub act/) for GTP and Gpp(NH)p is equal to 0.25 μM, while that for GDP and GDPβS is 14 and 110 μM, respectively. GDP free of admixtures of other nucleotides does not activate phosphodiesterase at concentrations up to 1 mM, but is bound to transducin and inhibits the Gpp(NH)p-dependent activation of phosphodiesterase. The nature of the interaction of transducin with depolarized rhodopsin also depends on the type of guanine nucleotide bound: in the presence of GDP rhodopsin-containing membranes bind 70-100% of the transducin, whereas in the presence of Gpp(NH)p only 13% of the protein is bound. The data obtained indicate that GDP and GTP convert transducin to two different functional states: the transducin-GTP complex is bound to phosphodiesterase and activates it, while the transducin-GDP complex is bound primarily to rhodopsin

  17. Fluoro derivatives of retinal illuminate the decisive role of the C(12)-H element in photoisomerization and rhodopsin activation.

    NARCIS (Netherlands)

    Bovee-Geurts, P.H.M.; Fernandez Fernandez, I.; Liu, R.S.; Mathies, R.A.; Lugtenburg, J.; Grip, W.J. de

    2009-01-01

    Rhodopsin, the visual pigment of the vertebrate rod cell, is among the best investigated members of the G-protein-coupled receptor family. Within this family a unique characteristic of visual pigments is their covalently bound chromophore, 11-cis retinal, which acts as an inverse agonist. Upon

  18. Opsin cDNA sequences of a UV and green rhodopsin of the satyrine butterfly Bicyclus anynana.

    NARCIS (Netherlands)

    Vanhoutte, K.J.A.; Eggen, B.J.L.; Janssen, J.J.M.; Stavenga, D.G.

    2002-01-01

    The cDNAs of an ultraviolet (UV) and long-wavelength (LW) (green) absorbing rhodopsin of the bush brown Bicyclus anynana were partially identified. The UV sequence, encoding 377 amino acids, is 76-79% identical to the UV sequences of the papilionids Papilio glaucus and Papilio xuthus and the moth

  19. Opsin cDNA sequences of a UV and green rhodopsin of the satyrine butterfly Bicyclus anynana

    NARCIS (Netherlands)

    Vanhoutte, Kürt; Eggen, BJL; Janssen, JJM; Stavenga, DG

    The cDNAs of an ultraviolet (UV) and long-wavelength (LW) (green) absorbing rhodopsin of the bush brown Bicyclus anynana were partially identified. The UV sequence, encoding 377 amino acids, is 76-79% identical to the UV sequences of the papilionids Papilio glaucus and Papilio xuthus and the moth

  20. Variation in incorporation of tritiated amino acids into rhodopsin and opsin during the 12 hour light-dark cycle

    International Nuclear Information System (INIS)

    Matsumoto, B.

    1981-01-01

    This is a study of the variation in incorporation of labeled amino acids into opsin and rhodopsin during the 12 hour light-dark cycle. Groups of 12 adult, light-entrained R. pipiens were injected with tritiated amino acids at selected times of the day and night. Twenty four hours later, the frogs were sacrificed and their rhodopsin purified by column chromatography. It was found that the peak incorporation of amino acids into rhodopsin occurred shortly after light onset and declined to lower levels at later hours. Light microscopic autoradiography revealed the presence of radioactive disc membranes in the rod outer segments. However there was no correlation between outer segment grain density and rhodopsin specific activity. Succeeding experiments showed that light onset, rather than the time of day, played an important role in stimulating isotope incorporation. Electro-immunoprecipitation experiments revealed a changing specific activity for inner segment opsin during the light-dark cycle. Peak levels of amino acid incorporation occurred shortly after light onset and then declined to lower levels. For all time points, opsin was found to be radioactive, indicating opsin biosynthesis occurred continually throughout the diurnal cycle

  1. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex

    Science.gov (United States)

    Zhou, X. Edward; Gao, Xiang; Barty, Anton; Kang, Yanyong; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; de Waal, Parker W.; Suino-Powell, Kelly M.; Boutet, Sébastien; Williams, Garth J.; Wang, Meitian; Li, Dianfan; Caffrey, Martin; Chapman, Henry N.; Spence, John C. H.; Fromme, Petra; Weierstall, Uwe; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric

    2016-04-01

    Serial femtosecond X-ray crystallography (SFX) using an X-ray free electron laser (XFEL) is a recent advancement in structural biology for solving crystal structures of challenging membrane proteins, including G-protein coupled receptors (GPCRs), which often only produce microcrystals. An XFEL delivers highly intense X-ray pulses of femtosecond duration short enough to enable the collection of single diffraction images before significant radiation damage to crystals sets in. Here we report the deposition of the XFEL data and provide further details on crystallization, XFEL data collection and analysis, structure determination, and the validation of the structural model. The rhodopsin-arrestin crystal structure solved with SFX represents the first near-atomic resolution structure of a GPCR-arrestin complex, provides structural insights into understanding of arrestin-mediated GPCR signaling, and demonstrates the great potential of this SFX-XFEL technology for accelerating crystal structure determination of challenging proteins and protein complexes.

  2. Sensory rhodopsins I and II modulate a methylation/demethylation system in Halobacterium halobium phototaxis

    International Nuclear Information System (INIS)

    Spudich, E.N.; Takahashi, T.; Spudich, J.L.

    1989-01-01

    This work demonstrates that phototaxis stimuli in the archaebacterium Halobacterium halobium control a methylation/demethylation system in vivo through photoactivation of sensory rhodopsin I (SR-I) in either its attractant or repellent signaling form as well as through the repellent receptor sensory rhodopsin II (SR-II, also called phoborhodopsin). The effects of positive stimuli that suppress swimming reversals (i.e., an increase in attractant or decrease in repellent light) and negative stimuli that induce swimming reversals (i.e., a decrease in attractant or increase in repellent light) through each photoreceptor were monitored by assaying release of volatile [3H]methyl groups. This assay has been used to measure [3H]methanol produced during the process of adaptation to chemotactic stimuli in eubacteria. In H. halobium positive photostimuli produce a transient increase in the rate of demethylation followed by a decrease below the unstimulated value, whereas negative photostimuli cause an increase followed by a rate similar to that of the unstimulated value. Photoactivation of the SR-I attractant and simultaneous photoactivation of the SR-II repellent receptors cancel in their effects on demethylation, demonstrating the methylation system is regulated by an integrated signal. Analysis of mutants indicates that the source for the volatile methyl groups is intrinsic membrane proteins distinct from the chromoproteins that share the membrane. A methyl-accepting protein (94 kDa) previously correlated in amount with the SR-I chromoprotein (25 kDa) is shown here to be missing in a recently isolated SR-I-SR-II+ mutant (Flx3b), thus confirming the association of this protein with SR-I. Photoactivated SR-II in mutant Flx3b controls demethylation, predicting the existence of a photomodulated methyl-accepting component distinct from the 94-kDa protein of SR-I

  3. The N-terminal region of the dopamine D2 receptor, a rhodopsin-like GPCR, regulates correct integration into the plasma membrane and endocytic routes

    Science.gov (United States)

    Cho, DI; Min, C; Jung, KS; Cheong, SY; Zheng, M; Cheong, SJ; Oak, MH; Cheong, JH; Lee, BK; Kim, KM

    2012-01-01

    BACKGROUND AND PURPOSE Functional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D2 and D3 receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH The N-terminal region of the D2 receptor was gradually shortened or switched with that of the D3 receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY RESULTS Shortening the N-terminal region of the D2 receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D2 and D3 receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D2 receptors. CONCLUSIONS AND IMPLICATIONS Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D2 receptors. The N-terminal region of the D2 receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties. PMID:22117524

  4. Phosphoribosylpyrophosphate synthetase of Escherichia coli. Properties of the purified enzyme and primary structure of the prs gene

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne; Harlow, Kenneth W.; King, Cheryl J.

    1986-01-01

    Phosphoribosylpyrophosphate (P-Rib-PP) synthetase of Escherichia coli has been purified to near homogeneity from a strain harboring the prs gene, encoding P-Rib-PP synthetase, on a multicopy plasmid. Analysis of the enzyme showed that it required inorganic phosphate for activity and for stability...... the UAA translation stop codon, within a Thy-rich region following an inverted repeat sequence, indicative of an rho-independent transcription terminator....

  5. Light-induced, GTP-binding protein mediated membrane currents of Xenopus oocytes injected with rhodopsin of cephalopods.

    Science.gov (United States)

    Ando, H; Seidou, M; Kito, Y

    1991-01-01

    Xenopus oocytes that were injected with rhabdomeric membranes of squid and octopus photoreceptors acquired light sensitivity. The injected oocytes showed a light-induced current having characteristics similar to other G-protein-mediated Cl- currents induced by the activation of other membrane receptors. Pretreatment of the oocytes with pertussis toxin before the injection suppressed the generation of the light-induced current, indicating an ability of cephalopod rhodopsin to cross-react with an endogenous G-protein of Xenopus oocytes.

  6. Spectral methods for study of the G-protein-coupled receptor rhodopsin: I. Vibrational and electronic spectroscopy

    Science.gov (United States)

    Struts, A. V.; Barmasov, A. V.; Brown, M. F.

    2015-05-01

    Here we review the application of modern spectral methods for the study of G-protein-coupled receptors (GPCRs) using rhodopsin as a prototype. Because X-ray analysis gives us immobile snapshots of protein conformations, it is imperative to apply spectroscopic methods for elucidating their function: vibrational (Raman, FTIR), electronic (UV-visible absorption, fluorescence) spectroscopies, and magnetic resonance (electron paramagnetic resonance, EPR), and nuclear magnetic resonance (NMR). In the first of the two companion articles, we discuss the application of optical spectroscopy for studying rhodopsin in a membrane environment. Information is obtained regarding the time-ordered sequence of events in rhodopsin activation. Isomerization of the chromophore and deprotonation of the retinal Schiff base leads to a structural change of the protein involving the motion of helices H5 and H6 in a pH-dependent process. Information is obtained that is unavailable from X-ray crystallography, which can be combined with spectroscopic studies to achieve a more complete understanding of GPCR function.

  7. Transient Resonance Raman Spectroscopy of a Light-Driven Sodium-Ion-Pump Rhodopsin from Indibacter alkaliphilus.

    Science.gov (United States)

    Kajimoto, Kousuke; Kikukawa, Takashi; Nakashima, Hiroki; Yamaryo, Haruki; Saito, Yuta; Fujisawa, Tomotsumi; Demura, Makoto; Unno, Masashi

    2017-05-04

    Sodium-ion-pump rhodopsin (NaR) is a microbial rhodopsin that transports Na + during its photocycle. Here we explore the photocycle mechanism of NaR from Indibacter alkaliphilus with transient absorption and transient resonance Raman spectroscopy. The transient absorption data indicate that the photocycle of NaR is K (545 nm) → L (490 nm)/M (420 nm) → O 1 (590 nm) → O 2 (560 nm) → NaR, where the L and M are formed as equilibrium states. The presence of K, L, M, and O intermediates was confirmed by the resonance Raman spectra with 442 and 532 nm excitation. The main component of the transient resonance Raman spectra was due to L which contains a 13-cis retinal protonated Schiff base. The presence of an enhanced hydrogen out-of-plane band as well as its sensitivity to the H/D exchange indicate that the retinal chromophore is distorted near the Schiff base region in L. Moreover, the retinal Schiff base of the L state forms a hydrogen bond that is stronger than that of the dark state. These observations are consistent with a Na + pumping mechanism that involves a proton transfer from the retinal Schiff base to a key aspartate residue (Asp116 in Krokinobacter eikastus rhodopsin 2) in the L/M states.

  8. Probing the remarkable thermal kinetics of visual rhodopsin with E181Q and S186A mutants

    Science.gov (United States)

    Guo, Ying; Hendrickson, Heidi P.; Videla, Pablo E.; Chen, Ya-Na; Ho, Junming; Sekharan, Sivakumar; Batista, Victor S.; Tully, John C.; Yan, Elsa C. Y.

    2017-06-01

    We recently reported a very unusual temperature dependence of the rate of thermal reaction of wild type bovine rhodopsin: the Arrhenius plot exhibits a sharp "elbow" at 47 °C and, in the upper temperature range, an unexpectedly large activation energy (114 ± 8 kcal/mol) and an enormous prefactor (1072±5 s-1). In this report, we present new measurements and a theoretical model that establish convincingly that this behavior results from a collective, entropy-driven breakup of the rigid hydrogen bonding networks (HBNs) that hinder the reaction at lower temperatures. For E181Q and S186A, two rhodopsin mutants that disrupt the HBNs near the binding pocket of the 11-cis retinyl chromophore, we observe significant decreases in the activation energy (˜90 kcal/mol) and prefactor (˜1060 s-1), consistent with the conclusion that the reaction rate is enhanced by breakup of the HBN. The results provide insights into the molecular mechanism of dim-light vision and eye diseases caused by inherited mutations in the rhodopsin gene that perturb the HBNs.

  9. Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

    Science.gov (United States)

    Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

    2017-07-18

    Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

  10. Light activation of one rhodopsin molecule causes the phosphorylation of hundreds of others. A reaction observed in electropermeabilized frog rod outer segments exposed to dim illumination

    International Nuclear Information System (INIS)

    Binder, B.M.; Biernbaum, M.S.; Bownds, M.D.

    1990-01-01

    A rhodopsin phosphorylation reaction that occurs with high-gain is observed if measurements are made in electropermeabilized frog rod outer segments (ROS) stimulated by a dim flash of light in the operating range of the photoreceptor. Flashes of light exciting 1000 or fewer of the 3 x 10(9) rhodopsins present/ROS results in the incorporation of 1400 phosphates from ATP into the rhodopsin pool for each excited rhodopsin (Rho*). This amplification decreases with increasing light intensity, falling most sharply after each disk has absorbed one photon. The high-gain reaction is lost if the ROS are broken into vesicles by shearing, leaving a low-gain rhodopsin phosphorylation characterized in previous studies using brighter illumination. The high-gain but not the low-gain phosphorylation appears to be regulated by G-protein and by calcium levels in the range over which intracellular calcium changes when rod photoreceptors are illuminated. Kinetic measurements made on the phosphorylation observed at higher light intensities shows that it initially occurs rapidly enough for a role in terminating the photoresponse. The high-gain phosphorylation observed at lower light intensities may play a global role in regulating light-adaptation of the rod photoreceptor, and its existence suggests that a search for a similar high-gain modification in systems using the homologous beta-adrenergic or muscarinic acetylcholine receptors might be rewarding

  11. The defective phosphoribosyl diphosphate synthase in a temperature-sensitive prs-2 mutant of Escherichia coli is compensated by increased enzyme synthesis

    DEFF Research Database (Denmark)

    Post, David A.; Switzer, Robert L.; Hove-Jensen, Bjarne

    1996-01-01

    An Escherichia coli strain which is temperature-sensitive for growth due to a mutation (prs-2) causing a defective phosphoribosyl diphosphate (PRPP) synthase has been characterized. The temperature-sensitive mutation was mapped to a 276 bp HindIII-BssHII DNA fragment located within the open reading...... temperature shift to 42 degrees C. The other mutation was a C -> T transition located 39 bp upstream of the G -> A mutation, i.e. outside the coding sequence and close to the Shine-Dalgarno sequence. Cells harbouring only the C -> T mutation in a plasmid contained approximately three times as much PRPP...

  12. Isolation and structure-function characterization of a signaling-active rhodopsin-G protein complex.

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W; Cerione, Richard A; Skiniotis, Georgios; Ramachandran, Sekar

    2017-08-25

    The visual photo-transduction cascade is a prototypical G protein-coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (G T ). This results in the dissociation of G T into its component α T -GTP and β 1 γ 1 subunit complex. Structural information for the Rho*-G T complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (G T *) comprising a Gα T /Gα i1 chimera (α T *) and β 1 γ 1 The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to Gα T * is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one G T *. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β 2 -adrenergic receptor-G S complex, including a flexible α T * helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Agonists and partial agonists of rhodopsin: retinal polyene methylation affects receptor activation.

    Science.gov (United States)

    Vogel, Reiner; Lüdeke, Steffen; Siebert, Friedrich; Sakmar, Thomas P; Hirshfeld, Amiram; Sheves, Mordechai

    2006-02-14

    Using Fourier transform infrared (FTIR) difference spectroscopy, we have studied the impact of sites and extent of methylation of the retinal polyene with respect to position and thermodynamic parameters of the conformational equilibrium between the Meta I and Meta II photoproducts of rhodopsin. Deletion of methyl groups to form 9-demethyl and 13-demethyl analogues, as well as addition of a methyl group at C10 or C12, shifted the Meta I/Meta II equilibrium toward Meta I, such that the retinal analogues behaved like partial agonists. This equilibrium shift resulted from an apparent reduction of the entropy gain of the transition of up to 65%, which was only partially offset by a concomitant reduction of the enthalpy increase. The analogues produced Meta II photoproducts with relatively small alterations, while their Meta I states were significantly altered, which accounted for the aberrant transitions to Meta II. Addition of a methyl group at C14 influenced the thermodynamic parameters but had little impact on the position of the Meta I/Meta II equilibrium. Neutralization of the residue 134 in the E134Q opsin mutant increased the Meta II content of the 13-demethyl analogue, but not of the 9-demethyl analogue, indicating a severe impairment of the allosteric coupling between the conserved cytoplasmic ERY motif involved in proton uptake and the Schiff base/Glu 113 microdomain in the 9-demethyl analogue. The 9-methyl group appears therefore essential for the correct positioning of retinal to link protonation of the cytoplasmic motif with protonation of Glu 113 during receptor activation.

  14. Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig

    DEFF Research Database (Denmark)

    Klassen, H; Kiilgaard, Jens Folke; Warfvinge, K

    2012-01-01

    Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig....... Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival...

  15. Crystallization, X-ray diffraction analysis and SIRAS/molecular-replacenent phasing of three crystal forms of Anabaena sensory rhodopsin transducer

    International Nuclear Information System (INIS)

    Vogeley, Lutz; Luecke, Hartmut

    2006-01-01

    Crystals of Anabaena sensory rhodopsin transducer, the transducer for the cyanobacterial photosensor Anabaena sensory rhodopsin, obtained in the space groups P4, C2 and P2 1 2 1 2 1 diffract to 1.8, 2.1 and 2.0 Å, respectively. Phases for these crystal forms were obtained by SIRAS phasing using an iodide quick-soak derivative (P4) and molecular replacement (C2 and P2 1 2 1 2 1 ). Anabaena sensory rhodopsin transducer (ASRT) is a 14.7 kDa soluble signaling protein associated with the membrane-embedded light receptor Anabaena sensory rhodopsin (ASR) from Anabaena sp., a freshwater cyanobacterium. Crystals of ASRT were obtained in three different space groups, P4, C2 and P2 1 2 1 2 1 , which diffract to 1.8, 2.1 and 2.0 Å, respectively. Phases for one of these crystal forms (P4) were obtained by SIRAS phasing using an iodide quick-soak derivative and a partial model was built. Phases for the remaining crystal forms were obtained by molecular replacement using the partial model from the P4 crystal form

  16. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  17. The Photosensitivity of Rhodopsin Bleaching and Light-Induced Increases of Fundus Reflectance in Mice Measured In Vivo With Scanning Laser Ophthalmoscopy

    Science.gov (United States)

    Zhang, Pengfei; Goswami, Mayank; Zawadzki, Robert J.; Pugh, Edward N.

    2016-01-01

    Purpose To quantify bleaching-induced changes in fundus reflectance in the mouse retina. Methods Light reflected from the fundus of albino (Balb/c) and pigmented (C57Bl/6J) mice was measured with a multichannel scanning laser ophthalmoscopy optical coherence tomography (SLO-OCT) optical system. Serial scanning of small retinal regions was used for bleaching rhodopsin and measuring reflectance changes. Results Serial scanning generated a saturating reflectance increase centered at 501 nm with a photosensitivity of 1.4 × 10−8 per molecule μm2 in both strains, 2-fold higher than expected were irradiance at the rod outer segment base equal to that at the retinal surface. The action spectrum of the reflectance increase corresponds to the absorption spectrum of mouse rhodopsin in situ. Spectra obtained before and after bleaching were fitted with a model of fundus reflectance, quantifying contributions from loss of rhodopsin absorption with bleaching, absorption by oxygenated hemoglobin (HbO2) in the choroid (Balb/c), and absorption by melanin (C57Bl/6J). Both mouse strains exhibited light-induced broadband reflectance changes explained as bleaching-induced reflectivity increases at photoreceptor inner segment/outer segment (IS/OS) junctions and OS tips. Conclusions The elevated photosensitivity of rhodopsin bleaching in vivo is explained by waveguide condensing of light in propagation from rod inner segment (RIS) to rod outer segment (ROS). The similar photosensitivity of rhodopsin in the two strains reveals that little light backscattered from the sclera can enter the ROS. The bleaching-induced increases in reflectance at the IS/OS junctions and OS tips resemble results previously reported in human cones, but are ascribed to rods due to their 30/1 predominance over cones in mice and to the relatively minor amount of cone M-opsin in the regions scanned. PMID:27403994

  18. Characterization of the Escherichia coli prsA1-encoded mutant phosphoribosylpyrophosphate synthetase identifies a divalent cation-nucleotide binding site

    DEFF Research Database (Denmark)

    Bower, Stanley G.; Harlow, Kenneth W.; Switzer, Robert L.

    1989-01-01

    : DLHAXQIQGFFDI/VPI/VD. There was little alteration in the Km for ribose 5-phosphate. The Km for ATP of the mutant enzyme was increased 27-fold when Mg2+ was the activating cation but only 5-fold when Mn2+ was used. Maximal velocities of the wild type and mutant enzymes were the same. The mutant enzyme has a 6......-fold lower affinity for Ca2+, as judged by the ability of Ca2+ to inhibit the reaction in the presence of 10 mM Mg2+. Wild type PRPP synthetase is subject to product inhibition by AMP, but AMP inhibition of the prsA1 mutant enzyme could not be detected. It has been previously proposed that a divalent...

  19. Synthesis of 13C and 2H labelled retinals: spectroscopic investigations on isotopically labelled rhodopsin and bacteriorhodopsin

    International Nuclear Information System (INIS)

    Pardoen, J.A.

    1986-01-01

    In order to develop probes of the structure of chromophores, the author introduces isotopic modifications at specific chromophoric positions as structural probes. To obtain bacteriorhodopsin, rhodopsin and their photoproducts labelled in the chromophore at selected positions, bacterioopsin and opsin were reacted with the appropriate labelled a11-trans and 11-cis retinals. The author describes the synthesis of a11-trans retinal selectively 13 C labelled at different positions. The characterization of these labelled a11-trans retinals by mass spectrometry, 300 MHz 1 H NMR and 75 MHz 13 C NMR spectroscopy is given. The photochemical preparation and isolation of the pure 9-, 11- and 13-cis forms is described in the experimental part. (Auth.)

  20. Folding and Function of Proteorhodopsins in Photoenergy Transducing Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Spudich, John L. [University of Texas Medical School, Houston, TX (United States). Health Science Center, Dept. of Biochemistry and Molecular Biology

    2012-08-10

    The overall research objectives are to develop proteorhodopsin (PR) proteins as a model system for α-helical membrane protein insertion and folding, and to advance understanding of the diversity and mechanisms of PRs, a large family of photoenergy transducers (~4000 identified) abundant in the world’s oceans. Specific aims are: (1) To develop a high-efficiency genetic selection procedure for light-driven proton-pumping in E. coli cells. Such a procedure would provide a positive selection method for proper folding and function of PRs in the E. coli membrane. (2) Characterize flash-induced absorption changes and photocurrents in PR variants in organisms from various environments, and their expression level and function when expressed in E. coli. Subaims are to: (a) elucidate the relationship of the transport mechanism to mechanisms of other microbial rhodopsins, some of which like PRs function as ion transporters and some of which use light energy to activate signaling pathways (sensory rhodopsins); and (b) identify important residues and chemical events in light-driven proton transport by PRs. In addition to their importance to the energy of the biosphere PRs have attracted interest for their potential for use in making photoenergy-transducing membranes for bioengineering applications.

  1. EXPRESS

    International Nuclear Information System (INIS)

    Ancelin, C.; Le, P.; DeSaint-Quentin, S.; Villatte, N.

    1987-01-01

    This paper presents EXPRESS, an expert system developed for the automation of reliability studies. The first part consists in the description of the method for static thermohydraulic systems. In this step, the authors define the knowledge representation based on the two inference engines - ALOUETTE and LCR developed by EDF. They explain all the process to construct a fault tree from a topological and functional description of the system. Numerous examples are exhibited in illustration of the method. This is followed by the lessons derived from the studies performed on some safety systems of the PALUEL nuclear plant. The development of the same approach for electric power systems is described, insisting on the difference resulting from the sequential nature of these systems. Finally, they show the main advantages identified during the studies

  2. Segmental isotope labeling of proteins for NMR structural study using a protein S tag for higher expression and solubility

    International Nuclear Information System (INIS)

    Kobayashi, Hiroshi; Swapna, G. V. T.; Wu, Kuen-Phon; Afinogenova, Yuliya; Conover, Kenith; Mao, Binchen; Montelione, Gaetano T.; Inouye, Masayori

    2012-01-01

    A common obstacle to NMR studies of proteins is sample preparation. In many cases, proteins targeted for NMR studies are poorly expressed and/or expressed in insoluble forms. Here, we describe a novel approach to overcome these problems. In the protein S tag-intein (PSTI) technology, two tandem 92-residue N-terminal domains of protein S (PrS 2 ) from Myxococcus xanthus is fused at the N-terminal end of a protein to enhance its expression and solubility. Using intein technology, the isotope-labeled PrS 2 -tag is replaced with non-isotope labeled PrS 2 -tag, silencing the NMR signals from PrS 2 -tag in isotope-filtered 1 H-detected NMR experiments. This method was applied to the E. coli ribosome binding factor A (RbfA), which aggregates and precipitates in the absence of a solubilization tag unless the C-terminal 25-residue segment is deleted (RbfAΔ25). Using the PrS 2 -tag, full-length well-behaved RbfA samples could be successfully prepared for NMR studies. PrS 2 (non-labeled)-tagged RbfA (isotope-labeled) was produced with the use of the intein approach. The well-resolved TROSY-HSQC spectrum of full-length PrS 2 -tagged RbfA superimposes with the TROSY-HSQC spectrum of RbfAΔ25, indicating that PrS 2 -tag does not affect the structure of the protein to which it is fused. Using a smaller PrS-tag, consisting of a single N-terminal domain of protein S, triple resonance experiments were performed, and most of the backbone 1 H, 15 N and 13 C resonance assignments for full-length E. coli RbfA were determined. Analysis of these chemical shift data with the Chemical Shift Index and heteronuclear 1 H– 15 N NOE measurements reveal the dynamic nature of the C-terminal segment of the full-length RbfA protein, which could not be inferred using the truncated RbfAΔ25 construct. CS-Rosetta calculations also demonstrate that the core structure of full-length RbfA is similar to that of the RbfAΔ25 construct.

  3. Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

    Science.gov (United States)

    Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

    2014-10-01

    Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft

  4. Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA (A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.

    Science.gov (United States)

    Wu, Guofeng; Wang, Likun; Hong, Zhen; Ren, Siying; Zhou, Feng

    2017-08-01

    The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats). A stimulation electrode was implanted into the hippocampus of all of the rats. Hip-LFS was administered twice per day in the PRS group for two weeks. Simultaneously, amygdala stimulus-induced seizures and afterdischarge were recorded. After the hippocampal stimulation was terminated, the brain tissues were obtained to determine the GABA (A) receptors by a method of immumohistochemistry and a real-time polymerase chain reaction. The stages and duration of the amygdala stimulus-induced epileptic seizures were decreased in the PRS group. The afterdischarge threshold was increased and the duration as well as the afterdischarge frequency was decreased. Simultaneously, the GABA (A) expression was significantly increased in the PRS group. Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects of hippocampal stimulation may be partly achieved by increasing the GABA (A) receptor.

  5. pH-dependent absorption spectra of rhodopsin mutant E113Q: On the role of counterions and protein

    Science.gov (United States)

    Xie, Peng; Zhou, Panwang; Alsaedi, Ahmed; Zhang, Yan

    2017-03-01

    The absorption spectra of bovine rhodopsin mutant E113Q in solutions were investigated at the molecular level by using a hybrid quantum mechanics/molecular mechanics (QM/MM) method. The calculations suggest the mechanism of the absorption variations of E113Q at different pH values. The results indicate that the polarizations of the counterions in the vicinity of Schiff base under protonation and unprotonation states of the mutant E113Q would be a crucial factor to change the energy gap of the retinal to tune the absorption spectra. Glu-181 residue, which is close to the chromophore, cannot serve as the counterion of the protonated Schiff base of E113Q in dark state. Moreover, the results of the absorption maximum in mutant E113Q with the various anions (Cl-, Br-, I- and NO3-) manifested that the mutant E113Q could have the potential for use as a template of anion biosensors at visible wavelength.

  6. Clinical and ERG data in a family with autosomal dominant RP and Pro-347-Arg mutation in the rhodopsin gene.

    Science.gov (United States)

    Niemeyer, G; Trüb, P; Schinzel, A; Gal, A

    1992-01-01

    In a family with autosomal dominant retinitis pigmentosa, documented over six generations, a previously undescribed point mutation in the rhodopsin gene could be identified. The mutation found in the six affected members examined but in none of the controls, including healthy members of the family, was a point mutation in codon 347 predicting a substitution of the amino acid arginine for proline, designated Pro-347-Arg. Six affected members from two generations were examined clinically and with ganzfeld rod and cone electroretinography. The cone and, more dramatically, the rod electroretinograms were reduced to residual b-wave amplitudes or were non-detectable as early as ages 18 to 22 years. The Pro-347-Arg mutation resulted in a subjectively and clinically homogeneous phenotype: early onset of night blindness before age 11, relatively preserved usable visual fields until about age 30, blindness at ages 40 to 60, and change from an initial apparently sine pigmento to a hyperpigmented and atrophic fundus picture between 30 and 50 years of age.

  7. An audit to assess the consequences of the use of a pluripotential risk syndrome: the case to move on from "psychosis risk syndrome (PRS) ".

    Science.gov (United States)

    Agius, Mark; Zaman, Rashid; Hanafy, Dean

    2013-09-01

    An audit has been carried out of the patients who have been assessed using the CAARMS tool in order to assess patients who have been judged to have a prodromal psychotic syndrome. Instead of advocating PRS, Johannessen & McGorry (Johannessen 2010), have offered an alternative: a 'Pluripotent risk syndrome'. This less specific prodrome reflects the unpredictable nature of "Ultra-High Risk" states which have been shown to be more likely to develop into a non-psychotic mood disorder than schizophrenia (Hoon 2012). The corollary this is thus; could patients who exhibit significant depressive features (regardless of diagnosis) be initially identified as having a 'Pluripotent risk syndrome'? Ten adult patients (6 males & 4 females, aged 19-26 years old) with four broad psychiatric diagnoses (Depression, Schizoaffective disorder, Borderline personality disorder and psychotic illness) were chosen from an anonimised database of the patients and their symptomatology as assessed by CAARMS was retrospectively assessed to see if the presence of depressive symptoms supported the case for a "Pluripotent risk syndrome". Though patients diagnosed with depression frequently exhibited depressive symptoms, psychotic symptoms were also apparent, albeit in comparatively decreased severity. Patients diagnosed with schizoaffective disorder had depressive symptoms more frequently than psychotic symptoms, but these were comparatively less severe. Borderline personality disorder patients exhibited depressive symptoms more frequently than psychotic symptoms. Psychotic illnesses frequently had depressive symptoms, but more typically (and unsurprisingly) had comparatively more severe psychotic than depressive symptoms. Hence we propose that the concept of a "Pluripotent risk syndrome" is in our view born out.

  8. Photo-induced bleaching of sensory rhodopsin II (phoborhodopsin) from Halobacterium salinarum by hydroxylamine: identification of the responsible intermediates.

    Science.gov (United States)

    Tamogami, Jun; Kikukawa, Takashi; Ikeda, Yoichi; Demura, Makoto; Nara, Toshifumi; Kamo, Naoki

    2012-01-05

    Sensory rhodopsin II from Halobacterium salinarum (HsSRII) is a retinal protein in which retinal binds to a specific lysine residue through a Schiff base. Here, we investigated the photobleaching of HsSRII in the presence of hydroxylamine. For identification of intermediate(s) attacked by hydroxylamine, we employed the flash-induced bleaching method. In order to change the concentration of intermediates, such as M- and O-intermediates, experiments were performed under varying flashlight intensities and concentrations of azide that accelerated only the M-decay. We found the proportional relationship between the bleaching rate and area under the concentration-time curve of M, indicating a preferential attack of hydroxylamine on M. Since hydroxylamine is a water-soluble reagent, we hypothesize that for M, hydrophilicity or water-accessibility increases specifically in the moiety of Schiff base. Thus, hydroxylamine bleaching rates may be an indication of conformational changes near the Schiff base. We also considered the possibility that azide may induce a small conformational change around the Schiff base. We compared the hydroxylamine susceptibility between HsSRII and NpSRII (SRII from Natronomonas pharaonis) and found that the M of HsSRII is about three times more susceptible than that of the stable NpSRII. In addition, long illumination to HsSRII easily produced M-like photoproduct, P370. We thus infer that the instability of HsSRII under illumination may be related to this increase of hydrophilicity at M and P370. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Eye Development in Sepia officinalis Embryo: What the Uncommon Gene Expression Profiles Tell Us about Eye Evolution.

    Science.gov (United States)

    Imarazene, Boudjema; Andouche, Aude; Bassaglia, Yann; Lopez, Pascal-Jean; Bonnaud-Ponticelli, Laure

    2017-01-01

    In metazoans, there is a remarkable diversity of photosensitive structures; their shapes, physiology, optical properties, and development are different. To approach the evolution of photosensitive structures and visual function, cephalopods are particularly interesting organisms due to their most highly centralized nervous system and their camerular eyes which constitute a convergence with those of vertebrates. The eye morphogenesis in numerous metazoans is controlled mainly by a conserved Retinal Determination Gene Network (RDGN) including pax, six, eya , and dac playing also key developmental roles in non-retinal structures and tissues of vertebrates and Drosophila . Here we have identified and explored the role of Sof-dac, Sof-six1/2, Sof-eya in eye morphogenesis, and nervous structures controlling the visual function in Sepia officinalis . We compare that with the already shown expressions in eye development of Sof-otx and Sof-pax genes. Rhodopsin is the pigment responsible for light sensitivity in metazoan, which correlate to correlate visual function and eye development. We studied Sof-rhodopsin expression during retina differentiation. By in situ hybridization, we show that (1) all of the RDGN genes, including Sof-pax6 , are expressed in the eye area during the early developmental stages but they are not expressed in the retina, unlike Sof-otx , which could have a role in retina differentiation; (2) Sof-rhodopsin is expressed in the retina just before vision gets functional, from stage 23 to hatching. Our results evidence a role of Sof-six1/2, Sof-eya , and Sof-dac in eye development. However, the gene network involved in the retinal photoreceptor differentiation remains to be determined. Moreover, for the first time, Sof-rhodopsin expression is shown in the embryonic retina of cuttlefish suggesting the evolutionary conservation of the role of rhodopsin in visual phototransduction within metazoans. These findings are correlated with the physiological and

  10. Eye Development in Sepia officinalis Embryo: What the Uncommon Gene Expression Profiles Tell Us about Eye Evolution

    Directory of Open Access Journals (Sweden)

    Boudjema Imarazene

    2017-08-01

    Full Text Available In metazoans, there is a remarkable diversity of photosensitive structures; their shapes, physiology, optical properties, and development are different. To approach the evolution of photosensitive structures and visual function, cephalopods are particularly interesting organisms due to their most highly centralized nervous system and their camerular eyes which constitute a convergence with those of vertebrates. The eye morphogenesis in numerous metazoans is controlled mainly by a conserved Retinal Determination Gene Network (RDGN including pax, six, eya, and dac playing also key developmental roles in non-retinal structures and tissues of vertebrates and Drosophila. Here we have identified and explored the role of Sof-dac, Sof-six1/2, Sof-eya in eye morphogenesis, and nervous structures controlling the visual function in Sepia officinalis. We compare that with the already shown expressions in eye development of Sof-otx and Sof-pax genes. Rhodopsin is the pigment responsible for light sensitivity in metazoan, which correlate to correlate visual function and eye development. We studied Sof-rhodopsin expression during retina differentiation. By in situ hybridization, we show that (1 all of the RDGN genes, including Sof-pax6, are expressed in the eye area during the early developmental stages but they are not expressed in the retina, unlike Sof-otx, which could have a role in retina differentiation; (2 Sof-rhodopsin is expressed in the retina just before vision gets functional, from stage 23 to hatching. Our results evidence a role of Sof-six1/2, Sof-eya, and Sof-dac in eye development. However, the gene network involved in the retinal photoreceptor differentiation remains to be determined. Moreover, for the first time, Sof-rhodopsin expression is shown in the embryonic retina of cuttlefish suggesting the evolutionary conservation of the role of rhodopsin in visual phototransduction within metazoans. These findings are correlated with the

  11. Functional genomics identifies regulators of the phototransduction machinery in the Drosophila larval eye and adult ocelli.

    Science.gov (United States)

    Mishra, Abhishek Kumar; Bargmann, Bastiaan O R; Tsachaki, Maria; Fritsch, Cornelia; Sprecher, Simon G

    2016-02-15

    Sensory perception of light is mediated by specialized Photoreceptor neurons (PRs) in the eye. During development all PRs are genetically determined to express a specific Rhodopsin (Rh) gene and genes mediating a functional phototransduction pathway. While the genetic and molecular mechanisms of PR development is well described in the adult compound eye, it remains unclear how the expression of Rhodopsins and the phototransduction cascade is regulated in other visual organs in Drosophila, such as the larval eye and adult ocelli. Using transcriptome analysis of larval PR-subtypes and ocellar PRs we identify and study new regulators required during PR differentiation or necessary for the expression of specific signaling molecules of the functional phototransduction pathway. We found that the transcription factor Krüppel (Kr) is enriched in the larval eye and controls PR differentiation by promoting Rh5 and Rh6 expression. We also identified Camta, Lola, Dve and Hazy as key genes acting during ocellar PR differentiation. Further we show that these transcriptional regulators control gene expression of the phototransduction cascade in both larval eye and adult ocelli. Our results show that PR cell type-specific transcriptome profiling is a powerful tool to identify key transcriptional regulators involved during several aspects of PR development and differentiation. Our findings greatly contribute to the understanding of how combinatorial action of key transcriptional regulators control PR development and the regulation of a functional phototransduction pathway in both larval eye and adult ocelli. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. PBN (Phenyl-N-Tert-Butylnitrone-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

    Directory of Open Access Journals (Sweden)

    Megan Stiles

    Full Text Available A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD, and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control. In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat

  13. PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

    Science.gov (United States)

    Stiles, Megan; Moiseyev, Gennadiy P; Budda, Madeline L; Linens, Annette; Brush, Richard S; Qi, Hui; White, Gary L; Wolf, Roman F; Ma, Jian-Xing; Floyd, Robert; Anderson, Robert E; Mandal, Nawajes A

    2015-01-01

    A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from

  14. Espécies do gênero Munida Leach (Crustacea, Decapoda, Galatheidae coletadas entre Torres (Rio Grande do Sul, Brasil e Maldonado (Uruguai pelo Programa Rio Grande do Sul (PRS I-II, GEDIP Species of the genus Munida Leach (Crustacea, Decapoda, Galatheidae collected between Torres (Rio Grande do Sul, Brazil and Maldonado (Uruguay, by the Project Rio Grande do Sul (PRS I-II, GEDIP

    Directory of Open Access Journals (Sweden)

    Gustavo A.S. de Melo-Filho

    2001-12-01

    Full Text Available The project PRS-GEDIP was carried out in the Rio Grande do Sul coast, with some few stations off Maldonado (Uruguay, by means of a convention between Instituto Oceanográfico USP (IOUSP and the Grupo Executivo do Desenvolvimento da Indústria da Pesca (GEDIP of Rio Grande do Sul. The purpose of this project was the acquisition of data in order to have a better biotic and abiotic characterization of the southern Brazilian coast. Among the Galatheidae, about 1200 specimens of the genus Munida Leach, 1820 were collected, including five species as follows: Munida flinti Benedict, 1902; M. forceps A. Milne Edwards, 1880; M. iris A. Milne Edwards, 1880; M. irrasa A. Milne Edwards. 1880 and M. longipes A. Milne Edwards, 1880. The description, material examined, remarks and maps of the stations where each species was collected are done.

  15. Age- and Wavelength-Dependency of Drosophila Larval Phototaxis and Behavioral Responses to Natural Lighting Conditions

    Directory of Open Access Journals (Sweden)

    Simon G. Sprecher

    2017-04-01

    Full Text Available Animals use various environmental cues as key determinant for their behavioral decisions. Visual systems are hereby responsible to translate light-dependent stimuli into neuronal encoded information. Even though the larval eyes of the fruit fly Drosophila melanogaster are comparably simple, they comprise two types of photoreceptor neurons (PRs, defined by different Rhodopsin genes expressed. Recent findings support that for light avoidance Rhodopsin5 (Rh5 expressing photoreceptors are crucial, while Rhodopsin6 (Rh6 expressing photoreceptors are dispensable under laboratory conditions. However, it remains debated how animals change light preference during larval live. We show that larval negative phototaxis is age-independent as it persists in larvae from foraging to wandering developmental stages. Moreover, if spectrally different Rhodopsins are employed for the detection of different wavelength of light remains unexplored. We found that negative phototaxis can be elicit by light with wavelengths ranging from ultraviolet (UV to green. This behavior is uniquely mediated by Rh5 expressing photoreceptors, and therefore suggest that this photoreceptor-type is able to perceive UV up to green light. In contrast to laboratory our field experiments revealed that Drosophila larvae uses both types of photoreceptors under natural lighting conditions. All our results, demonstrate that Drosophila larval eyes mediate avoidance of light stimuli with a wide, ecological relevant range of quantity (intensities and quality (wavelengths. Thus, the two photoreceptor-types appear more likely to play a role in different aspects of phototaxis under natural lighting conditions, rather than color discrimination.

  16. Homology-based Modeling of Rhodopsin-like Family Members in the Inactive State: Structural Analysis and Deduction of Tips for Modeling and Optimization.

    Science.gov (United States)

    Pappalardo, Matteo; Rayan, Mahmoud; Abu-Lafi, Saleh; Leonardi, Martha E; Milardi, Danilo; Guccione, Salvatore; Rayan, Anwar

    2017-08-01

    Modeling G-Protein Coupled Receptors (GPCRs) is an emergent field of research, since utility of high-quality models in receptor structure-based strategies might facilitate the discovery of interesting drug candidates. The findings from a quantitative analysis of eighteen resolved structures of rhodopsin family "A" receptors crystallized with antagonists and 153 pairs of structures are described. A strategy termed endeca-amino acids fragmentation was used to analyze the structures models aiming to detect the relationship between sequence identity and Root Mean Square Deviation (RMSD) at each trans-membrane-domain. Moreover, we have applied the leave-one-out strategy to study the shiftiness likelihood of the helices. The type of correlation between sequence identity and RMSD was studied using the aforementioned set receptors as representatives of membrane proteins and 98 serine proteases with 4753 pairs of structures as representatives of globular proteins. Data analysis using fragmentation strategy revealed that there is some extent of correlation between sequence identity and global RMSD of 11AA width windows. However, spatial conservation is not always close to the endoplasmic side as was reported before. A comparative study with globular proteins shows that GPCRs have higher standard deviation and higher slope in the graph with correlation between sequence identity and RMSD. The extracted information disclosed in this paper could be incorporated in the modeling protocols while using technique for model optimization and refinement. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster

    Science.gov (United States)

    Rosenbaum, Erica E.; Vasiljevic, Eva; Brehm, Kimberley S.; Colley, Nansi Jo

    2014-01-01

    As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan) undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II), α-mannosidase-IIb (α-Man-IIb), a β-N-acetylglucosaminidase called fused lobes (Fdl), and hexosaminidase 1 (Hexo1). We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights into the

  18. Cas9/sgRNA selective targeting of the P23H Rhodopsin mutant allele for treating retinitis pigmentosa by intravitreal AAV9.PHP.B-based delivery.

    Science.gov (United States)

    Giannelli, Serena G; Luoni, Mirko; Castoldi, Valerio; Massimino, Luca; Cabassi, Tommaso; Angeloni, Debora; Demontis, Gian Carlo; Leocani, Letizia; Andreazzoli, Massimiliano; Broccoli, Vania

    2018-03-01

    P23H is the most common mutation in the RHODOPSIN (RHO) gene leading to a dominant form of retinitis pigmentosa (RP), a rod photoreceptor degeneration that invariably causes vision loss. Specific disruption of the disease P23H RHO mutant while preserving the wild-type (WT) functional allele would be an invaluable therapy for this disease. However, various technologies tested in the past failed to achieve effective changes and consequently therapeutic benefits. We validated a CRISPR/Cas9 strategy to specifically inactivate the P23H RHO mutant, while preserving the WT allele in vitro. We, then, translated this approach in vivo by delivering the CRISPR/Cas9 components in murine Rho+/P23H mutant retinae. Targeted retinae presented a high rate of cleavage in the P23H but not WT Rho allele. This gene manipulation was sufficient to slow photoreceptor degeneration and improve retinal functions. To improve the translational potential of our approach, we tested intravitreal delivery of this system by means of adeno-associated viruses (AAVs). To this purpose, the employment of the AAV9-PHP.B resulted the most effective in disrupting the P23H Rho mutant. Finally, this approach was translated successfully in human cells engineered with the homozygous P23H RHO gene mutation. Overall, this is a significant proof-of-concept that gene allele specific targeting by CRISPR/Cas9 technology is specific and efficient and represents an unprecedented tool for treating RP and more broadly dominant genetic human disorders affecting the eye, as well as other tissues.

  19. Mutations in four glycosyl hydrolases reveal a highly coordinated pathway for rhodopsin biosynthesis and N-glycan trimming in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Erica E Rosenbaum

    2014-05-01

    Full Text Available As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II, α-mannosidase-IIb (α-Man-IIb, a β-N-acetylglucosaminidase called fused lobes (Fdl, and hexosaminidase 1 (Hexo1. We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights

  20. Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis

    Science.gov (United States)

    Song, Hongman; Bush, Ronald A.; Vijayasarathy, Camasamudram; Fariss, Robert N.; Kjellstrom, Sten; Sieving, Paul A.

    2014-01-01

    Purpose. Dominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsin-null mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1. Methods. Transgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts. Results. Constitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day (P)6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors. Conclusions. Constitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis. PMID:24651551

  1. An atlas of Caenorhabditis elegans chemoreceptor expression.

    Directory of Open Access Journals (Sweden)

    Berta Vidal

    2018-01-01

    Full Text Available One goal of modern day neuroscience is the establishment of molecular maps that assign unique features to individual neuron types. Such maps provide important starting points for neuron classification, for functional analysis, and for developmental studies aimed at defining the molecular mechanisms of neuron identity acquisition and neuron identity diversification. In this resource paper, we describe a nervous system-wide map of the potential expression sites of 244 members of the largest gene family in the C. elegans genome, rhodopsin-like (class A G-protein-coupled receptor (GPCR chemoreceptors, using classic gfp reporter gene technology. We cover representatives of all sequence families of chemoreceptor GPCRs, some of which were previously entirely uncharacterized. Most reporters are expressed in a very restricted number of cells, often just in single cells. We assign GPCR reporter expression to all but two of the 37 sensory neuron classes of the sex-shared, core nervous system. Some sensory neurons express a very small number of receptors, while others, particularly nociceptive neurons, coexpress several dozen GPCR reporter genes. GPCR reporters are also expressed in a wide range of inter- and motorneurons, as well as non-neuronal cells, suggesting that GPCRs may constitute receptors not just for environmental signals, but also for internal cues. We observe only one notable, frequent association of coexpression patterns, namely in one nociceptive amphid (ASH and two nociceptive phasmid sensory neurons (PHA, PHB. We identified GPCRs with sexually dimorphic expression and several GPCR reporters that are expressed in a left/right asymmetric manner. We identified a substantial degree of GPCR expression plasticity; particularly in the context of the environmentally-induced dauer diapause stage when one third of all tested GPCRs alter the cellular specificity of their expression within and outside the nervous system. Intriguingly, in a number of

  2. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas.

    Science.gov (United States)

    Felsberg, Jörg; Thon, Niklas; Eigenbrod, Sabina; Hentschel, Bettina; Sabel, Michael C; Westphal, Manfred; Schackert, Gabriele; Kreth, Friedrich Wilhelm; Pietsch, Torsten; Löffler, Markus; Weller, Michael; Reifenberger, Guido; Tonn, Jörg C

    2011-08-01

    Epigenetic silencing of the O(6) -methylguanine-DNA methyltransferase (MGMT) gene promoter is associated with prolonged survival in glioblastoma patients treated with temozolomide (TMZ). We investigated whether glioblastoma recurrence is associated with changes in the promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated with radiotherapy and TMZ after the first operation. Among the primary tumors, the MGMT promoter was methylated in 31 patients and unmethylated in 49 patients. In 71 patients (89%), the MGMT promoter methylation status of the primary tumor was retained at recurrence. MGMT promoter methylation, but not MGMT protein expression, was associated with longer progression-free survival, overall survival and postrecurrence survival (PRS). Moreover, PRS was increased under salvage chemotherapy. Investigation of primary and recurrent glioblastomas of 43 patients did not identify promoter methylation in any of the four MMR genes. However, recurrent glioblastomas demonstrated significantly lower MSH2, MSH6 and PMS2 protein expression as detected by immunohistochemistry. In conclusion, reduced expression of MMR proteins, but not changes in MGMT promoter methylation, is characteristic of glioblastomas recurring after the current standards of care. Copyright © 2011 UICC.

  3. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    Science.gov (United States)

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice.

  4. Path Expressions

    Science.gov (United States)

    1975-06-01

    Traditionally, synchronization of concurrent processes is coded in line by operations on semaphores or similar objects. Path expressions move the...discussion about a variety of synchronization primitives . An analysis of their relative power is found in [3]. Path expressions do not introduce yet...another synchronization primitive . A path expression relates to such primitives as a for- or while-statement of an ALGOL-like language relates to a JUMP

  5. Two types of Tet-On transgenic lines for doxycycline-inducible gene expression in zebrafish rod photoreceptors and a gateway-based tet-on toolkit.

    Directory of Open Access Journals (Sweden)

    Leah J Campbell

    Full Text Available The ability to control transgene expression within specific tissues is an important tool for studying the molecular and cellular mechanisms of development, physiology, and disease. We developed a Tet-On system for spatial and temporal control of transgene expression in zebrafish rod photoreceptors. We generated two transgenic lines using the Xenopus rhodopsin promoter to drive the reverse tetracycline-controlled transcriptional transactivator (rtTA, one with self-reporting GFP activity and one with an epitope tagged rtTA. The self-reporting line includes a tetracycline response element (TRE-driven GFP and, in the presence of doxycycline, expresses GFP in larval and adult rods. A time-course of doxycycline treatment demonstrates that maximal induction of GFP expression, as determined by the number of GFP-positive rods, is reached within approximately 24 hours of drug treatment. The epitope-tagged transgenic line eliminates the need for the self-reporting GFP activity by expressing a FLAG-tagged rtTA protein. Both lines demonstrate strong induction of TRE-driven transgenes from plasmids microinjected into one-cell embryos. These results show that spatial and temporal control of transgene expression can be achieved in rod photoreceptors. Additionally, system components are constructed in Gateway compatible vectors for the rapid cloning of doxycycline-inducible transgenes and use in other areas of zebrafish research.

  6. The Latin American experience with the PRS approach

    NARCIS (Netherlands)

    K. Komives (Kristin); A.G. Dijkstra (Geske)

    2009-01-01

    textabstractIntroduction In 1999, countries that wished to qualify for the Enhanced Initiative for the Heavily Indebted Poor Countries (HIPC initiative) had to elaborate Poverty Reduction Strategy Papers (PRSP) and had to do so with participation of civil society. Since then, the elaboration and

  7. Rhodopsin mutations are scarcely implicated in autosomal ...

    African Journals Online (AJOL)

    Reem Mebed

    2015-04-23

    Apr 23, 2015 ... of the disorder in the male and female progeny of unaffected persons [29]. ... a light stimulus and is used for the diagnosis of various retinal diseases. Dim flash ERG is performed on a dark-adapted eye, so the response is ...

  8. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  9. Melanopsin-expressing amphioxus photoreceptors transduce light via a phospholipase C signaling cascade.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Angueyra

    Full Text Available Melanopsin, the receptor molecule that underlies light sensitivity in mammalian 'circadian' receptors, is homologous to invertebrate rhodopsins and has been proposed to operate via a similar signaling pathway. Its downstream effectors, however, remain elusive. Melanopsin also expresses in two distinct light-sensitive cell types in the neural tube of amphioxus. This organism is the most basal extant chordate and can help outline the evolutionary history of different photoreceptor lineages and their transduction mechanisms; moreover, isolated amphioxus photoreceptors offer unique advantages, because they are unambiguously identifiable and amenable to single-cell physiological assays. In the present study whole-cell patch clamp recording, pharmacological manipulations, and immunodetection were utilized to investigate light transduction in amphioxus photoreceptors. A G(q was identified and selectively localized to the photosensitive microvillar membrane, while the pivotal role of phospholipase C was established pharmacologically. The photocurrent was profoundly depressed by IP₃ receptor antagonists, highlighting the importance of IP₃ receptors in light signaling. By contrast, surrogates of diacylglycerol (DAG, as well as poly-unsaturated fatty acids failed to activate a membrane conductance or to alter the light response. The results strengthen the notion that calcium released from the ER via IP₃-sensitive channels may fulfill a key role in conveying--directly or indirectly--the melanopsin-initiated light signal to the photoconductance; moreover, they challenge the dogma that microvillar photoreceptors and phoshoinositide-based light transduction are a prerogative of invertebrate eyes.

  10. High-level expression, purification and characterization of a constitutively active thromboxane A2 receptor polymorphic variant.

    Directory of Open Access Journals (Sweden)

    Bing Xu

    Full Text Available G protein-coupled receptors (GPCRs exhibit some level of basal signaling even in the absence of a bound agonist. This basal or constitutive signaling can have important pathophysiological roles. In the past few years, a number of high resolution crystal structures of GPCRs have been reported, including two crystal structures of constitutively active mutants (CAM of the dim-light receptor, rhodopsin. The structural characterizations of CAMs are impeded by the lack of proper expression systems. The thromboxane A2 receptor (TP is a GPCR that mediates vasoconstriction and promotes thrombosis in response to the binding of thromboxane. Here, we report on the expression and purification of a genetic variant and CAM in TP, namely A160T, using tetracycline-inducible HEK293S-TetR and HEK293S (GnTI¯-TetR cell lines. Expression of the TP and the A160T genes in these mammalian cell lines resulted in a 4-fold increase in expression to a level of 15.8 ±0.3 pmol of receptor/mg of membrane protein. The receptors expressed in the HEK293S (GnTI(--TetR cell line showed homogeneous glycosylation. The functional yield of the receptors using a single step affinity purification was 45 µg/10⁶ cells. Temperature- dependent secondary structure changes of the purified TP and A160T receptors were characterized using circular dichroism (CD spectropolarimetry. The CD spectra shows that the loss of activity or thermal sensitivity that was previously observed for the A160T mutant, is not owing to large unfolding of the protein but rather to a more subtle effect. This is the first study to report on the successful high-level expression, purification, and biophysical characterization of a naturally occurring, diffusible ligand activated GPCR CAM.

  11. [Differential gene expression in incompatible interaction between Lilium regale Wilson and Fusarium oxysporum f. sp. lilii revealed by combined SSH and microarray analysis].

    Science.gov (United States)

    Rao, J; Liu, D; Zhang, N; He, H; Ge, F; Chen, C

    2014-01-01

    Fusarium wilt, caused by a soilborne pathogen Fusarium oxysporum f. sp. lilii, is the major disease of lily (Lilium L.). In order to isolate the genes differentially expressed in a resistant reaction to F. oxysporum in L. regale Wilson, a cDNA library was constructed with L. regale root during F. oxysporum infection using the suppression subtractive hybridization (SSH), and a total of 585 unique expressed sequence tags (ESTs) were obtained. Furthermore, the gene expression profiles in the incompatible interaction between L. regale and F. oxysporum were revealed by oligonucleotide microarray analysis of 585 unique ESTs comparison to the compatible interaction between a susceptible Lilium Oriental Hybrid 'Siberia' and F. oxysporum. The result of expression profile analysis indicated that the genes encoding pathogenesis-related proteins (PRs), antioxidative stress enzymes, secondary metabolism enzymes, transcription factors, signal transduction proteins as well as a large number of unknown genes were involved in early defense response of L. regale to F. oxysporum infection. Moreover, the following quantitative reverse transcription PCR (QRT-PCR) analysis confirmed reliability of the oligonucleotide microarray data. In the present study, isolation of differentially expressed genes in L. regale during response to F. oxysporum helped to uncover the molecular mechanism associated with the resistance of L. regale against F. oxysporum.

  12. Heterooligomeric phosphoribosyl diphosphate synthase of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne

    2004-01-01

    The yeast Saccharomyces cerevisiae contains five phosphoribosyl diphosphate (PRPP) synthase-homologous genes (PRS1-5), which specify PRPP synthase subunits 1-5. Expression of the five S. cerevisiae PRS genes individually in an Escherichia coli PRPP-less strain (Deltaprs) showed that a single PRS...

  13. S187. SEARCHING FOR BRAIN CO-EXPRESSION MODULES THAT CONTRIBUTE DISPROPORTIONATELY TO THE COMMON POLYGENIC RISK FOR SCHIZOPHRENIA

    Science.gov (United States)

    Costas, Javier; Paramo, Mario; Arrojo, Manuel

    2018-01-01

    Abstract Background Genomic research has revealed that schizophrenia is a highly polygenic disease. Recent estimates indicate that at least 71% of genomic segments of 1 Mb include one or more risk loci for schizophrenia (Loh et al., Nature Genet 2015). This extremely high polygenicity represents a challenge to decipher the biological basis of schizophrenia, as it is expected that any set of SNPs with enough size will be associated with the disorder. Among the different gene sets available for study (such as those from Gene Ontology, KEGG pathway, Reactome pathways or protein protein interaction datasets), those based on brain co-expression networks represent putative functional relationships in the relevant tissue. The aim of this work was to identify brain co-expression networks that contribute disproportionately to the common polygenic risk for schizophrenia to get more insight on schizophrenia etiopathology. Methods We analyzed a case -control dataset consisting of 582 schizophrenia patients from Galicia, NW Spain, and 591 ancestrally matched controls, genotyped with the Illumina PsychArray. Using as discovery sample the summary results from the largest GWAS of schizophrenia to date (Psychiatric Genomics Consortium, SCZ2), we generated polygenic risk scores (PRS) in our sample based on SNPs located at genes belonging to brain co-expression modules determined by the CommonMind Consortium (Fromer et al., Nature Neurosci 2016). PRS were generated using the clumping procedure of PLINK, considering several different thresholds to select SNPs from the discovery sample. In order to test if any specific module increased risk to schizophrenia more than expected by their size, we generated up to 10,000 random permutations of the same number of SNPs, matched by frequency, distance to nearest gene, number of SNPs in LD and gene density, using SNPsnap. Results As expected, most modules with enough number of independent SNPs belonging to them showed a significant increase in

  14. Enhanced expression of membrane proteins in E. coli with a PBAD promoter mutant: synergies with chaperone pathway engineering strategies

    Directory of Open Access Journals (Sweden)

    Nannenga Brent L

    2011-12-01

    Full Text Available Abstract Background Membrane proteins (MPs populate 20-30% of genomes sequenced to date and hold potential as therapeutic targets as well as for practical applications in bionanotechnology. However, MP toxicity and low yields in normally robust expression hosts such as E. coli has curtailed progress in our understanding of their structure and function. Results Using the seven transmembrane segments H. turkmenica deltarhodopsin (HtdR as a reporter, we isolated a spontaneous mutant in the arabinose-inducible PBAD promoter leading to improved cell growth and a twofold increase in the recovery of active HtdR at 37°C. A single transversion in a conserved region of the cyclic AMP receptor protein binding site caused the phenotype by reducing htdR transcript levels by 65%. When the mutant promoter was used in conjunction with a host lacking the molecular chaperone Trigger Factor (Δtig cells, toxicity was further suppressed and the amount of correctly folded HtdR was 4-fold that present in the membranes of control cells. More importantly, while improved growth barely compensated for the reduction in transcription rates when another polytopic membrane protein (N. pharonis sensory rhodopsin II was expressed under control of the mutant promoter in wild type cells, a 4-fold increase in productivity could be achieved in a Δtig host. Conclusions Our system, which combines a downregulated version of the tightly repressed PBAD promoter with a TF-deficient host may prove a valuable alternative to T7-based expression for the production of membrane proteins that have so far remained elusive targets.

  15. Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity

    Directory of Open Access Journals (Sweden)

    Anna M. Klawonn

    2018-04-01

    Full Text Available The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs in dopamine D1 receptor (D1R expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT, during various reward-enforced behaviors and in a “waiting”-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs in the 5-choice-serial-reaction-time-task (5CSRTT than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG expression (cFos and FosB induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

  16. Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.

    Science.gov (United States)

    Klawonn, Anna M; Wilhelms, Daniel B; Lindström, Sarah H; Singh, Anand Kumar; Jaarola, Maarit; Wess, Jürgen; Fritz, Michael; Engblom, David

    2018-01-01

    The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression ( cFos and FosB ) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

  17. Express web application development

    CERN Document Server

    Yaapa, Hage

    2013-01-01

    Express Web Application Development is a practical introduction to learning about Express. Each chapter introduces you to a different area of Express, using screenshots and examples to get you up and running as quickly as possible.If you are looking to use Express to build your next web application, ""Express Web Application Development"" will help you get started and take you right through to Express' advanced features. You will need to have an intermediate knowledge of JavaScript to get the most out of this book.

  18. Effect of hyperthyroidism on circulating prolactin and hypothalamic expression of tyrosine hydroxylase, prolactin signaling cascade members and estrogen and progesterone receptors during late pregnancy and lactation in the rat.

    Science.gov (United States)

    Pennacchio, Gisela E; Neira, Flavia J; Soaje, Marta; Jahn, Graciela A; Valdez, Susana R

    2017-02-15

    Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-induced PRL release and litter growth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. After Effects expressions

    CERN Document Server

    Geduld, Marcus

    2013-01-01

    Put the power of Expressions to work in your animations with controls and efficiencies impossible to achieve with traditional keyframing techniques. No programming skills are required. Foundation concepts and skills orient the new designer and serve as a handy reference to the experienced one. Basics of creating expressions, variables, commands, and expression helpers precede the leap into javascript and math essentials for more advanced expressions that include randomness, physical simularions and 3D. Full color illustrations display the scripts and the resulti

  20. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction...... previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely...

  1. Regular Expression Pocket Reference

    CERN Document Server

    Stubblebine, Tony

    2007-01-01

    This handy little book offers programmers a complete overview of the syntax and semantics of regular expressions that are at the heart of every text-processing application. Ideal as a quick reference, Regular Expression Pocket Reference covers the regular expression APIs for Perl 5.8, Ruby (including some upcoming 1.9 features), Java, PHP, .NET and C#, Python, vi, JavaScript, and the PCRE regular expression libraries. This concise and easy-to-use reference puts a very powerful tool for manipulating text and data right at your fingertips. Composed of a mixture of symbols and text, regular exp

  2. Regular expressions cookbook

    CERN Document Server

    Goyvaerts, Jan

    2009-01-01

    This cookbook provides more than 100 recipes to help you crunch data and manipulate text with regular expressions. Every programmer can find uses for regular expressions, but their power doesn't come worry-free. Even seasoned users often suffer from poor performance, false positives, false negatives, or perplexing bugs. Regular Expressions Cookbook offers step-by-step instructions for some of the most common tasks involving this tool, with recipes for C#, Java, JavaScript, Perl, PHP, Python, Ruby, and VB.NET. With this book, you will: Understand the basics of regular expressions through a

  3. Noninvasive optical inhibition with a red-shifted microbial rhodopsin

    DEFF Research Database (Denmark)

    Chuong, Amy S; Miri, Mitra L; Busskamp, Volker

    2014-01-01

    Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium......) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also...... demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied...

  4. Biochemistry and pharmacology of rhodopsin regeneration in the vertebrate eye

    International Nuclear Information System (INIS)

    Bernstein, P.S.

    1988-01-01

    In this thesis, the missing reaction of the vertebrate visual cycle, the energy-dependent isomerization of all-trans-retinoids to 11-cis-retinoids, is investigated through biochemical and pharmacological means. The biochemical processes of vision are first probed through the use of 1,5-di-(p-aminophenoxy) pentane (DAPP), the most powerful and selective pharmacological inhibitor of dark adaptation known. Next, the biochemical pathway of isomerization of retinoids in living animals is examined through double-label radioisotope studies in normal animals and in animals treated with DAPP or other inhibitors of dark adaptation. Finally, a novel retinoid isomerase activity was discovered in homogenates of frog retina/pigment epithelium that catalyzes the endergonic isomerization of all-trans-retinoids to 11-cis-retinoids in darkness. In partially purified preparations, added [11,12- 3 H]-all-trans-retinol is converted to 11-cis-retinol and other 11-cis-retinoids, while added labeled all-trans-retinal and all-trans-retinyl palmitate are not isomerized to a significant extent

  5. Darwin and Emotion Expression

    Science.gov (United States)

    Hess, Ursula; Thibault, Pascal

    2009-01-01

    In his book "The Expression of the Emotions in Man and Animals," Charles Darwin (1872/1965) defended the argument that emotion expressions are evolved and adaptive (at least at some point in the past) and serve an important communicative function. The ideas he developed in his book had an important impact on the field and spawned rich domains of…

  6. Freedom of Expression.

    Science.gov (United States)

    Update on Law-Related Education, 1988

    1988-01-01

    Presents an activity which uses hypothetical situations to explore the proper boundaries of freedom of expression and the role of the U.S. Supreme Court in interpreting its limits. Appropriate for grades 4-12, the lesson includes such topics as the "clear and present danger" clause, student expression, obscenity, and defamation. (GEA)

  7. Caricaturing facial expressions.

    Science.gov (United States)

    Calder, A J; Rowland, D; Young, A W; Nimmo-Smith, I; Keane, J; Perrett, D I

    2000-08-14

    The physical differences between facial expressions (e.g. fear) and a reference norm (e.g. a neutral expression) were altered to produce photographic-quality caricatures. In Experiment 1, participants rated caricatures of fear, happiness and sadness for their intensity of these three emotions; a second group of participants rated how 'face-like' the caricatures appeared. With increasing levels of exaggeration the caricatures were rated as more emotionally intense, but less 'face-like'. Experiment 2 demonstrated a similar relationship between emotional intensity and level of caricature for six different facial expressions. Experiments 3 and 4 compared intensity ratings of facial expression caricatures prepared relative to a selection of reference norms - a neutral expression, an average expression, or a different facial expression (e.g. anger caricatured relative to fear). Each norm produced a linear relationship between caricature and rated intensity of emotion; this finding is inconsistent with two-dimensional models of the perceptual representation of facial expression. An exemplar-based multidimensional model is proposed as an alternative account.

  8. Materiality for Musical Expressions

    DEFF Research Database (Denmark)

    Lindell, Rikard; Tahiroğlu, Koray; Riis, Morten S.

    2016-01-01

    Nordic universities. Electronic music instrument makers participated in providing the course. In eleven days the students designed and built interfaces for musical expressions , composed a piece, and performed at the Norberg electronic music festival. The students explored the relationship between......We organised an elven day intense course in materiality for musical expressions to explore underlying principles of New Interfaces for Musical Expression (NIME) in higher education. We grounded the course in different aspects of ma-teriality and gathered interdisciplinary student teams from three...... technology and possible musical expression with a strong connection to culture and place. The emphasis on performance provided closure and motivated teams to move forward in their design and artistic processes. On the basis of the course we discuss an interdisciplinary NIME course syllabus, and we infer...

  9. Localizing Expression of Ambiguity

    National Research Council Canada - National Science Library

    Bear, John; Hobbs, Sr, Jerry R

    1987-01-01

    In this paper we describe an implemented program for localizing the expression of many types of syntactic ambiguity, in the logical forms of sentences, in a manner convenient for subsequent inferential processing...

  10. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  11. Express.js blueprints

    CERN Document Server

    Augarten, Ben; Lin, Eric; Shaikh, Aidha; Soriani, Fabiano Pereira; Tisserand, Geoffrey; Zhang, Chiqing; Zhang, Kan

    2015-01-01

    This book is for beginners to Node.js and also for those who are technically advanced. By the end of this book, every competent developer will have achieved expertise in building web applications with Express.js.

  12. The expressions of emotions

    DEFF Research Database (Denmark)

    Vishnivetz, Berta

    Abstract On the broadness of the vast field called “Expressions of Emotions” this study focuses on the whole bodily emotional expression. The main question posed is: Whether there are movement patterns specific to each emotion?. I carried out a thorough review of the theories of emotion...... and of expressions of emotions and movement notation that provided the sources for a careful research plan for the empirical process of this study. On this basis I chose to record onto video the four previously choreographed movements that I considered to correspond each of the following emotions: joy, fear, sadness......, anger. The selection of these four emotions demanded previously to clear up the problems the above named survey ensued. When researchers want to describe a certain movement in the field of psychology and non-verbal communication, it may result in disagreements and misunderstandings which sometimes lead...

  13. Freedom of Expression

    Directory of Open Access Journals (Sweden)

    Guilherme Canela

    2007-06-01

    Full Text Available The freedoms of expression and of the press are basic pillars of the western democracies. The contemporary theoretical framework which gives support to these rights was generated in the wake of the liberal revolutions which took place in Western Europe and in North America starting from the second half of the 1600s. Our purpose in this text is to present the current scene regarding this topic, focusing whenever pertinent on the Brazilian case, and seeking to question the unconditional defense of the freedoms of expression and of the press made by the thinkers who founded these principles vis-á-vis contemporary issues of the communicational universe. Going beyond theoretical-conceptual refl ections, we present and analyze the results of a content analysis showing how 53 Brazilian newspapers and 4 magazines with nationwide circulation report (or not topics relating to freedom of expression and of the press.

  14. Regular expression containment

    DEFF Research Database (Denmark)

    Henglein, Fritz; Nielsen, Lasse

    2011-01-01

    We present a new sound and complete axiomatization of regular expression containment. It consists of the conventional axiomatiza- tion of concatenation, alternation, empty set and (the singleton set containing) the empty string as an idempotent semiring, the fixed- point rule E* = 1 + E × E......* for Kleene-star, and a general coin- duction rule as the only additional rule. Our axiomatization gives rise to a natural computational inter- pretation of regular expressions as simple types that represent parse trees, and of containment proofs as coercions. This gives the axiom- atization a Curry......-Howard-style constructive interpretation: Con- tainment proofs do not only certify a language-theoretic contain- ment, but, under our computational interpretation, constructively transform a membership proof of a string in one regular expres- sion into a membership proof of the same string in another regular expression. We...

  15. In Silico Expression Analysis.

    Science.gov (United States)

    Bolívar, Julio; Hehl, Reinhard; Bülow, Lorenz

    2016-01-01

    Information on the specificity of cis-sequences enables the design of functional synthetic plant promoters that are responsive to specific stresses. Potential cis-sequences may be experimentally tested, however, correlation of genomic sequence with gene expression data enables an in silico expression analysis approach to bioinformatically assess the stress specificity of candidate cis-sequences prior to experimental verification. The present chapter demonstrates an example for the in silico validation of a potential cis-regulatory sequence responsive to cold stress. The described online tool can be applied for the bioinformatic assessment of cis-sequences responsive to most abiotic and biotic stresses of plants. Furthermore, a method is presented based on a reverted in silico expression analysis approach that predicts highly specific potentially functional cis-regulatory elements for a given stress.

  16. PRS: PERSONNEL RECOMMENDATION SYSTEM FOR HUGE DATA ANALYSIS USING PORTER STEMMER

    OpenAIRE

    T N Chiranjeevi; R H Vishwanath

    2016-01-01

    Personal recommendation system is one which gives better and preferential recommendation to the users to satisfy their personalized requirements such as practical applications like Webpage Preferences, Sport Videos preferences, Stock selection based on price, TV preferences, Hotel preferences, books, Mobile phones, CDs and various other products now use recommender systems. The existing Pearson Correlation Coefficient (PCC) and item-based algorithm using PCC, are called as UPCC and IPCC respe...

  17. Gender Equity and Public Policies in Latin America: Opportunities and Risks in the PRS Approach

    OpenAIRE

    Geske Dijkstra

    2011-01-01

    Cet article cherche à déterminer dans quelle mesure les programmes de l’initiative de la Stratégie de Réduction de la Pauvreté ont contribué à promouvoir l’égalité des sexes dans les politiques publiques en Bolivie, au Honduras et au Nicaragua. Les processus de SRP présentent, en théorie, des opportunités pour promouvoir l’égalité entre les sexes à travers la participation de la société civile dans l’élaboration des stratégies ainsi que leur gestion et suivi, et aussi par l’intermédiaire des ...

  18. Designing Emotionally Expressive Robots

    DEFF Research Database (Denmark)

    Tsiourti, Christiana; Weiss, Astrid; Wac, Katarzyna

    2017-01-01

    Socially assistive agents, be it virtual avatars or robots, need to engage in social interactions with humans and express their internal emotional states, goals, and desires. In this work, we conducted a comparative study to investigate how humans perceive emotional cues expressed by humanoid...... robots through five communication modalities (face, head, body, voice, locomotion) and examined whether the degree of a robot's human-like embodiment affects this perception. In an online survey, we asked people to identify emotions communicated by Pepper -a highly human-like robot and Hobbit – a robot...... for robots....

  19. Mining frequent binary expressions

    NARCIS (Netherlands)

    Calders, T.; Paredaens, J.; Kambayashi, Y.; Mohania, M.K.; Tjoa, A.M.

    2000-01-01

    In data mining, searching for frequent patterns is a common basic operation. It forms the basis of many interesting decision support processes. In this paper we present a new type of patterns, binary expressions. Based on the properties of a specified binary test, such as reflexivity, transitivity

  20. Facial Expression Recognition

    NARCIS (Netherlands)

    Pantic, Maja; Li, S.; Jain, A.

    2009-01-01

    Facial expression recognition is a process performed by humans or computers, which consists of: 1. Locating faces in the scene (e.g., in an image; this step is also referred to as face detection), 2. Extracting facial features from the detected face region (e.g., detecting the shape of facial

  1. Sensual expressions on faces

    NARCIS (Netherlands)

    Hendriks, A.W.C.J.; Engels, R.C.M.E.; Roek, M.A.E.

    2009-01-01

    We explored the possibility that an emotional facial expression exists specifically for signalling sexual interest. We selected photographs of twenty-eight fashion models (male and female) with large portfolios (range 81 - 1593), choosing only face photographs in which the model was looking into the

  2. Experience and Expression

    Science.gov (United States)

    Hanes, Jay Michael; Weisman, Eleanor

    2016-01-01

    Two artist-educators analyzed their creative process informed by John Dewey's concepts regarding the act of expression. The essay interweaves a description of their performance piece with a discussion of conceptual processes, including intermediality and collaboration as crucial in art making, learning, and pedagogical efficacy. Both the creation…

  3. Facial expressions recognition with an emotion expressive robotic head

    Science.gov (United States)

    Doroftei, I.; Adascalitei, F.; Lefeber, D.; Vanderborght, B.; Doroftei, I. A.

    2016-08-01

    The purpose of this study is to present the preliminary steps in facial expressions recognition with a new version of an expressive social robotic head. So, in a first phase, our main goal was to reach a minimum level of emotional expressiveness in order to obtain nonverbal communication between the robot and human by building six basic facial expressions. To evaluate the facial expressions, the robot was used in some preliminary user studies, among children and adults.

  4. Changes in the Expression of Biofilm-Associated Surface Proteins in Staphylococcus aureus Food-Environmental Isolates Subjected to Sublethal Concentrations of Disinfectants

    Directory of Open Access Journals (Sweden)

    Lenka Cincarova

    2016-01-01

    Full Text Available Sublethal concentrations (sub-MICs of certain disinfectants are no longer effective in removing biofilms from abiotic surfaces and can even promote the formation of biofilms. Bacterial cells can probably adapt to these low concentrations of disinfectants and defend themselves by way of biofilm formation. In this paper, we report on three Staphylococcus aureus biofilm formers (strong B+++, moderate B++, and weak B+ that were cultivated with sub-MICs of commonly used disinfectants, ethanol or chloramine T, and quantified using Syto9 green fluorogenic nucleic acid stain. We demonstrate that 1.25–2.5% ethanol and 2500 μg/mL chloramine T significantly enhanced S. aureus biofilm formation. To visualize differences in biofilm compactness between S. aureus biofilms in control medium, 1.25% ethanol, or 2500 μg/mL chloramine T, scanning electron microscopy was used. To describe changes in abundance of surface-exposed proteins in ethanol- or chloramine T-treated biofilms, surface proteins were prepared using a novel trypsin shaving approach and quantified after dimethyl labeling by LC-LTQ/Orbitrap MS. Our data show that some proteins with adhesive functions and others with cell maintenance functions and virulence factor EsxA were significantly upregulated by both treatments. In contrast, immunoglobulin-binding protein A was significantly downregulated for both disinfectants. Significant differences were observed in the effect of the two disinfectants on the expression of surface proteins including some adhesins, foldase protein PrsA, and two virulence factors.

  5. ERG protein expression over time

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Brasso, Klaus; Thomsen, Frederik Birkebæk

    2015-01-01

    AIMS: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. METHODS: ERG expression was assessed by immunohistochem......AIMS: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. METHODS: ERG expression was assessed...

  6. Matching faces with emotional expressions

    Directory of Open Access Journals (Sweden)

    Wenfeng eChen

    2011-08-01

    Full Text Available There is some evidence that faces with a happy expression are recognized better than faces with other expressions. However, little is known about whether this happy face advantage also applies to perceptual face matching, and whether similar differences exist among other expressions. Using a sequential matching paradigm, we systematically compared the effects of seven basic facial expressions on identity recognition. Identity matching was quickest when a pair of faces had an identical happy/sad/neutral expression, poorer when they had a fearful/surprise/angry expression, and poorest when they had a disgust expression. Faces with a happy/sad/fear/surprise expression were matched faster than those with an anger/disgust expression when the second face in a pair had a neutral expression. These results demonstrate that effects of facial expression on identity recognition are not limited to happy faces when a learned face is immediately tested. The results suggest different influences of expression in perceptual matching and long-term recognition memory.

  7. Expressing emotions in blogs

    DEFF Research Database (Denmark)

    Rodriguez-Hidalgo, Carmina Rodriguez-Hidalgo; Tan, Ed S.; Verlegh, Peeter

    2017-01-01

    Textual paralanguage cues (TPC) have been signaled as effective emotion transmitters online. Though several studies have investigated their properties and occurrence, there remains a gap concerning their communicative impact within specific psychological processes, such as the social sharing...... of emotion (SSE, Rimé, 2009). This study content-analyzed Live Journal blogposts for the occurrence of TPC in three phases of online SSE: initiation, feedback and repost. We compared these to TPC on a second type of emotional expression, emotional venting. Based on Social Information processing theory (SIP......, Walther, 1992), and on the Emotional Mimicry in Context (EMC, Hess & Fischer, 2013) framework, we study predictive relationships in TPC usage in our phased model of online SSE. Results showed that TPC prevailed in SSE blogposts and strongly dominated in emotional venting posts. TPC was more common...

  8. Natural Art, False Expressions

    Directory of Open Access Journals (Sweden)

    Oscar Hernando Nossa García

    2011-05-01

    Full Text Available In the documentary My Kid Could Paint That, directed by Bar-Lev, which deals with Marla Olmstead, the child prodigy of painting, several interviews with persons in the art world are conducted, among them an artist who uses a magnifying glass and the thinnest brushes to do his work. This man, although happy for the success of the child’s abstract paintings, saw in the whole spectacle a mockery of art, and stood firmly by her work. The girl’s father, also an artist, was accused of plagiarism. Cameras entered the child’s studio in order to prove that Marla was the real artist. Why should such relevance be given to authorship? What is the cause of the dispute between the expressive and the rational?

  9. The Expressive Organization

    DEFF Research Database (Denmark)

    This text challenges beliefs about organizational identity, reputation, and branding. It contains a wealth of new ideas for finding the elusive answers to questions troubling contemporary organizations. How does an organization create a strong reputation? What are the implications of corporate br...... students of management, business strategy, accounting, marketing, and communication studies; MBA students; Managers and consultants.......This text challenges beliefs about organizational identity, reputation, and branding. It contains a wealth of new ideas for finding the elusive answers to questions troubling contemporary organizations. How does an organization create a strong reputation? What are the implications of corporate...... branding on organizational structures and processes? How do organizations discover their identities? These are some of the vexing problems addressed in this book by a diverse international team of contributors. According to the authors, the future lies with "the expressive organization". Such organizations...

  10. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

    2015-01-01

    Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue

  11. Facial Expressivity at 4 Months: A Context by Expression Analysis.

    Science.gov (United States)

    Bennett, David S; Bendersky, Margaret; Lewis, Michael

    2002-01-01

    The specificity predicted by differential emotions theory (DET) for early facial expressions in response to 5 different eliciting situations was studied in a sample of 4-month-old infants (n = 150). Infants were videotaped during tickle, sour taste, jack-in-the-box, arm restraint, and masked-stranger situations and their expressions were coded second by second. Infants showed a variety of facial expressions in each situation; however, more infants exhibited positive (joy and surprise) than negative expressions (anger, disgust, fear, and sadness) across all situations except sour taste. Consistent with DET-predicted specificity, joy expressions were the most common in response to tickling, and were less common in response to other situations. Surprise expressions were the most common in response to the jack-in-the-box, as predicted, but also were the most common in response to the arm restraint and masked-stranger situations, indicating a lack of specificity. No evidence of predicted specificity was found for anger, disgust, fear, and sadness expressions. Evidence of individual differences in expressivity within situations, as well as stability in the pattern across situations, underscores the need to examine both child and contextual factors in studying emotional development. The results provide little support for the DET postulate of situational specificity and suggest that a synthesis of differential emotions and dynamic systems theories of emotional expression should be considered.

  12. What emotion does the "facial expression of disgust" express?

    Science.gov (United States)

    Pochedly, Joseph T; Widen, Sherri C; Russell, James A

    2012-12-01

    The emotion attributed to the prototypical "facial expression of disgust" (a nose scrunch) depended on what facial expressions preceded it. In two studies, the majority of 120 children (5-14 years) and 135 adults (16-58 years) judged the nose scrunch as expressing disgust when the preceding set included an anger scowl, but as angry when the anger scowl was omitted. An even greater proportion of observers judged the nose scrunch as angry when the preceding set also included a facial expression of someone about to be sick. The emotion attributed to the nose scrunch therefore varies with experimental context. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  13. Generational Differences of Emotional Expression

    Institute of Scientific and Technical Information of China (English)

    李学勇

    2014-01-01

    As a kind of subjective psychological activity, emotion can only be known and perceived by a certain expressive form. Varies as the different main bodies, difference of emotional expression can be reflected not only among individuals but between generations. The old conceals their emotions inside, the young express their emotions boldly, and the middle-aged are rational and deep in their expressions. Facing and understanding such differences is the premise and foundation of the con-struction of a harmonious relationship between different generations.

  14. Precise Analysis of String Expressions

    DEFF Research Database (Denmark)

    Christensen, Aske Simon; Møller, Anders; Schwartzbach, Michael Ignatieff

    2003-01-01

    We perform static analysis of Java programs to answer a simple question: which values may occur as results of string expressions? The answers are summarized for each expression by a regular language that is guaranteed to contain all possible values. We present several applications of this analysis...... are automatically produced. We present extensive benchmarks demonstrating that the analysis is efficient and produces results of useful precision......., including statically checking the syntax of dynamically generated expressions, such as SQL queries. Our analysis constructs flow graphs from class files and generates a context-free grammar with a nonterminal for each string expression. The language of this grammar is then widened into a regular language...

  15. Oracle Application Express 4 Recipes

    CERN Document Server

    Zehoo, Edmund

    2011-01-01

    Oracle Application Express 4 Recipes provides an example-based approach to learning Application Express - the ground-breaking, rapid application development platform included with every Oracle Database license. The recipes format is ideal for the quick-study who just wants a good example or two to kick start their thinking and get pointed in the right direction. The recipes cover the gamut of Application Express development. Author and Application Express expert Edmund Zehoo shows how to create data entry screens, visualize data in the form of reports and charts, implement validation and back-

  16. Expression modeling for expression-invariant face recognition

    NARCIS (Netherlands)

    Haar, F.B. Ter; Veltkamp, R.C.

    2010-01-01

    Morphable face models have proven to be an effective tool for 3D face modeling and face recognition, but the extension to 3D face scans with expressions is still a challenge. The two main difficulties are (1) how to build a new morphable face model that deals with expressions, and (2) how to fit

  17. Human papillomavirus gene expression

    International Nuclear Information System (INIS)

    Chow, L.T.; Hirochika, H.; Nasseri, M.; Stoler, M.H.; Wolinsky, S.M.; Chin, M.T.; Hirochika, R.; Arvan, D.S.; Broker, T.R.

    1987-01-01

    To determine the role of tissue differentiation on expression of each of the papillomavirus mRNA species identified by electron microscopy, the authors prepared exon-specific RNA probes that could distinguish the alternatively spliced mRNA species. Radioactively labeled single-stranded RNA probes were generated from a dual promoter vector system and individually hybridized to adjacent serial sections of formalin-fixed, paraffin-embedded biopsies of condylomata. Autoradiography showed that each of the message species had a characteristic tissue distribution and relative abundance. The authors have characterized a portion of the regulatory network of the HPVs by showing that the E2 ORF encodes a trans-acting enhancer-stimulating protein, as it does in BPV-1 (Spalholz et al. 1985). The HPV-11 enhancer was mapped to a 150-bp tract near the 3' end of the URR. Portions of this region are duplicated in some aggressive strains of HPV-6 (Boshart and zur Hausen 1986; Rando et al. 1986). To test the possible biological relevance of these duplications, they cloned tandem arrays of the enhancer and demonstrated, using a chloramphenicol acetyltransferase (CAT) assay, that they led to dramatically increased transcription proportional to copy number. Using the CAT assays, the authors found that the E2 proteins of several papillomavirus types can cross-stimulate the enhancers of most other types. This suggests that prior infection of a tissue with one papillomavirus type may provide a helper effect for superinfection and might account fo the HPV-6/HPV-16 coinfections in condylomata that they have observed

  18. Pheromone binding proteins enhance the sensitivity of olfactory receptors to sex pheromones in Chilo suppressalis.

    Science.gov (United States)

    Chang, Hetan; Liu, Yang; Yang, Ting; Pelosi, Paolo; Dong, Shuanglin; Wang, Guirong

    2015-08-27

    Sexual communication in moths offers a simplified scenario to model and investigate insect sensory perception. Both PBPs (pheromone-binding proteins) and PRs (pheromone receptors) are involved in the detection of sex pheromones, but the interplay between them still remains largely unknown. In this study, we have measured the binding affinities of the four recombinant PBPs of Chilo suppressalis (CsupPBPs) to pheromone components and analogs and characterized the six PRs using the Xenopus oocytes expression system. Interestingly, when the responses of PRs were recorded in the presence of PBPs, we measured in several combinations a dramatic increase in signals as well as in sensitivity of such combined systems. Furthermore, the discrimination ability of appropriate combinations of PRs and PBPs was improved compared with the performance of PBPs or PRs alone. Besides further supporting a role of PBPs in the pheromone detection and discrimination, our data shows for the first time that appropriate combinations of PRs and PBPs improved the discrimination ability of PBPs or PRs alone. The variety of responses measured with different pairing of PBPs and PRs indicates the complexity of the olfaction system, which, even for the relatively simple task of detecting sex pheromones, utilises a highly sophisticated combinatorial approach.

  19. Differential Gene Expression and Aging

    Directory of Open Access Journals (Sweden)

    Laurent Seroude

    2002-01-01

    Full Text Available It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

  20. Measuring facial expression of emotion.

    Science.gov (United States)

    Wolf, Karsten

    2015-12-01

    Research into emotions has increased in recent decades, especially on the subject of recognition of emotions. However, studies of the facial expressions of emotion were compromised by technical problems with visible video analysis and electromyography in experimental settings. These have only recently been overcome. There have been new developments in the field of automated computerized facial recognition; allowing real-time identification of facial expression in social environments. This review addresses three approaches to measuring facial expression of emotion and describes their specific contributions to understanding emotion in the healthy population and in persons with mental illness. Despite recent progress, studies on human emotions have been hindered by the lack of consensus on an emotion theory suited to examining the dynamic aspects of emotion and its expression. Studying expression of emotion in patients with mental health conditions for diagnostic and therapeutic purposes will profit from theoretical and methodological progress.

  1. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    (ectoderm) specification with co-opted functions in notochord formation in chordates and left/right determination in ambulacrarians and vertebrates. The caudal ortholog, TtrCdx, is first expressed in the ectoderm of the gastrulating embryo in the posterior region of the blastopore. Its expression stays......The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa...... completion of larval development, which is marked by a three-lobed body with larval setae. Expression starts at gastrulation in two areas lateral to the blastopore and subsequently extends over the animal pole of the gastrula. With elongation of the gastrula, expression at the animal pole narrows to a small...

  2. Nestin expression in neuroepithelial tumors.

    Science.gov (United States)

    Schiffer, Davide; Manazza, Andrea; Tamagno, Ilaria

    2006-05-29

    Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.

  3. The expressive stance: intentionality, expression, and machine art

    OpenAIRE

    Linson, Adam

    2013-01-01

    This paper proposes a new interpretive stance for interpreting artistic works and performances that is relevant to artificial intelligence research but also has broader implications. Termed the expressive stance, this stance makes intelligible a critical distinction between present-day machine art and human art, but allows for the possibility that future machine art could find a place alongside our own. The expressive stance is elaborated as a response to Daniel Dennett's notion of the intent...

  4. [Prosopagnosia and facial expression recognition].

    Science.gov (United States)

    Koyama, Shinichi

    2014-04-01

    This paper reviews clinical neuropsychological studies that have indicated that the recognition of a person's identity and the recognition of facial expressions are processed by different cortical and subcortical areas of the brain. The fusiform gyrus, especially the right fusiform gyrus, plays an important role in the recognition of identity. The superior temporal sulcus, amygdala, and medial frontal cortex play important roles in facial-expression recognition. Both facial recognition and facial-expression recognition are highly intellectual processes that involve several regions of the brain.

  5. Expression in E. coli systems

    DEFF Research Database (Denmark)

    Krogsdam, Anne-M; Kristiansen, Karsten; Nøhr, Jane

    2003-01-01

    intracellularly in soluble form. In E. coli, proteins containing disulfide bonds are best produced by secretion because the disulfide forming foldases reside in the periplasm. Likewise, a correct N-terminus is more likely to be obtained upon secretion. Moreover, potentially toxic proteins are more likely......Owing to cost advantage, speed of production, and often high product yield (up to 50% of total cell protein), expression in Escherichia coli is generally the first choice when attempting to express a recombinant protein. Expression systems exist to produce recombinant protein intracellularly...

  6. Analysis of Facial Expression by Taste Stimulation

    Science.gov (United States)

    Tobitani, Kensuke; Kato, Kunihito; Yamamoto, Kazuhiko

    In this study, we focused on the basic taste stimulation for the analysis of real facial expressions. We considered that the expressions caused by taste stimulation were unaffected by individuality or emotion, that is, such expressions were involuntary. We analyzed the movement of facial muscles by taste stimulation and compared real expressions with artificial expressions. From the result, we identified an obvious difference between real and artificial expressions. Thus, our method would be a new approach for facial expression recognition.

  7. A Tattoo Is Expression, Too.

    Science.gov (United States)

    Dowling-Sendor, Benjamin

    1997-01-01

    In "Stephenson v. Davenport Community School District," the U.S. Eighth Circuit Court of Appeals ruled that schools cannot adopt unduly vague policies to regulate student expression, in this case, a cross-shaped tattoo. (LMI)

  8. Online handwritten mathematical expression recognition

    Science.gov (United States)

    Büyükbayrak, Hakan; Yanikoglu, Berrin; Erçil, Aytül

    2007-01-01

    We describe a system for recognizing online, handwritten mathematical expressions. The system is designed with a user-interface for writing scientific articles, supporting the recognition of basic mathematical expressions as well as integrals, summations, matrices etc. A feed-forward neural network recognizes symbols which are assumed to be single-stroke and a recursive algorithm parses the expression by combining neural network output and the structure of the expression. Preliminary results show that writer-dependent recognition rates are very high (99.8%) while writer-independent symbol recognition rates are lower (75%). The interface associated with the proposed system integrates the built-in recognition capabilities of the Microsoft's Tablet PC API for recognizing textual input and supports conversion of hand-drawn figures into PNG format. This enables the user to enter text, mathematics and draw figures in a single interface. After recognition, all output is combined into one LATEX code and compiled into a PDF file.

  9. Emerald Express '95: Analysis Report

    National Research Council Canada - National Science Library

    Newett, Sandra

    1996-01-01

    The purpose of Emerald Express was to bring together senior representatives from military, relief, political, and diplomatic communities to address issues that arise during Humanitarian Assistance and Peace Operations (HA/POs...

  10. Race, Reparations, and Free Expression.

    Science.gov (United States)

    Brownstein, Andrew

    2001-01-01

    Describes how a controversial newspaper ad opposing slavery reparations and the subsequent trashing of the student daily have set off a debate at Brown University about the competing values of sensitivity and free expression. (EV)

  11. Expression of Recombinant Human Butyrylcholinesterase

    National Research Council Canada - National Science Library

    Lockridge, Oksana

    1997-01-01

    .... The G117H enzyme has the potential to be useful for decontamination of skin and eye. To determine how many amino acids could be deleted from butyrylcholinesterase without loss of activity, deletion mutants were expressed...

  12. Regulation of eucaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Brent, R.; Ptashne, M.S

    1989-05-23

    This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

  13. Novel class III phosphoribosyl diphosphate synthase: structure and properties of the tetrameric, phosphate-activated, non-allosterically inhibited enzyme from Methanocaldococcus jannaschii

    DEFF Research Database (Denmark)

    Kadziola, Anders; Jepsen, Clemens H; Johansson, Eva

    2005-01-01

    The prs gene encoding phosphoribosyl diphosphate (PRPP) synthase of the hyperthermophilic autotrophic methanogenic archaeon Methanocaldococcus jannaschii has been cloned and expressed in Escherichia coli. Subsequently, M.jannaschii PRPP synthase has been purified, characterised, crystallised, and...

  14. Craniopharyngioma: Survivin expression and ultrastructure

    Science.gov (United States)

    ZHU, JIANG; YOU, CHAO

    2015-01-01

    The aim of the present study was to investigate the significance of survivin protein expression levels in craniopharyngioma. Tumor samples and clinical data were obtained from 50 patients with craniopharyngioma who were admitted to the West China Hospital of Sichuan University (Chengdu, China). The morphology of the craniopharyngioma samples was observed using optical and electron microscopes, and survivin expression was investigated in the samples by immunohistochemical analysis. The immunohistochemical results revealed survivin expression in all of the craniopharyngioma samples, but not in the healthy brain tissue samples. It was identified that survivin was expressed at a higher level in cases of the adamantinomatous type compared with those of the squamous-papillary type, in male patients compared with female patients, in children compared with adults and in recurrent cases compared with non-recurrent cases. Furthermore, no significant difference was detected in survivin expression levels among the tumors of different subtypes and different disease stages. The results of the present study indicate that survivin is significant in the development of craniopharyngioma, and that survivin protein expression levels are a meaningful indicator for assessing craniopharyngioma recurrence. PMID:25435936

  15. The motivation to express prejudice

    Science.gov (United States)

    Forscher, Patrick S.; Cox, William T. L.; Graetz, Nicholas; Devine, Patricia G.

    2015-01-01

    Contemporary prejudice research focuses primarily on people who are motivated to respond without prejudice and the ways in which unintentional bias can cause these people to act inconsistent with this motivation. However, some real-world phenomena (e.g., hate speech, hate crimes) and experimental findings (e.g., Plant & Devine, 2001; 2009) suggest that some expressions of prejudice are intentional. These phenomena and findings are difficult to explain solely from the motivations to respond without prejudice. We argue that some people are motivated to express prejudice, and we develop the motivation to express prejudice (MP) scale to measure this motivation. In seven studies involving more than 6,000 participants, we demonstrate that, across scale versions targeted at Black people and gay men, the MP scale has good reliability and convergent, discriminant, and predictive validity. In normative climates that prohibit prejudice, the internal and external motivations to express prejudice are functionally non-independent, but they become more independent when normative climates permit more prejudice toward a target group. People high in the motivation to express prejudice are relatively likely to resist pressure to support programs promoting intergroup contact and vote for political candidates who support oppressive policies. The motivation to express prejudice predicted these outcomes even when controlling for attitudes and the motivations to respond without prejudice. This work encourages contemporary prejudice researchers to broaden the range of samples, target groups, and phenomena that they study, and more generally to consider the intentional aspects of negative intergroup behavior. PMID:26479365

  16. Pericentrin expression in Down's syndrome.

    Science.gov (United States)

    Salemi, Michele; Barone, Concetta; Romano, Carmelo; Salluzzo, Roberto; Caraci, Filippo; Cantarella, Rita Anna; Salluzzo, Maria Grazia; Drago, Filippo; Romano, Corrado; Bosco, Paolo

    2013-11-01

    Down's syndrome (DS) is the most frequent genetic cause of intellectual disability and is a chromosomal abnormality of chromosome 21 trisomy. The pericentrin gene (PCNT) has sequenced in 21q22.3 inside of the minimal critical region for Down's syndrome. Alterations of PCNT gene are associated with dwarfism, cardiomyopathy and other pathologies. In this study, we have evaluated the possible differential expression of PCNT mRNA, by qRT-PCR, in peripheral blood leukocytes of DS subjects compared with the normal population. In the present case-control study, PCNT gene expression was increased by 72.72% in 16 out 22 DS samples compared with normal subjects. Our data suggest that changes in the expression levels of PCNT in DS subjects may be involved into the molecular mechanism of Down's syndrome.

  17. Converting nested algebra expressions into flat algebra expressions

    NARCIS (Netherlands)

    Paredaens, J.; Van Gucht, D.

    1992-01-01

    Nested relations generalize ordinary flat relations by allowing tuple values to be either atomic or set valued. The nested algebra is a generalization of the flat relational algebra to manipulate nested relations. In this paper we study the expressive power of the nested algebra relative to its

  18. EXPRESS Service to the International Space Station: EXPRESS Pallet

    Science.gov (United States)

    Primm, Lowell; Bergmann, Alan

    1998-01-01

    The International Space Station (ISS) will be the ultimate scientific accomplishment in the history of NASA, with its primary objective of providing unique scientific investigation opportunities. This objective is the basis for the creation of the EXPRESS Pallet System (ExPs). The EXPRESS Pallet will provide extremal/unpressurized accommodations for a wide variety of external users. The payload developers represent many science disciplines, including earth observation, communications, solar and deep space viewing, long-term exposure, and many others. The EXPRESS Pallet will provide a mechanism to maximum utilization of the limited ISS unpressurized payload volume, standard physical payload interfaces for users, a standard integration template for users and the capability to changeout payloads on-orbit. The EXPRESS Pallet provides access to Ram, Wake, Starboard, Port, Nadir, Zenith and Earth Limb for exposure and viewing. 'Me ExPs consists of the Pallet structure, payload Adapters, and a subsystem assembly which includes data controller, power distribution and conversion, and Extra Vehicular Robotics/Extra-Vehicular Activity systems.

  19. Construction of PVX virus-expression vector to express enterotoxin ...

    African Journals Online (AJOL)

    Potato X potyvirus (PVX)-based vector has been comprehensively applied in transient expression system. In order to produce the heterologous proteins more quickly and stably, the ClaI and NotI enzyme sites were introduced into the Enterotoxin fusion gene LTB-ST by polymerase chain reaction (PCR) and the LTB-ST ...

  20. Advanced express web application development

    CERN Document Server

    Keig, Andrew

    2013-01-01

    A practical book, guiding the reader through the development of a single page application using a feature-driven approach.If you are an experienced JavaScript developer who wants to build highly scalable, real-world applications using Express, this book is ideal for you. This book is an advanced title and assumes that the reader has some experience with node, Javascript MVC web development frameworks, and has heard of Express before, or is familiar with it. You should also have a basic understanding of Redis and MongoDB. This book is not a tutorial on Node, but aims to explore some of the more

  1. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  2. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  3. Microsoft Expression Web for dummies

    CERN Document Server

    Hefferman, Linda

    2013-01-01

    Expression Web is Microsoft's newest tool for creating and maintaining dynamic Web sites. This FrontPage replacement offers all the simple ""what-you-see-is-what-you-get"" tools for creating a Web site along with some pumped up new features for working with Cascading Style Sheets and other design options. Microsoft Expression Web For Dummies arrives in time for early adopters to get a feel for how to build an attractive Web site. Author Linda Hefferman teams up with longtime FrontPage For Dummies author Asha Dornfest to show the easy way for first-time Web designers, FrontPage ve

  4. The change of expression configuration affects identity-dependent expression aftereffect but not identity-independent expression aftereffect

    Directory of Open Access Journals (Sweden)

    Miao eSong

    2015-12-01

    Full Text Available The present study examined the influence of expression configuration on cross-identity expression aftereffect. The expression configuration refers to the spatial arrangement of facial features in a face for conveying an emotion, e.g., an open-mouth smile versus a closed-mouth smile. In the first of two experiments, the expression aftereffect is measured using across-identity/cross-expression configuration factorial design. The facial identities of test faces were the same or different from the adaptor, while orthogonally, the expression configurations of those facial identities were also the same or different. The result shows that the change of expression configuration impaired the expression aftereffect when the facial identities of adaptor and tests were the same; however, the impairment effect disappears when facial identities were different, indicating the identity-independent expression representation is more robust to the change of the expression configuration in comparison with the identity-dependent expression representation. In the second experiment, we used schematic line faces as adaptors and real faces as tests to minimize the similarity between the adaptor and tests, which is expected to exclude the contribution from the identity-dependent expression representation to expression aftereffect. The second experiment yields a similar result as the identity-independent expression aftereffect observed in Experiment 1. The findings indicate the different neural sensitivities to expression configuration for identity-dependent and identity-independent expression systems.

  5. 'Endurance' Courtesy of Mars Express

    Science.gov (United States)

    2004-01-01

    NASA's Mars Exploration Rover Opportunity used its panoramic camera to capture this false-color image of the interior of 'Endurance Crater' on the rover's 188th martian day (Aug. 4, 2004). The image data were relayed to Earth by the European Space Agency's Mars Express orbiter. The image was generated from separate frames using the cameras 750-, 530- and 480-nanometer filters.

  6. Communicating emotions in expressive avatars

    NARCIS (Netherlands)

    Kierkegaard, P.M.

    2010-01-01

    Avatars have become a fundamental part of collaborative virtual environments. They are the visual embodiment of the user and are designed to address key issues in the interaction process between the user and the CVE. Giving avatars expressive abilities has been considered essential in computer-human

  7. Spirit Boxes: Expressions of Culture.

    Science.gov (United States)

    DeMuro, Ted

    1984-01-01

    After studying the culture and art of the ancient civilizations of South America, Mesopotamia, Greece, and Egypt, secondary level art students made spirit boxes as expressions of the various cultures. How to make the boxes and how to prepare the face molds are described. (RM)

  8. Mapping and Manipulating Facial Expression

    Science.gov (United States)

    Theobald, Barry-John; Matthews, Iain; Mangini, Michael; Spies, Jeffrey R.; Brick, Timothy R.; Cohn, Jeffrey F.; Boker, Steven M.

    2009-01-01

    Nonverbal visual cues accompany speech to supplement the meaning of spoken words, signify emotional state, indicate position in discourse, and provide back-channel feedback. This visual information includes head movements, facial expressions and body gestures. In this article we describe techniques for manipulating both verbal and nonverbal facial…

  9. The SSETI-express Mission

    DEFF Research Database (Denmark)

    Alminde, Lars; Bisgaard, Morten; Melville, N.

    In January 2004 a group of students met at the European Space Technology and Research Centre (ESTEC) in Holland to discuss the feasibility of building a micro-satellite, dubbed SSETI-Express, from parts derived from other student satellite projects and launch it within one and a half year...

  10. The SSETI-Express Mission

    DEFF Research Database (Denmark)

    Alminde, Lars; Bisgaard, Morten; Melville, Neil

    2005-01-01

    In January 2004 a group of students met at the European Space Technology and Research Centre (ESTEC) in Holland to discuss the feasibility of building a micro-satellite, dubbed SSETI-Express, from parts derived from other student satellite projects and launch it within one and a half year...

  11. Color vision of the coelacanth (Latimeria chalumnae) and adaptive evolution of rhodopsin (RH1) and rhodopsin-like (RH2) pigments.

    Science.gov (United States)

    Yokoyama, S

    2000-01-01

    The coelacanth, a "living fossil," lives at a depth of about 200 m near the coast of the Comoros archipelago in the Indian Ocean and receives only a narrow range of light at about 480 nm. To see the entire range of "color" the Comoran coelacanth appears to use only rod-specific RH1 and cone-specific RH2 visual pigments, with the optimum light sensitivities (lambda max) at 478 nm and 485 nm, respectively. These blue-shifted lambda max values of RH1 and RH2 pigments are fully explained by independent double amino acid replacements E122Q/A292S and E122Q/M207L, respectively. More generally, currently available mutagenesis experiments identify only 10 amino acid changes that shift the lambda max values of visual pigments more than 5 nm. Among these, D83N, E1220, M207L, and A292S are associated strongly with the adaptive blue shifts in the lambda max values of RH1 and RH2 pigments in vertebrates.

  12. The motivation to express prejudice.

    Science.gov (United States)

    Forscher, Patrick S; Cox, William T L; Graetz, Nicholas; Devine, Patricia G

    2015-11-01

    Contemporary prejudice research focuses primarily on people who are motivated to respond without prejudice and the ways in which unintentional bias can cause these people to act in a manner inconsistent with this motivation. However, some real-world phenomena (e.g., hate speech, hate crimes) and experimental findings (e.g., Plant & Devine, 2001, 2009) suggest that some prejudice is intentional. These phenomena and findings are difficult to explain solely from the motivations to respond without prejudice. We argue that some people are motivated to express prejudice, and we develop the Motivation to Express Prejudice Scale (MP) to measure this motivation. In 7 studies involving more than 6,000 participants, we demonstrate that, across scale versions targeted at Black people and gay men, the MP has good reliability and convergent, discriminant, and predictive validity. In normative climates that prohibit prejudice, the internal and external motivations to express prejudice are functionally nonindependent, but they become more independent when normative climates permit more prejudice toward a target group. People high in the motivation to express prejudice are relatively likely to resist pressure to support programs promoting intergroup contact and to vote for political candidates who support oppressive policies. The motivation to express prejudice predicted these outcomes even when controlling for attitudes and the motivations to respond without prejudice. This work encourages contemporary prejudice researchers to give greater consideration to the intentional aspects of negative intergroup behavior and to broaden the range of phenomena, target groups, and samples that they study. (c) 2015 APA, all rights reserved).

  13. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  14. Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E.

    Directory of Open Access Journals (Sweden)

    Ashwini Y Ramdasi

    Full Text Available High mortality in pregnant women (PR is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients and subclinical-HEV-infections in pregnant women in the first (SC-PR-1 and later (2nd and 3rd, SC-PR-2+3 trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001. IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001, CCL2(p<0.01, CXCL8(P<0.05, IL1B(p<0.05 and IL10(P<0.0001 and decrease in CXCL10(<0.05 in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.

  15. DNA expressions - A formal notation for DNA

    NARCIS (Netherlands)

    Vliet, Rudy van

    2015-01-01

    We describe a formal notation for DNA molecules that may contain nicks and gaps. The resulting DNA expressions denote formal DNA molecules. Different DNA expressions may denote the same molecule. Such DNA expressions are called equivalent. We examine which DNA expressions are minimal, which

  16. Recombination-ready Sindbis replicon expression vectors for transgene expression

    Directory of Open Access Journals (Sweden)

    Olson Ken E

    2007-10-01

    Full Text Available Abstract Background Sindbis viruses have been widely used as tools to study gene function in cells. Despite the utility of these systems, the construction and production of alphavirus replicons is time consuming and inefficient due to potential additional restriction sites within the insert region and lack of directionality for insert ligation. In this report, we present a system useful for producing recombinant Sindbis replicons that uses lambda phage recombination technology to rapidly and specifically construct replicon expression plasmids that contain insert regions in the desired orientation. Results Recombination of the gene of interest with the replicon plasmid resulted in nearly 100% recombinants, each of which contained a correctly orientated insert. Replicons were easily produced in cell culture and packaged into pseudo-infectious viral particles. Insect and mammalian cells infected with pseudo-infectious viral particles expressed various transgenes at high levels. Finally, inserts from persistently replicating replicon RNA were easily isolated and recombined back into entry plasmids for sequencing and subsequent analysis. Conclusion Replication-ready replicon expression plasmids make the use of alphavirus replicons fast and easy as compared to traditional replicon production methods. This system represents a significant step forward in the utility and ease of use of alphavirus replicons in the study of gene function.

  17. Dynamic Facial Expression of Emotion Made Easy

    OpenAIRE

    Broekens, Joost; Qu, Chao; Brinkman, Willem-Paul

    2012-01-01

    Facial emotion expression for virtual characters is used in a wide variety of areas. Often, the primary reason to use emotion expression is not to study emotion expression generation per se, but to use emotion expression in an application or research project. What is then needed is an easy to use and flexible, but also validated mechanism to do so. In this report we present such a mechanism. It enables developers to build virtual characters with dynamic affective facial expressions. The mecha...

  18. Emotional Expression in Reality TV

    DEFF Research Database (Denmark)

    Rasmussen, Tove Arendt

    Reality TV has been disputed and discussed along many lines for the last 20 years; the media themselves always with a twist of concern about reality programs crossing moral borderlines while research has put more interest in questions of genre and representation of more or less useful and maybe...... empowering social identities. In the latest generation of reality TV which Misha Kava has described as the “celebrity generation”, it seems that reality creates new standards for mixing facts and fiction and even different “realities” as participants become media stars while more traditional celebrities...... are being treated as ordinary people. My article will discuss different presentations of selves and especially the emotional verbal and nonverbal expressions in reality TV communication. Aspects of the intimate self and its emotional expressions seem to be strategically managed in reality TV and even...

  19. On the Expressiveness of Joining

    Directory of Open Access Journals (Sweden)

    Thomas Given-Wilson

    2015-08-01

    Full Text Available The expressiveness of communication primitives has been explored in a common framework based on the pi-calculus by considering four features: synchronism (asynchronous vs synchronous, arity (monadic vs polyadic data, communication medium (shared dataspaces vs channel-based, and pattern-matching (binding to a name vs testing name equality vs intensionality. Here another dimension coordination is considered that accounts for the number of processes required for an interaction to occur. Coordination generalises binary languages such as pi-calculus to joining languages that combine inputs such as the Join Calculus and general rendezvous calculus. By means of possibility/impossibility of encodings, this paper shows coordination is unrelated to the other features. That is, joining languages are more expressive than binary languages, and no combination of the other features can encode a joining language into a binary language. Further, joining is not able to encode any of the other features unless they could be encoded otherwise.

  20. Architecture between construction and expression

    Directory of Open Access Journals (Sweden)

    Luca Lanini

    2015-11-01

    Full Text Available I think that the problem is basically the same as always: to redefine the relationship between Construction and Expression. On one hand, construction is considered an endeavor, on the other hand, a tendency to contest architecture only with expression. The relationship between architecture and control of urban phenomena is a relationship that has been gradually lost in the past three decades and has been replaced by the relationship between finance and planning. A useful object is very different from a building: for its time and costs of construction. Buildings are expected to last many years and are paid with everybody’s taxes, a design object’s lifespan is perhaps fifty years, then it’s ready to be modernized or for the landfill ... I believe that the main tool that a designer must have, beyond necessary technical skills, is the capacity of his/her own critical thought.

  1. Transgenic Arabidopsis Gene Expression System

    Science.gov (United States)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  2. Podoplanin Expression in Canine Melanoma

    OpenAIRE

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  3. Summer Oral Expression English Course

    CERN Document Server

    HR Department

    2011-01-01

    An English Oral Expression course will take place between 15 August and 30 September 2011. Schedule: to be determined (2 sessions of 2 hours per week). Please note that this course is for learners who have a good knowledge of English (CERN level 7 upwards). If you are interested in following this course, please enrol here. Or contact: Kerstin FUHRMEISTER (70896) Tessa OSBORNE (72957)  

  4. Children's expression through play therapy

    Directory of Open Access Journals (Sweden)

    Ljubomirović Nataša

    2015-01-01

    Full Text Available Play as a child's expression, is a skill through which children speaks to adults. Play therapy is a broad field of therapeutic intervention based on the play in order to help the child to cope with problems. Through play, children learn to communicate with others, to express their feelings. Through play they learn and can improve their cognitive, emotional and social capabilities. Play therapy is a nondirective technique focused on the child. It is not focused on the problem, at present even the past, but focused on the expression of the child feelings, accepting the child, rather than correction. The focus has been on the wisdom of a child, not on expertise therapists, guiding the child through play rather than instructing. The aim of play therapy is to encourage healthy growth and development, developing skills in problem solving, reduction of undesirable behavior, confidence building and the development of self-control. This method is effective for a wide range of children's problems, such as the state of stress, anxiety, problem behavior, hyperkinetic syndrome, depression, loss, trauma, the problem of bonding situations parents divorced, somatic disorders, autism spectrum disorders, social problems.

  5. Gene expression profile of pulpitis.

    Science.gov (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A

    2016-06-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

  6. Abrupt onset of mutations in a developmentally regulated gene during terminal differentiation of post-mitotic photoreceptor neurons in mice.

    Directory of Open Access Journals (Sweden)

    Ivette M Sandoval

    Full Text Available For sensitive detection of rare gene repair events in terminally differentiated photoreceptors, we generated a knockin mouse model by replacing one mouse rhodopsin allele with a form of the human rhodopsin gene that causes a severe, early-onset form of retinitis pigmentosa. The human gene contains a premature stop codon at position 344 (Q344X, cDNA encoding the enhanced green fluorescent protein (EGFP at its 3' end, and a modified 5' untranslated region to reduce translation rate so that the mutant protein does not induce retinal degeneration. Mutations that eliminate the stop codon express a human rhodopsin-EGFP fusion protein (hRho-GFP, which can be readily detected by fluorescence microscopy. Spontaneous mutations were observed at a frequency of about one per retina; in every case, they gave rise to single fluorescent rod cells, indicating that each mutation occurred during or after the last mitotic division. Additionally, the number of fluorescent rods did not increase with age, suggesting that the rhodopsin gene in mature rod cells is less sensitive to mutation than it is in developing rods. Thus, there is a brief developmental window, coinciding with the transcriptional activation of the rhodopsin locus, in which somatic mutations of the rhodopsin gene abruptly begin to appear.

  7. Children's Representations of Facial Expression and Identity: Identity-Contingent Expression Aftereffects

    Science.gov (United States)

    Vida, Mark D.; Mondloch, Catherine J.

    2009-01-01

    This investigation used adaptation aftereffects to examine developmental changes in the perception of facial expressions. Previous studies have shown that adults' perceptions of ambiguous facial expressions are biased following adaptation to intense expressions. These expression aftereffects are strong when the adapting and probe expressions share…

  8. Nonverbal and verbal emotional expression and health.

    Science.gov (United States)

    Berry, D S; Pennebaker, J W

    1993-01-01

    The spontaneous nonverbal expression of emotion is related to immediate reductions in autonomic nervous system activity. Similar changes in specific autonomic channels occur when individuals are encouraged to verbally express their emotions. Indeed, these physiological changes are most likely to occur among individuals who are either verbally or nonverbally highly expressive. These data suggest that when individuals must actively inhibit emotional expression, they are at increased risk for a variety of health problems. Several experiments are summarized which indicate that verbally expressing traumatic experiences by writing or talking improves physical health, enhances immune function, and is associated with fewer medical visits. Although less research is available regarding nonverbal expression, it is also likely that the nonverbal expression of emotion bears some relation to health status. We propose that the effectiveness of many common expressive therapies (e.g., art, music, cathartic) would be enhanced if clients are encouraged to both express their feelings nonverbally and to put their experiences into words.

  9. Misrecognition of facial expressions in delinquents

    Directory of Open Access Journals (Sweden)

    Matsuura Naomi

    2009-09-01

    Full Text Available Abstract Background Previous reports have suggested impairment in facial expression recognition in delinquents, but controversy remains with respect to how such recognition is impaired. To address this issue, we investigated facial expression recognition in delinquents in detail. Methods We tested 24 male adolescent/young adult delinquents incarcerated in correctional facilities. We compared their performances with those of 24 age- and gender-matched control participants. Using standard photographs of facial expressions illustrating six basic emotions, participants matched each emotional facial expression with an appropriate verbal label. Results Delinquents were less accurate in the recognition of facial expressions that conveyed disgust than were control participants. The delinquents misrecognized the facial expressions of disgust as anger more frequently than did controls. Conclusion These results suggest that one of the underpinnings of delinquency might be impaired recognition of emotional facial expressions, with a specific bias toward interpreting disgusted expressions as hostile angry expressions.

  10. Cloning and expression of a widely expressed receptor tyrosine phosphatase

    DEFF Research Database (Denmark)

    Sap, J; D'Eustachio, P; Givol, D

    1990-01-01

    We describe the identification of a widely expressed receptor-type (transmembrane) protein tyrosine phosphatase (PTPase; EC 3.1.3.48). Screening of a mouse brain cDNA library under low-stringency conditions with a probe encompassing the intracellular (phosphatase) domain of the CD45 lymphocyte...... antigen yielded cDNA clones coding for a 794-amino acid transmembrane protein [hereafter referred to as receptor protein tyrosine phosphatase alpha (R-PTP-alpha)] with an intracellular domain displaying clear homology to the catalytic domains of CD45 and LAR (45% and 53%, respectively). The 142-amino acid...

  11. Summer Oral Expression English course

    CERN Multimedia

    2012-01-01

    An English Oral Expression course will take place this summer from 20 August to 29 September.   Schedule: to be determined (2 sessions of 2 hours per week). Please note that this course is for learners who have a good knowledge of English (CERN level 7 upwards). If you are interested in following this course, please enroll through this link. Please be sure to indicate your planned absences in the comments field so we can schedule the course. If you need more information please send a message to English.training@cern.ch

  12. Summer Oral Expression English course

    CERN Document Server

    2012-01-01

    An English Oral Expression course will take place this summer at some time between 25 June and 28 September. The exact dates will be decided according to the preferences of the students.   Schedule: to be determined (2 sessions of 2 hours per week). Please note that this course is for learners who have a good knowledge of English (CERN level 7 upwards). If you are interested in following this course, please enroll through this link. Please be sure to indicate your planned absences in the comments field so we can schedule the course. If you need more information please send a message to English.training@cern.ch

  13. Summer Oral Expression English course

    CERN Document Server

    2013-01-01

    An English Oral Expression course will take place this summer at some time between August 19 and October 4.   Schedule: to be determined (2 sessions of 2 hours per week). Please note that this course is for learners who have a good knowledge of English (CERN level 7 upwards). If you are interested in following this course, please enroll through this link. Please be sure to indicate your planned absences in the comments field so we can schedule the course. If you need more information please send a message to English.training@cern.ch.

  14. Summer Oral Expression English Course

    CERN Multimedia

    HR Department

    2011-01-01

    An English Oral Expression course will take place between 15 August and 30 September 2011. Schedule: to be determined (2 sessions of 2 hours per week). Please note that this course is for learners who have a good knowledge of English (CERN level 7 upwards). If you are interested in following this course, please enrol through the following link https://cta.cern.ch/cta2/f?p=110:9:1576796470009589::::X_STATUS,XS_COURSE_NAME,XS_PROGRAMME,XS_SUBCATEGORY,X_COURSE_ID,XS_LANGUAGE,XS_SESSION:D,,1,,4368,B, Or contact: Kerstin FUHRMEISTER (70896) Tessa OSBORNE (72957)  

  15. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko

    2015-12-23

    Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

  16. Helping children express grief through symbolic communication.

    Science.gov (United States)

    Segal, R M

    1984-12-01

    Communication barriers erected by grieving children delay problem resolution. Use of the expressive arts--music, art, and body movement--in symbolic communication helps them to express overwhelming feelings and cope with trauma and stress.

  17. The College Student's Freedom of Expression

    Science.gov (United States)

    Gibbs, Annette

    1974-01-01

    Discussion of means to ensure freedom of expression by college students. Areas of expression noted are student newspapers, lectures by off-campus speakers, freedom to assemble peaceably and freedom to associate. (EK)

  18. Moxibustion upregulates hippocampal progranulin expression

    Directory of Open Access Journals (Sweden)

    Tao Yi

    2016-01-01

    Full Text Available In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4 and Zusanli (ST36, bilateral were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

  19. Hepcidin expression in psoriasis patients

    Directory of Open Access Journals (Sweden)

    Nursel Dilek

    2014-01-01

    Full Text Available Background: Iron is an essential nutrient for mammals. Accelerated loss of nutrients through hyperproliferation and desquamation from the skin in psoriasis is known. Hepcidin is an important and recently discovered regulator of iron homeostasis. Aims and Objectives: The present study was undertaken to investigate the hepcidin expression in psoriasis patients. Materials and Methods: We examined peripheral blood cell counts, serum Fe, ferritin, interleukin-6 (IL-6 and hepcidin levels using respectively automated hematology analyzer, Iron assay on the AEROSET system, chemiluminescent microparticle immunoassay with automated analyzer, and enzyme-linked immunosorbent assay. Results: The independent comparison of Fe, ferritin, IL-6 and hepcidin levels in psoriasis patients and control group (healthy volunteers revealed lower Fe and higher IL-6, hepcidin levels in psoriasis patients. No significant difference was seen in the ferritin level between the psoriasis and the control group. Conclusions: We think that studies on hepcidin expression in psoriatic plaques will contribute to our understanding the role of iron and hepcidin in the pathogenesis of psoriasis.

  20. Edix: A Software for Editing Algebraic Expressions.

    OpenAIRE

    Bouhineau , Denis; Nicaud , Jean-François; Pavard , X.

    2001-01-01

    International audience; The paper presents a computer software, called Edix, devoted to the edition of algebraic expressions in their usual 2D representation. At present, many systems display fine algebraic expressions, but the edition of such expressions is weak. Systems like Word and FrameMaker place sub-expressions in too many boxes so that many editing actions are not simple, while usual CAS (computer algebra systems) just use a 1D representation for the edition. Furthermore, Edix allows ...

  1. Kivy and Langer on expressiveness in music

    Directory of Open Access Journals (Sweden)

    van der Schoot Albert

    2013-01-01

    Full Text Available From 1980 onwards, Peter Kivy has put forward that music does not so much express emotions but rather is expressive of emotions. The character of the music does not represent the character or mood of the composer, but reflects his knowledge of emotional life. Unfortunately, Kivy fails to give credit to Susanne Langer, who brought these views to the fore as early as 1942, claiming that the vitality of music lies in expressiveness, not in expression.

  2. The evolution of gene expression in primates

    OpenAIRE

    Tashakkori Ghanbarian, Avazeh

    2015-01-01

    The evolution of a gene’s expression profile is commonly assumed to be independent of its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between expression of neighboring genes in extant taxa. Indeed, in all eukaryotic genomes, genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their e...

  3. Intrahepatic expression of interferon alpha & interferon alpha ...

    African Journals Online (AJOL)

    kemrilib

    IFN-α and IFN-α Receptor mRNA expression in the liver. All the patients showed IFN-α gene expression except one patient who had the highest degree of fibrosis (fibrosis grade 5) and HAI Index of 9. IFN- α Receptor mRNA was expressed in 30% (9/30). (Figure 4). Non of the patients with HCC had. IFNα-Rc expression and ...

  4. Generating Expressive Speech for Storytelling Applications

    NARCIS (Netherlands)

    Bailly, G.; Theune, Mariet; Meijs, Koen; Campbell, N.; Hamza, W.; Heylen, Dirk K.J.; Ordelman, Roeland J.F.; Hoge, H.; Jianhua, T.

    Work on expressive speech synthesis has long focused on the expression of basic emotions. In recent years, however, interest in other expressive styles has been increasing. The research presented in this paper aims at the generation of a storytelling speaking style, which is suitable for

  5. 75 FR 473 - Community Express Pilot Program

    Science.gov (United States)

    2010-01-05

    ... SMALL BUSINESS ADMINISTRATION Community Express Pilot Program AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of extension of the Community Express Pilot Program. SUMMARY: This notice extends the Community Express Pilot Program in its current form through December 31, 2010. Based upon the...

  6. 75 FR 80561 - Community Express Pilot Program

    Science.gov (United States)

    2010-12-22

    ... SMALL BUSINESS ADMINISTRATION Community Express Pilot Program AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of short-term extension and termination of the Community Express Pilot Program. SUMMARY: This notice announces the termination of the Community Express Pilot Program following a...

  7. A constructive approach to gene expression dynamics

    International Nuclear Information System (INIS)

    Ochiai, T.; Nacher, J.C.; Akutsu, T.

    2004-01-01

    Recently, experiments on mRNA abundance (gene expression) have revealed that gene expression shows a stationary organization described by a scale-free distribution. Here we propose a constructive approach to gene expression dynamics which restores the scale-free exponent and describes the intermediate state dynamics. This approach requires only one assumption: Markov property

  8. Vocal Emotion Expressions Effects on Cooperation Behavior

    Science.gov (United States)

    Caballero Meneses, Jonathan Azael; Menez Díaz, Judith Marina

    2017-01-01

    Emotional expressions have been proposed to be important for regulating social interaction as they can serve as cues for behavioral intentions. The issue has been mainly addressed analyzing the effects of facial emotional expressions in cooperation behavior, but there are contradictory results regarding the impact of emotional expressions on that…

  9. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene. (PEP-cDNA) in prokaryotic and mammalian expression vectors in chimeric cDNA types, encompassing. GST and FLAG with PEP-cDNA. PEP-cDNA was sub-cloned in pGEX6p2 prokaryotic expression ...

  10. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

  11. Expressiveness modulo Bisimilarity of Regular Expressions with Parallel Composition (Extended Abstract

    Directory of Open Access Journals (Sweden)

    Jos C. M. Baeten

    2010-11-01

    Full Text Available The languages accepted by finite automata are precisely the languages denoted by regular expressions. In contrast, finite automata may exhibit behaviours that cannot be described by regular expressions up to bisimilarity. In this paper, we consider extensions of the theory of regular expressions with various forms of parallel composition and study the effect on expressiveness. First we prove that adding pure interleaving to the theory of regular expressions strictly increases its expressiveness up to bisimilarity. Then, we prove that replacing the operation for pure interleaving by ACP-style parallel composition gives a further increase in expressiveness. Finally, we prove that the theory of regular expressions with ACP-style parallel composition and encapsulation is expressive enough to express all finite automata up to bisimilarity. Our results extend the expressiveness results obtained by Bergstra, Bethke and Ponse for process algebras with (the binary variant of Kleene's star operation.

  12. Recognising and Interpreting Named Temporal Expressions

    DEFF Research Database (Denmark)

    Brucato, Matteo; Derczynski, Leon; Llorens, Hectjor

    2013-01-01

    This paper introduces a new class of temporal expression – named temporal expressions – and methods for recognising and interpreting its members. The commonest temporal expressions typically contain date and time words, like April or hours. Research into recognising and interpreting these typical...... expressions is mature in many languages. However, there is a class of expressions that are less typical, very varied, and difficult to automatically interpret. These indicate dates and times, but are harder to detect because they often do not contain time words and are not used frequently enough to appear...

  13. Synthetic promoter libraries- tuning of gene expression

    DEFF Research Database (Denmark)

    Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

    2006-01-01

    knockout and strong overexpression. However, applications such as metabolic optimization and control analysis necessitate a continuous set of expression levels with only slight increments in strength to cover a specific window around the wildtype expression level of the studied gene; this requirement can......The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene...

  14. Expressing Model Constraints Visually with VMQL

    DEFF Research Database (Denmark)

    Störrle, Harald

    2011-01-01

    ) for specifying constraints on UML models. We examine VMQL's usability by controlled experiments and its expressiveness by a representative sample. We conclude that VMQL is less expressive than OCL, although expressive enough for most of the constraints in the sample. In terms of usability, however, VMQL......OCL is the de facto standard language for expressing constraints and queries on UML models. However, OCL expressions are very difficult to create, understand, and maintain, even with the sophisticated tool support now available. In this paper, we propose to use the Visual Model Query Language (VMQL...

  15. Abstract Expression Grammar Symbolic Regression

    Science.gov (United States)

    Korns, Michael F.

    This chapter examines the use of Abstract Expression Grammars to perform the entire Symbolic Regression process without the use of Genetic Programming per se. The techniques explored produce a symbolic regression engine which has absolutely no bloat, which allows total user control of the search space and output formulas, which is faster, and more accurate than the engines produced in our previous papers using Genetic Programming. The genome is an all vector structure with four chromosomes plus additional epigenetic and constraint vectors, allowing total user control of the search space and the final output formulas. A combination of specialized compiler techniques, genetic algorithms, particle swarm, aged layered populations, plus discrete and continuous differential evolution are used to produce an improved symbolic regression sytem. Nine base test cases, from the literature, are used to test the improvement in speed and accuracy. The improved results indicate that these techniques move us a big step closer toward future industrial strength symbolic regression systems.

  16. E-mail: Outlook Express

    Directory of Open Access Journals (Sweden)

    Zainul Bakri

    2012-10-01

    Full Text Available Salah satu layanan Internet yang sangat penting adalah electronic mail atau sering hanya disebut sebagai e-mail. Untuk menggunakan e-mail, diperlukan piranti lunak khusus supaya pengguna dapat mengirim dan menerima e-mail. Jenis piranti lunak e-mail diantaranya adalah Outlook Express yang merupakan satu paket yang didistribusikan bersama Internet Explorer versi 4. Piranti lunak ini dijalankan pada PC yang mempunyai sistem operasi Windows 95 atau 98. Jenis piranti lunak e-mail yang lain adalah Eudora, Pegasus dan sebagainya. Bahkan ada yang diintegrasikan dengan Web Browser (alat untuk menelusuri situs Web misalnya IE,dan Netscape.Sebagai layaknya pelayanan pos, maka setiap pengguna e-mail mempunyai alamat tertentu yang tidak mungkin dipunyai oleh pengguna lainnya diseluruh dunia. Untuk keperluan pendistribusian, maka e-mail mempunyai semacam kantor pos yang ditempatkan dalam sebuah komputer server (mail server atau sering disebut sebagai host. 

  17. Generalized Expression for Polarization Density

    International Nuclear Information System (INIS)

    Wang, Lu; Hahm, T.S.

    2009-01-01

    A general polarization density which consists of classical and neoclassical parts is systematically derived via modern gyrokinetics and bounce-kinetics by employing a phase-space Lagrangian Lie-transform perturbation method. The origins of polarization density are further elucidated. Extending the work on neoclassical polarization for long wavelength compared to ion banana width [M. N. Rosenbluth and F. L. Hinton, Phys. Rev. Lett. 80, 724 (1998)], an analytical formula for the generalized neoclassical polarization including both finite-banana-width (FBW) and finite-Larmor-radius (FLR) effects for arbitrary radial wavelength in comparison to banana width and gyroradius is derived. In additional to the contribution from trapped particles, the contribution of passing particles to the neoclassical polarization is also explicitly calculated. Our analytic expression agrees very well with the previous numerical results for a wide range of radial wavelength.

  18. Perceived intimacy of expressed emotion.

    Science.gov (United States)

    Howell, A; Conway, M

    1990-08-01

    Research on norms for emotional expression and self-disclosure provided the basis for two hypotheses concerning the perceived intimacy of emotional self-disclosure. The first hypothesis was that the perceived intimacy of negative emotional disclosure would be greater than that of positive emotional disclosure; the second was that disclosures of more intense emotional states would be perceived as more intimate than disclosures of less intense emotional states for both negative and positive disclosures. Both hypotheses received support when male students in Canada rated the perceived intimacy of self-disclosures that were equated for topic and that covered a comprehensive sample of emotions and a range of emotional intensities. The effects were observed across all the topics of disclosure examined.

  19. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  20. Definition, Detection and Generation of Iyashi Expressions

    Science.gov (United States)

    Kitaoka, Tetsuko; Diago, Luis A.; Hagiwara, Ichiro; Kitazaki, Satoshi; Yamane, Shigeru

    This paper concerns the engineering analysis of “Iyashi”, a peculiar concept to the Japanese, which affect person's heart and may change their expression and behavior. We have integrated the advocator's view of “Iyashi”, analyzed the social background of “Iyashi” and have defined Iyashi and also the Iyashi expression. As the facial expression is the special and important stimulus for both observers and people who show expressions, we want to prove the existence of expressions that change the observer's emotion with Iyashi. We have developed the system to clarify the combination of facial features important for Iyashi through the psychological experiments and the analysis by Holographic Neural Networks (HNN). HNN analysis gave the structure of the Iyashi expression, that is the important combination of the physical facial parameters contributing to the high degree of Iyashi. Based on the structure of Iyashi we are able to generate the Iyashi expression appropriate for each person.

  1. Adaptive Evolution of Gene Expression in Drosophila

    Directory of Open Access Journals (Sweden)

    Armita Nourmohammad

    2017-08-01

    Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

  2. Anticausatives are weak scalar expressions, not reflexive expressions

    Directory of Open Access Journals (Sweden)

    Florian Schäfer

    2016-07-01

    Full Text Available We discuss conceptual and empirical arguments from Germanic, Romance and Slavic languages against an analysis treating anticausative verbs as derived from their lexical causative counterparts under reflexivization. Instead, we defend the standard account to the semantics of the causative alternation according to which anticausatives in general, and anticausatives marked with reflexive morphology in particular, denote simple one-place inchoative events that are logically entailed by their lexical causative counterparts. Under such an account, anticausative verbs are weak scalar expressions that stand in a semantico-pragmatic opposition to their strong lexical causative counterparts. Due to this scalar relation, the use of an anticausative can trigger the implicature that the use of its lexical causative counterpart is too strong. As usual with implicatures, they can be ‘metalinguistically’ denied, cancelled, or reinforced and we argue that these mechanisms explain all central empirical facts brought up in the literature in favor of a treatment of anticausatives as semantically reflexive predicates. Our results reinforce the view that the reflexive morphemes used in many (Indo-European languages to mark anticausatives do not necessarily trigger reflexive semantics. However, we also show that a string involving a reflexively marked (anti-causative verb can be forced into a semantically reflexive construal under particular conceptual or grammatical circumstances.

  3. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

    2011-01-01

    Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...... and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

  4. Facial expressions and pair bonds in hylobatids.

    Science.gov (United States)

    Florkiewicz, Brittany; Skollar, Gabriella; Reichard, Ulrich H

    2018-06-06

    Facial expressions are an important component of primate communication that functions to transmit social information and modulate intentions and motivations. Chimpanzees and macaques, for example, produce a variety of facial expressions when communicating with conspecifics. Hylobatids also produce various facial expressions; however, the origin and function of these facial expressions are still largely unclear. It has been suggested that larger facial expression repertoires may have evolved in the context of social complexity, but this link has yet to be tested at a broader empirical basis. The social complexity hypothesis offers a possible explanation for the evolution of complex communicative signals such as facial expressions, because as the complexity of an individual's social environment increases so does the need for communicative signals. We used an intraspecies, pair-focused study design to test the link between facial expressions and sociality within hylobatids, specifically the strength of pair-bonds. The current study compared 206 hr of video and 103 hr of focal animal data for ten hylobatid pairs from three genera (Nomascus, Hoolock, and Hylobates) living at the Gibbon Conservation Center. Using video footage, we explored 5,969 facial expressions along three dimensions: repertoire use, repertoire breadth, and facial expression synchrony [FES]. We then used focal animal data to compare dimensions of facial expressiveness to pair bond strength and behavioral synchrony. Hylobatids in our study overlapped in only half of their facial expressions (50%) with the only other detailed, quantitative study of hylobatid facial expressions, while 27 facial expressions were uniquely observed in our study animals. Taken together, hylobatids have a large facial expression repertoire of at least 80 unique facial expressions. Contrary to our prediction, facial repertoire composition was not significantly correlated with pair bond strength, rates of territorial synchrony

  5. Expressiveness in musical performance: Pedagogic aspect

    Directory of Open Access Journals (Sweden)

    Jović Natalija R.

    2016-01-01

    Full Text Available The subject of our research relates to pedagogic aspects of expressive vocal-instrumental musical performance. We intended to examine: (1 how undergraduate students see/conceptualize and evaluate expressiveness in musical performance; (2 whether and how they were trained in the skill of expressive musical performance during their musical training; (3 whether and in which way they rehearse the expressive component of musical performance and interpretation and (4 whether there are any differences regarding gender, age, instrument, department, year of study and years of instrument playing in relation to the group of dependant variables related to expressiveness, tuition and practice. The sample for the research included 82 students of instrumental and theory departments at the Faculty of Music in Belgrade. Psychological and pedagogical aspects of musical expressiveness during vocal-instrumental performance were analyzed. The results show that students highly evaluate expressiveness but its place is secondary compared to mastering technical and tonal requirements. Statistically significant differences were shown regarding gender, age and departments. It can be concluded that there is a potential for the development and enhancement of expressiveness of students if we abandon the traditional view that expressiveness is linked exclusively to talent. The findings indicate that pedagogical work should be directed towards finding purposeful strategies for training individual expressiveness.

  6. Widespread ectopic expression of olfactory receptor genes

    Directory of Open Access Journals (Sweden)

    Yanai Itai

    2006-05-01

    Full Text Available Abstract Background Olfactory receptors (ORs are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication of such ectopic expression. Results We analyzed the expression of hundreds of human and mouse OR transcripts, via EST and microarray data, in several dozens of human and mouse tissues. Different tissues had specific, relatively small OR gene subsets which had particularly high expression levels. In testis, average expression was not particularly high, and very few highly expressed genes were found, none corresponding to ORs previously implicated in sperm chemotaxis. Higher expression levels were more common for genes with a non-OR genomic neighbor. Importantly, no correlation in expression levels was detected for human-mouse orthologous pairs. Also, no significant difference in expression levels was seen between intact and pseudogenized ORs, except for the pseudogenes of subfamily 7E which has undergone a human-specific expansion. Conclusion The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information.

  7. Platelet cyclooxygenase expression in normal dogs.

    Science.gov (United States)

    Thomason, J; Lunsford, K; Mullins, K; Stokes, J; Pinchuk, L; Wills, R; McLaughlin, R; Langston, C; Pruett, S; Mackin, A

    2011-01-01

    Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin. The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs. Eight female, intact hounds. A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100(®) (collagen/epinephrine), and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100(®) closure times, and urine 11-dTXB(2 ): creatinine ratio were analyzed before and after aspirin administration. Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63-476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100(®) closure times were prolonged and urine 11-dTXB(2) concentration decreased in all dogs after aspirin administration. Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  8. Ancestral gene reconstruction and synthesis of ancient rhodopsins in the laboratory.

    Science.gov (United States)

    Chang, Belinda S W

    2003-08-01

    Laboratory synthesis of ancestral proteins offers an intriguing opportunity to study the past directly. The development of Bayesian methods to infer ancestral sequences, combined with advances in models of molecular evolution, and synthetic gene technology make this an increasingly promising approach in evolutionary studies of molecular function. Visual pigments form the first step in the biochemical cascade of events in the retina in all animals known to possess visual capabilities. In vertebrates, the necessity of spanning a dynamic range of light intensities of many orders of magnitude has given rise to two different types of photoreceptors, rods specialized for dim-light conditions, and cones for daylight and color vision. These photoreceptors contain different types of visual pigment genes. Reviewed here are methods of inferring ancestral sequences, chemical synthesis of artificial ancestral genes in the laboratory, and applications to the evolution of vertebrate visual systems and the experimental recreation of an archosaur rod visual pigment. The ancestral archosaurs gave rise to several notable lineages of diapsid reptiles, including the birds and the dinosaurs, and would have existed over 200 MYA. What little is known of their physiology comes from fossil remains, and inference based on the biology of their living descendants. Despite its age, an ancestral archosaur pigment was successfully recreated in the lab, and showed interesting properties of its wavelength sensitivity that may have implications for the visual capabilities of the ancestral archosaurs in dim light.

  9. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.

    Directory of Open Access Journals (Sweden)

    Gunnar Kleinau

    Full Text Available In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR and different subtypes of G-proteins. The thyrotropin receptor (TSHR binds G-proteins promiscuously and activates both Gs (cAMP and Gq (IP. Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G-protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443 and helix 8 (R687 that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein subtypes.

  10. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.

    Science.gov (United States)

    Kleinau, Gunnar; Jaeschke, Holger; Worth, Catherine L; Mueller, Sandra; Gonzalez, Jorge; Paschke, Ralf; Krause, Gerd

    2010-03-18

    In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR) and different subtypes of G-proteins. The thyrotropin receptor (TSHR) binds G-proteins promiscuously and activates both Gs (cAMP) and Gq (IP). Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL) 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G-protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443) and helix 8 (R687) that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein subtypes.

  11. Expressiveness and definability in circumscription

    Directory of Open Access Journals (Sweden)

    Francicleber Martins Ferreira

    2011-06-01

    Full Text Available We investigate expressiveness and definability issues with respect to minimal models, particularly in the scope of Circumscription. First, we give a proof of the failure of the Löwenheim-Skolem Theorem for Circumscription. Then we show that, if the class of P; Z-minimal models of a first-order sentence is Δ-elementary, then it is elementary. That is, whenever the circumscription of a first-order sentence is equivalent to a first-order theory, then it is equivalent to a finitely axiomatizable one. This means that classes of models of circumscribed theories are either elementary or not Δ-elementary. Finally, using the previous result, we prove that, whenever a relation Pi is defined in the class of P; Z-minimal models of a first-order sentence Φ and whenever such class of P; Z-minimal models is Δ-elementary, then there is an explicit definition ψ for Pi such that the class of P; Z-minimal models of Φ is the class of models of Φ ∧ ψ. In order words, the circumscription of P in Φ with Z varied can be replaced by Φ plus this explicit definition ψ for Pi.

  12. Adipocyte differentiation and leptin expression

    DEFF Research Database (Denmark)

    Hwang, C S; Loftus, T M; Mandrup, S

    1997-01-01

    Adipose tissue has long been known to house the largest energy reserves in the animal body. Recent research indicates that in addition to this role, the adipocyte functions as a global regulator of energy metabolism. Adipose tissue is exquisitely sensitive to a variety of endocrine and paracrine ...... of energy intake and expenditure. The hormonal and transcriptional control of adipocyte differentiation is discussed, as is the role of leptin and other factors secreted by the adipocyte that participate in the regulation of adipose homeostasis.......Adipose tissue has long been known to house the largest energy reserves in the animal body. Recent research indicates that in addition to this role, the adipocyte functions as a global regulator of energy metabolism. Adipose tissue is exquisitely sensitive to a variety of endocrine and paracrine......, most notably those of the C/EBP and PPAR families, which combine to regulate each other and to control the expression of adipocyte-specific genes. One such gene, i.e. the obese gene, was recently identified and found to encode a hormone, referred to as leptin, that plays a major role in the regulation...

  13. Recognizing Facial Expressions Automatically from Video

    Science.gov (United States)

    Shan, Caifeng; Braspenning, Ralph

    Facial expressions, resulting from movements of the facial muscles, are the face changes in response to a person's internal emotional states, intentions, or social communications. There is a considerable history associated with the study on facial expressions. Darwin [22] was the first to describe in details the specific facial expressions associated with emotions in animals and humans, who argued that all mammals show emotions reliably in their faces. Since that, facial expression analysis has been a area of great research interest for behavioral scientists [27]. Psychological studies [48, 3] suggest that facial expressions, as the main mode for nonverbal communication, play a vital role in human face-to-face communication. For illustration, we show some examples of facial expressions in Fig. 1.

  14. Stochastic gene expression in Arabidopsis thaliana.

    Science.gov (United States)

    Araújo, Ilka Schultheiß; Pietsch, Jessica Magdalena; Keizer, Emma Mathilde; Greese, Bettina; Balkunde, Rachappa; Fleck, Christian; Hülskamp, Martin

    2017-12-14

    Although plant development is highly reproducible, some stochasticity exists. This developmental stochasticity may be caused by noisy gene expression. Here we analyze the fluctuation of protein expression in Arabidopsis thaliana. Using the photoconvertible KikGR marker, we show that the protein expressions of individual cells fluctuate over time. A dual reporter system was used to study extrinsic and intrinsic noise of marker gene expression. We report that extrinsic noise is higher than intrinsic noise and that extrinsic noise in stomata is clearly lower in comparison to several other tissues/cell types. Finally, we show that cells are coupled with respect to stochastic protein expression in young leaves, hypocotyls and roots but not in mature leaves. Our data indicate that stochasticity of gene expression can vary between tissues/cell types and that it can be coupled in a non-cell-autonomous manner.

  15. Osteopontin expression in salivary gland carcinomas

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Godballe, Christian

    2011-01-01

    J Oral Pathol Med (2010) Background:  In several cancer types, osteopontin (OPN) expression has been correlated with tumor progression and prognosis. Two earlier studies have examined OPN expression in salivary gland carcinomas with contradictory results. Methods:  One hundred and seventy......:  Osteopontin was expressed in all salivary gland carcinomas. Adenoid cystic carcinomas had the highest mean sum score (7.3) and a significantly higher proportion of carcinomas with high OPN sum score than both mucoepidermoid carcinoma and acinic cell carcinoma. Correlation of OPN expression with known...... prognostic factors in salivary gland carcinomas was insignificant. Conclusions:  Salivary gland carcinomas express OPN. The expression does not correlate with known prognostic factors....

  16. "Express yourself": culture and the effect of self-expression on choice.

    Science.gov (United States)

    Kim, Heejung S; Sherman, David K

    2007-01-01

    Whereas self-expression is valued in the United States, it is not privileged with such a cultural emphasis in East Asia. Four studies demonstrate the psychological implications of this cultural difference. Studies 1 and 2 found that European Americans value self-expression more than East Asians/East Asian Americans. Studies 3 and 4 examined the roles of expression in preference judgments. In Study 3, the expression of choice led European Americans but not East Asian Americans to be more invested in what they chose. Study 4 examined the connection between the value of expression and the effect of choice expression and showed that European Americans place greater emphasis on self-expression than East Asian Americans, and this difference explained the cultural difference in Study 3. This research highlights the importance of the cultural meanings of self-expression and the moderating role of cultural beliefs on the psychological effect of self-expression. 2007 APA, all rights reserved

  17. Generating Expressive Speech for Storytelling Applications

    OpenAIRE

    Bailly, G.; Theune, Mariet; Meijs, Koen; Campbell, N.; Hamza, W.; Heylen, Dirk K.J.; Ordelman, Roeland J.F.; Hoge, H.; Jianhua, T.

    2006-01-01

    Work on expressive speech synthesis has long focused on the expression of basic emotions. In recent years, however, interest in other expressive styles has been increasing. The research presented in this paper aims at the generation of a storytelling speaking style, which is suitable for storytelling applications and more in general, for applications aimed at children. Based on an analysis of human storytellers' speech, we designed and implemented a set of prosodic rules for converting "neutr...

  18. Willingness to Express Emotions to Caregiving Spouses

    OpenAIRE

    Monin, Joan K.; Martire, Lynn M.; Schulz, Richard; Clark, Margaret S.

    2009-01-01

    This study examined the association between care-recipients’ willingness to express emotions to spousal caregivers and caregiver’s well-being and support behaviors. Using self-report measures in the context of a larger study, 262 care-recipients with osteoarthritis reported on their willingness to express emotions to caregivers, and caregivers reported on their stress and insensitive responding to care-recipients. Results revealed that care-recipients’ willingness to express happiness was ass...

  19. Comparative gene expression between two yeast species

    Directory of Open Access Journals (Sweden)

    Guan Yuanfang

    2013-01-01

    Full Text Available Abstract Background Comparative genomics brings insight into sequence evolution, but even more may be learned by coupling sequence analyses with experimental tests of gene function and regulation. However, the reliability of such comparisons is often limited by biased sampling of expression conditions and incomplete knowledge of gene functions across species. To address these challenges, we previously systematically generated expression profiles in Saccharomyces bayanus to maximize functional coverage as compared to an existing Saccharomyces cerevisiae data repository. Results In this paper, we take advantage of these two data repositories to compare patterns of ortholog expression in a wide variety of conditions. First, we developed a scalable metric for expression divergence that enabled us to detect a significant correlation between sequence and expression conservation on the global level, which previous smaller-scale expression studies failed to detect. Despite this global conservation trend, between-species gene expression neighborhoods were less well-conserved than within-species comparisons across different environmental perturbations, and approximately 4% of orthologs exhibited a significant change in co-expression partners. Furthermore, our analysis of matched perturbations collected in both species (such as diauxic shift and cell cycle synchrony demonstrated that approximately a quarter of orthologs exhibit condition-specific expression pattern differences. Conclusions Taken together, these analyses provide a global view of gene expression patterns between two species, both in terms of the conditions and timing of a gene's expression as well as co-expression partners. Our results provide testable hypotheses that will direct future experiments to determine how these changes may be specified in the genome.

  20. Structural development of child's artistic expression

    OpenAIRE

    Sanja Filipović; Milica Vojvodić

    2017-01-01

    Abstract Structural development implies control and capability of the expression usage in terms of independent creative expression and making. Understanding of structural development of child's artistic expression as a phenomenon (which is suitable to child's age) has some implications on methodical acts considering artistic education of children and youngsters. Therefore, it is of unexceptional importance to know these laws as well as methodical acts which encourage the structural develop...

  1. Methods for monitoring multiple gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Berka, Randy [Davis, CA; Bachkirova, Elena [Davis, CA; Rey, Michael [Davis, CA

    2012-05-01

    The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

  2. Methods for monitoring multiple gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Berka, Randy; Bachkirova, Elena; Rey, Michael

    2013-10-01

    The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

  3. Identification of Emotional Facial Expressions: Effects of Expression, Intensity, and Sex on Eye Gaze.

    Directory of Open Access Journals (Sweden)

    Laura Jean Wells

    Full Text Available The identification of emotional expressions is vital for social interaction, and can be affected by various factors, including the expressed emotion, the intensity of the expression, the sex of the face, and the gender of the observer. This study investigates how these factors affect the speed and accuracy of expression recognition, as well as dwell time on the two most significant areas of the face: the eyes and the mouth. Participants were asked to identify expressions from female and male faces displaying six expressions (anger, disgust, fear, happiness, sadness, and surprise, each with three levels of intensity (low, moderate, and normal. Overall, responses were fastest and most accurate for happy expressions, but slowest and least accurate for fearful expressions. More intense expressions were also classified most accurately. Reaction time showed a different pattern, with slowest response times recorded for expressions of moderate intensity. Overall, responses were slowest, but also most accurate, for female faces. Relative to male observers, women showed greater accuracy and speed when recognizing female expressions. Dwell time analyses revealed that attention to the eyes was about three times greater than on the mouth, with fearful eyes in particular attracting longer dwell times. The mouth region was attended to the most for fearful, angry, and disgusted expressions and least for surprise. These results extend upon previous findings to show important effects of expression, emotion intensity, and sex on expression recognition and gaze behaviour, and may have implications for understanding the ways in which emotion recognition abilities break down.

  4. Identification of Emotional Facial Expressions: Effects of Expression, Intensity, and Sex on Eye Gaze.

    Science.gov (United States)

    Wells, Laura Jean; Gillespie, Steven Mark; Rotshtein, Pia

    2016-01-01

    The identification of emotional expressions is vital for social interaction, and can be affected by various factors, including the expressed emotion, the intensity of the expression, the sex of the face, and the gender of the observer. This study investigates how these factors affect the speed and accuracy of expression recognition, as well as dwell time on the two most significant areas of the face: the eyes and the mouth. Participants were asked to identify expressions from female and male faces displaying six expressions (anger, disgust, fear, happiness, sadness, and surprise), each with three levels of intensity (low, moderate, and normal). Overall, responses were fastest and most accurate for happy expressions, but slowest and least accurate for fearful expressions. More intense expressions were also classified most accurately. Reaction time showed a different pattern, with slowest response times recorded for expressions of moderate intensity. Overall, responses were slowest, but also most accurate, for female faces. Relative to male observers, women showed greater accuracy and speed when recognizing female expressions. Dwell time analyses revealed that attention to the eyes was about three times greater than on the mouth, with fearful eyes in particular attracting longer dwell times. The mouth region was attended to the most for fearful, angry, and disgusted expressions and least for surprise. These results extend upon previous findings to show important effects of expression, emotion intensity, and sex on expression recognition and gaze behaviour, and may have implications for understanding the ways in which emotion recognition abilities break down.

  5. Profiling Gene Expression in Germinating Brassica Roots.

    Science.gov (United States)

    Park, Myoung Ryoul; Wang, Yi-Hong; Hasenstein, Karl H

    2014-01-01

    Based on previously developed solid-phase gene extraction (SPGE) we examined the mRNA profile in primary roots of Brassica rapa seedlings for highly expressed genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK (glucokinase) during the first day post-germination. The assessment was based on the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the investigated genes changed spatially along the length of primary roots. The expression level of all genes differed significantly at each sample position. Among the examined genes ACT7 expression was most even along the root. UBQ was highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary root emergence and higher than at any other sample position. Expressions of GLK in EZ and RS increased gradually over time. SPGE extraction is the result of oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be used for gene expression profiling at high spatial and temporal resolution. SPGE needles can be used within two weeks when stored at 4 °C. Our data indicate that gene expression studies that are based on the entire root miss important differences in gene expression that SPGE is able to resolve for example growth adjustments during gravitropism.

  6. TRPM4 protein expression in prostate cancer

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Soldini, Davide; Jung, Maria

    2016-01-01

    BACKGROUND: Transient receptor potential cation channel, subfamily M, member 4 (TRPM4) messenger RNA (mRNA) has been shown to be upregulated in prostate cancer (PCa) and might be a new promising tissue biomarker. We evaluated TRPM4 protein expression and correlated the expression level.......79-2.62; p = 0.01-0.03 for the two observers) when compared to patients with a lower staining intensity. CONCLUSIONS: TRPM4 protein expression is widely expressed in benign and cancerous prostate tissue, with highest staining intensities found in PCa. Overexpression of TRPM4 in PCa (combination of high...

  7. Automatic emotional expression analysis from eye area

    Science.gov (United States)

    Akkoç, Betül; Arslan, Ahmet

    2015-02-01

    Eyes play an important role in expressing emotions in nonverbal communication. In the present study, emotional expression classification was performed based on the features that were automatically extracted from the eye area. Fırst, the face area and the eye area were automatically extracted from the captured image. Afterwards, the parameters to be used for the analysis through discrete wavelet transformation were obtained from the eye area. Using these parameters, emotional expression analysis was performed through artificial intelligence techniques. As the result of the experimental studies, 6 universal emotions consisting of expressions of happiness, sadness, surprise, disgust, anger and fear were classified at a success rate of 84% using artificial neural networks.

  8. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  9. Judgments of subtle facial expressions of emotion.

    Science.gov (United States)

    Matsumoto, David; Hwang, Hyisung C

    2014-04-01

    Most studies on judgments of facial expressions of emotion have primarily utilized prototypical, high-intensity expressions. This paper examines judgments of subtle facial expressions of emotion, including not only low-intensity versions of full-face prototypes but also variants of those prototypes. A dynamic paradigm was used in which observers were shown a neutral expression followed by the target expression to judge, and then the neutral expression again, allowing for a simulation of the emergence of the expression from and then return to a baseline. We also examined how signal and intensity clarities of the expressions (explained more fully in the Introduction) were associated with judgment agreement levels. Low-intensity, full-face prototypical expressions of emotion were judged as the intended emotion at rates significantly greater than chance. A number of the proposed variants were also judged as the intended emotions. Both signal and intensity clarities were individually associated with agreement rates; when their interrelationships were taken into account, signal clarity independently predicted agreement rates but intensity clarity did not. The presence or absence of specific muscles appeared to be more important to agreement rates than their intensity levels, with the exception of the intensity of zygomatic major, which was positively correlated with agreement rates for judgments of joy.

  10. Examining emotional expressions in discourse: methodological considerations

    Science.gov (United States)

    Hufnagel, Elizabeth; Kelly, Gregory J.

    2017-10-01

    This methodological paper presents an approach for examining emotional expressions through discourse analysis and ethnographic methods. Drawing on trends in the current literature in science education, we briefly explain the importance of emotions in science education and examine the current research methodologies used in interactional emotion studies. We put forth and substantiate a methodological approach that attends to the interactional, contextual, intertextual, and consequential aspects of emotional expressions. By examining emotional expressions in the discourse in which they are constructed, emotional expressions are identified through semantics, contextualization, and linguistic features. These features make salient four dimensions of emotional expressions: aboutness, frequency, type, and ownership. Drawing on data from a large empirical study of pre-service elementary teachers' emotional expressions about climate change in a science course, we provide illustrative examples to describe what counts as emotional expressions in situ. In doing so we explain how our approach makes salient the nuanced nature of such expressions as well as the broader discourse in which they are constructed and the implications for researching emotional expressions in science education discourse. We suggest reasons why this discourse orientated research methodology can contribute to the interactional study of emotions in science education contexts.

  11. Social Use of Facial Expressions in Hylobatids

    Science.gov (United States)

    Scheider, Linda; Waller, Bridget M.; Oña, Leonardo; Burrows, Anne M.; Liebal, Katja

    2016-01-01

    Non-human primates use various communicative means in interactions with others. While primate gestures are commonly considered to be intentionally and flexibly used signals, facial expressions are often referred to as inflexible, automatic expressions of affective internal states. To explore whether and how non-human primates use facial expressions in specific communicative interactions, we studied five species of small apes (gibbons) by employing a newly established Facial Action Coding System for hylobatid species (GibbonFACS). We found that, despite individuals often being in close proximity to each other, in social (as opposed to non-social contexts) the duration of facial expressions was significantly longer when gibbons were facing another individual compared to non-facing situations. Social contexts included grooming, agonistic interactions and play, whereas non-social contexts included resting and self-grooming. Additionally, gibbons used facial expressions while facing another individual more often in social contexts than non-social contexts where facial expressions were produced regardless of the attentional state of the partner. Also, facial expressions were more likely ‘responded to’ by the partner’s facial expressions when facing another individual than non-facing. Taken together, our results indicate that gibbons use their facial expressions differentially depending on the social context and are able to use them in a directed way in communicative interactions with other conspecifics. PMID:26978660

  12. Clusterin expression in elastofibroma dorsi.

    Science.gov (United States)

    Aigelsreiter, Ariane; Pichler, Martin; Pixner, Thomas; Janig, Elke; Schuller, Monika; Lackner, Carolin; Scheipl, Susanne; Beham, Alfred; Regauer, Sigrid

    2013-05-01

    Elastofibroma dorsi is a benign soft tissue lesion composed of abnormal elastic fibers. Degenerated elastic fibers in skin and liver are associated with clusterin, an apoprotein that shares functional properties with small heat shock proteins. We evaluated the staining pattern and possible role of clusterin in elastofibroma dorsi. Twenty-one subcutaneous elastofibromas from the scapular region were evaluated with Elastica van Gieson and Orcein stains, immunohistochemically with antibodies to clusterin, smooth muscle actin, S-100, vimentin and CD34 and correlated with clinical data with respect to physical trauma. Clusterin correlated with the staining pattern of Elastica van Gieson and labelled abnormal broad coarse fibrillar and globular elastic fibers in all elastofibromas. Orcein stains additionally identified fine oxytalan fibers which were not stained by clusterin. Clusterin staining was observed only on the outside of the elastin fibers, while the cores of fibers and globules were unstained. 4/21 elastofibromas showed cellular nodules with a myxoid/collagenous stroma. The round to oval cells showed cytoplasmic staining with vimentin and clusterin; CD34 labelled mostly cell membranes. The cells lacked SMA and S-100 expression. The central areas of the nodules were devoid of elastic fibers, but the periphery contained coarse fibers and globules. 9/ 11 patients, for whom clinical data were available, reported trauma to the scapular region. Many investigated ED were associated with trauma, which supports a reactive/degenerative etiology of ED. The abnormal large elastic fibers in all ED were enveloped by clusterin. Clusterin deposition may protect elastic fibers from degradation and thus contribute indirectly to the tumor-like presentation of ED.

  13. Gene expression inference with deep learning.

    Science.gov (United States)

    Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

    2016-06-15

    Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Expression of CD133 in acute leukemia.

    Science.gov (United States)

    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients.

  15. Foxp3 expression in human cancer cells

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2008-04-01

    Full Text Available Abstract Objective Transcription factor forkhead box protein 3 (Foxp3 specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs. Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

  16. Explanations for Contempt Expressed Towards Old People.

    Science.gov (United States)

    Maxwell, Eleanor Krassen; Maxwell, Robert J.

    The issue of contempt expressed towards the aged was examined from a cross-cultural perspective. Eight reasons for expressions of contempt emerged from a study of 95 societies drawn from the Standard Cross-Cultural Sample, and were treated as independent variables, with the overall level of contempt as the dependent variable, in a application of…

  17. Equilibrium-constant expressions for aqueous plutonium

    International Nuclear Information System (INIS)

    Silver, G.L.

    2010-01-01

    Equilibrium-constant expressions for Pu disproportionation reactions traditionally contain three or four terms representing the concentrations or fractions of the oxidation states. The expressions can be rewritten so that one of the oxidation states is replaced by a term containing the oxidation number of the plutonium. Experimental estimations of the numerical values of the constants can then be checked in several ways. (author)

  18. Behavior, Experience and Expression: Some Research Considerations.

    Science.gov (United States)

    Romanyshyn, Robert D.

    Utilizing research conducted on nostalgia, this paper shows how a phenomenological approach assists in understanding behavior, experience and expression. Moreover, a clearer understanding of them aids one's research with and comprehension of nostalgia. Human action can be studied from the experiential, behavioral and expressive perspectives. These…

  19. Serial analysis of gene expression (SAGE)

    NARCIS (Netherlands)

    van Ruissen, Fred; Baas, Frank

    2007-01-01

    In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE

  20. Dihydrotestostenone increase the gene expression of androgen ...

    African Journals Online (AJOL)

    HNTEP cells were grown in basal medium and treated with DHT in different conditions. HNTEP cells under treatment with DHT (10-13 M) induced an increase in FHL-2 expression. In turn, high DHT concentrations (10-8 M) induced an increase in the expression SHP-1. The present data suggest that the SHP-1 and FHL-2 ...

  1. Predictable tuning of protein expression in bacteria

    DEFF Research Database (Denmark)

    Bonde, Mads; Pedersen, Margit; Klausen, Michael Schantz

    2016-01-01

    We comprehensively assessed the contribution of the Shine-Dalgarno sequence to protein expression and used the data to develop EMOPEC (Empirical Model and Oligos for Protein Expression Changes; http://emopec.biosustain.dtu.dk). EMOPEC is a free tool that makes it possible to modulate the expressi...

  2. A Robot with Complex Facial Expressions

    Directory of Open Access Journals (Sweden)

    J. Takeno

    2009-08-01

    Full Text Available The authors believe that the consciousness of humans basically originates from languages and their association-like flow of consciousness, and that feelings are generated accompanying respective languages. We incorporated artificial consciousness into a robot; achieved an association flow of language like flow of consciousness; and developed a robot called Kansei that expresses its feelings according to the associations occurring in the robot. To be able to fully communicate with humans, robots must be able to display complex expressions, such as a sense of being thrilled. We therefore added to the Kansei robot a device to express complex feelings through its facial expressions. The Kansei robot is actually an artificial skull made of aluminum, with servomotors built into it. The face is made of relatively soft polyethylene, which is formed to appear like a human face. Facial expressions are generated using 19 servomotors built into the skull, which pull metal wires attached to the facial “skin” to create expressions. The robot at present is capable of making six basic expressions as well as complex expressions, such as happiness and fear combined.

  3. Automating InDesign with Regular Expressions

    CERN Document Server

    Kahrel, Peter

    2006-01-01

    If you need to make automated changes to InDesign documents beyond what basic search and replace can handle, you need regular expressions, and a bit of scripting to make them work. This Short Cut explains both how to write regular expressions, so you can find and replace the right things, and how to use them in InDesign specifically.

  4. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene (PEP-cDNA) in prokaryotic and mammalian expression vectors in ... pGEX6p2-PEP and pUcD3-FLAG-PEP constructed vectors were transformed into the one shot TOP10 and JM105 bacterial competent cells, respectively.

  5. Assessment of Outcomes of Free Expression Courses.

    Science.gov (United States)

    Andsager, Julie; Ross, Susan Dente

    1999-01-01

    Assesses outcomes of instruction in three college-senior-level courses on freedom of expression. Suggests that increased attention to freedom-of-expression issues may have resulted in broader understanding of First Amendment issues, and individual and media rights. Notes that students seem to develop an appreciation of the reflexive nature of…

  6. Local expressions for one-loop calculations

    International Nuclear Information System (INIS)

    Wasson, D.A.; Koonin, S.E.

    1991-01-01

    We develop local expressions for the contributions of the short-wavelength vacuum modes to the one-loop vacuum energy. These expressions significantly improve the convergence properties of various ''brute-force'' calculational methods. They also provide a continuous series of approximations that interpolate between the brute-force calculations and the derivative expansion

  7. Artistic Expression: Another Challenge for Rural Education

    Directory of Open Access Journals (Sweden)

    Sonia Álvarez-Castro

    2012-12-01

    Full Text Available This paper identifies the parameters required to create opportunities that would strengthen the social fabric and would promote a comprehensive development through the artistic expression as a method for expressing feelings and constructing –cultural and social– identities as individuals, which, in our global context have been eroded by the homogenization of experiences.

  8. Dirichlet expression for L(1, χ )

    Indian Academy of Sciences (India)

    We show that this expression with obvious modification is valid for the general primitive Dirichlet character χ. Keywords. Hurwitz zeta function; Dirichlet character; Dirichlet L-series; primitive character. 1. Introduction. In Dirichlet's famous work dealing with class number formula, the value of L(1,χ) is expressed in terms of finite ...

  9. Sad Facial Expressions Increase Choice Blindness

    Directory of Open Access Journals (Sweden)

    Yajie Wang

    2018-01-01

    Full Text Available Previous studies have discovered a fascinating phenomenon known as choice blindness—individuals fail to detect mismatches between the face they choose and the face replaced by the experimenter. Although previous studies have reported a couple of factors that can modulate the magnitude of choice blindness, the potential effect of facial expression on choice blindness has not yet been explored. Using faces with sad and neutral expressions (Experiment 1 and faces with happy and neutral expressions (Experiment 2 in the classic choice blindness paradigm, the present study investigated the effects of facial expressions on choice blindness. The results showed that the detection rate was significantly lower on sad faces than neutral faces, whereas no significant difference was observed between happy faces and neutral faces. The exploratory analysis of verbal reports found that participants who reported less facial features for sad (as compared to neutral expressions also tended to show a lower detection rate of sad (as compared to neutral faces. These findings indicated that sad facial expressions increased choice blindness, which might have resulted from inhibition of further processing of the detailed facial features by the less attractive sad expressions (as compared to neutral expressions.

  10. Sad Facial Expressions Increase Choice Blindness.

    Science.gov (United States)

    Wang, Yajie; Zhao, Song; Zhang, Zhijie; Feng, Wenfeng

    2017-01-01

    Previous studies have discovered a fascinating phenomenon known as choice blindness-individuals fail to detect mismatches between the face they choose and the face replaced by the experimenter. Although previous studies have reported a couple of factors that can modulate the magnitude of choice blindness, the potential effect of facial expression on choice blindness has not yet been explored. Using faces with sad and neutral expressions (Experiment 1) and faces with happy and neutral expressions (Experiment 2) in the classic choice blindness paradigm, the present study investigated the effects of facial expressions on choice blindness. The results showed that the detection rate was significantly lower on sad faces than neutral faces, whereas no significant difference was observed between happy faces and neutral faces. The exploratory analysis of verbal reports found that participants who reported less facial features for sad (as compared to neutral) expressions also tended to show a lower detection rate of sad (as compared to neutral) faces. These findings indicated that sad facial expressions increased choice blindness, which might have resulted from inhibition of further processing of the detailed facial features by the less attractive sad expressions (as compared to neutral expressions).

  11. Biased Facial Expression Interpretation in Shy Children

    Science.gov (United States)

    Kokin, Jessica; Younger, Alastair; Gosselin, Pierre; Vaillancourt, Tracy

    2016-01-01

    The relationship between shyness and the interpretations of the facial expressions of others was examined in a sample of 123 children aged 12 to 14?years. Participants viewed faces displaying happiness, fear, anger, disgust, sadness, surprise, as well as a neutral expression, presented on a computer screen. The children identified each expression…

  12. Characterization of differentially expressed genes using high-dimensional co-expression networks

    DEFF Research Database (Denmark)

    Coelho Goncalves de Abreu, Gabriel; Labouriau, Rodrigo S.

    2010-01-01

    We present a technique to characterize differentially expressed genes in terms of their position in a high-dimensional co-expression network. The set-up of Gaussian graphical models is used to construct representations of the co-expression network in such a way that redundancy and the propagation...... that allow to make effective inference in problems with high degree of complexity (e.g. several thousands of genes) and small number of observations (e.g. 10-100) as typically occurs in high throughput gene expression studies. Taking advantage of the internal structure of decomposable graphical models, we...... construct a compact representation of the co-expression network that allows to identify the regions with high concentration of differentially expressed genes. It is argued that differentially expressed genes located in highly interconnected regions of the co-expression network are less informative than...

  13. Polycistronic gene expression in Aspergillus niger.

    Science.gov (United States)

    Schuetze, Tabea; Meyer, Vera

    2017-09-25

    Genome mining approaches predict dozens of biosynthetic gene clusters in each of the filamentous fungal genomes sequenced so far. However, the majority of these gene clusters still remain cryptic because they are not expressed in their natural host. Simultaneous expression of all genes belonging to a biosynthetic pathway in a heterologous host is one approach to activate biosynthetic gene clusters and to screen the metabolites produced for bioactivities. Polycistronic expression of all pathway genes under control of a single and tunable promoter would be the method of choice, as this does not only simplify cloning procedures, but also offers control on timing and strength of expression. However, polycistronic gene expression is a feature not commonly found in eukaryotic host systems, such as Aspergillus niger. In this study, we tested the suitability of the viral P2A peptide for co-expression of three genes in A. niger. Two genes descend from Fusarium oxysporum and are essential to produce the secondary metabolite enniatin (esyn1, ekivR). The third gene (luc) encodes the reporter luciferase which was included to study position effects. Expression of the polycistronic gene cassette was put under control of the Tet-On system to ensure tunable gene expression in A. niger. In total, three polycistronic expression cassettes which differed in the position of luc were constructed and targeted to the pyrG locus in A. niger. This allowed direct comparison of the luciferase activity based on the position of the luciferase gene. Doxycycline-mediated induction of the Tet-On expression cassettes resulted in the production of one long polycistronic mRNA as proven by Northern analyses, and ensured comparable production of enniatin in all three strains. Notably, gene position within the polycistronic expression cassette matters, as, luciferase activity was lowest at position one and had a comparable activity at positions two and three. The P2A peptide can be used to express at

  14. Expression of Sox genes in tooth development.

    Science.gov (United States)

    Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

    2015-01-01

    Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

  15. Emotion Expression of Robot with Personality

    Directory of Open Access Journals (Sweden)

    Xue Hu

    2013-01-01

    Full Text Available A robot emotional expression model based on Hidden Markov Model (HMM is built to enable robots which have different personalities to response in a more satisfactory emotional level. Gross emotion regulation theory and Five Factors Model (FFM which are the theoretical basis are firstly described. And then the importance of the personality effect on the emotion expression process is proposed, and how to make the effect quantization is discussed. After that, the algorithm of HMM is used to describe the process of emotional state transition and expression, and the performance transferring probability affected by personality is calculated. At last, the algorithm model is simulated and applied in a robot platform. The results prove that the emotional expression model can acquire humanlike expressions and improve the human-computer interaction.

  16. Willingness to express emotions to caregiving spouses.

    Science.gov (United States)

    Monin, Joan K; Martire, Lynn M; Schulz, Richard; Clark, Margaret S

    2009-02-01

    This study examined the association between care-recipients' willingness to express emotions to spousal caregivers and caregiver's well-being and support behaviors. Using self-report measures in the context of a larger study, 262 care-recipients with osteoarthritis reported on their willingness to express emotions to caregivers, and caregivers reported on their stress and insensitive responding to care-recipients. Results revealed that care-recipients' willingness to express happiness was associated with less insensitive caregiver responding, and willingness to express interpersonal emotions (e.g., compassion, guilt) was associated with less caregiving stress. There were also gender differences, such that caregiving wives, in particular, benefited from their husband's willingness to express vulnerable (e.g., anxiety, sadness) and interpersonal emotions. (c) 2009 APA, all rights reserved

  17. Personality expression in Chinese language use.

    Science.gov (United States)

    Qiu, Lin; Lu, Jiahui; Ramsay, Jonathan; Yang, Shanshan; Qu, Weina; Zhu, Tingshao

    2017-12-01

    To date, little research has investigated personality expressions in languages other than English. Given that the Chinese language has the largest number of native speakers in the world, it is vitally important to examine the associations between personality and Chinese language use. In this research, we analysed Chinese microblogs and identified word categories and factorial structures associated with personality traits. We also compared our results with previous findings in English and showed that linguistic expression of personality has both universal- and language-specific aspects. Expression of personality via content words is more likely to be consistent across languages than expression via function words. This makes an important step towards uncovering universal patterns of personality expression in language. © 2016 International Union of Psychological Science.

  18. PRAME gene expression profile in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Tânia Maria Vulcani-Freitas

    2011-02-01

    Full Text Available Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

  19. Accelerated Evolution and Functional Divergence of the Dim Light Visual Pigment Accompanies Cichlid Colonization of Central America.

    Science.gov (United States)

    Hauser, Frances E; Ilves, Katriina L; Schott, Ryan K; Castiglione, Gianni M; López-Fernández, Hernán; Chang, Belinda S W

    2017-10-01

    Cichlids encompass one of the most diverse groups of fishes in South and Central America, and show extensive variation in life history, morphology, and colouration. While studies of visual system evolution in cichlids have focussed largely on the African rift lake species flocks, Neotropical cichlids offer a unique opportunity to investigate visual system evolution at broader temporal and geographic scales. South American cichlid colonization of Central America has likely promoted accelerated rates of morphological evolution in Central American lineages as they encountered reduced competition, renewed ecological opportunity, and novel aquatic habitats. To investigate whether such transitions have influenced molecular evolution of vision in Central American cichlids, we sequenced the dim-light rhodopsin gene in 101 Neotropical cichlid species, spanning the diversity of the clade. We find strong evidence for increased rates of evolution in Central American cichlid rhodopsin relative to South American lineages, and identify several sites under positive selection in rhodopsin that likely contribute to adaptation to different photic environments. We expressed a Neotropical cichlid rhodopsin protein invitro for the first time, and found that while its spectral tuning properties were characteristic of typical vertebrate rhodopsin pigments, the rate of decay of its active signalling form was much slower, consistent with dim light adaptation in other vertebrate rhodopsins. Using site-directed mutagenesis combined with spectroscopic assays, we found that a key amino acid substitution present in some Central American cichlids accelerates the rate of decay of active rhodopsin, which may mediate adaptation to clear water habitats. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data

    OpenAIRE

    Ezer, Daphne; Moignard, Victoria; G?ttgens, Berthold; Adryan, Boris

    2016-01-01

    Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete ...

  1. The MPI facial expression database--a validated database of emotional and conversational facial expressions.

    Directory of Open Access Journals (Sweden)

    Kathrin Kaulard

    Full Text Available The ability to communicate is one of the core aspects of human life. For this, we use not only verbal but also nonverbal signals of remarkable complexity. Among the latter, facial expressions belong to the most important information channels. Despite the large variety of facial expressions we use in daily life, research on facial expressions has so far mostly focused on the emotional aspect. Consequently, most databases of facial expressions available to the research community also include only emotional expressions, neglecting the largely unexplored aspect of conversational expressions. To fill this gap, we present the MPI facial expression database, which contains a large variety of natural emotional and conversational expressions. The database contains 55 different facial expressions performed by 19 German participants. Expressions were elicited with the help of a method-acting protocol, which guarantees both well-defined and natural facial expressions. The method-acting protocol was based on every-day scenarios, which are used to define the necessary context information for each expression. All facial expressions are available in three repetitions, in two intensities, as well as from three different camera angles. A detailed frame annotation is provided, from which a dynamic and a static version of the database have been created. In addition to describing the database in detail, we also present the results of an experiment with two conditions that serve to validate the context scenarios as well as the naturalness and recognizability of the video sequences. Our results provide clear evidence that conversational expressions can be recognized surprisingly well from visual information alone. The MPI facial expression database will enable researchers from different research fields (including the perceptual and cognitive sciences, but also affective computing, as well as computer vision to investigate the processing of a wider range of natural

  2. The MPI Facial Expression Database — A Validated Database of Emotional and Conversational Facial Expressions

    Science.gov (United States)

    Kaulard, Kathrin; Cunningham, Douglas W.; Bülthoff, Heinrich H.; Wallraven, Christian

    2012-01-01

    The ability to communicate is one of the core aspects of human life. For this, we use not only verbal but also nonverbal signals of remarkable complexity. Among the latter, facial expressions belong to the most important information channels. Despite the large variety of facial expressions we use in daily life, research on facial expressions has so far mostly focused on the emotional aspect. Consequently, most databases of facial expressions available to the research community also include only emotional expressions, neglecting the largely unexplored aspect of conversational expressions. To fill this gap, we present the MPI facial expression database, which contains a large variety of natural emotional and conversational expressions. The database contains 55 different facial expressions performed by 19 German participants. Expressions were elicited with the help of a method-acting protocol, which guarantees both well-defined and natural facial expressions. The method-acting protocol was based on every-day scenarios, which are used to define the necessary context information for each expression. All facial expressions are available in three repetitions, in two intensities, as well as from three different camera angles. A detailed frame annotation is provided, from which a dynamic and a static version of the database have been created. In addition to describing the database in detail, we also present the results of an experiment with two conditions that serve to validate the context scenarios as well as the naturalness and recognizability of the video sequences. Our results provide clear evidence that conversational expressions can be recognized surprisingly well from visual information alone. The MPI facial expression database will enable researchers from different research fields (including the perceptual and cognitive sciences, but also affective computing, as well as computer vision) to investigate the processing of a wider range of natural facial expressions

  3. Vitamin D Receptor Expression in Dogs

    Science.gov (United States)

    Gow, A.G.; Milne, E.; Drummond, D.; Smith, S.; Handel, I.; Mellanby, R.J.

    2018-01-01

    Background There is growing evidence linking low blood vitamin D concentration to numerous diseases in people and in dogs. Vitamin D influences cellular function by signaling through the vitamin D receptor (VDR). Little is known about which non‐skeletal tissues express the VDR or how inflammation influences its expression in the dog. Objectives To define which non‐skeletal canine tissues express the VDR and to investigate expression in inflamed small intestine. Animals Thirteen non‐skeletal tissues were collected prospectively from 6 control dogs. Thirty‐five dogs diagnosed with a chronic enteropathy (CE) and 24 control dogs were prospectively enrolled and duodenal biopsies were evaluated for VDR expression. Methods Prospective; blinded assessment of canine intestinal VDR. Dogs with CE were included once other identifiable causes of intestinal disease were excluded. Age matched controls were included with no intestinal clinical signs. VDR expression was assessed immunohistochemically in all samples, using a Rat IgG VDR monoclonal antibody. Quantitative real‐time polymerase chain reaction (qPCR) was also used for duodenal biopsies. Results VDR expression as assessed by immunohistochemistry (IHC) was highest in the kidney, duodenum, skin, ileum and spleen, and weak in the colon, heart, lymph node, liver, lung, and ovary. Gastric and testicular tissue did not express the VDR. There was no statistical difference in duodenal VDR expression between the 24 healthy dogs and 34 dogs with CE when quantified by either qPCR (P = 0.87) or IHC (P = 0.099). Conclusions and Clinical Importance The lack of down regulation of VDR expression in inflamed intestine contrasts with previous studies in humans. Our findings support future studies to investigate whether vitamin D and its analogues can be used to modulate intestinal inflammation in the dog. PMID:29469965

  4. The functional landscape of mouse gene expression

    Directory of Open Access Journals (Sweden)

    Zhang Wen

    2004-12-01

    Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

  5. Simultaneous Breast Expression in Breastfeeding Women Is More Efficacious Than Sequential Breast Expression

    Science.gov (United States)

    Garbin, Catherine P.; Hartmann, Peter E.; Kent, Jacqueline C.

    2012-01-01

    Abstract Introduction Simultaneous (SIM) breast expression saves mothers time compared with sequential (SEQ) expression, but it remains unclear whether the two methods differ in milk output efficiency and efficacy. Subjects and Methods The Showmilk device (Medela AG, Baar, Switzerland) was used to measure milk output and milk ejection during breast expression (electric pump) in 31 Australian breastfeeding mothers of term infants (median age, 19 weeks [interquartile range, 10–33 weeks]). The order of expression type (SIM/SEQ) and breast (left/right) was randomized. Results SIM expression yielded more milk ejections (p≤0.001) and greater amounts of milk at 2, 5, and 10 minutes (p≤0.01) and removed a greater total amount of milk (p≤0.01) and percentage of available milk (p<0.05) than SEQ expression. After SIM expression the cream content of both the overall (8.3% [p≤0.05]) and postexpression (12.6% [p≤0.001]) milk were greater. During SEQ expression, the breast expressed first had a shorter time to 50% and 80% of the total amount of milk than the breast expressed second (p≤0.05), but, overall, a similar percentage of available milk was removed from both breasts. Conclusions SIM expression stimulated more milk ejections and was a more efficient and efficacious method of expression, yielding milk with a higher energy content. PMID:23039397

  6. The Relations of Mothers' Negative Expressivity to Children's Experience and Expression of Negative Emotion

    Science.gov (United States)

    Valiente, Carlos; Eisenberg, Nancy; Shepard, Stephanie A.; Fabes, Richard A.; Cumberland, Amanda J.; Losoya, Sandra H.; Spinrad, Tracy L.

    2004-01-01

    Guided by the heuristic model proposed by Eisenberg et al. [Psychol. Inq. 9 (1998) 241], we examined the relations of mothers' reported and observed negative expressivity to children's (N = 159; 74 girls; M age = 7.67 years) experience and expression of emotion. Children's experience and/or expression of emotion in response to a distressing film…

  7. Recognition, Expression, and Understanding Facial Expressions of Emotion in Adolescents with Nonverbal and General Learning Disabilities

    Science.gov (United States)

    Bloom, Elana; Heath, Nancy

    2010-01-01

    Children with nonverbal learning disabilities (NVLD) have been found to be worse at recognizing facial expressions than children with verbal learning disabilities (LD) and without LD. However, little research has been done with adolescents. In addition, expressing and understanding facial expressions is yet to be studied among adolescents with LD…

  8. ["Les Impatients": expression through art].

    Science.gov (United States)

    Lamontagne, Céline; Palardy, Lorraine

    2015-01-01

    The organization called "Les Impatients" was founded in 1992. Using a unique model, Les Impatients welcomes those with mental health issues who would like to express themselves through art. Les Impatients offers free creative workshops and encourages exchanges with the community through the sharing of its participants' creations. The name Les Impatients reinforces the idea that the organization does not consider those attending its workshops as patients, but rather creators who are eager to heal, develop their craft and find their place in society. The participants contribute to the collective objective of breaking down the stigma that surrounds mental illness.Les Impatients collaborates with various mental health organizations in Quebec, such as the Institut universitaire en santé mentale de Montréal (IUSMM) affiliated to the Université de Montréal, Douglas Mental Health University Institute (DMHUI), the Centre de santé et services sociaux Drummond (CSSS Drummond) and the Centre de santé et services sociaux Pierre-Boucher (CSSS Pierre-Boucher). Les Impatients offers more than 48 workshops in eight different locations to around 450 participants each week.Dissemination activities, remarkable events, original projects: Les Impatients stands out through its realizations. Examples are exhibitions, collections of love letters, comic books, CD, concerts, and reading nights. The organization's originality resides in the exploration of the links between the work of the participants and that of professional artists. An illustration of this interest is the annual Parle-moi d'amour auction-exhibition, which has been one of Les Impatients' major events since 1999.As part of its mission, Les Impatients conserves the works of art created by the participants during the workshops. Its collection includes more than 15,000 works of art from Les Impatients as well as pieces donated by collectors of unconventional art, commonly known as "art brut" or "outsider art". The

  9. Micro-Expression Recognition Using Color Spaces.

    Science.gov (United States)

    Wang, Su-Jing; Yan, Wen-Jing; Li, Xiaobai; Zhao, Guoying; Zhou, Chun-Guang; Fu, Xiaolan; Yang, Minghao; Tao, Jianhua

    2015-12-01

    Micro-expressions are brief involuntary facial expressions that reveal genuine emotions and, thus, help detect lies. Because of their many promising applications, they have attracted the attention of researchers from various fields. Recent research reveals that two perceptual color spaces (CIELab and CIELuv) provide useful information for expression recognition. This paper is an extended version of our International Conference on Pattern Recognition paper, in which we propose a novel color space model, tensor independent color space (TICS), to help recognize micro-expressions. In this paper, we further show that CIELab and CIELuv are also helpful in recognizing micro-expressions, and we indicate why these three color spaces achieve better performance. A micro-expression color video clip is treated as a fourth-order tensor, i.e., a four-dimension array. The first two dimensions are the spatial information, the third is the temporal information, and the fourth is the color information. We transform the fourth dimension from RGB into TICS, in which the color components are as independent as possible. The combination of dynamic texture and independent color components achieves a higher accuracy than does that of RGB. In addition, we define a set of regions of interests (ROIs) based on the facial action coding system and calculated the dynamic texture histograms for each ROI. Experiments are conducted on two micro-expression databases, CASME and CASME 2, and the results show that the performances for TICS, CIELab, and CIELuv are better than those for RGB or gray.

  10. Glucose transporters: expression, regulation and cancer

    Directory of Open Access Journals (Sweden)

    RODOLFO A. MEDINA

    2002-01-01

    Full Text Available Mammalian cells depend on glucose as a major substrate for energy production. Glucose is transported into the cell via facilitative glucose transporters (GLUT present in all cell types. Many GLUT isoforms have been described and their expression is cell-specific and subject to hormonal and environmental control. The kinetic properties and substrate specificities of the different isoforms are specifically suited to the energy requirements of the particular cell types. Due to the ubiquitousness of these transporters, their differential expression is involved in various disease states such as diabetes, ischemia and cancer. The majority of cancers and isolated cancer cell lines over-express the GLUT family members which are present in the respective tissue of origin under non-cancerous conditions. Moreover, due to the requirement of energy to feed uncontrolled proliferation, cancer cells often express GLUTs which under normal conditions would not be present in these tissues. This over-expression is predominantly associated with the likelihood of metastasis and hence poor patient prognosis. This article presents a review of the current literature on the regulation and expression of GLUT family members and has compiled clinical and research data on GLUT expression in human cancers and in isolated human cancer cell lines.

  11. Regular Expression Matching and Operational Semantics

    Directory of Open Access Journals (Sweden)

    Asiri Rathnayake

    2011-08-01

    Full Text Available Many programming languages and tools, ranging from grep to the Java String library, contain regular expression matchers. Rather than first translating a regular expression into a deterministic finite automaton, such implementations typically match the regular expression on the fly. Thus they can be seen as virtual machines interpreting the regular expression much as if it were a program with some non-deterministic constructs such as the Kleene star. We formalize this implementation technique for regular expression matching using operational semantics. Specifically, we derive a series of abstract machines, moving from the abstract definition of matching to increasingly realistic machines. First a continuation is added to the operational semantics to describe what remains to be matched after the current expression. Next, we represent the expression as a data structure using pointers, which enables redundant searches to be eliminated via testing for pointer equality. From there, we arrive both at Thompson's lockstep construction and a machine that performs some operations in parallel, suitable for implementation on a large number of cores, such as a GPU. We formalize the parallel machine using process algebra and report some preliminary experiments with an implementation on a graphics processor using CUDA.

  12. The Communicative Function of Sad Facial Expressions.

    Science.gov (United States)

    Reed, Lawrence Ian; DeScioli, Peter

    2017-01-01

    What are the communicative functions of sad facial expressions? Research shows that people feel sadness in response to losses but it's unclear whether sad expressions function to communicate losses to others and if so, what makes these signals credible. Here we use economic games to test the hypothesis that sad expressions lend credibility to claims of loss. Participants play the role of either a proposer or recipient in a game with a fictional backstory and real monetary payoffs. The proposers view a (fictional) video of the recipient's character displaying either a neutral or sad expression paired with a claim of loss. The proposer then decided how much money to give to the recipient. In three experiments, we test alternative theories by using situations in which the recipient's losses were uncertain (Experiment 1), the recipient's losses were certain (Experiment 2), or the recipient claims failed gains rather than losses (Experiment 3). Overall, we find that participants gave more money to recipients who displayed sad expressions compared to neutral expressions, but only under conditions of uncertain loss. This finding supports the hypothesis that sad expressions function to increase the credibility of claims of loss.

  13. Expressive Dissonance: When Emotional Inconsistency Arouses Dissonance

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    Audrey Pelt

    2018-05-01

    Full Text Available The aim of the two studies was to explore a new dissonance paradigm–expressive dissonance–based on the inconsistency between what people feel and what people express behaviorally. Expressive dissonance was aroused by asking participants to watch a film with a high emotional content, either positive (joy or negative (sadness. In the no-dissonance condition, they received the instruction to naturally watch the film. In the expressive dissonance condition, they received the instruction to facially express emotions that were the opposite of what they felt. We expected that the expressive dissonance situation would: 1 require cognitive resources leading to a decrease in cognitive performance (studies 1 and 2; 2 be accompanied by emotional regulation strategies (study 1; 3 be accompanied by an increase in dissonance-related affects (study 2. Although our results (studies 1 and 2 corroborated those obtained previously in terms of performance, they also showed that participants in the expressive dissonance situation use emotional regulation strategies: exaggeration and suppression (study 1, and that they felt self-directed negative affects (study 2, just like the participants in a cognitive dissonance situation. These first results allowed us to establish a theoretical bridge between the theories of emotions–particularly those related to the emotional regulation processes–and to widen the scope of relevance of the dissonance theory.

  14. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

  15. Expression of multidrug resistance proteins in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Swati Shukla

    2017-11-01

    Full Text Available AIM: To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. METHODS: Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. RESULTS: Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1 expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION: Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.

  16. Facial Expression Recognition Through Machine Learning

    Directory of Open Access Journals (Sweden)

    Nazia Perveen

    2015-08-01

    Full Text Available Facial expressions communicate non-verbal cues which play an important role in interpersonal relations. Automatic recognition of facial expressions can be an important element of normal human-machine interfaces it might likewise be utilized as a part of behavioral science and in clinical practice. In spite of the fact that people perceive facial expressions for all intents and purposes immediately solid expression recognition by machine is still a challenge. From the point of view of automatic recognition a facial expression can be considered to comprise of disfigurements of the facial parts and their spatial relations or changes in the faces pigmentation. Research into automatic recognition of the facial expressions addresses the issues encompassing the representation and arrangement of static or dynamic qualities of these distortions or face pigmentation. We get results by utilizing the CVIPtools. We have taken train data set of six facial expressions of three persons and for train data set purpose we have total border mask sample 90 and 30 border mask sample for test data set purpose and we use RST- Invariant features and texture features for feature analysis and then classified them by using k- Nearest Neighbor classification algorithm. The maximum accuracy is 90.

  17. Family emotional expressiveness and family structure

    Directory of Open Access Journals (Sweden)

    Čotar-Konrad Sonja

    2016-01-01

    Full Text Available The present paper scrutinizes the relationship between family emotional expressiveness (i.e., the tendency to express dominant and/or submissive positive and negative emotions and components of family structure as proposed in Olson’s Circumplex model (i.e., cohesion and flexibility, family communication, and satisfaction in families with adolescents. The study was conducted on a sample of 514 Slovenian adolescents, who filled out two questionnaires: the Slovenian version of Family Emotional Expressiveness - FEQ and FACES IV. The results revealed that all four basic dimensions of family functioning were significantly associated with higher/more frequent expressions of positive submissive emotions, as well as with lower/less frequent expressions of negative dominant emotions. Moreover, expressions of negative submissive emotions explained a small, but significant amount of variance in three out of four family functioning variables (satisfaction, flexibility, and communication. The importance of particular aspects of emotional expressiveness for family cohesion, flexibility, communication, and satisfaction is discussed, and the relevance of present findings for family counselling is outlined.

  18. The Communicative Function of Sad Facial Expressions

    Directory of Open Access Journals (Sweden)

    Lawrence Ian Reed

    2017-03-01

    Full Text Available What are the communicative functions of sad facial expressions? Research shows that people feel sadness in response to losses but it’s unclear whether sad expressions function to communicate losses to others and if so, what makes these signals credible. Here we use economic games to test the hypothesis that sad expressions lend credibility to claims of loss. Participants play the role of either a proposer or recipient in a game with a fictional backstory and real monetary payoffs. The proposers view a (fictional video of the recipient’s character displaying either a neutral or sad expression paired with a claim of loss. The proposer then decided how much money to give to the recipient. In three experiments, we test alternative theories by using situations in which the recipient’s losses were uncertain (Experiment 1, the recipient’s losses were certain (Experiment 2, or the recipient claims failed gains rather than losses (Experiment 3. Overall, we find that participants gave more money to recipients who displayed sad expressions compared to neutral expressions, but only under conditions of uncertain loss. This finding supports the hypothesis that sad expressions function to increase the credibility of claims of loss.

  19. CNPase Expression in Olfactory Ensheathing Cells

    Directory of Open Access Journals (Sweden)

    Christine Radtke

    2011-01-01

    Full Text Available A large body of work supports the proposal that transplantation of olfactory ensheathing cells (OECs into nerve or spinal cord injuries can promote axonal regeneration and remyelination. Yet, some investigators have questioned whether the transplanted OECs associate with axons and form peripheral myelin, or if they recruit endogenous Schwann cells that form myelin. Olfactory bulbs from transgenic mice expressing the enhanced green fluorescent protein (eGFP under the control of the 2-3-cyclic nucleotide 3-phosphodiesterase (CNPase promoter were studied. CNPase is expressed in myelin-forming cells throughout their lineage. We examined CNPase expression in both in situ in the olfactory bulb and in vitro to determine if OECs express CNPase commensurate with their myelination potential. eGFP was observed in the outer nerve layer of the olfactory bulb. Dissociated OECs maintained in culture had both intense eGFP expression and CNPase immunostaining. Transplantation of OECs into transected peripheral nerve longitudinally associated with the regenerated axons. These data indicate that OECs in the outer nerve layer of the olfactory bulb of CNPase transgenic mice express CNPase. Thus, while OECs do not normally form myelin on olfactory nerve axons, their expression of CNPase is commensurate with their potential to form myelin when transplanted into injured peripheral nerve.

  20. Expression of multidrug resistance proteins in retinoblastoma.

    Science.gov (United States)

    Shukla, Swati; Srivastava, Arpna; Kumar, Sunil; Singh, Usha; Goswami, Sandeep; Chawla, Bhavna; Bajaj, Mandeep Singh; Kashyap, Seema; Kaur, Jasbir

    2017-01-01

    To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.

  1. Expression of multidrug resistance proteins in retinoblastoma

    Science.gov (United States)

    Shukla, Swati; Srivastava, Arpna; Kumar, Sunil; Singh, Usha; Goswami, Sandeep; Chawla, Bhavna; Bajaj, Mandeep Singh; Kashyap, Seema; Kaur, Jasbir

    2017-01-01

    AIM To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. METHODS Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. RESULTS Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy. PMID:29181307

  2. A comparative gene expression database for invertebrates

    Directory of Open Access Journals (Sweden)

    Ormestad Mattias

    2011-08-01

    Full Text Available Abstract Background As whole genome and transcriptome sequencing gets cheaper and faster, a great number of 'exotic' animal models are emerging, rapidly adding valuable data to the ever-expanding Evo-Devo field. All these new organisms serve as a fantastic resource for the research community, but the sheer amount of data, some published, some not, makes detailed comparison of gene expression patterns very difficult to summarize - a problem sometimes even noticeable within a single lab. The need to merge existing data with new information in an organized manner that is publicly available to the research community is now more necessary than ever. Description In order to offer a homogenous way of storing and handling gene expression patterns from a variety of organisms, we have developed the first web-based comparative gene expression database for invertebrates that allows species-specific as well as cross-species gene expression comparisons. The database can be queried by gene name, developmental stage and/or expression domains. Conclusions This database provides a unique tool for the Evo-Devo research community that allows the retrieval, analysis and comparison of gene expression patterns within or among species. In addition, this database enables a quick identification of putative syn-expression groups that can be used to initiate, among other things, gene regulatory network (GRN projects.

  3. Adaptive Evolution of Gene Expression in Drosophila.

    Science.gov (United States)

    Nourmohammad, Armita; Rambeau, Joachim; Held, Torsten; Kovacova, Viera; Berg, Johannes; Lässig, Michael

    2017-08-08

    Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Cyclin D1 expression in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

  5. Cyclin D1 expression in prostate carcinoma

    International Nuclear Information System (INIS)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S.; Tucci, S.; Muglia, V.F.; Reis, R.B. Dos; Silva, G.E.B.

    2014-01-01

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness

  6. Effects of Expressive Writing on Psychological and Physical Health: The Moderating Role of Emotional Expressivity

    Science.gov (United States)

    Haltom, Kate E.; Mulvenna, Catherine M.; Lieberman, Matthew D.; Stanton, Annette L.

    2013-01-01

    The current study assessed main effects and moderators (including emotional expressiveness, emotional processing and ambivalence over emotional expression) of the effects of expressive writing in a sample of healthy adults. Young adult participants (N = 116) were randomly assigned to write for 20 minutes on four occasions about deepest thoughts and feelings regarding their most stressful/traumatic event in the past five years (expressive writing) or about a control topic (control). Dependent variables were indicators of anxiety, depression, and physical symptoms. No significant effects of writing condition were evident on anxiety, depressive symptoms, or physical symptoms. Emotional expressiveness emerged as a significant moderator of anxiety outcomes, however. Within the expressive writing group, participants high in expressiveness evidenced a significant reduction in anxiety at three-month follow-up, and participants low in expressiveness showed a significant increase in anxiety. Expressiveness did not predict change in anxiety in the control group. These findings on anxiety are consistent with the matching hypothesis, which suggests that matching a person’s naturally elected coping approach with an assigned intervention is beneficial. These findings also suggest that expressive writing about a stressful event may be contraindicated for individuals who do not typically express emotions. PMID:23742666

  7. Expression-dependent susceptibility to face distortions in processing of facial expressions of emotion.

    Science.gov (United States)

    Guo, Kun; Soornack, Yoshi; Settle, Rebecca

    2018-03-05

    Our capability of recognizing facial expressions of emotion under different viewing conditions implies the existence of an invariant expression representation. As natural visual signals are often distorted and our perceptual strategy changes with external noise level, it is essential to understand how expression perception is susceptible to face distortion and whether the same facial cues are used to process high- and low-quality face images. We systematically manipulated face image resolution (experiment 1) and blur (experiment 2), and measured participants' expression categorization accuracy, perceived expression intensity and associated gaze patterns. Our analysis revealed a reasonable tolerance to face distortion in expression perception. Reducing image resolution up to 48 × 64 pixels or increasing image blur up to 15 cycles/image had little impact on expression assessment and associated gaze behaviour. Further distortion led to decreased expression categorization accuracy and intensity rating, increased reaction time and fixation duration, and stronger central fixation bias which was not driven by distortion-induced changes in local image saliency. Interestingly, the observed distortion effects were expression-dependent with less deterioration impact on happy and surprise expressions, suggesting this distortion-invariant facial expression perception might be achieved through the categorical model involving a non-linear configural combination of local facial features. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Regulation of Gene Expression in Protozoa Parasites

    Directory of Open Access Journals (Sweden)

    Consuelo Gomez

    2010-01-01

    Full Text Available Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

  9. Regulation of gene expression in protozoa parasites.

    Science.gov (United States)

    Gomez, Consuelo; Esther Ramirez, M; Calixto-Galvez, Mercedes; Medel, Olivia; Rodríguez, Mario A

    2010-01-01

    Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

  10. Lunar Plants Prototype for Moon Express

    Data.gov (United States)

    National Aeronautics and Space Administration — The goal of our project is to bring the first full life cycle to the moon: to demonstrate germination of plants in lunar gravity and radiation.The Moon Express...

  11. Proteomic Analysis of Bacterial Expression Profiles Following ...

    African Journals Online (AJOL)

    mass spectrometry (GC-MS) were performed to determine the phytochemicals in the active fraction. Results: Five differentially expressed bacterial proteins (four from Escherichia coli and one from Staphylococcus aureus), were identified via ...

  12. Inferring gene networks from discrete expression data

    KAUST Repository

    Zhang, L.; Mallick, B. K.

    2013-01-01

    graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which

  13. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    blood glucose > 16.7 mmol/L were used as the model group and treated with Dendrobium mixture. (DEN ... Keywords: Diabetes, Gene expression, Dendrobium mixture, Microarray testing ..... homeostasis in airway smooth muscle. Am J.

  14. Decreased decorin expression in the tumor microenvironment

    International Nuclear Information System (INIS)

    Bozoky, Benedek; Savchenko, Andrii; Guven, Hayrettin; Ponten, Fredrik; Klein, George; Szekely, Laszlo

    2014-01-01

    Decorin is a small leucine-rich proteoglycan, synthesized and deposited by fibroblasts in the stroma where it binds to collagen I. It sequesters several growth factors and antagonizes numerous members of the receptor tyrosine kinase family. In experimental murine systems, it acted as a potent tumor suppressor. Examining the Human Protein Atlas online database of immunostained tissue samples we have surveyed decorin expression in silico in several different tumor types, comparing them with corresponding normal tissues. We found that decorin is abundantly secreted and deposited in normal connective tissue but its expression is consistently decreased in the tumor microenvironment. We developed a software to quantitate the difference in expression. The presence of two closely related proteoglycans in the newly formed tumor stroma indicated that the decreased decorin expression was not caused by the delay in proteoglycan deposition in the newly formed connective tissue surrounding the tumor

  15. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease....... the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P bladder cell line HU609, SOX4...

  16. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    3Department of Natural Sciences, International Christian University, Mitaka, Tokyo 181-8585, Japan ... the changes of expression predicted from gene function suggested association ... ate School of Science and Technology, Niigata University.

  17. Drosophila melanogaster gene expression changes after spaceflight.

    Data.gov (United States)

    National Aeronautics and Space Administration — Gene expression levels were determined in 3rd instar and adult Drosophila melanogaster reared during spaceflight to elucidate the genetic and molecular mechanisms...

  18. Expression of maize prolamins in Escherichia Coli

    International Nuclear Information System (INIS)

    Wang, Szu-zhen; Esen, Asim

    1985-01-01

    We have constructed a cDNA expression library of developing corn (Zea manys L.) endosperm using plasmid pUC8 as vector and Escherichia coli strain DH1 as host. The expression library was screened with non-radioactive immunological probes to detect the expression of gamma-zein and alpha-zein. When anti-gamma-zein antibody was used as the probe, 23 colonies gave positive reactions. The lengths of cDNA inserts of the 23 colonies were found to be 250-900 base pairs. When anti-alpha zein antibody was used, however, fewer colonies gave positive reactions. The library was also screened by colony-hybridization with 32 P-labeled DNA probes. Based on immunological and hybridization screening of the library and other evidence, we conclude that alpha-zein was either toxic to E. coli cells or rapidly degraded whereas gamma-zein and its fragments were readily expressed. (author)

  19. Determinants of human adipose tissue gene expression

    DEFF Research Database (Denmark)

    Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

    2012-01-01

    weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong...... interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index...... on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently...

  20. Exertional Heat Illness and Human Gene Expression

    National Research Council Canada - National Science Library

    Sonna, L.A; Sawka, M. N; Lilly, C. M

    2007-01-01

    Microarray analysis of gene expression at the level of RNA has generated new insights into the relationship between cellular responses to acute heat shock in vitro, exercise, and exertional heat illness...

  1. Deriving Trading Rules Using Gene Expression Programming

    Directory of Open Access Journals (Sweden)

    Adrian VISOIU

    2011-01-01

    Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

  2. The human endolymphatic sac expresses natriuretic peptides

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2017-01-01

    : Several natriuretic peptides were found expressed significantly in the ES, including uroguanylin and brain natriuretic peptide, but also peptides regulating vascular tone, including adrenomedullin 2. In addition, both neurophysin and oxytocin (OXT) were found significantly expressed. All peptides were...... verified by immunohistochemistry. CONCLUSION: The present data support the hypothesis that the human ES may have an endocrine/paracrine capacity through expression of several peptides with potent natriuretic activity. Furthermore, the ES may influence the hypothalamo-pituitary-adrenal axis and may regulate...... vasopressin receptors and aquaporin-2 channels in the inner ear via OXT expression. We hypothesize that the ES is likely to regulate inner ear endolymphatic homeostasis, possibly through secretion of several peptides, but it may also influence systemic and/or intracranial blood pressure through direct...

  3. Expression Profiling of Tyrosine Kinase Genes

    National Research Council Canada - National Science Library

    Weier, Heinz

    2000-01-01

    ... of these genes parallels the progression of tumors to a more malignant phenotype. We developed a DNA micro-array based screening system to monitor the level of expression of tyrosine kinase (tk...

  4. Regulation of meiotic gene expression in plants

    Directory of Open Access Journals (Sweden)

    Adele eZhou

    2014-08-01

    Full Text Available With the recent advances in genomics and sequencing technologies, databases of transcriptomes representing many cellular processes have been built. Meiotic transcriptomes in plants have been studied in Arabidopsis thaliana, rice (Oryza sativa, wheat (Triticum aestivum, petunia (Petunia hybrida, sunflower (Helianthus annuus, and maize (Zea mays. Studies in all organisms, but particularly in plants, indicate that a very large number of genes are expressed during meiosis, though relatively few of them seem to be required for the completion of meiosis. In this review, we focus on gene expression at the RNA level and analyze the meiotic transcriptome datasets and explore expression patterns of known meiotic genes to elucidate how gene expression could be regulated during meiosis. We also discuss mechanisms, such as chromatin organization and non-coding RNAs, that might be involved in the regulation of meiotic transcription patterns.

  5. Temporal protein expression pattern in intracellular signalling ...

    Indian Academy of Sciences (India)

    Supplementary figure 1. Protein expression dynamics observed in Experiment, Synchronous and. Asynchronous simulation. .... molecular basis for T cell suppression by IL-10: CD28-asso- ciated IL-10 receptor inhibits CD28 tyrosine ...

  6. Identification of genes preferentially expressed during

    African Journals Online (AJOL)

    雨林木风

    2012-08-16

    Aug 16, 2012 ... The suppression subtractive hybridization (SSH) method conducted to generate ... which showed the lack of genomic information currently available for lily. ..... characterization of genes expressed during somatic embryo.

  7. Fast and compact regular expression matching

    DEFF Research Database (Denmark)

    Bille, Philip; Farach-Colton, Martin

    2008-01-01

    We study 4 problems in string matching, namely, regular expression matching, approximate regular expression matching, string edit distance, and subsequence indexing, on a standard word RAM model of computation that allows logarithmic-sized words to be manipulated in constant time. We show how...... to improve the space and/or remove a dependency on the alphabet size for each problem using either an improved tabulation technique of an existing algorithm or by combining known algorithms in a new way....

  8. Unsupervised learning of facial expression components

    OpenAIRE

    Egede, Joy Onyekachukwu

    2013-01-01

    The face is one of the most important means of non-verbal communication. A lot of information can be gotten about the emotional state of a person just by merely observing their facial expression. This is relatively easy in face to face communication but not so in human computer interaction. Supervised learning has been widely used by researchers to train machines to recognise facial expressions just like humans. However, supervised learning has significant limitations one of which is the fact...

  9. Gauge choice in Witten's energy expression

    International Nuclear Information System (INIS)

    Parker, T.H.

    1985-01-01

    Witten's equation Dpsi=0 can be interpreted as a gauge fixing condition for classical supergravity. We rigorously prove the existence of asymptotically constant solutions of the more general gauge condition Dpsi=Apsi for almost all endomorphisms A of the spin bundle. Each gives an expression for the gravitational energy similar to Witten's. These include the choice A=√R, which yields the particularly elegant energy expression first noticed by Deser. (orig.)

  10. Analytical expressions for the electron backscattering coefficient

    International Nuclear Information System (INIS)

    August, H.J.; Wernisch, J.

    1989-01-01

    Several analytical expressions for the electron backscattering coefficient for massive homogeneous samples are compared with experimental data, directing special attention to the dependence of this quantity on the electron acceleration energy. It is shown that this dependence generally cannot be neglected. The expression proposed by Hunger and Kuechler turns out to be better than that of Love and Scott, although even the better formula can be slightly improved by a small modification. (author)

  11. Le tappe italiane del Trimble Express 2010

    Directory of Open Access Journals (Sweden)

    Sandra Leonardi

    2010-03-01

    Full Text Available Trimble Express stopped over Italy Trimble Express stopped in Italy, in 6 cities. The european road show has been set up to promote the latest news regarding Trimble technologies such as Trimble Access, the software that offers to survey teams a new approach in surveying; Trimble Access expedites data collection, processing, analysis, and delivery through improved workflows, collaboration and control.

  12. Le tappe italiane del Trimble Express 2010

    Directory of Open Access Journals (Sweden)

    Sandra Leonardi

    2010-03-01

    Full Text Available Trimble Express stopped over ItalyTrimble Express stopped in Italy, in 6 cities. The european road show has been set up to promote the latest news regarding Trimble technologies such as Trimble Access, the software that offers to survey teams a new approach in surveying; Trimble Access expedites data collection, processing, analysis, and delivery through improved workflows, collaboration and control.

  13. Hepatocyte specific expression of human cloned genes

    Energy Technology Data Exchange (ETDEWEB)

    Cortese, R

    1986-01-01

    A large number of proteins are specifically synthesized in the hepatocyte. Only the adult liver expresses the complete repertoire of functions which are required at various stages during development. There is therefore a complex series of regulatory mechanisms responsible for the maintenance of the differentiated state and for the developmental and physiological variations in the pattern of gene expression. Human hepatoma cell lines HepG2 and Hep3B display a pattern of gene expression similar to adult and fetal liver, respectively; in contrast, cultured fibroblasts or HeLa cells do not express most of the liver specific genes. They have used these cell lines for transfection experiments with cloned human liver specific genes. DNA segments coding for alpha1-antitrypsin and retinol binding protein (two proteins synthesized both in fetal and adult liver) are expressed in the hepatoma cell lines HepG2 and Hep3B, but not in HeLa cells or fibroblasts. A DNA segment coding for haptoglobin (a protein synthesized only after birth) is only expressed in the hepatoma cell line HepG2 but not in Hep3B nor in non hepatic cell lines. The information for tissue specific expression is located in the 5' flanking region of all three genes. In vivo competition experiments show that these DNA segments bind to a common, apparently limiting, transacting factor. Conventional techniques (Bal deletions, site directed mutagenesis, etc.) have been used to precisely identify the DNA sequences responsible for these effects. The emerging picture is complex: they have identified multiple, separate transcriptional signals, essential for maximal promoter activation and tissue specific expression. Some of these signals show a negative effect on transcription in fibroblast cell lines.

  14. Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

    Directory of Open Access Journals (Sweden)

    Hossein Mostafavi

    2014-02-01

    Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

  15. Dlx homeobox gene family expression in osteoclasts.

    Science.gov (United States)

    Lézot, F; Thomas, B L; Blin-Wakkach, C; Castaneda, B; Bolanos, A; Hotton, D; Sharpe, P T; Heymann, D; Carles, G F; Grigoriadis, A E; Berdal, A

    2010-06-01

    Skeletal growth and homeostasis require the finely orchestrated secretion of mineralized tissue matrices by highly specialized cells, balanced with their degradation by osteoclasts. Time- and site-specific expression of Dlx and Msx homeobox genes in the cells secreting these matrices have been identified as important elements in the regulation of skeletal morphology. Such specific expression patterns have also been reported in osteoclasts for Msx genes. The aim of the present study was to establish the expression patterns of Dlx genes in osteoclasts and identify their function in regulating skeletal morphology. The expression patterns of all Dlx genes were examined during the whole osteoclastogenesis using different in vitro models. The results revealed that Dlx1 and Dlx2 are the only Dlx family members with a possible function in osteoclastogenesis as well as in mature osteoclasts. Dlx5 and Dlx6 were detected in the cultures but appear to be markers of monocytes and their derivatives. In vivo, Dlx2 expression in osteoclasts was examined using a Dlx2/LacZ transgenic mouse. Dlx2 is expressed in a subpopulation of osteoclasts in association with tooth, brain, nerve, and bone marrow volumetric growths. Altogether the present data suggest a role for Dlx2 in regulation of skeletal morphogenesis via functions within osteoclasts. (c) 2010 Wiley-Liss, Inc.

  16. Cyclin d1 expression in odontogenic cysts.

    Science.gov (United States)

    Taghavi, Nasim; Modabbernia, Shirin; Akbarzadeh, Alireza; Sajjadi, Samad

    2013-01-01

    In the present study expression of cyclin D1 in the epithelial lining of odontogenic keratocyst, radicular cyst, dentigerous cyst and glandular odontogenic cyst was investigated to compare proliferative activity in these lesions. Immunohistochemical staining of cyclin D1 on formalin-fixed, paraffin-embedded tissue sections of odontogenic keratocysts (n=23), dentigerous cysts (n=20), radicular cysts (n=20) and glandular odontogenic cysts (n=5) was performed by standard EnVision method. Then, slides were studied to evaluate the following parameters in epithelial lining of cysts: expression, expression pattern, staining intensity and localization of expression. The data analysis showed statistically significant difference in cyclin D1 expression in studied groups (p keratocysts, but difference was not statistically significant among groups respectively (p=0.204, 0.469). Considering expression localization, cyclin D1 positive cells in odontogenic keratocysts and dentigerous cysts were frequently confined in parabasal layer, different from radicular cysts and glandular odontogenic cysts. The difference was statistically significant (p keratocyst and the entire cystic epithelium of glandular odontogenic cysts comparing to dentigerous cysts and radicular cysts, implying the possible role of G1-S cell cycle phase disturbances in the aggressiveness of odontogenic keratocyst and glandular odontogenic cyst.

  17. Rho GTPase expression in human myeloid cells.

    Directory of Open Access Journals (Sweden)

    Suzanne F G van Helden

    Full Text Available Myeloid cells are critical for innate immunity and the initiation of adaptive immunity. Strict regulation of the adhesive and migratory behavior is essential for proper functioning of these cells. Rho GTPases are important regulators of adhesion and migration; however, it is unknown which Rho GTPases are expressed in different myeloid cells. Here, we use a qPCR-based approach to investigate Rho GTPase expression in myeloid cells.We found that the mRNAs encoding Cdc42, RhoQ, Rac1, Rac2, RhoA and RhoC are the most abundant. In addition, RhoG, RhoB, RhoF and RhoV are expressed at low levels or only in specific cell types. More differentiated cells along the monocyte-lineage display lower levels of Cdc42 and RhoV, while RhoC mRNA is more abundant. In addition, the Rho GTPase expression profile changes during dendritic cell maturation with Rac1 being upregulated and Rac2 downregulated. Finally, GM-CSF stimulation, during macrophage and osteoclast differentiation, leads to high expression of Rac2, while M-CSF induces high levels of RhoA, showing that these cytokines induce a distinct pattern. Our data uncover cell type specific modulation of the Rho GTPase expression profile in hematopoietic stem cells and in more differentiated cells of the myeloid lineage.

  18. Shadows alter facial expressions of Noh masks.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Kawai

    Full Text Available BACKGROUND: A Noh mask, worn by expert actors during performance on the Japanese traditional Noh drama, conveys various emotional expressions despite its fixed physical properties. How does the mask change its expressions? Shadows change subtly during the actual Noh drama, which plays a key role in creating elusive artistic enchantment. We here describe evidence from two experiments regarding how attached shadows of the Noh masks influence the observers' recognition of the emotional expressions. METHODOLOGY/PRINCIPAL FINDINGS: In Experiment 1, neutral-faced Noh masks having the attached shadows of the happy/sad masks were recognized as bearing happy/sad expressions, respectively. This was true for all four types of masks each of which represented a character differing in sex and age, even though the original characteristics of the masks also greatly influenced the evaluation of emotions. Experiment 2 further revealed that frontal Noh mask images having shadows of upward/downward tilted masks were evaluated as sad/happy, respectively. This was consistent with outcomes from preceding studies using actually tilted Noh mask images. CONCLUSIONS/SIGNIFICANCE: Results from the two experiments concur that purely manipulating attached shadows of the different types of Noh masks significantly alters the emotion recognition. These findings go in line with the mysterious facial expressions observed in Western paintings, such as the elusive qualities of Mona Lisa's smile. They also agree with the aesthetic principle of Japanese traditional art "yugen (profound grace and subtlety", which highly appreciates subtle emotional expressions in the darkness.

  19. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2017-04-24

    Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

  20. The molecular origin and evolution of dim-light vision in mammals.

    Science.gov (United States)

    Bickelmann, Constanze; Morrow, James M; Du, Jing; Schott, Ryan K; van Hazel, Ilke; Lim, Steve; Müller, Johannes; Chang, Belinda S W

    2015-11-01

    The nocturnal origin of mammals is a longstanding hypothesis that is considered instrumental for the evolution of endothermy, a potential key innovation in this successful clade. This hypothesis is primarily based on indirect anatomical inference from fossils. Here, we reconstruct the evolutionary history of rhodopsin--the vertebrate visual pigment mediating the first step in phototransduction at low-light levels--via codon-based model tests for selection, combined with gene resurrection methods that allow for the study of ancient proteins. Rhodopsin coding sequences were reconstructed for three key nodes: Amniota, Mammalia, and Theria. When expressed in vitro, all sequences generated stable visual pigments with λMAX values similar to the well-studied bovine rhodopsin. Retinal release rates of mammalian and therian ancestral rhodopsins, measured via fluorescence spectroscopy, were significantly slower than those of the amniote ancestor, indicating altered molecular function possibly related to nocturnality. Positive selection along the therian branch suggests adaptive evolution in rhodopsin concurrent with therian ecological diversification events during the Mesozoic that allowed for an exploration of the environment at varying light levels. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  1. Differential expression of granulopoiesis related genes in neutrophil subsets distinguished by membrane expression of CD177

    DEFF Research Database (Denmark)

    Hu, Nan; Mora-Jensen, Helena; Theilgaard-Mønch, Kim

    2014-01-01

    OBJECTIVE: Differential gene expression in CD177+ and CD177- neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). METHODS: Neutrophils were isolated from healthy controls (HC......) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177- subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177- subsets in microarray analysis were re-assessed using...... quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. RESULTS: The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177...

  2. cis sequence effects on gene expression

    Directory of Open Access Journals (Sweden)

    Jacobs Kevin

    2007-08-01

    Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

  3. Metallothionein gene expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Deeksha Pal

    2014-01-01

    Full Text Available Introduction: Metallothioneins (MTs are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1 the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2 apoptosis and (3 the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC. No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01 in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05, while no change was observed in high-grade tumor (grade III and IV in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis.

  4. Channel properties of Nax expressed in neurons.

    Directory of Open Access Journals (Sweden)

    Masahito Matsumoto

    Full Text Available Nax is a sodium-concentration ([Na+]-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95 through its PSD95/Disc-large/ZO-1 (PDZ-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells.

  5. LocExpress: a web server for efficiently estimating expression of novel transcripts.

    Science.gov (United States)

    Hou, Mei; Tian, Feng; Jiang, Shuai; Kong, Lei; Yang, Dechang; Gao, Ge

    2016-12-22

    The temporal and spatial-specific expression pattern of a transcript in multiple tissues and cell types can indicate key clues about its function. While several gene atlas available online as pre-computed databases for known gene models, it's still challenging to get expression profile for previously uncharacterized (i.e. novel) transcripts efficiently. Here we developed LocExpress, a web server for efficiently estimating expression of novel transcripts across multiple tissues and cell types in human (20 normal tissues/cells types and 14 cell lines) as well as in mouse (24 normal tissues/cell types and nine cell lines). As a wrapper to RNA-Seq quantification algorithm, LocExpress efficiently reduces the time cost by making abundance estimation calls increasingly within the minimum spanning bundle region of input transcripts. For a given novel gene model, such local context-oriented strategy allows LocExpress to estimate its FPKMs in hundreds of samples within minutes on a standard Linux box, making an online web server possible. To the best of our knowledge, LocExpress is the only web server to provide nearly real-time expression estimation for novel transcripts in common tissues and cell types. The server is publicly available at http://loc-express.cbi.pku.edu.cn .

  6. Morphing between expressions dissociates continuous from categorical representations of facial expression in the human brain

    Science.gov (United States)

    Harris, Richard J.; Young, Andrew W.; Andrews, Timothy J.

    2012-01-01

    Whether the brain represents facial expressions as perceptual continua or as emotion categories remains controversial. Here, we measured the neural response to morphed images to directly address how facial expressions of emotion are represented in the brain. We found that face-selective regions in the posterior superior temporal sulcus and the amygdala responded selectively to changes in facial expression, independent of changes in identity. We then asked whether the responses in these regions reflected categorical or continuous neural representations of facial expression. Participants viewed images from continua generated by morphing between faces posing different expressions such that the expression could be the same, could involve a physical change but convey the same emotion, or could differ by the same physical amount but be perceived as two different emotions. We found that the posterior superior temporal sulcus was equally sensitive to all changes in facial expression, consistent with a continuous representation. In contrast, the amygdala was only sensitive to changes in expression that altered the perceived emotion, demonstrating a more categorical representation. These results offer a resolution to the controversy about how facial expression is processed in the brain by showing that both continuous and categorical representations underlie our ability to extract this important social cue. PMID:23213218

  7. Expression of Na,K-ATPase and H,K-ATPase Isoforms with the Baculovirus Expression System

    NARCIS (Netherlands)

    Koenderink, J.B.; Swarts, H.G.

    2016-01-01

    P-type ATPases can be expressed in several cell systems. The baculovirus expressions system uses an insect virus to enter and express proteins in Sf9 insect cells. This expression system is a lytic system in which the cells will die a few days after viral infection. Subsequently, the expressed

  8. Gene expression analysis of flax seed development

    Science.gov (United States)

    2011-01-01

    Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise

  9. Gene expression analysis of flax seed development

    Directory of Open Access Journals (Sweden)

    Sharpe Andrew

    2011-04-01

    Full Text Available Abstract Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages seed coats (globular and torpedo stages and endosperm (pooled globular to torpedo stages and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST (GenBank accessions LIBEST_026995 to LIBEST_027011 were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152 had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid

  10. Transgene expression in cowpea ( Vigna unguiculata (L.) Walp ...

    African Journals Online (AJOL)

    Transgene expression in cowpea ( Vigna unguiculata (L.) Walp.) ... and Bar genes for β-glucuronidase expression and bialaphos resistance respectively. ... expression also showed positive signals under PCR and Southern analysis giving ...

  11. Three new shuttle vectors for heterologous expression in Zymomonas mobilis

    Directory of Open Access Journals (Sweden)

    Qinghua Cao

    2016-01-01

    Conclusions: These results indicated that these expression vectors are useful tools for gene expression in Z. mobilis and this could provide a solid foundation for further studies of heterologous gene expression in Z. mobilis.

  12. Preventing, detecting & revising flaws in object property expressions

    CSIR Research Space (South Africa)

    Keet, CM

    2013-09-01

    Full Text Available The OWL 2 DL ontology language is very expressive and has many features for declaring complex object property expressions. Standard reasoning services for OWL ontologies take these expressions as correct and according to the ontologist's intention...

  13. Processing of emotional facial expressions in Korsakoff's syndrome.

    NARCIS (Netherlands)

    Montagne, B.; Kessels, R.P.C.; Wester, A.J.; Haan, E.H.F. de

    2006-01-01

    Interpersonal contacts depend to a large extent on understanding emotional facial expressions of others. Several neurological conditions may affect proficiency in emotional expression recognition. It has been shown that chronic alcoholics are impaired in labelling emotional expressions. More

  14. Time perception and dynamics of facial expressions of emotions.

    Directory of Open Access Journals (Sweden)

    Sophie L Fayolle

    Full Text Available Two experiments were run to examine the effects of dynamic displays of facial expressions of emotions on time judgments. The participants were given a temporal bisection task with emotional facial expressions presented in a dynamic or a static display. Two emotional facial expressions and a neutral expression were tested and compared. Each of the emotional expressions had the same affective valence (unpleasant, but one was high-arousing (expressing anger and the other low-arousing (expressing sadness. Our results showed that time judgments are highly sensitive to movements in facial expressions and the emotions expressed. Indeed, longer perceived durations were found in response to the dynamic faces and the high-arousing emotional expressions compared to the static faces and low-arousing expressions. In addition, the facial movements amplified the effect of emotions on time perception. Dynamic facial expressions are thus interesting tools for examining variations in temporal judgments in different social contexts.

  15. Decomposition of gene expression state space trajectories.

    Directory of Open Access Journals (Sweden)

    Jessica C Mar

    2009-12-01

    Full Text Available Representing and analyzing complex networks remains a roadblock to creating dynamic network models of biological processes and pathways. The study of cell fate transitions can reveal much about the transcriptional regulatory programs that underlie these phenotypic changes and give rise to the coordinated patterns in expression changes that we observe. The application of gene expression state space trajectories to capture cell fate transitions at the genome-wide level is one approach currently used in the literature. In this paper, we analyze the gene expression dataset of Huang et al. (2005 which follows the differentiation of promyelocytes into neutrophil-like cells in the presence of inducers dimethyl sulfoxide and all-trans retinoic acid. Huang et al. (2005 build on the work of Kauffman (2004 who raised the attractor hypothesis, stating that cells exist in an expression landscape and their expression trajectories converge towards attractive sites in this landscape. We propose an alternative interpretation that explains this convergent behavior by recognizing that there are two types of processes participating in these cell fate transitions-core processes that include the specific differentiation pathways of promyelocytes to neutrophils, and transient processes that capture those pathways and responses specific to the inducer. Using functional enrichment analyses, specific biological examples and an analysis of the trajectories and their core and transient components we provide a validation of our hypothesis using the Huang et al. (2005 dataset.

  16. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R

    2014-03-26

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  17. Pragmatic expressions in cross-linguistic perspective

    Directory of Open Access Journals (Sweden)

    Maryann Overstreet

    2012-09-01

    Full Text Available This paper focuses on some pragmatic expressions that are characteristic of informal spoken English, their possible equivalents in some other languages, and their use by EFL learners from different backgrounds. These expressions, called general extenders (e.g. and stuff, or something, are shown to be different from discourse markers and to exhibit variation in form, function and distribution across varieties of English, as well as in other languages. In EFL contexts, students are reported to use fewer pragmatic expressions and a smaller range of possible forms. They also tend to favor expressions more often associated with writing and formal speaking (e.g. and so on, include literal translation equivalents from their first language that are not used in English (e.g. and, and, and, or used only in restricted contexts (e.g. or so, and often seem not to realize that some forms may carry negative connotations (e.g. and blah, blah, blah. The possibility of fostering better pragmatic awareness among EFL students is discussed in terms of an explicit cross-linguistic focus on the forms and functions of pragmatic expressions.

  18. The perception of emotion in body expressions.

    Science.gov (United States)

    de Gelder, B; de Borst, A W; Watson, R

    2015-01-01

    During communication, we perceive and express emotional information through many different channels, including facial expressions, prosody, body motion, and posture. Although historically the human body has been perceived primarily as a tool for actions, there is now increased understanding that the body is also an important medium for emotional expression. Indeed, research on emotional body language is rapidly emerging as a new field in cognitive and affective neuroscience. This article reviews how whole-body signals are processed and understood, at the behavioral and neural levels, with specific reference to their role in emotional communication. The first part of this review outlines brain regions and spectrotemporal dynamics underlying perception of isolated neutral and affective bodies, the second part details the contextual effects on body emotion recognition, and final part discusses body processing on a subconscious level. More specifically, research has shown that body expressions as compared with neutral bodies draw upon a larger network of regions responsible for action observation and preparation, emotion processing, body processing, and integrative processes. Results from neurotypical populations and masking paradigms suggest that subconscious processing of affective bodies relies on a specific subset of these regions. Moreover, recent evidence has shown that emotional information from the face, voice, and body all interact, with body motion and posture often highlighting and intensifying the emotion expressed in the face and voice. © 2014 John Wiley & Sons, Ltd.

  19. A validated battery of vocal emotional expressions

    Directory of Open Access Journals (Sweden)

    Pierre Maurage

    2007-11-01

    Full Text Available For a long time, the exploration of emotions focused on facial expression, and vocal expression of emotion has only recently received interest. However, no validated battery of emotional vocal expressions has been published and made available to the researchers’ community. This paper aims at validating and proposing such material. 20 actors (10 men recorded sounds (words and interjections expressing six basic emotions (anger, disgust, fear, happiness, neutral and sadness. These stimuli were then submitted to a double validation phase: (1 preselection by experts; (2 quantitative and qualitative validation by 70 participants. 195 stimuli were selected for the final battery, each one depicting a precise emotion. The ratings provide a complete measure of intensity and specificity for each stimulus. This paper provides, to our knowledge, the first validated, freely available and highly standardized battery of emotional vocal expressions (words and intonations. This battery could constitute an interesting tool for the exploration of prosody processing among normal and pathological populations, in neuropsychology as well as psychiatry. Further works are nevertheless needed to complement the present material.

  20. IL-21 Receptor Expression in Human Tendinopathy

    Directory of Open Access Journals (Sweden)

    Abigail L. Campbell

    2014-01-01

    Full Text Available The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

  1. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, John Kenneth; De Hoon, Michiel Jl L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha Madhusudan; Jurman, Giuseppe; Kaczkowski, Bogumił; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Mungall, Christopher J.; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Meehan, Terrence F.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, Svend Peter; Knox, Alan; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Schmeier, Sebastian; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Bertin, Nicolas; Lipovich, Leonard; MacKay-Sim, Alan; Manabe, Riichiroh; Mar, Jessica; Marchand, Benoî t; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison M.; Mizuno, Yosuke; De Morais, David A Lima; Jø rgensen, Mette Christine; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Dimont, Emmanuel; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; Van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Arner, Erik; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert C J J; Patrikakis, Margaret; Schmidl, Christian; Persson, Helena A.; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Schaefer, Ulf; Rye, Morten Beck; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Medvedeva, Yulia; Schneider, Claudio H.; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Chris M.; Plessy, Charles; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter Ac Chr; Tagami, Michihira; Tagami, Naokotakahashi; Takai, Jun; Tanaka, Hiroshi; Vitezic, Morana; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; Van De Wetering, Marc L.; Van Den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Severin, Jessica M.; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise Natalie; Wolvetang, Ernst Jurgen; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Semple, Colin Am M; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten Olivier; Kawai, Jun; Ishizu, Yuri; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Young, Robert S.; Hayashizaki, Yoshihide Yoshihide; Francescatto, Margherita; Altschuler, Intikhab Alam; Albanese, Davide; Altschule, Gabriel M.; Arakawa, Takahiro; Archer, John A.C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James A.; Brombacher, Frank; Burroughs, Alexander Maxwell; Califano, Andrea C.; Cannistraci, Carlo; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie Anne; Detmar, Michael J.; Diehl, Alexander D.; Dohi, Taeko; Drablø s, Finn; Edge, Albert SB B; Edinger, Matthias G.; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey R.; Fang, Hai; Farach-Carson, Mary Cindy; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Junichi; Geijtenbeek, Teunis Bh H; Gibson, Andrew P.; Gingeras, Thomas R.; Goldowitz, Dan; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard F.; Hitchens, Kelly J.; Sui, Shannan J Ho; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Łukasz B.

    2014-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  2. Differential gene expression during Trypanosoma cruzi metacyclogenesis

    Directory of Open Access Journals (Sweden)

    Marco Aurelio Krieger

    1999-09-01

    Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

  3. Developmental Hypothyroidism Reduces the Expression of ...

    Science.gov (United States)

    Disruption of thyroid hormone (TH) is a known effect of environmental contaminants. Neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been implicated in brain dysfunction resulting from severe developmental TH insufficiency. Neurotrophins are also implicated in activity-dependent plasticity, a process critical for appropriate use-dependent connectivity in the developing brain and for memory formation in the adult. This study examined activity-induced expression of neurotrophin gene products in the hippocampus using the long-term potentiation (LTP) after developmental hypothyroidism induced by propylthiouracil (PTU). Pregnant rats were exposed to PTU (0 or I0ppm) via the drinking water from early gestation to weaning. Adult male offspring were anesthetized with urethane and implanted with electrodes in the dentate gyrus (00) and perforant path (PP). LTP was induced by PP stimulation and responses from 00 were monitored at 15m intervals until sacrifice of the animals 5 h later. The 00 was dissected from the stimulated and nonstimulated hemispheres for rtPCR analysis of the neurotrophins Bdnf, Ngf, Ntf3 and related genes Egrl, Arc, Klf9. We found no PTU-induced difference in basal levels of expression of any of these genes in the nonstimulated 00. LTP increased expression of Bdnf, Ngf, Arc and Klj9 in the control DG, and reduced expression of Ntf3. LTP in DG from PTU animals failed to increase expression of Bdnf,

  4. Mothers' pupillary responses to infant facial expressions.

    Science.gov (United States)

    Yrttiaho, Santeri; Niehaus, Dana; Thomas, Eileen; Leppänen, Jukka M

    2017-02-06

    Human parental care relies heavily on the ability to monitor and respond to a child's affective states. The current study examined pupil diameter as a potential physiological index of mothers' affective response to infant facial expressions. Pupillary time-series were measured from 86 mothers of young infants in response to an array of photographic infant faces falling into four emotive categories based on valence (positive vs. negative) and arousal (mild vs. strong). Pupil dilation was highly sensitive to the valence of facial expressions, being larger for negative vs. positive facial expressions. A separate control experiment with luminance-matched non-face stimuli indicated that the valence effect was specific to facial expressions and cannot be explained by luminance confounds. Pupil response was not sensitive to the arousal level of facial expressions. The results show the feasibility of using pupil diameter as a marker of mothers' affective responses to ecologically valid infant stimuli and point to a particularly prompt maternal response to infant distress cues.

  5. Function and Evolutionary Origin of Unicellular Camera-Type Eye Structure

    KAUST Repository

    Hayakawa, Shiho; Takaku, Yasuharu; Hwang, Jung Shan; Horiguchi, Takeo; Suga, Hiroshi; Gehring, Walter; Ikeo, Kazuho; Gojobori, Takashi

    2015-01-01

    The ocelloid is an extraordinary eyespot organelle found only in the dinoflagellate family Warnowiaceae. It contains retina- and lens-like structures called the retinal body and the hyalosome. The ocelloid has been an evolutionary enigma because of its remarkable resemblance to the multicellular camera-type eye. To determine if the ocelloid is functionally photoreceptive, we investigated the warnowiid dinoflagellate Erythropsidinium. Here, we show that the morphology of the retinal body changed depending on different illumination conditions and the hyalosome manifests the refractile nature. Identifying a rhodopsin gene fragment in Erythropsidinium ESTs that is expressed in the retinal body by in situ hybridization, we also show that ocelloids are actually light sensitive photoreceptors. The rhodopsin gene identified is most closely related to bacterial rhodopsins. Taken together, we suggest that the ocelloid is an intracellular camera-type eye, which might be originated from endosymbiotic origin. © 2015 Hayakawa et al.

  6. Function and Evolutionary Origin of Unicellular Camera-Type Eye Structure

    KAUST Repository

    Hayakawa, Shiho

    2015-03-03

    The ocelloid is an extraordinary eyespot organelle found only in the dinoflagellate family Warnowiaceae. It contains retina- and lens-like structures called the retinal body and the hyalosome. The ocelloid has been an evolutionary enigma because of its remarkable resemblance to the multicellular camera-type eye. To determine if the ocelloid is functionally photoreceptive, we investigated the warnowiid dinoflagellate Erythropsidinium. Here, we show that the morphology of the retinal body changed depending on different illumination conditions and the hyalosome manifests the refractile nature. Identifying a rhodopsin gene fragment in Erythropsidinium ESTs that is expressed in the retinal body by in situ hybridization, we also show that ocelloids are actually light sensitive photoreceptors. The rhodopsin gene identified is most closely related to bacterial rhodopsins. Taken together, we suggest that the ocelloid is an intracellular camera-type eye, which might be originated from endosymbiotic origin. © 2015 Hayakawa et al.

  7. Evaluating Haskell expressions in a tutoring environment

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    Tim Olmer

    2014-12-01

    Full Text Available A number of introductory textbooks for Haskell use calculations right from the start to give the reader insight into the evaluation of expressions and the behavior of functional programs. Many programming concepts that are important in the functional programming paradigm, such as recursion, higher-order functions, pattern-matching, and lazy evaluation, can be partially explained by showing a stepwise computation. A student gets a better understanding of these concepts if she performs these evaluation steps herself. Tool support for experimenting with the evaluation of Haskell expressions is currently lacking. In this paper we present a prototype implementation of a stepwise evaluator for Haskell expressions that supports multiple evaluation strategies, specifically targeted at education. Besides performing evaluation steps the tool also diagnoses steps that are submitted by a student, and provides feedback. Instructors can add or change function definitions without knowledge of the tool's internal implementation. We discuss some preliminary results of a small survey about the tool.

  8. IER3 Expression in Childhood Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

    Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3...... (IER3) gene, which is located on chromosome 6p21, encodes for a glycoprotein that plays a role in the regulation of apoptosis and cell cycle progression. Recently, it was shown that IER3 gene aberrations frequently occur in adult MDS patients, which are not restricted to patients with chromosome 6...... aberrations and that low IER3 expression was associated with a worse outcome. Therefore, we investigated the frequency and prognostic impact of IER3 expression in childhood MDS. Methods: IER3 mRNA expression was determined by quantitative real-time PCR in 58 childhood MDS patients of which 17 carried...

  9. Greater perceptual sensitivity to happy facial expression.

    Science.gov (United States)

    Maher, Stephen; Ekstrom, Tor; Chen, Yue

    2014-01-01

    Perception of subtle facial expressions is essential for social functioning; yet it is unclear if human perceptual sensitivities differ in detecting varying types of facial emotions. Evidence diverges as to whether salient negative versus positive emotions (such as sadness versus happiness) are preferentially processed. Here, we measured perceptual thresholds for the detection of four types of emotion in faces--happiness, fear, anger, and sadness--using psychophysical methods. We also evaluated the association of the perceptual performances with facial morphological changes between neutral and respective emotion types. Human observers were highly sensitive to happiness compared with the other emotional expressions. Further, this heightened perceptual sensitivity to happy expressions can be attributed largely to the emotion-induced morphological change of a particular facial feature (end-lip raise).

  10. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael

    2010-01-01

    Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug......-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments....... In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We...

  11. Podocalyxin expression in malignant astrocytic tumors

    International Nuclear Information System (INIS)

    Hayatsu, Norihito; Kaneko, Mika Kato; Mishima, Kazuhiko; Nishikawa, Ryo; Matsutani, Masao; Price, Janet E.; Kato, Yukinari

    2008-01-01

    Podocalyxin is an anti-adhesive mucin-like transmembrane sialoglycoprotein that has been implicated in the development of aggressive forms of cancer. Podocalyxin is also known as keratan sulfate (KS) proteoglycan. Recently, we revealed that highly sulfated KS or another mucin-like transmembrane sialoglycoprotein podoplanin/aggrus is upregulated in malignant astrocytic tumors. The aim of this study is to examine the relationship between podocalyxin expression and malignant progression of astrocytic tumors. In this study, 51 astrocytic tumors were investigated for podocalyxin expression using immunohistochemistry, Western blot analysis, and quantitative real-time PCR. Immunohistochemistry detected podocalyxin on the surface of tumor cells in six of 14 anaplastic astrocytomas (42.9%) and in 17 of 31 glioblastomas (54.8%), especially around proliferating endothelial cells. In diffuse astrocytoma, podocalyxin expression was observed only in vascular endothelial cells. Podocalyxin might be associated with the malignant progression of astrocytic tumors, and be a useful prognostic marker for astrocytic tumors

  12. EXPRESSING DISTRESS IN PATIENTS WITH ADVANCED CANCER

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    Maura Gabriela FELEA

    2014-11-01

    Full Text Available Negative emotions (distress are recognized as part of the psychological profile of patients diagnosed with advanced stage cancer. However, most patients are not accustomed to verbalize feelings towards their physician, and generally towards family and medical care personnel. The purpose of this paper is to analyze the expression of emotions by patients in advanced stages of cancer, respectively the means by which they get to express emotions. To this respect, we identified the most common types of emotions expressed, or metaphors used by patients to describe their emotions and topics that trigger emotions. Words and phrases most commonly used are in relation to: fear, anxiety, depression, guilt, negligence, concern. They are uttered in order to depict the network created between disclosed emotions and topics on health status, symptoms, adverse effects and therapeutic choice, patient privacy, and social and family issues.

  13. Snail1 Expression Is Required for Sarcomagenesis

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    Lorena Alba-Castellón

    2014-05-01

    Full Text Available Snail1 transcriptional repressor is a major inducer of epithelial-to mesenchymal transition but is very limitedly expressed in adult animals. We have previously demonstrated that Snail1 is required for the maintenance of mesenchymal stem cells (MSCs, preventing their premature differentiation. Now, we show that Snail1 controls the tumorigenic properties of mesenchymal cells. Increased Snail1 expression provides tumorigenic capabilities to fibroblastic cells; on the contrary, Snail1 depletion decreases tumor growth. Genetic depletion of Snail1 in MSCs that are deficient in p53 tumor suppressor downregulates MSC markers and prevents the capability of these cells to originate sarcomas in immunodeficient SCID mice. Notably, an analysis of human sarcomas shows that, contrarily to epithelial tumors, these neoplasms display high Snail1 expression. This is particularly clear for undifferentiated tumors, which are associated with poor outcome. Together, our results indicate a role for Snail1 in the generation of sarcomas.

  14. Mental Health and Emotional Expression in Facebook

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    Eglee Duran Rodríguez

    2013-12-01

    Full Text Available The article reports the results of the project “Mental health and emotional expression in Facebook”. The research was approached from the qualitative paradigm under virtual ethnographic approach, interpreting the findings through their own players and triangulated with the views of researchers and experts in the area of mental health, emotions and information technology and communication. We concluded that a good part of users vented their secrets on Facebook, where they are able to confide and express a range of emotions and intimacies that in the real context is unlikely to give. Along these findings show that the use of Facebook serves as a space for emotional expression impacting the mental and emotional health.

  15. Structural development of child's artistic expression

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    Sanja Filipović

    2017-03-01

    Full Text Available Structural development implies control and capability of the expression usage in terms of independent creative expression and making. Understanding of structural development of child's artistic expression as a phenomenon (which is suitable to child's age has some implications on methodical acts considering the artistic education of children and youngsters. Therefore, it is of unexceptional importance to know these laws as well as methodical acts which encourage the structural development of artistic capabilities from an early age. Various experts dealt with this phenomenon, particularly Bogomil Karlavaris. In his methodical research, he has given an unexceptional part to this problem. It has been a starting point for analysis of certain methodical questions which are included in this work.

  16. Capsular Polysaccharide Expression in Commensal Streptococcus Species

    DEFF Research Database (Denmark)

    Skov Sørensen, Uffe B; Yao, Kaihu; Yang, Yonghong

    2016-01-01

    Expression of a capsular polysaccharide is considered a hallmark of most invasive species of bacteria, including Streptococcus pneumoniae, in which the capsule is among the principal virulence factors and is the basis for successful vaccines. Consequently, it was previously assumed that capsule....... pneumoniae evolved by import of cps fragments from commensal Streptococcus species, resulting in a mosaic of genes of different origins. The demonstrated antigenic identity of at least eight of the numerous capsular polysaccharide structures expressed by commensal streptococci with recognized serotypes of S...... of Streptococcus pneumoniae and is the basis for successful vaccines against infections caused by this important pathogen. Contrasting with previous assumptions, this study showed that expression of capsular polysaccharides by the same genetic mechanisms is a general property of closely related species...

  17. Brachyury expression in tailless Molgulid ascidian embryos.

    Science.gov (United States)

    Takada, Norio; York, Jonathan; Davis, J Muse; Schumpert, Brenda; Yasuo, Hitoyoshi; Satoh, Nori; Swalla, Billie J

    2002-01-01

    The T-box transcription factor gene Brachyury is important for the differentiation of notochord in all chordates, including the ascidians Halocynthia roretzi and Ciona intestinalis. We isolated Brachyury from molgulid ascidians, which have evolved tailless larvae multiple times independently, and found the genes appear functional by cDNA sequence analyses. We then compared the expression of Mocu-Bra in tailed Molgula oculata embryos to two tailless species, Molgula occulta (Mocc-Bra) and Molgula tectiformis (Mt-Bra). Here we show that both tailless species express Brachyury in the notochord lineage during embryogenesis. Initial expression of Mocu-Bra is normal in tailed M. oculata embryos; 10 precursor notochord cells divide twice to result in 40 notochord cells that converge and extend to make a notochord down the center of the tail. In contrast, in tailless Molgula occulta, Mocc-Bra expression disappears prematurely, and there is only one round of division, resulting in 20 cells in the final notochord lineage that never converge or extend. In M. occulta x M. oculata hybrid embryos, expression of Mocu-Bra is prolonged, and the embryos form a tail with 20 notochord cells that converge and extend normally. However, in Molgula tectiformis, a different tailless ascidian, Mt-Bra was expressed only in the 10 notochord precursor cells, which never divide, converge, or extend. In summary, neither Brachyury function nor the early establishment of the notochord lineage appears to be impaired in tailless embryos. In light of these results, we are continuing to investigate how and why notochord development is lost in tailless molgulid ascidian embryos.

  18. Population-expression models of immune response

    International Nuclear Information System (INIS)

    Stromberg, Sean P; Antia, Rustom; Nemenman, Ilya

    2013-01-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable. (paper)

  19. Gene expression in periodontal tissues following treatment

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    Eisenacher Martin

    2008-07-01

    Full Text Available Abstract Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A, Versican (CSPG-2, Matrixmetalloproteinase-1 (MMP-1, Down syndrome critical region protein-1 (DSCR-1, Macrophage inflammatory protein-2β (Cxcl-3, Inhibitor of apoptosis protein-1 (BIRC-1, Cluster of differentiation antigen 38 (CD38, Regulator of G-protein signalling-1 (RGS-1, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS; the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2, Complement component 3 (C3, Prostaglandin-endoperoxide synthase-2 (COX-2, Interleukin-8 (IL-8, Endothelin-1 (EDN-1, Plasminogen activator inhibitor type-2 (PAI-2, Matrix-metalloproteinase-14 (MMP-14, and Interferon regulating factor-7 (IRF-7. Conclusion Gene expression profiles found in periodontal tissues following

  20. Shadows Alter Facial Expressions of Noh Masks

    Science.gov (United States)

    Kawai, Nobuyuki; Miyata, Hiromitsu; Nishimura, Ritsuko; Okanoya, Kazuo

    2013-01-01

    Background A Noh mask, worn by expert actors during performance on the Japanese traditional Noh drama, conveys various emotional expressions despite its fixed physical properties. How does the mask change its expressions? Shadows change subtly during the actual Noh drama, which plays a key role in creating elusive artistic enchantment. We here describe evidence from two experiments regarding how attached shadows of the Noh masks influence the observers’ recognition of the emotional expressions. Methodology/Principal Findings In Experiment 1, neutral-faced Noh masks having the attached shadows of the happy/sad masks were recognized as bearing happy/sad expressions, respectively. This was true for all four types of masks each of which represented a character differing in sex and age, even though the original characteristics of the masks also greatly influenced the evaluation of emotions. Experiment 2 further revealed that frontal Noh mask images having shadows of upward/downward tilted masks were evaluated as sad/happy, respectively. This was consistent with outcomes from preceding studies using actually tilted Noh mask images. Conclusions/Significance Results from the two experiments concur that purely manipulating attached shadows of the different types of Noh masks significantly alters the emotion recognition. These findings go in line with the mysterious facial expressions observed in Western paintings, such as the elusive qualities of Mona Lisa’s smile. They also agree with the aesthetic principle of Japanese traditional art “yugen (profound grace and subtlety)”, which highly appreciates subtle emotional expressions in the darkness. PMID:23940748