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Sample records for functionally active thermus

  1. Genetic analysis of lipolytic activities in Thermus thermophilus HB27.

    Science.gov (United States)

    Leis, Benedikt; Angelov, Angel; Li, Haijuan; Liebl, Wolfgang

    2014-12-10

    The extremely thermophilic bacterium Thermus thermophilus HB27 displays lipolytic activity for the hydrolysis of triglycerides. In this study we performed a mutational in vivo analysis of esterases and lipases that confer growth on tributyrin. We interrupted 10 ORFs suspected to encode lipolytic enzymes. Two chromosomal loci were identified that resulted in reduced hydrolysis capabilities against tributyrin and various para-nitrophenyl acyl esters. By implementation of a convenient new one-step method which abstains from the use of selectable markers, a mutant strain with multiple scar-less deletions was constructed by sequentially deleting ORFs TT_C1787, TT_C0340, TT_C0341 and TT_C0904. The quadruple deletion mutant of T. thermophilus exhibited significantly lower lipolytic activity (approximately 25% residual activity compared to wild type strain) over a broad range of fatty acyl esters and had lost the ability to grow on agar plates containing tributyrin as the sole carbon source. Furthermore, we were able to determine the impact of each gene disruption on the lipolytic activity profile in this model organism and show that the esterase activity in T. thermophilus HB27 is due to a concerted action of several hydrolases having different substrate preferences and activities. The esterase-less T. thermophilus multi-deletion mutant from this study can be used as a screening and expression host for esterase genes from thermophiles or metagenomes.

  2. First glycoside hydrolase family 2 enzymes from Thermus antranikianii and Thermus brockianus with β-glucosidase activity

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    Carola eSchröder

    2015-06-01

    Full Text Available Two genes tagh2 and tbgh2 coding for enzymes with hydrolytic activity towards esculin were identified from the extreme thermophilic, aerobic bacteria Thermus antranikianii (Ta and T. brockianus (Tb. Shortened conserved domains predicted a membership of the enzymes of glycoside hydrolase (GH family 2. At present, β-galactosidase activity is found frequently in GH family 2 but β-glucosidase activity has not been reported in this family before. The enzymes TaGH2 and TbGH2 preferred hydrolysis of nitrophenol-linked β-D-glucopyranosides with specific activities of 3,966 U/mg and 660 U/mg, respectively. Residual activities of 40 % (TaGH2 and 51 % (TbGH2 towards 4-NP-β-D-galactopyranoside were observed. Furthermore, TaGH2 hydrolyzed cellobiose. TbGH2, however, showed no activity on cellobiose or lactose. The enzymes exhibited highest activity at 95 °C (TaGH2 and 90 °C (TbGH2 at pH 6.5. Both enzymes were extremely thermostable and thermal activation up to 250 % was observed at temperatures between 50 and 60 °C. Accordingly, the first thermoactive glycoside hydrolase family 2 enzymes with β glucosidase activity have been identified and characterized. The hydrolysis of cellobiose is a unique property of TaGH2 when compared to the enzymes of GH family 2.

  3. Functional characterization of a NapA Na(+)/H(+) antiporter from Thermus thermophilus.

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    Furrer, Esther M; Ronchetti, Mirco F; Verrey, François; Pos, Klaas M

    2007-02-06

    Na(+)/H(+) antiporters are ubiquitous membrane proteins and play an important role in cell homeostasis. We amplified a gene encoding a member of the monovalent cation:proton antiporter-2 (CPA2) family (TC 2.A.37) from the Thermus thermophilus genome and expressed it in Escherichia coli. The gene product was identified as a member of the NapA subfamily and was found to be an active Na(+)(Li(+))/H(+) antiporter as it conferred resistance to the Na(+) and Li(+) sensitive strain E. coli EP432 (DeltanhaA, DeltanhaB) upon exposure to high concentration of these salts in the growth medium. Fluorescence measurements using the pH sensitive dye 9-amino-6-chloro-2-methoxyacridine in everted membrane vesicles of complemented E. coli EP432 showed high Li(+)/H(+) exchange activity at pH 6, but marginal Na(+)/H(+) antiport activity. Towards more alkaline conditions, Na(+)/H(+) exchange activity increased to a relative maximum at pH 8, where by contrast the Li(+)/H(+) exchange activity reached its relative minimum. Substitution of conserved residues D156 and D157 (located in the putative transmembrane helix 6) with Ala resulted in the complete loss of Na(+)/H(+) activity. Mutation of K305 (putative transmembrane helix 10) to Ala resulted in a compromised phenotype characterized by an increase in apparent K(m) for Na(+) (36 vs. 7.6 mM for the wildtype) and Li(+) (17 vs. 0.22 mM), In summary, the Na(+)/H(+) antiport activity profile of the NapA type transporter of T. thermophilus resembles that of NhaA from E. coli, whereas in contrast to NhaA the T. thermophilus NapA antiporter is characterized by high Li(+)/H(+) antiport activity at acidic pH.

  4. Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase.

    OpenAIRE

    1991-01-01

    The 5'----3' exonuclease activity of the thermostable enzyme Thermus aquaticus DNA polymerase may be employed in a polymerase chain reaction product detection system to generate a specific detectable signal concomitantly with amplification. An oligonucleotide probe, nonextendable at the 3' end, labeled at the 5' end, and designed to hybridize within the target sequence, is introduced into the polymerase chain reaction assay. Annealing of probe to one of the polymerase chain reaction product s...

  5. Active site dynamics in NADH oxidase from Thermus thermophilus studied by NMR spin relaxation.

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    Miletti, Teresa; Farber, Patrick J; Mittermaier, Anthony

    2011-09-01

    We have characterized the backbone dynamics of NADH oxidase from Thermus thermophilus (NOX) using a recently-developed suite of NMR experiments designed to isolate exchange broadening, together with (15)N R (1), R (1ρ ), and {(1)H}-(15)N steady-state NOE relaxation measurements performed at 11.7 and 18.8 T. NOX is a 54 kDa homodimeric enzyme that belongs to a family of structurally homologous flavin reductases and nitroreductases with many potential biotechnology applications. Prior studies have suggested that flexibility is involved in the catalytic mechanism of the enzyme. The active site residue W47 was previously identified as being particularly important, as its level of solvent exposure correlates with enzyme activity, and it was observed to undergo "gating" motions in computer simulations. The NMR data are consistent with these findings. Signals from W47 are dynamically broadened beyond detection and several other residues in the active site have significant R ( ex ) contributions to transverse relaxation rates. In addition, the backbone of S193, whose side chain hydroxyl proton hydrogen bonds directly with the FMN cofactor, exhibits extensive mobility on the ns-ps timescale. We hypothesize that these motions may facilitate structural rearrangements of the active site that allow NOX to accept both FMN and FAD as cofactors.

  6. Site-directed mutation of a laccase from Thermus thermophilus: Effect on the activity profile

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    Liu Xin

    2012-01-01

    Full Text Available A site-directed mutant R453T of a laccase from Thermus thermophilus HB27 (Tth-laccase was constructed in order to investigate the effect on laccase catalytic properties. The mutated gene was cloned and overexpressed in Escherichia coli. Nickel-affinity purification was achieved and followed by copper ion incorporation. The mature mutated enzyme was quantitatively equal to the wild type. A photometric assay based on the oxidation of the substrate 2,2-azino-bis-(3- ethylbenzthiazoline-6-sulfonate (ABTS was employed in comparison with the wild-type Tth-laccase on catalytic properties. The R453T mutant exhibited improvement in substrate affinity and specific activity at room temperature, whereas those parameters were not significantly influenced when the temperature increased up to 65°C or higher. The mutant had better catalytic activity than that of the wild type at acidic pH. Investigated by circular dichroism spectroscopy, the mutant Tth-laccase displayed similar profiles at low and high temperatures.

  7. Identification of novel esterase-active enzymes from hot environments by use of the host bacterium Thermus thermophilus.

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    Leis, Benedikt; Angelov, Angel; Mientus, Markus; Li, Haijuan; Pham, Vu T T; Lauinger, Benjamin; Bongen, Patrick; Pietruszka, Jörg; Gonçalves, Luís G; Santos, Helena; Liebl, Wolfgang

    2015-01-01

    Functional metagenomic screening strategies, which are independent of known sequence information, can lead to the identification of truly novel genes and enzymes. Since E. coli has been used exhaustively for this purpose as a host, it is important to establish alternative expression hosts and to use them for functional metagenomic screening for new enzymes. In this study we show that Thermus thermophilus HB27 is an excellent screening host and can be used as an alternative provider of truly novel biocatalysts. In a previous study we constructed mutant strain BL03 with multiple markerless deletions in genes for major extra- and intracellular lipolytic activities. This esterase-diminished strain was no longer able to grow on defined minimal medium supplemented with tributyrin as the sole carbon source and could be used as a host to screen for metagenomic DNA fragments that could complement growth on tributyrin. Several thousand single fosmid clones from thermophilic metagenomic libraries from heated compost and hot spring water samples were subjected to a comparative screening for esterase activity in both T. thermophilus strain BL03 and E. coli EPI300. We scored a greater number of active esterase clones in the thermophilic bacterium than in the mesophilic E. coli. From several thousand functionally screened clones only two thermostable α/β-fold hydrolase enzymes with high amino acid sequence similarity to already characterized enzymes were identifiable in E. coli. In contrast, five further fosmids were found that conferred lipolytic activities in T. thermophilus only. Four open reading frames (ORFs) were found which did not share significant similarity to known esterase enzymes but contained the conserved GXSXG motif regularly found in lipolytic enzymes. Two of the genes were expressed in both hosts and the novel thermophilic esterases, which based on their primary structures could not be assigned to known esterase or lipase families, were purified and

  8. Identification of novel esterase-active enzymes from hot environments by use of the host bacterium Thermus thermophilus

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    Benedikt eLeis

    2015-04-01

    Full Text Available Functional metagenomic screening strategies, which are independent of known sequence information, can lead to the identification of truly novel genes and enzymes. Since E. coli has been used exhaustively for this purpose as a host, it is important to establish alternative expression hosts and to use them for functional metagenomic screening for new enzymes. In this study we show that Thermus thermophilus HB27 is an excellent screening host and can be used as an alternative provider of truly novel biocatalysts. In a previous study we constructed the mutant strain BL03 that was no longer able to grow on defined minimal medium supplemented with tributyrin as the sole carbon source and could be used as a host to screen for metagenomic DNA fragments that could complement growth on tributyrin. Several thousand single fosmid clones from thermophilic metagenomic libraries from heated compost and hot spring water samples were subjected to a comparative screening for esterase activity in both T. thermophilus strain BL03 and E. coli EPI300. We scored a greater number of active clones in the thermophilic bacterium than in the mesophilic E. coli. From all clones functionally screened in E. coli, only two thermostable α/β-fold hydrolase enzymes with high amino acid sequence similarity to already characterized enzymes were identifiable. In contrast, five further fosmids were found that conferred lipolytic activities in T. thermophilus. Four open reading frames (ORFs were found which did not share significant similarity to known esterase enzymes. Two of the genes were expressed in both hosts and the novel thermophilic esterases, which based on their primary structures could not be assigned to known esterase or lipase families, were purified and preliminarily characterized. Our work underscores the benefit of using additional screening hosts other than E. coli for the identification of novel biocatalysts with industrial relevance.

  9. Functional expression of a penicillin acylase from the extreme thermophile Thermus thermophilus HB27 in Escherichia coli

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    Torres Leticia L

    2012-08-01

    Full Text Available Abstract Background Penicillin acylases (PACs are enzymes of industrial relevance in the manufacture of β-lactam antibiotics. Development of a PAC with a longer half-life under the reaction conditions used is essential for the improvement of the operational stability of the process. A gene encoding a homologue to Escherichia coli PAC was found in the genome of the thermophilic bacterium Thermus thermophilus (Tth HB27. Because of the nature of this PAC and its complex maturation that is crucial to reach its functional heterodimeric final conformation, the overexpression of this enzyme in a heterologous mesophilic host was a challenge. Here we describe the purification and characterization of the PAC protein from Tth HB27 overexpressed in Escherichia coli. Results Fusions to a superfolder green fluorescent protein and differential membrane solubilization assays indicated that the native enzyme remains attached through its amino-terminal end to the outer side of the cytoplasmic membrane of Tth cells. In order to overexpress this PAC in E. coli cells, a variant of the protein devoid of its membrane anchoring segment was constructed. The effect of the co-expression of chaperones and calcium supplementation of the culture medium was investigated. The total production of PAC was enhanced by the presence of DnaK/J and GrpE and even more by trigger factor and GroEL/ES. In addition, 10 mM calcium markedly improved both PAC specific and volumetric activities. Recombinant PAC was affinity-purified and proper maturation of the protein was confirmed by SDS-PAGE and MALDI-TOF analysis of the subunits. The recombinant protein was tested for activity towards several penicillins, cephalosporins and homoserine lactones. Hydrophobic acyl-chain penicillins were preferred over the rest of the substrates. Penicillin K (octanoyl penicillin was the best substrate, with the highest specificity constant value (16.12 mM-1.seg-1. The optimum pH was aprox. 4 and the optimum

  10. Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity.

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    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2009-04-01

    The X-family DNA polymerases (PolXs) comprise a highly conserved DNA polymerase family found in all kingdoms. Mammalian PolXs are known to be involved in several DNA-processing pathways including repair, but the cellular functions of bacterial PolXs are less known. Many bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain at their C-termini in addition to a PolX core (POLXc) domain, and possess 3'-5' exonuclease activity. Although both domains are highly conserved in bacteria, their molecular functions, especially for a PHP domain, are unknown. We found Thermus thermophilus HB8 PolX (ttPolX) has Mg(2+)/Mn(2+)-dependent DNA/RNA polymerase, Mn(2+)-dependent 3'-5' exonuclease and DNA-binding activities. We identified the domains of ttPolX by limited proteolysis and characterized their biochemical activities. The POLXc domain was responsible for the polymerase and DNA-binding activities but exonuclease activity was not detected for either domain. However, the POLXc and PHP domains interacted with each other and a mixture of the two domains had Mn(2+)-dependent 3'-5' exonuclease activity. Moreover, site-directed mutagenesis revealed catalytically important residues in the PHP domain for the 3'-5' exonuclease activity. Our findings provide a molecular insight into the functional domain organization of bacterial PolXs, especially the requirement of the PHP domain for 3'-5' exonuclease activity.

  11. Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3′–5′ exonuclease activity

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    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2009-01-01

    The X-family DNA polymerases (PolXs) comprise a highly conserved DNA polymerase family found in all kingdoms. Mammalian PolXs are known to be involved in several DNA-processing pathways including repair, but the cellular functions of bacterial PolXs are less known. Many bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain at their C-termini in addition to a PolX core (POLXc) domain, and possess 3′–5′ exonuclease activity. Although both domains are highly conserved in bacteria, their molecular functions, especially for a PHP domain, are unknown. We found Thermus thermophilus HB8 PolX (ttPolX) has Mg2+/Mn2+-dependent DNA/RNA polymerase, Mn2+-dependent 3′–5′ exonuclease and DNA-binding activities. We identified the domains of ttPolX by limited proteolysis and characterized their biochemical activities. The POLXc domain was responsible for the polymerase and DNA-binding activities but exonuclease activity was not detected for either domain. However, the POLXc and PHP domains interacted with each other and a mixture of the two domains had Mn2+-dependent 3′–5′ exonuclease activity. Moreover, site-directed mutagenesis revealed catalytically important residues in the PHP domain for the 3′–5′ exonuclease activity. Our findings provide a molecular insight into the functional domain organization of bacterial PolXs, especially the requirement of the PHP domain for 3′–5′ exonuclease activity. PMID:19211662

  12. Toward a chemical mechanism of proton pumping by the B-type cytochrome c oxidases: application of density functional theory to cytochrome ba3 of Thermus thermophilus.

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    Fee, James A; Case, David A; Noodleman, Louis

    2008-11-12

    A mechanism for proton pumping by the B-type cytochrome c oxidases is presented in which one proton is pumped in conjunction with the weakly exergonic, two-electron reduction of Fe-bound O 2 to the Fe-Cu bridging peroxodianion and three protons are pumped in conjunction with the highly exergonic, two-electron reduction of Fe(III)- (-)O-O (-)-Cu(II) to form water and the active oxidized enzyme, Fe(III)- (-)OH,Cu(II). The scheme is based on the active-site structure of cytochrome ba 3 from Thermus thermophilus, which is considered to be both necessary and sufficient for coupled O 2 reduction and proton pumping when appropriate gates are in place (not included in the model). Fourteen detailed structures obtained from density functional theory (DFT) geometry optimization are presented that are reasonably thought to occur during the four-electron reduction of O 2. Each proton-pumping step takes place when a proton resides on the imidazole ring of I-His376 and the large active-site cluster has a net charge of +1 due to an uncompensated, positive charge formally associated with Cu B. Four types of DFT were applied to determine the energy of each intermediate, and standard thermochemical approaches were used to obtain the reaction free energies for each step in the catalytic cycle. This application of DFT generally conforms with previously suggested criteria for a valid model (Siegbahn, P. E. M.; Blomberg, M. A. R. Chem. Rev. 2000, 100, 421-437) and shows how the chemistry of O 2 reduction in the heme a 3 -Cu B dinuclear center can be harnessed to generate an electrochemical proton gradient across the lipid bilayer.

  13. Structure and Activity of the RNA-Targeting Type III-B CRISPR-Cas Complex of Thermus thermophilus

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    Staals, R.H.J.; Agari, Y.; Maki-Yonekura, S.; Zhu, Y.; Taylor, D.W.; van Duijn, E.; Barendregt, A.; Vlot, M.C.; Koehorst, J.J.; Sakamoto, K.; Masuda, A.; Dohmae, N.; Schaap, P.J.; Doudna, J.A.; Heck, A.J.R.; Yonekura, K.; van der Oost, J.; Shinkai, A.

    2013-01-01

    The CRISPR-Cas system is a prokaryotic host defense system against genetic elements. The Type III-B CRISPR-Cas system of the bacterium Thermus thermophilus, the TtCmr complex, is composed of six different protein subunits (Cmr1-6) and one crRNA with a stoichiometry of Cmr112131445361:crRNA1. The TtC

  14. The cytochrome ba3 oxygen reductase from Thermus thermophilus uses a single input channel for proton delivery to the active site and for proton pumping.

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    Chang, Hsin-Yang; Hemp, James; Chen, Ying; Fee, James A; Gennis, Robert B

    2009-09-22

    The heme-copper oxygen reductases are redox-driven proton pumps that generate a proton motive force in both prokaryotes and mitochondria. These enzymes have been divided into 3 evolutionarily related groups: the A-, B- and C-families. Most experimental work on proton-pumping mechanisms has been performed with members of the A-family. These enzymes require 2 proton input pathways (D- and K-channels) to transfer protons used for oxygen reduction chemistry and for proton pumping, with the D-channel transporting all pumped protons. In this work we use site-directed mutagenesis to demonstrate that the ba(3) oxygen reductase from Thermus thermophilus, a representative of the B-family, does not contain a D-channel. Rather, it utilizes only 1 proton input channel, analogous to that of the A-family K-channel, and it delivers protons to the active site for both O2 chemistry and proton pumping. Comparison of available subunit I sequences reveals that the only structural elements conserved within the oxygen reductase families that could perform these functions are active-site components, namely the covalently linked histidine-tyrosine, the Cu(B) and its ligands, and the active-site heme and its ligands. Therefore, our data suggest that all oxygen reductases perform the same chemical reactions for oxygen reduction and comprise the essential elements of the proton-pumping mechanism (e.g., the proton-loading and kinetic-gating sites). These sites, however, cannot be located within the D-channel. These results along with structural considerations point to the A-propionate region of the active-site heme and surrounding water molecules as the proton-loading site.

  15. Functional role of C-terminal domain of Thermus thermophilus leucyl-tRNA synthetase

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    Tukalo M. A.

    2010-11-01

    Full Text Available Aim. To study a role of C-terminal domain of T. thermophilus leucyl-tRNA synthetase (LeuRSTT in the reactions of aminoacylation and editing. Methods. A mutant of LeuRSTT without C- terminal domain (ΔС was obtained by the method of mutagenesis. The kinetic constants in aminoacylation reaction catalyzed by LeuRS and its mutant (ΔС were determined by the methods of equilibrium enzyme kinetics. To evaluate the contribution of C-terminal domain to interaction of the enzyme with tRNALeu, Kd of a complex between tRNA and LeuRSTT and its mutant ΔС was determined by fluorescence titration. Results. The C-terminal domain is shown to play a significant role in the aminoacylation and editing reactions of LeuRSTT and not essential for the activity in the reaction of amino acid activation. The kinetic parameters of aminoacylation of tRNALeu and tRNATyr by LeuRS and ΔС mutant were also determined, their analysis suggests that the C-domain is not critical for the manifestation of specificity of the enzyme in the recognition of homologous RNAs. At the same time a significant influence of the C-terminal domain on the value of catalytic constant was shown. At the domain deletion the kcat value is lower by 152-fold. Conclusion. The C-terminal domain of LeuRSTT is evolutionarily acquired to enhance the rate of catalysis in the aminoacylation and editing reactions, and makes no significant contribution to the specificity of the enzyme in the recognition of tRNA.

  16. Identification of Iron-reducing Thermus strains as Thermus scotoductus

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    Balkwill, David L.; Kieft, T L.; Tsukuda, Toyoko; Kostandarithes, Heather M.; Onstott, T C.; Macnaughton, S.; Bownas, J.; Fredrickson, Jim K.

    2004-02-01

    Thermus strain SA-01, previously isolated from a deep (3.2) South African gold mine, is closely related to Thermus strains NMX2 A.1 and VI-7 (previously isolated from thermal springs in New Mexico USA and Portugal, respectively). Thermus strains SA-01 and NMX2 A.1 have also been shown previously to grow using nitrate, Fe(III), , Mn(IV) or So as terminal electron acceptors and to be capable of reducing Cr(VI), U(VI), Co(III), and the quinine-containing compound anthraquinone-2,6-disulfonate. The objectives of this study were to determine the phylogenetic positions of the three known metal-reducing Thermus strains and to determine the phylogenetic significance of metal reduction within the genus Thermus. Phylogenetic analyses of 16S rDNA sequences, BOX PCR genomic fingerprinting, and DNA-DNA reassociation analyses indicated that these strains belong to the previously described genospecies T. scotoductus. The morphologies and lipid fatty acid profiles of these metal-reducing strains are consistent with their identification as T. scotoductus; however, the T. scotoductus strains tested in this study evinced a wide intraspecies variability in some other phenotypic traits, e.g., carbon substrate utilization and pigmentation. Iron reduction occurred in all strains of T. scotoductus tested except the mixotrophic, sulfur-oxidizing strain IT-7254. Thermus strains belonging to other species did not reduce Fe(III) to Fe(II) or reduced it only poorly.

  17. Structure of the β-Galactosidase Gene from Thermus sp. Strain T2: Expression in Escherichia coli and Purification in a Single Step of an Active Fusion Protein

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    Vian, Alejandro; Carrascosa, Alfonso V.; García, José L.; Cortés, Estrella

    1998-01-01

    The nucleotide sequence of both the bgaA gene, coding for a thermostable β-galactosidase of Thermus sp. strain T2, and its flanking regions was determined. The deduced amino acid sequence of the enzyme predicts a polypeptide of 645 amino acids (Mr, 73,595). Comparative analysis of the open reading frames located in the flanking regions of the bgaA gene revealed that they might encode proteins involved in the transport and hydrolysis of sugars. The observed homology between the deduced amino acid sequences of BgaA and the β-galactosidase of Bacillus stearothermophilus allows us to classify the new enzyme within family 42 of glycosyl hydrolases. BgaA was overexpressed in its active form in Escherichia coli, but more interestingly, an active chimeric β-galactosidase was constructed by fusing the BgaA protein to the choline-binding domain of the major pneumococcal autolysin. This chimera illustrates a novel approach for producing an active and thermostable hybrid enzyme that can be purified in a single step by affinity chromatography on DEAE-cellulose, retaining the catalytic properties of the native enzyme. The chimeric enzyme showed a specific activity of 191,000 U/mg at 70°C and a Km value of 1.6 mM with o-nitrophenyl-β-d-galactopyranoside as a substrate, and it retained 50% of its initial activity after 1 h of incubation at 70°C. PMID:9603833

  18. Density functional study for the bridged dinuclear center based on a high-resolution X-ray crystal structure of ba3 cytochrome c oxidase from Thermus thermophilus.

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    Du, Wen-Ge Han; Noodleman, Louis

    2013-12-16

    Strong electron density for a peroxide type dioxygen species bridging the Fea3 and CuB dinuclear center (DNC) was observed in the high-resolution (1.8 Å) X-ray crystal structures (PDB entries 3S8G and 3S8F) of ba3 cytochrome c oxidase (CcO) from Thermus thermophilus. The crystals represent the as-isolated X-ray photoreduced CcO structures. The bridging peroxide was proposed to arise from the recombination of two radiation-produced HO(•) radicals formed either very near to or even in the space between the two metals of the DNC. It is unclear whether this peroxide species is in the O2(2-), O2(•)(-), HO2(-), or the H2O2 form and what is the detailed electronic structure and binding geometry including the DNC. In order to answer what form of this dioxygen species was observed in the DNC of the 1.8 Å X-ray CcO crystal structure (3S8G), we have applied broken-symmetry density functional theory (BS-DFT) geometric and energetic calculations (using OLYP potential) on large DNC cluster models with different Fea3-CuB oxidation and spin states and with O2(2-), O2(•)(-), HO2(-), or H2O2 in the bridging position. By comparing the DFT optimized geometries with the X-ray crystal structure (3S8G), we propose that the bridging peroxide is HO2(-). The X-ray crystal structure is likely to represent the superposition of the Fea3(2+)-(HO2(-))-CuB(+) DNC's in different states (Fe(2+) in low spin (LS), intermediate spin (IS), or high spin (HS)) with the majority species having the proton of the HO2(-) residing on the oxygen atom (O1) which is closer to the Fea3(2+) site in the Fea3(2+)-(HO-O)(-)-CuB(+) conformation. Our calculations show that the side chain of Tyr237 is likely trapped in the deprotonated Tyr237(-) anion form in the 3S8G X-ray crystal structure.

  19. Growth models of Thermus aquaticus and Thermus scotoductus

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    Libor Babák

    2012-01-01

    Full Text Available Members of the genus Thermus family are signifiant producers of secondary metabolites, which are very commonly used in industry. Beside the productivity, it is also important to study the growth curve of each strain. The mathematical models which are commonly used to describe behavior of microbial strains under different physical and chemical conditions can reduce measured data.In this study, the mathematical models which describe only the microbial count were used. For analysis, Verhulst model, von Bertalanffy model and Richards model were chosen.During the cultivation of Thermus aquaticus and Thermus scotoductus strains, optical density (OD and concentration of microorganisms were measured. The mathematical models were fitted to experimental data. The fitting was made in program MATLAB. The coefficients of models and statistical evaluation of goodness of fit of models were identified from mathematical analyses. Graphs of individual models were plotted with prediction bounds. 95% confidence levels were used to statistical evaluation of goodness of fit of models and prediction bounds.Richards model was evaluted as the most corresponding with experimental data. Similar results were reached using Verhulst model. Von Bertalanffy model was not coresponded with experimental data.

  20. Structural Rearrangements in the Active Site of the Thermus thermophilus 16S rRNA Methyltransferase KsgA in a Binary Complex with 5'-Methylthioadenosine

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    Demirci, H.; Belardinelli, R; Seri, E; Gregory, S; Gualerzi, C; Dahlberg, A; Jogl, G

    2009-01-01

    Posttranscriptional modification of ribosomal RNA (rRNA) occurs in all kingdoms of life. The S-adenosyl-l-methionine-dependent methyltransferase KsgA introduces the most highly conserved rRNA modification, the dimethylation of A1518 and A1519 of 16S rRNA. Loss of this dimethylation confers resistance to the antibiotic kasugamycin. Here, we report biochemical studies and high-resolution crystal structures of KsgA from Thermus thermophilus. Methylation of 30S ribosomal subunits by T. thermophilus KsgA is more efficient at low concentrations of magnesium ions, suggesting that partially unfolded RNA is the preferred substrate. The overall structure is similar to that of other methyltransferases but contains an additional ?-helix in a novel N-terminal extension. Comparison of the apoenzyme with complex structures with 5?-methylthioadenosine or adenosine bound in the cofactor-binding site reveals novel features when compared with related enzymes. Several mobile loop regions that restrict access to the cofactor-binding site are observed. In addition, the orientation of residues in the substrate-binding site indicates that conformational changes are required for binding two adjacent residues of the substrate rRNA.

  1. Carotenoid biosynthesis in extremophilic Deinococcus-Thermus bacteria.

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    Tian, Bing; Hua, Yuejin

    2010-11-01

    Bacteria from the phylum Deinococcus-Thermus are known for their resistance to extreme stresses including radiation, oxidation, desiccation and high temperature. Cultured Deinococcus-Thermus bacteria are usually red or yellow pigmented because of their ability to synthesize carotenoids. Unique carotenoids found in these bacteria include deinoxanthin from Deinococcus radiodurans and thermozeaxanthins from Thermus thermophilus. Investigations of carotenogenesis will help to understand cellular stress resistance of Deinococcus-Thermus bacteria. Here, we discuss the recent progress toward identifying carotenoids, carotenoid biosynthetic enzymes and pathways in some species of Deinococcus-Thermus extremophiles. In addition, we also discuss the roles of carotenoids in these extreme bacteria.

  2. A broken-symmetry density functional study of structures, energies, and protonation states along the catalytic O-O bond cleavage pathway in ba3 cytochrome c oxidase from Thermus thermophilus.

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    Han Du, Wen-Ge; Götz, Andreas W; Yang, Longhua; Walker, Ross C; Noodleman, Louis

    2016-08-21

    Broken-symmetry density functional calculations have been performed on the [Fea3, CuB] dinuclear center (DNC) of ba3 cytochrome c oxidase from Thermus thermophilus in the states of [Fea3(3+)-(HO2)(-)-CuB(2+), Tyr237(-)] and [Fea3(4+)[double bond, length as m-dash]O(2-), OH(-)-CuB(2+), Tyr237˙], using both PW91-D3 and OLYP-D3 functionals. Tyr237 is a special tyrosine cross-linked to His233, a ligand of CuB. The calculations have shown that the DNC in these states strongly favors the protonation of His376, which is above propionate-A, but not of the carboxylate group of propionate-A. The energies of the structures obtained by constrained geometry optimizations along the O-O bond cleavage pathway between [Fea3(3+)-(O-OH)(-)-CuB(2+), Tyr237(-)] and [Fea3(4+)[double bond, length as m-dash]O(2-)HO(-)-CuB(2+), Tyr237˙] have also been calculated. The transition of [Fea3(3+)-(O-OH)(-)-CuB(2+), Tyr237(-)] → [Fea3(4+)[double bond, length as m-dash]O(2-)HO(-)-CuB(2+), Tyr237˙] shows a very small barrier, which is less than 3.0/2.0 kcal mol(-1) in PW91-D3/OLYP-D3 calculations. The protonation state of His376 does not affect this O-O cleavage barrier. The rate limiting step of the transition from state A (in which O2 binds to Fea3(2+)) to state PM ([Fea3(4+)[double bond, length as m-dash]O(2-), OH(-)-CuB(2+), Tyr237˙], where the O-O bond is cleaved) in the catalytic cycle is, therefore, the proton transfer originating from Tyr237 to O-O to form the hydroperoxo [Fea3(3+)-(O-OH)(-)-CuB(2+), Tyr237(-)] state. The importance of His376 in proton uptake and the function of propionate-A/neutral-Asp372 as a gate to prevent the proton from back-flowing to the DNC are also shown.

  3. Complete Genome Sequence of Thermus aquaticus Y51MC23.

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    Phillip J Brumm

    Full Text Available Thermus aquaticus Y51MC23 was isolated from a boiling spring in the Lower Geyser Basin of Yellowstone National Park. Remarkably, this T. aquaticus strain is able to grow anaerobically and produces multiple morphological forms. Y51MC23 is a Gram-negative, rod-shaped organism that grows well between 50°C and 80°C with maximum growth rate at 65°C to 70°C. Growth studies suggest that Y51MC23 primarily scavenges protein from the environment, supported by the high number of secreted and intracellular proteases and peptidases as well as transporter systems for amino acids and peptides. The genome was assembled de novo using a 350 bp fragment library (paired end sequencing and an 8 kb long span mate pair library. A closed and finished genome was obtained consisting of a single chromosome of 2.15 Mb and four plasmids of 11, 14, 70, and 79 kb. Unlike other Thermus species, functions usually found on megaplasmids were identified on the chromosome. The Y51MC23 genome contains two full and two partial prophage as well as numerous CRISPR loci. The high identity and synteny between Y51MC23 prophage 2 and that of Thermus sp. 2.9 is interesting, given the 8,800 km separation of the two hot springs from which they were isolated. The anaerobic lifestyle of Y51MC23 is complex, with multiple morphologies present in cultures. The use of fluorescence microscopy reveals new details about these unusual morphological features, including the presence of multiple types of large and small spheres, often forming a confluent layer of spheres. Many of the spheres appear to be formed not from cell envelope or outer membrane components as previously believed, but from a remodeled peptidoglycan cell wall. These complex morphological forms may serve multiple functions in the survival of the organism, including food and nucleic acid storage as well as colony attachment and organization.

  4. Expression and Characterization of Recombinant Thermostable Alkaline Phosphatase from a Novel Thermophilic Bacterium Thermus thermophilus XM

    Institute of Scientific and Technical Information of China (English)

    Jianbo LI; Limei XU; Feng YANG

    2007-01-01

    A gene (tap) encoding a thermostable alkaline phosphatase from the thermophilic bacterium Thermus thermophilus XM was cloned and sequenced. It is 1506 bp long and encodes a protein of 501 amino acid residues with a calculated molecular mass of 54.7 kDa. Comparison of the deduced amino acid sequence with other alkaline phosphatases showed that the regions in the vicinity of the phosphorylation site and metal binding sites are highly conserved. The recombinant thermostable alkaline phosphatase was expressed as a His6-tagged fusion protein in Escherichia coli and its enzymatic properties were characterized after purification. The pH and temperature optima for the recombinant thermostable alkaline phosphatases activity were pH 12 and 75 ℃. As expected, the enzyme displayed high thermostability, retaining more than 50% activity after incubating for 6 h at 80 ℃. Its catalytic function was accelerated in the presence of 0.1 mM Co2+, Fe2+, Mg2+, or Mn2+ but was strongly inhibited by 2.0 mM Fe2+. Under optimal conditions, the Michaelis constant (Km) for cleavage of p-nitrophenyl-phosphate was 0.034 mM. Although it has much in common with other alkaline phosphatases, the recombinant thermostable alkaline phosphatase possesses some unique features, such as high optimal pH and good thermostability.

  5. Genome Signature Difference between Deinococcus radiodurans and Thermus thermophilus

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    Hiromi Nishida

    2012-01-01

    Full Text Available The extremely radioresistant bacteria of the genus Deinococcus and the extremely thermophilic bacteria of the genus Thermus belong to a common taxonomic group. Considering the distinct living environments of Deinococcus and Thermus, different genes would have been acquired through horizontal gene transfer after their divergence from a common ancestor. Their guanine-cytosine (GC contents are similar; however, we hypothesized that their genomic signatures would be different. Our findings indicated that the genomes of Deinococcus radiodurans and Thermus thermophilus have different tetranucleotide frequencies. This analysis showed that the genome signature of D. radiodurans is most similar to that of Pseudomonas aeruginosa, whereas the genome signature of T. thermophilus is most similar to that of Thermanaerovibrio acidaminovorans. This difference in genome signatures may be related to the different evolutionary backgrounds of the 2 genera after their divergence from a common ancestor.

  6. The role of the PHP domain associated with DNA polymerase X from Thermus thermophilus HB8 in base excision repair.

    Science.gov (United States)

    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2012-11-01

    Base excision repair (BER) is one of the most commonly used DNA repair pathways involved in genome stability. X-family DNA polymerases (PolXs) play critical roles in BER, especially in filling single-nucleotide gaps. In addition to a polymerase core domain, bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain with phosphoesterase activity which is also required for BER. However, the role of the PHP domain of PolX in bacterial BER remains unresolved. We found that the PHP domain of Thermus thermophilus HB8 PolX (ttPolX) functions as two types of phosphoesterase in BER, including a 3'-phosphatase and an apurinic/apyrimidinic (AP) endonuclease. Experiments using T. thermophilus HB8 cell lysates revealed that the majority of the 3'-phosphatase and AP endonuclease activities are attributable to the another phosphoesterase in T. thermophilus HB8, endonuclease IV (ttEndoIV). However, ttPolX possesses significant 3'-phosphatase activity in ΔttendoIV cell lysate, indicating possible complementation. Our experiments also reveal that there are only two enzymes that display the 3'-phosphatase activity in the T. thermophilus HB8 cell, ttPolX and ttEndoIV. Furthermore, phenotypic analysis of ΔttpolX, ΔttendoIV, and ΔttpolX/ΔttendoIV using hydrogen peroxide and sodium nitrite supports the hypothesis that ttPolX functions as a backup for ttEndoIV in BER.

  7. Cloning and analysis of a bifunctional methyltransferase/restriction endonuclease TspGWI, the prototype of a Thermus sp. enzyme family

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    Zylicz-Stachula Agnieszka

    2009-05-01

    Full Text Available Abstract Background Restriction-modification systems are a diverse class of enzymes. They are classified into four major types: I, II, III and IV. We have previously proposed the existence of a Thermus sp. enzyme family, which belongs to type II restriction endonucleases (REases, however, it features also some characteristics of types I and III. Members include related thermophilic endonucleases: TspGWI, TaqII, TspDTI, and Tth111II. Results Here we describe cloning, mutagenesis and analysis of the prototype TspGWI enzyme that recognises the 5'-ACGGA-3' site and cleaves 11/9 nt downstream. We cloned, expressed, and mutagenised the tspgwi gene and investigated the properties of its product, the bifunctional TspGWI restriction/modification enzyme. Since TspGWI does not cleave DNA completely, a cloning method was devised, based on amino acid sequencing of internal proteolytic fragments. The deduced amino acid sequence of the enzyme shares significant sequence similarity with another representative of the Thermus sp. family – TaqII. Interestingly, these enzymes recognise similar, yet different sequences in the DNA. Both enzymes cleave DNA at the same distance, but differ in their ability to cleave single sites and in the requirement of S-adenosylmethionine as an allosteric activator for cleavage. Both the restriction endonuclease (REase and methyltransferase (MTase activities of wild type (wt TspGWI (either recombinant or isolated from Thermus sp. are dependent on the presence of divalent cations. Conclusion TspGWI is a bifunctional protein comprising a tandem arrangement of Type I-like domains; particularly noticeable is the central HsdM-like module comprising a helical domain and a highly conserved S-adenosylmethionine-binding/catalytic MTase domain, containing DPAVGTG and NPPY motifs. TspGWI also possesses an N-terminal PD-(D/EXK nuclease domain related to the corresponding domains in HsdR subunits, but lacks the ATP-dependent translocase module

  8. Thermus and the Pink Discoloration Defect in Cheese.

    Science.gov (United States)

    Quigley, Lisa; O'Sullivan, Daniel J; Daly, David; O'Sullivan, Orla; Burdikova, Zuzana; Vana, Rostislav; Beresford, Tom P; Ross, R Paul; Fitzgerald, Gerald F; McSweeney, Paul L H; Giblin, Linda; Sheehan, Jeremiah J; Cotter, Paul D

    2016-01-01

    A DNA sequencing-based strategy was applied to study the microbiology of Continental-type cheeses with a pink discoloration defect. The basis for this phenomenon has remained elusive, despite decades of research. The bacterial composition of cheese containing the defect was compared to that of control cheese using 16S rRNA gene and shotgun metagenomic sequencing as well as quantitative PCR (qPCR). Throughout, it was apparent that Thermus, a carotenoid-producing genus, was present at higher levels in defect-associated cheeses than in control cheeses. Prompted by this finding and data confirming the pink discoloration to be associated with the presence of a carotenoid, a culture-based approach was employed, and Thermus thermophilus was successfully cultured from defect-containing cheeses. The link between Thermus and the pinking phenomenon was then established through the cheese defect equivalent of Koch's postulates when the defect was recreated by the reintroduction of a T. thermophilus isolate to a test cheese during the manufacturing process. IMPORTANCE Pink discoloration in cheese is a defect affecting many cheeses throughout the world, leading to significant financial loss for the dairy industry. Despite decades of research, the cause of this defect has remained elusive. The advent of high-throughput, next-generation sequencing has revolutionized the field of food microbiology and, with respect to this study, provided a means of testing a possible microbial basis for this defect. In this study, a combined 16S rRNA, whole-genome sequencing, and quantitative PCR approach was taken. This resulted in the identification of Thermus, a carotenoid-producing thermophile, in defect-associated cheeses and the recreation of the problem in cheeses to which Thermus was added. This finding has the potential to lead to new strategies to eliminate this defect, and our method represents an approach that can be employed to investigate the role of microbes in other food defects

  9. Exploring the proton pump and exit pathway for pumped protons in cytochrome ba3 from Thermus thermophilus.

    Science.gov (United States)

    Chang, Hsin-Yang; Choi, Sylvia K; Vakkasoglu, Ahmet Selim; Chen, Ying; Hemp, James; Fee, James A; Gennis, Robert B

    2012-04-03

    The heme-copper oxygen reductases are redox-driven proton pumps. In the current work, the effects of mutations in a proposed exit pathway for pumped protons are examined in the ba(3)-type oxygen reductase from Thermus thermophilus, leading from the propionates of heme a(3) to the interface between subunits I and II. Recent studies have proposed important roles for His376 and Asp372, both of which are hydrogen-bonded to propionate-A of heme a(3), and for Glu126(II) (subunit II), which is hydrogen-bonded to His376. Based on the current results, His376, Glu126(II), and Asp372 are not essential for either oxidase activity or proton pumping. In addition, Tyr133, which is hydrogen-bonded to propionate-D of heme a(3), was also shown not to be essential for function. However, two mutations of the residues hydrogen-bonded to propionate-A, Asp372Ile and His376Asn, retain high electron transfer activity and normal spectral features but, in different preparations, either do not pump protons or exhibit substantially diminished proton pumping. It is concluded that either propionate-A of heme a(3) or possibly the cluster of groups centered about the conserved water molecule that hydrogen-bonds to both propionates-A and -D of heme a(3) is a good candidate to be the proton loading site.

  10. Lateral Transfer of the Denitrification Pathway Genes among Thermus thermophilus Strains▿

    Science.gov (United States)

    Alvarez, Laura; Bricio, Carlos; José Gómez, Manuel; Berenguer, José

    2011-01-01

    Nitrate respiration is a common and strain-specific property in Thermus thermophilus encoded by the nitrate respiration conjugative element (NCE) that can be laterally transferred by conjugation. In contrast, nitrite respiration and further denitrification steps are restricted to a few isolates of this species. These later steps of the denitrification pathway are under the regulatory control of an NCE-encoded transcription factor, but nothing is known about their coding sequences or its putative genetic linkage to the NCE. In this study we examine the genetic linkage between nitrate and nitrite respiration through lateral gene transfer (LGT) assays and describe a cluster of genes encoding the nitrite-nitric oxide respiration in T. thermophilus PRQ25. We show that the whole denitrification pathway can be transferred from the denitrificant strain PRQ25 to an aerobic strain, HB27, and that the genes coding for nitrite and nitric oxide respiration are encoded near the NCE. Sequence data from the draft genome of PRQ25 confirmed these results and allowed us to describe the most compact nor-nir cluster known thus far and to demonstrate the expression and activities of the encoded enzymes in the HB27 denitrificant derivatives obtained by LGT. We conclude that this NCE nor-nir supercluster constitutes a whole denitrification island that can be spread by lateral transfer among Thermus thermophilus strains. PMID:21169443

  11. Expression, purification and characterization of recombinant protein tyrosine phosphatase from Thermus thermophilus HB27

    Institute of Scientific and Technical Information of China (English)

    Yejing Wang; Fanguo Meng; Yingmei Zhang

    2009-01-01

    The low-molecular-weight protein tyrosine phospha-tases (PTPase) exist ubiquitously in prokaryotes and eukaryotes and play important roles in the regulation of physiological activities. We report here the expression, purification and characterization of an active and soluble PTPase from Thermus thermophilus HB27 in Escherichia coli. This PTPase has an optimum pH range of 2.8-4.8 when using p-nitrophenyl phos-phate as the substrate. The thermal inactivation results indicate a high thermal stability of this enzyme, with the optimum temperature of 75℃ for activity. It can be activated by Mn2+, Mg2+, Ca2+, Ba2+, and Ni2+, but inhibited by Zn2+, Cu2+, Cl-, and SO2-4. These results suggest that this heat-resistant PTPase may play impor-tant roles in vivo in the adaptation of the microorgan-ism to extreme temperatures and specific nutritional conditions.

  12. Whole Genome Comparison of Thermus sp. NMX2.A1 Reveals Principle Carbon Metabolism Differences with Closest Relation Thermus scotoductus SA-01

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    Walter J. Müller

    2016-09-01

    Full Text Available Genome sequencing of the yellow-pigmented, thermophilic bacterium Thermus sp. NMX2.A1 resulted in a 2.29 Mb draft genome that encodes for 2312 proteins. The genetic relationship between various strains from the genus Thermus was assessed based on phylogenomic analyses using a concatenated set of conserved proteins. The resulting phylogenetic tree illustrated that Thermus sp. NMX2 A.1 clusters together with Thermus scotoductus SA-01, despite being isolated from vastly different geographical locations. The close evolutionary relationship and metabolic parallels between the two strains has previously been recognized; however, neither strain’s genome data were available at that point in time. Genomic comparison of the Thermus sp. NMX2.A1 and T. scotoductus SA-01, as well as other closely related Thermus strains, revealed a high degree of synteny at both the genomic and proteomic level, with processes such as denitrification and natural cell competence appearing to be conserved. However, despite this high level of similarity, analysis revealed a complete, putative Calvin–Benson–Bassham (CBB cycle in NMX2.A1 that is absent in SA-01. Analysis of horizontally transferred gene islands provide evidence that NMX2 selected these genes due to pressure from its HCO3- rich environment, which is in stark contrast to that of the deep subsurface isolated SA-01.

  13. Crystal structure of amylomaltase from thermus aquaticus, a glycosyltransferase catalysing the production of large cyclic glucans.

    Science.gov (United States)

    Przylas, I; Tomoo, K; Terada, Y; Takaha, T; Fujii, K; Saenger, W; Sträter, N

    2000-02-25

    Amylomaltase is involved in the metabolism of starch, one of the most important polysaccharides in nature. A unique feature of amylomaltase is its ability to catalyze the formation of cyclic amylose. In contrast to the well studied cyclodextrin glucanotransferases (CGTases), which synthesize cycloamylose with a ring size (degree of polymerization or DP) of 6-8, the amylomaltase from Thermus aquaticus produces cycloamyloses with a DP of 22 and higher. The crystal structure of amylomaltase from Thermus aquaticus was determined to 2.0 A resolution. It is a member of the alpha-amylase superfamily of enzymes, whose core structure consists of a (beta, alpha)(8) barrel. In amylomaltase, the 8-fold symmetry of this barrel is disrupted by several insertions between the barrel strands. The largest insertions are between the third and fifth barrel strands, where two insertions form subdomain B1, as well as between the second and third barrel strands, forming the alpha-helical subdomain B2. Whereas part of subdomain B1 is also present in other enzyme structures of the alpha-amylase superfamily, subdomain B2 is unique to amylomaltase. Remarkably, the C-terminal domain C, which is present in all related enzymes of the alpha-amylase family, is missing in amylomaltase. Amylomaltase shows a similar arrangement of the catalytic side-chains (two Asp residues and one Glu residue) as in previously characterized members of the alpha-amylase superfamily, indicating similar mechanisms of the glycosyl transfer reaction. In amylomaltase, a conserved loop of around eight amino acid residues is partially shielding the active center. This loop, which is well conserved among other amylomaltases, may sterically hinder the formation of small cyclic products.

  14. Sequence of the hyperplastic genome of the naturally competent Thermus scotoductus SA-01

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    Gounder Kamini

    2011-11-01

    Full Text Available Abstract Background Many strains of Thermus have been isolated from hot environments around the world. Thermus scotoductus SA-01 was isolated from fissure water collected 3.2 km below surface in a South African gold mine. The isolate is capable of dissimilatory iron reduction, growth with oxygen and nitrate as terminal electron acceptors and the ability to reduce a variety of metal ions, including gold, chromate and uranium, was demonstrated. The genomes from two different Thermus thermophilus strains have been completed. This paper represents the completed genome from a second Thermus species - T. scotoductus. Results The genome of Thermus scotoductus SA-01 consists of a chromosome of 2,346,803 bp and a small plasmid which, together are about 11% larger than the Thermus thermophilus genomes. The T. thermophilus megaplasmid genes are part of the T. scotoductus chromosome and extensive rearrangement, deletion of nonessential genes and acquisition of gene islands have occurred, leading to a loss of synteny between the chromosomes of T. scotoductus and T. thermophilus. At least nine large inserts of which seven were identified as alien, were found, the most remarkable being a denitrification cluster and two operons relating to the metabolism of phenolics which appear to have been acquired from Meiothermus ruber. The majority of acquired genes are from closely related species of the Deinococcus-Thermus group, and many of the remaining genes are from microorganisms with a thermophilic or hyperthermophilic lifestyle. The natural competence of Thermus scotoductus was confirmed experimentally as expected as most of the proteins of the natural transformation system of Thermus thermophilus are present. Analysis of the metabolic capabilities revealed an extensive energy metabolism with many aerobic and anaerobic respiratory options. An abundance of sensor histidine kinases, response regulators and transporters for a wide variety of compounds are indicative

  15. Identification and molecular modeling of a family 5 endocellulase from Thermus caldophilus GK24, a cellulolytic strain of Thermus thermophilus

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    Dae-Sil Lee

    2006-12-01

    Full Text Available The genome of T. caldophilus GK24 was recently sequenced and annotated as 14contigs, equivalent to 2.3 mega basepairs (Mbp of DNA. In the current study, we identifieda unique 13.7 kbp DNA sequence, which included the endocellulase gene of T. caldophilusGK24, which did not appear to be present in the complete genomic sequence of the closelyrelated species T. thermophilus HB27 and HB8. Congo-red staining revealed a uniquephenotype of cellulose degradation by strain GK24 that was distinct from other closelyrelated Thermus strains. The results showed that strain GK24 is an aerobic, thermophilic,cellulolytic eubacterium which belongs to the group T. thermophilus. In order to understandthe mechanism of production of cellobiose in T. caldophilus GK24, a three-dimensionalmodel of the endocellulase, TcCel5A, was generated based on known crystal structures.Using this model, we carried out a flexible cellotetraose docking study.

  16. Complement Activation Alters Platelet Function

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  17. X-ray structure of a dihydropyrimidinase from Thermus sp. at 1.3 A resolution.

    Science.gov (United States)

    Abendroth, Jan; Niefind, Karsten; Schomburg, Dietmar

    2002-06-28

    Dihydropyrimidinases (hydantoinases) catalyse the reversible hydrolytic ring-opening of cyclic diamides such as dihydropyrimidines in the catabolism of pyrimidines. In biotechnology, these enzymes find application in the enantiospecific production of amino acids from racemic hydantoins. The crystal structure of a D-enantio-specific dihydropyrimidinase from Thermus sp. (D-hydantoinase) was solved de novo by multiwavelength anomalous diffraction phasing. In spite of a large unit cell the D-hydantoinase crystals exhibit excellent diffraction properties. The structure was subsequently refined at 1.30 A resolution against native data. The core of D-hydantoinase consists of a (alpha/beta)(8)-barrel, which is flanked by a beta-sheet domain and some additional helices. In the active site, a carboxylated lysine residue and the catalytically active hydroxide ion bridge a binuclear zinc centre. The tertiary structure and shape of the active site show strong homology to that of ureases, dihydroorotases, and phosphotriesterases. The homology of the active site was exploited for in silicio docking of substrates in the active site. This could shed light both on the substrate binding in hydantoinases and on the recently highly discussed origin of the proton in the course of hydantoinase catalysis.

  18. High Resolution Structure of the ba3 Cytochrome c Oxidase from Thermus thermophilus in a Lipidic Environment

    Energy Technology Data Exchange (ETDEWEB)

    Tiefenbrunn, Theresa; Liu, Wei; Chen, Ying; Katritch, Vsevolod; Stout, C. David; Fee, James A.; Cherezov, Vadim (Scripps); (UCSD)

    2012-06-27

    The fundamental chemistry underpinning aerobic life on Earth involves reduction of dioxygen to water with concomitant proton translocation. This process is catalyzed by members of the heme-copper oxidase (HCO) superfamily. Despite the availability of crystal structures for all types of HCO, the mode of action for this enzyme is not understood at the atomic level, namely how vectorial H{sup +} and e{sup -} transport are coupled. Toward addressing this problem, we report wild type and A120F mutant structures of the ba{sub 3}-type cytochrome c oxidase from Thermus thermophilus at 1.8 {angstrom} resolution. The enzyme has been crystallized from the lipidic cubic phase, which mimics the biological membrane environment. The structures reveal 20 ordered lipid molecules that occupy binding sites on the protein surface or mediate crystal packing interfaces. The interior of the protein encloses 53 water molecules, including 3 trapped in the designated K-path of proton transfer and 8 in a cluster seen also in A-type enzymes that likely functions in egress of product water and proton translocation. The hydrophobic O{sub 2}-uptake channel, connecting the active site to the lipid bilayer, contains a single water molecule nearest the Cu{sub B} atom but otherwise exhibits no residual electron density. The active site contains strong electron density for a pair of bonded atoms bridging the heme Fe{sub a3} and Cu{sub B} atoms that is best modeled as peroxide. The structure of ba{sub 3}-oxidase reveals new information about the positioning of the enzyme within the membrane and the nature of its interactions with lipid molecules. The atomic resolution details provide insight into the mechanisms of electron transfer, oxygen diffusion into the active site, reduction of oxygen to water, and pumping of protons across the membrane. The development of a robust system for production of ba{sub 3}-oxidase crystals diffracting to high resolution, together with an established expression system

  19. High resolution structure of the ba3 cytochrome c oxidase from Thermus thermophilus in a lipidic environment.

    Directory of Open Access Journals (Sweden)

    Theresa Tiefenbrunn

    Full Text Available The fundamental chemistry underpinning aerobic life on Earth involves reduction of dioxygen to water with concomitant proton translocation. This process is catalyzed by members of the heme-copper oxidase (HCO superfamily. Despite the availability of crystal structures for all types of HCO, the mode of action for this enzyme is not understood at the atomic level, namely how vectorial H(+ and e(- transport are coupled. Toward addressing this problem, we report wild type and A120F mutant structures of the ba(3-type cytochrome c oxidase from Thermus thermophilus at 1.8 Å resolution. The enzyme has been crystallized from the lipidic cubic phase, which mimics the biological membrane environment. The structures reveal 20 ordered lipid molecules that occupy binding sites on the protein surface or mediate crystal packing interfaces. The interior of the protein encloses 53 water molecules, including 3 trapped in the designated K-path of proton transfer and 8 in a cluster seen also in A-type enzymes that likely functions in egress of product water and proton translocation. The hydrophobic O(2-uptake channel, connecting the active site to the lipid bilayer, contains a single water molecule nearest the Cu(B atom but otherwise exhibits no residual electron density. The active site contains strong electron density for a pair of bonded atoms bridging the heme Fe(a3 and Cu(B atoms that is best modeled as peroxide. The structure of ba(3-oxidase reveals new information about the positioning of the enzyme within the membrane and the nature of its interactions with lipid molecules. The atomic resolution details provide insight into the mechanisms of electron transfer, oxygen diffusion into the active site, reduction of oxygen to water, and pumping of protons across the membrane. The development of a robust system for production of ba(3-oxidase crystals diffracting to high resolution, together with an established expression system for generating mutants, opens the

  20. Proton transfer in ba(3) cytochrome c oxidase from Thermus thermophilus.

    Science.gov (United States)

    von Ballmoos, Christoph; Adelroth, Pia; Gennis, Robert B; Brzezinski, Peter

    2012-04-01

    The respiratory heme-copper oxidases catalyze reduction of O(2) to H(2)O, linking this process to transmembrane proton pumping. These oxidases have been classified according to the architecture, location and number of proton pathways. Most structural and functional studies to date have been performed on the A-class oxidases, which includes those that are found in the inner mitochondrial membrane and bacteria such as Rhodobacter sphaeroides and Paracoccus denitrificans (aa(3)-type oxidases in these bacteria). These oxidases pump protons with a stoichiometry of one proton per electron transferred to the catalytic site. The bacterial A-class oxidases use two proton pathways (denoted by letters D and K, respectively), for the transfer of protons to the catalytic site, and protons that are pumped across the membrane. The B-type oxidases such as, for example, the ba(3) oxidase from Thermus thermophilus, pump protons with a lower stoichiometry of 0.5 H(+)/electron and use only one proton pathway for the transfer of all protons. This pathway overlaps in space with the K pathway in the A class oxidases without showing any sequence homology though. Here, we review the functional properties of the A- and the B-class ba(3) oxidases with a focus on mechanisms of proton transfer and pumping. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.

    Science.gov (United States)

    Bagautdinov, Bagautdin; Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-05-01

    The beta-ketoacyl-(acyl carrier protein) synthases (beta-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 A resolution. The crystal is orthorhombic, space group P2(1)2(1)2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 A, and contains one homodimer in the asymmetric unit. The subunits adopt the well known alpha-beta-alpha-beta-alpha thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ;open' conformation of the Phe396 side chain.

  2. Thermus thermophilus TMY isolated from silica scale taken from a geothermal power plant.

    Science.gov (United States)

    Fujino, Y; Kawatsu, R; Inagaki, F; Umeda, A; Yokoyama, T; Okaue, Y; Iwai, S; Ogata, S; Ohshima, T; Doi, K

    2008-01-01

    To identify an extreme thermophile, strain TMY, isolated from silica scale from the geothermal electric power plant and to examine microdiversity of Thermus thermophilus strains. The isolated strain TMY was identified by morphological, biochemical and physiological tests. Phylogenetic comparison of the strain and other Thermus strains with 16S rDNA analysis, RAPD and ERIC-PCR fingerprinting were performed. Strain TMY was closely related to strain which was isolated from a hot spring in New Zealand and shown to belong to the Japanese Thermus cluster. However, there were considerable genetic differences between strain TMY and other Thermus species using DNA fingerprinting. Based on morphological, physiological and genetic properties, strain TMY could be a strain of T. thermophilus. The distinct properties of strain TMY suggest that microdiversity of T. thermophilus strains should be considered. The results of this study have demonstrated genetic diversity within T. thermophilus strains, which were previously masked by an almost identical 16S rDNA sequence. RAPD and ERIC-PCR could be potential methods for distinguishing between Thermus strains.

  3. Crystallization and X-ray diffraction data of Thermus flavus 5S rRNA helices

    Science.gov (United States)

    Vallazza, Marco; Senge, Andrea; Lippmann, Corinna; Perbandt, Markus; Betzel, Christian; Bald, Rolf; Erdmann, Volker A.

    2001-11-01

    5S rRNA is an essential component of the large ribosomal subunit in prokaryotes and eukaryotes. Its unknown function in the ribosome will eventually be revealed in part by structural studies. To promote crystallization and enhance resolution in X-ray diffraction the molecule was subdivided into five domains A-E. Several RNA oligonucleotides were chemically produced by solid-phase phosphoramidite synthesis in order to construct the domains of the 5S rRNA. An improved RNA-MPD-screen was applied in crystallization which covers a complete 2D matrix for the components used. Crystallization analysis resulted in preferred combinations of pH, polyamine, monovalent and divalent cations for short RNA molecules. Six types of crystals corresponding to the domains B, C and E of Thermus flavus 5S rRNA could be obtained which were suitable for X-ray diffraction. Four RNA helices consist of seven base pairs and two of eight base pairs. As special features, they contain two adenines in a bulge position or G : U wobble base pairs assumed to be involved in RNA-protein recognition. With an increase in crystal size an increase in resolution by X-ray analysis was observed. X-ray diffraction data were collected to 1.5 Å resolution using synchrotron radiation and cryogenic cooling techniques.

  4. Comparative genomics of Thermus thermophilus and Deinococcus radiodurans: divergent routes of adaptation to thermophily and radiation resistance

    Directory of Open Access Journals (Sweden)

    Daly Michael J

    2005-10-01

    Full Text Available Abstract Background Thermus thermophilus and Deinococcus radiodurans belong to a distinct bacterial clade but have remarkably different phenotypes. T. thermophilus is a thermophile, which is relatively sensitive to ionizing radiation and desiccation, whereas D. radiodurans is a mesophile, which is highly radiation- and desiccation-resistant. Here we present an in-depth comparison of the genomes of these two related but differently adapted bacteria. Results By reconstructing the evolution of Thermus and Deinococcus after the divergence from their common ancestor, we demonstrate a high level of post-divergence gene flux in both lineages. Various aspects of the adaptation to high temperature in Thermus can be attributed to horizontal gene transfer from archaea and thermophilic bacteria; many of the horizontally transferred genes are located on the single megaplasmid of Thermus. In addition, the Thermus lineage has lost a set of genes that are still present in Deinococcus and many other mesophilic bacteria but are not common among thermophiles. By contrast, Deinococcus seems to have acquired numerous genes related to stress response systems from various bacteria. A comparison of the distribution of orthologous genes among the four partitions of the Deinococcus genome and the two partitions of the Thermus genome reveals homology between the Thermus megaplasmid (pTT27 and Deinococcus megaplasmid (DR177. Conclusion After the radiation from their common ancestor, the Thermus and Deinococcus lineages have taken divergent paths toward their distinct lifestyles. In addition to extensive gene loss, Thermus seems to have acquired numerous genes from thermophiles, which likely was the decisive contribution to its thermophilic adaptation. By contrast, Deinococcus lost few genes but seems to have acquired many bacterial genes that apparently enhanced its ability to survive different kinds of environmental stresses. Notwithstanding the accumulation of

  5. Dissimilatory Reduction of Fe(III) and Other Electron Acceptors by a Thermus Isolate

    Energy Technology Data Exchange (ETDEWEB)

    Kieft, T. L. [New Mexico Inst. of Mining and Technology, Socorro, NM (United States); Fredrickson, J. K. [Pacific Northwest National Lab., Richland, WA (United States); Onstott, T. C. [Princeton Univ., NJ (United States). Dept. of Geological and Geophysical Sciences; Gorby, Y. A. [Pacific Northwest National Lab., Richland, WA (United States); Kostandarithes, H. M. [Pacific Northwest National Lab., Richland, WA (United States); Bailey, T. J. [Pacific Northwest National Lab., Richland, WA (United States); Kennedy, D. W. [Pacific Northwest National Lab., Richland, WA (United States); Li, S. W. [Pacific Northwest National Lab., Richland, WA (United States); Plymale, A. E. [Pacific Northwest National Lab., Richland, WA (United States); Spadoni, C. M. [Pacific Northwest National Lab., Richland, WA (United States); Gray, M. S. [Pacific Northwest National Lab., Richland, WA (United States)

    1995-10-25

    A thermophilic bacterium that could use O{sub 2}, NO{sub 3}{sup -}, Fe(III), or S{sup o} as terminal electron acceptors for growth was isolated from groundwater sampled at 3.2 km depth in a South African gold mine. This organism, designated SA-01, clustered most closely with members of the genus Thermus, as determined by 16S rDNA gene sequence analysis. The 16S rDNA sequence of SA-01 was >98% similar to that of Thermus strain NMX2 A.1, which was previously isolated by other investigators from a thermal spring in New Mexico. Strain NMX2 A.1 was also able to reduce Fe(III) and other electron acceptors, whereas Thermus aquaticus (ATCC 25104) and Thermus filiformis (ATCC 43280) did not reduce NO{sub 3}{sup -} or Fe(III). Neither SA-01 nor NMX2 A.1 grew fermentatively, i.e., addition of an external electron acceptor was required for anaerobic growth. Thermus SA-01 reduced soluble Fe(III) complexed with citrate or nitrilotriacetic acid (NTA); however, it could only reduce relatively small quantities (0.5 mM) of hydrous ferric oxide (HFO) except when the humic acid analog 2,6-anthraquinone disulfonate (AQDS) was added as an electron shuttle, in which case 10 mM Fe(III) was reduced. Fe(III)-NTA was reduced quantitatively to Fe(II), was coupled to the oxidation of lactate, and could support growth through three consecutive transfers. Suspensions of Thermus SA-01 cells also reduced Mn(IV), Co(III)-EDTA, Cr(VI), and AQDS. Mn(IV)-oxide was reduced in the presence of either lactate or H{sub 2}. Both strains were also able to mineralize NTA to CO{sub 2} and to couple its oxidation to Fe(III) reduction and growth. The optimum temperature for growth and Fe(III) reduction by Thermus SA-01 and NMX2 A.1 is approximately 65 C; optimum pH is 6.5 to 7.0. This is the first report of a Thermus sp. being able to couple the oxidation of organic compounds to the reduction of Fe, Mn or S.

  6. Dissimilatory Reduction of Fe(III) and Other Electron Acceptors by a Thermus Isolate

    Energy Technology Data Exchange (ETDEWEB)

    Kieft, T. L. [New Mexico Inst. of Mining and Technology, Socorro, NM (United States); Fredrickson, J. K. [Pacific Northwest National Lab., Richland, WA (United States); Onstott, T. C. [Princeton Univ., NJ (United States). Dept. of Geological and Geophysical Sciences; Gorby, Y. A. [Pacific Northwest National Lab., Richland, WA (United States); Kostandarithes, H. M. [Pacific Northwest National Lab., Richland, WA (United States); Bailey, T. J. [Pacific Northwest National Lab., Richland, WA (United States); Kennedy, D. W. [Pacific Northwest National Lab., Richland, WA (United States); Li, S. W. [Pacific Northwest National Lab., Richland, WA (United States); Plymale, A. E. [Pacific Northwest National Lab., Richland, WA (United States); Spadoni, C. M. [Pacific Northwest National Lab., Richland, WA (United States); Gray, M. S. [Pacific Northwest National Lab., Richland, WA (United States)

    1995-10-25

    A thermophilic bacterium that could use O{sub 2}, NO{sub 3}{sup -}, Fe(III), or S{sup o} as terminal electron acceptors for growth was isolated from groundwater sampled at 3.2 km depth in a South African gold mine. This organism, designated SA-01, clustered most closely with members of the genus Thermus, as determined by 16S rDNA gene sequence analysis. The 16S rDNA sequence of SA-01 was >98% similar to that of Thermus strain NMX2 A.1, which was previously isolated by other investigators from a thermal spring in New Mexico. Strain NMX2 A.1 was also able to reduce Fe(III) and other electron acceptors, whereas Thermus aquaticus (ATCC 25104) and Thermus filiformis (ATCC 43280) did not reduce NO{sub 3}{sup -} or Fe(III). Neither SA-01 nor NMX2 A.1 grew fermentatively, i.e., addition of an external electron acceptor was required for anaerobic growth. Thermus SA-01 reduced soluble Fe(III) complexed with citrate or nitrilotriacetic acid (NTA); however, it could only reduce relatively small quantities (0.5 mM) of hydrous ferric oxide (HFO) except when the humic acid analog 2,6-anthraquinone disulfonate (AQDS) was added as an electron shuttle, in which case 10 mM Fe(III) was reduced. Fe(III)-NTA was reduced quantitatively to Fe(II), was coupled to the oxidation of lactate, and could support growth through three consecutive transfers. Suspensions of Thermus SA-01 cells also reduced Mn(IV), Co(III)-EDTA, Cr(VI), and AQDS. Mn(IV)-oxide was reduced in the presence of either lactate or H{sub 2}. Both strains were also able to mineralize NTA to CO{sub 2} and to couple its oxidation to Fe(III) reduction and growth. The optimum temperature for growth and Fe(III) reduction by Thermus SA-01 and NMX2 A.1 is approximately 65 C; optimum pH is 6.5 to 7.0. This is the first report of a Thermus sp. being able to couple the oxidation of organic compounds to the reduction of Fe, Mn or S.

  7. Effects of Argonaute on Gene Expression in Thermus thermophilus.

    Directory of Open Access Journals (Sweden)

    Daan C Swarts

    Full Text Available Eukaryotic Argonaute proteins mediate RNA-guided RNA interference, allowing both regulation of host gene expression and defense against invading mobile genetic elements. Recently, it has become evident that prokaryotic Argonaute homologs mediate DNA-guided DNA interference, and play a role in host defense. Argonaute of the bacterium Thermus thermophilus (TtAgo targets invading plasmid DNA during and after transformation. Using small interfering DNA guides, TtAgo can cleave single and double stranded DNAs. Although TtAgo additionally has been demonstrated to cleave RNA targets complementary to its DNA guide in vitro, RNA targeting by TtAgo has not been demonstrated in vivo.To investigate if TtAgo also has the potential to control RNA levels, we analyzed RNA-seq data derived from cultures of four T. thermophilus strain HB27 variants: wild type, TtAgo knockout (Δago, and either strain transformed with a plasmid. Additionally we determined the effect of TtAgo on expression of plasmid-encoded RNA and plasmid DNA levels.In the absence of exogenous DNA (plasmid, TtAgo presence or absence had no effect on gene expression levels. When plasmid DNA is present, TtAgo reduces plasmid DNA levels 4-fold, and a corresponding reduction of plasmid gene transcript levels was observed. We therefore conclude that TtAgo interferes with plasmid DNA, but not with plasmid-encoded RNA. Interestingly, TtAgo presence stimulates expression of specific endogenous genes, but only when exogenous plasmid DNA was present. Specifically, the presence of TtAgo directly or indirectly stimulates expression of CRISPR loci and associated genes, some of which are involved in CRISPR adaptation. This suggests that TtAgo-mediated interference with plasmid DNA stimulates CRISPR adaptation.

  8. Structural comparison between the open and closed forms of citrate synthase from Thermus thermophilus HB8.

    Science.gov (United States)

    Kanamori, Eiji; Kawaguchi, Shin-Ichi; Kuramitsu, Seiki; Kouyama, Tsutomu; Murakami, Midori

    2015-01-01

    The crystal structures of citrate synthase from the thermophilic eubacteria Thermus thermophilus HB8 (TtCS) were determined for an open form at 1.5 Å resolution and for closed form at 2.3 Å resolution, respectively. In the absence of ligands TtCS in the open form was crystalized into a tetragonal form with a single subunit in the asymmetric unit. TtCS was also co-crystallized with citrate and coenzyme-A to form an orthorhombic crystal with two homodimers in the asymmetric unit. Citrate and CoA are found in the active site situated between the large domain and the small domain in all subunit whereas the complex shows two distinct closed conformations, the fully closed form and partially closed form. Structural comparisons are performed to describe conformational changes associated with binding of products of TtCS. Upon binding of citrate, basic residues in the active site move toward citrate and make a hydrogen bond network in the active site, inducing a large-scale rotation of the small domain relative to the large domain. CoA is sandwiched between the small and large domains and then the cysteamine tail is inserted into the active site with a cooperative rotation around mainchain dihedrals in the hinge region connecting helices M and N. According to this rotation these helices are extended to close the active site completely. The considerable flexibility and structural rearrangements in the hinge region are crucial for an ordered bibi reaction in catalysis for microbial CSs.

  9. Crystal structure of a thermostable Old Yellow Enzyme from Thermus scotoductus SA-01

    Energy Technology Data Exchange (ETDEWEB)

    Opperman, Diederik J. [Department of Microbial, Biochemical and Food Biotechnology, BioPAD Metagenomics Platform, University of the Free State, Bloemfontein 9300 (South Africa); Sewell, Bryan T. [Electron Microscope Unit, University of Cape Town, Rondebosch 7701 (South Africa); Litthauer, Derek [Department of Microbial, Biochemical and Food Biotechnology, BioPAD Metagenomics Platform, University of the Free State, Bloemfontein 9300 (South Africa); Isupov, Mikhail N.; Littlechild, Jennifer A. [School of Biosciences, Henry Wellcome Building for Biocatalysis, University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom); Heerden, Esta van, E-mail: vheerde.sci@ufs.ac.za [Department of Microbial, Biochemical and Food Biotechnology, BioPAD Metagenomics Platform, University of the Free State, Bloemfontein 9300 (South Africa)

    2010-03-12

    Recent characterization of the chromate reductase (CrS) from the thermophile Thermus scotoductus SA-01 revealed this enzyme to be related to the Old Yellow Enzyme (OYE) family. Here, we report the structure of a thermostable OYE homolog in its holoform at 2.2 A as well as its complex with p-hydroxybenzaldehyde (pHBA). The enzyme crystallized as octamers with the monomers showing a classical TIM barrel fold which upon dimerization yields the biologically active form of the protein. A sulfate ion is bound above the si-side of the non-covalently bound FMN cofactor in the oxidized solved structure but is displaced upon pHBA binding. The active-site architecture is highly conserved as with other members of this enzyme family. The pHBA in the CrS complex is positioned by hydrogen bonding to the two conserved catalytic-site histidines. The most prominent structural difference between CrS and other OYE homologs is the size of the 'capping domain'. Thermostabilization of the enzyme is achieved in part through increased proline content within loops and turns as well as increased intersubunit interactions through hydrogen bonding and complex salt bridge networks. CrS is able to reduce the C=C bonds of {alpha},{beta}-unsaturated carbonyl compounds with a preference towards cyclic substrates however no activity was observed towards {beta}-substituted substrates. Mutational studies have confirmed the role of Tyr177 as the proposed proton donor although reduction could still occur at a reduced rate when this residue was mutated to phenylalanine.

  10. The structures of glycolipids isolated from the highly thermophilic bacterium Thermus thermophilus Samu-SA1.

    Science.gov (United States)

    Leone, Serena; Molinaro, Antonio; Lindner, Buko; Romano, Ida; Nicolaus, Barbara; Parrilli, Michelangelo; Lanzetta, Rosa; Holst, Otto

    2006-08-01

    Thermophiles constitute a class of microorganisms able to grow at extremely elevated temperatures. Some of these species are classified as Gram-negative bacteria, because of the presence of an outer membrane in the cell envelope, which is located on the top of a thick murein layer. Unlike typical Gram-negative bacteria, the outer membranes of Thermus species are not composed of lipopolysaccharides but of peculiar glycolipids (GL), whose structures seem to be strictly involved in the adaptation to high temperatures. In this work, the complete structures of the major GL components from the cell envelope of the thermophilic bacterium Thermus thermophilus Samu-SA1 are presented. Protocols conventionally adopted for Gram-negative bacteria were used, and, for the first time, GL from Thermus were analyzed in their native form. Two GL and one phosphoglycolipid (PGL) were detected and characterized. The two GL, analyzed by nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR) mass spectrometry, possessed the same tetrasaccharide structure linked to a glycerol unit or, alternatively, to a long-chain diol. Moreover, a PGL from Thermus was characterized for the first time, in which N-glyceroyl-heptadecaneamine was present. These molecules are chemically related to other GL from thermophile bacteria, in which they play a crucial role in the adaptation of cell membranes to heat.

  11. Thermus thermophilus Glycoside Hydrolase Family 57 Branching Enzyme : Crystal Structure, Mechanism of Action, and Products Formed

    NARCIS (Netherlands)

    Palomo, Marta; Pijning, Tjaard; Booiman, Thijs; Dobruchowska, Justyna M.; Vlist, Jeroen van der; Kralj, Slavko; Planas, Antoni; Loos, Katja; Kamerling, Johannis P.; Dijkstra, Bauke W.; Maarel, Marc J.E.C. van der; Dijkhuizen, Lubbert; Leemhuis, Hans

    2011-01-01

    Branching enzyme (EC 2.4.1.18; glycogen branching enzyme; GBE) catalyzes the formation of alpha 1,6-branching points in glycogen. Until recently it was believed that all GBEs belong to glycoside hydrolase family 13 (GH13). Here we describe the cloning and expression of the Thermus thermophilus

  12. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

    Energy Technology Data Exchange (ETDEWEB)

    Bagautdinov, Bagautdin, E-mail: bagautdi@spring8.or.jp; Ukita, Yoko [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Miyano, Masashi [Structural Biophysics Laboratory, RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Kunishima, Naoki [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan)

    2008-05-01

    The crystal structure of 3-oxoacyl-(acyl-carrier protein) synthase II from T. thermophilus HB8 has been determined at 2.0 Å resolution and compared with the structures of β-keto-ACP synthases from other sources. The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. The crystal is orthorhombic, space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 Å, and contains one homodimer in the asymmetric unit. The subunits adopt the well known α-β-α-β-α thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ‘open’ conformation of the Phe396 side chain.

  13. Crystal structure of a hypothetical protein, TTHA0829 from Thermus thermophilus HB8, composed of cystathionine-β-synthase (CBS) and aspartate-kinase chorismate-mutase tyrA (ACT) domains.

    Science.gov (United States)

    Nakabayashi, Makoto; Shibata, Naoki; Ishido-Nakai, Emi; Kanagawa, Mayumi; Iio, Yota; Komori, Hirofumi; Ueda, Yasufumi; Nakagawa, Noriko; Kuramitsu, Seiki; Higuchi, Yoshiki

    2016-05-01

    TTHA0829 from Thermus thermophilus HB8 has a molecular mass of 22,754 Da and is composed of 210 amino acid residues. The expression of TTHA0829 is remarkably elevated in the latter half of logarithmic growth phase. TTHA0829 can form either a tetrameric or dimeric structure, and main-chain folding provides an N-terminal cystathionine-β-synthase (CBS) domain and a C-terminal aspartate-kinase chorismate-mutase tyrA (ACT) domain. Both CBS and ACT are regulatory domains to which a small ligand molecule can bind. The CBS domain is found in proteins from organisms belonging to all kingdoms and is observed frequently as two or four tandem copies. This domain is considered as a small intracellular module with a regulatory function and is typically found adjacent to the active (or functional) site of several enzymes and integral membrane proteins. The ACT domain comprises four β-strands and two α-helices in a βαββαβ motif typical of intracellular small molecule binding domains that help control metabolism, solute transport and signal transduction. We discuss the possible role of TTHA0829 based on its structure and expression pattern. The results imply that TTHA0829 acts as a cell-stress sensor or a metabolite acceptor.

  14. CFTR activity and mitochondrial function

    Directory of Open Access Journals (Sweden)

    Angel Gabriel Valdivieso

    2013-01-01

    Full Text Available Cystic Fibrosis (CF is a frequent and lethal autosomal recessive disease, caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR. Before the discovery of the CFTR gene, several hypotheses attempted to explain the etiology of this disease, including the possible role of a chloride channel, diverse alterations in mitochondrial functions, the overexpression of the lysosomal enzyme α-glucosidase and a deficiency in the cytosolic enzyme glucose 6-phosphate dehydrogenase. Because of the diverse mitochondrial changes found, some authors proposed that the affected gene should codify for a mitochondrial protein. Later, the CFTR cloning and the demonstration of its chloride channel activity turned the mitochondrial, lysosomal and cytosolic hypotheses obsolete. However, in recent years, using new approaches, several investigators reported similar or new alterations of mitochondrial functions in Cystic Fibrosis, thus rediscovering a possible role of mitochondria in this disease. Here, we review these CFTR-driven mitochondrial defects, including differential gene expression, alterations in oxidative phosphorylation, calcium homeostasis, oxidative stress, apoptosis and innate immune response, which might explain some characteristics of the complex CF phenotype and reveals potential new targets for therapy.

  15. [Isolation of tyrosyl-tRNA-synthetase from Thermus thermophilus HB-27].

    Science.gov (United States)

    Iaremchuk, A D; Tukalo, M A; Egorova, S P; Konovalenko, A V; Matsuka, G Kh

    1990-01-01

    A method for isolating tyrosyl-tRNA synthetase from Thermus thermophilus is described, including ammonium sulfate fractionation, chromatography on DEAE-sepharose, hydroxyapatite, heparin-sepharose and hydrophobic chromatography on Toyopearl HW-65. The yield of the purified enzyme was 1.6 mg per 1 kg of T. thermophilus cells. The enzyme is a dimer protein of the alpha 2 type with molecular weight of 100 kDa.

  16. Complete Genome Sequence of Thermus thermophilus TMY, Isolated from a Geothermal Power Plant

    Science.gov (United States)

    Fujino, Yasuhiro; Nagayoshi, Yuko; Ohshima, Toshihisa; Ogata, Seiya

    2017-01-01

    ABSTRACT Thermus thermophilus TMY (JCM 10668) was isolated from silica scale formed at a geothermal power plant in Japan. Here, we report the complete genome sequence for this strain, which contains a chromosomal DNA of 2,121,526 bp with 2,500 predicted genes and a pTMY plasmid of 19,139 bp, with 28 predicted genes. PMID:28153912

  17. Molecular docking and molecular dynamics simulation studies on Thermus thermophilus leucyl-tRNA synthetase complexed with different amino acids and pre-transfer editing substrates

    Directory of Open Access Journals (Sweden)

    Rayevsky A. V.

    2016-02-01

    Full Text Available Aim. To investigate the structural bases for the amino acid selectivity of the Thermus thermophilus leucyl-tRNA synthetase (LeuRSTT aminoacylation site and to disclose the binding pattern of pre-transfer editing substrates. Methods. Eight amino acids proposed as semi-cognate substrates for aminoacylation and eight aminoacyl-adenylates (formed from AMP and eight amino acids were prepared in zwitterions form. The protein structure with a co-crystallized substrate in the aminoacylation site [PDBID: 1OBH] was taken from RCSB. Docking settings and evaluation of substrate efficiency were followed by twofold docking function analysis for each conformation with Gold CCDC. The molecular dynamics simulation was performed using Gromacs. The procedures of relaxation and binding study were separated in two different subsequent simulations for 50ns and 5ns. Results. The evaluation of substrate efficiency for 8 amino acids by twofold docking function analysis, based on score values,has shown that the ligands of LeuRSTT can be positioned in the following order: Leu>Nva>Hcy>Nle>Met>Cys>Ile >Val. MD simulation has revealed lower electrostatic interactions of isoleucine with the active site of the enzyme compared with those for norvaline and leucine. In the case of aminoacyl-adenylates no significant differences were found based on score values for both GoldScore and Asp functions. Molecular dynamics of leucyl-, isoleucyl- and norvalyl-adenylates showed that the most stable and conformationally favorable is leucine, then follow norvaline and isoleucine. It has been also found that the TYR43 of the active site covers carboxyl group of leucine and norvaline like a shield and deflected towards isoleucine, allowing water molecules to come closer. Conclusions. In this study we revealed some structural basis for screening unfavorable substrates by shape, size and flexibility of a radical. The results obtained for different amino acids by molecular docking and MD studies

  18. Inactivation and unfolding of protein tyrosine phosphatase from Thermus thermophilus HB27 during urea and guanidine hydrochloride denaturation.

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    Yejing Wang

    Full Text Available The effects of urea and guanidine hydrochloride (GdnHCl on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase, a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV circular dichroism (CD, Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase.

  19. Accuracy of replication in the polymerase chain reaction. Comparison between Thermotoga maritima DNA polymerase and Thermus aquaticus DNA polymerase

    Directory of Open Access Journals (Sweden)

    R.S. Diaz

    1998-10-01

    Full Text Available For certain applications of the polymerase chain reaction (PCR, it may be necessary to consider the accuracy of replication. The breakthrough that made PCR user friendly was the commercialization of Thermus aquaticus (Taq DNA polymerase, an enzyme that would survive the high temperatures needed for DNA denaturation. The development of enzymes with an inherent 3' to 5' exonuclease proofreading activity, lacking in Taq polymerase, would be an improvement when higher fidelity is needed. We used the forward mutation assay to compare the fidelity of Taq polymerase and Thermotoga maritima (ULTMA™ DNA polymerase, an enzyme that does have proofreading activity. We did not find significant differences in the fidelity of either enzyme, even when using optimal buffer conditions, thermal cycling parameters, and number of cycles (0.2% and 0.13% error rates for ULTMA™ and Taq, respectively, after reading about 3,000 bases each. We conclude that for sequencing purposes there is no difference in using a DNA polymerase that contains an inherent 3' to 5' exonuclease activity for DNA amplification. Perhaps the specificity and fidelity of PCR are complex issues influenced by the nature of the target sequence, as well as by each PCR component.

  20. Efficient trans-cleavage by the Schistosoma mansoni SMalpha1 hammerhead ribozyme in the extreme thermophile Thermus thermophilus.

    Science.gov (United States)

    Vazquez-Tello, Alejandro; Castán, Pablo; Moreno, Renata; Smith, James M; Berenguer, José; Cedergren, Robert

    2002-04-01

    The catalytic hammerhead structure has been found in association with repetitive DNA from several animals, including salamanders, crickets and schistosomes, and functions to process in cis the long multimer transcripts into monomer RNA in vivo. The cellular role of these repetitive elements and their transcripts is unknown. Moreover, none of these natural hammerheads have been shown to trans-cleave a host mRNA in vivo. We analyzed the cis- and trans-cleavage properties of the hammerhead ribozyme associated with the SMalpha DNA family from the human parasite Schistosoma mansoni. The efficiency of trans-cleavage of a target RNA in vitro was affected mainly by both the temperature-dependent chemical step and the ribozyme-product dissociation step. The optimal temperature for trans-cleavage was 70 degrees C. This result was confirmed when both the SMalpha1 ribozyme and the target RNA were expressed in the extreme thermophile Thermus thermophilus. Moreover, SMalpha1 RNA showed a remarkable thermostability, equal or superior to that of the most stable RNAs in this species, suggesting that SMalpha1 RNA has been selected for stability. Computer analysis predicts that the monomer and multimer transcripts fold into highly compact secondary structures, which may explain their exceptional stability in vivo.

  1. The transjugation machinery of Thermus thermophilus: Identification of TdtA, an ATPase involved in DNA donation

    Science.gov (United States)

    Blesa, Alba; Mata, Carlos P.

    2017-01-01

    In addition to natural competence, some Thermus thermophilus strains show a high rate of DNA transfer via direct cell-to-cell contact. The process is bidirectional and follows a two-step model where the donor cell actively pushes out DNA and the recipient cell employs the natural competence system to take up the DNA, in a hybrid transformation-dependent conjugation process (transjugation). While the DNA uptake machinery is well known as in other bacterial species that undergo transformation, the pushing step of transjugation remains to be characterized. Here we have searched for hypothetical DNA translocases putatively involved in the pushing step of transjugation. Among candidates encoded by T. thermophilus HB27, the TdtA protein was found to be required for DNA pushing but not for DNA pulling during transjugation, without affecting other cellular processes. Purified TdtA shows ATPase activity and oligomerizes as hexamers with a central opening that can accommodate double-stranded DNA. The tdtA gene was found to belong to a mobile 14 kbp-long DNA element inserted within the 3′ end of a tRNA gene, flanked by 47 bp direct repeats. The insertion also encoded a homolog of bacteriophage site-specific recombinases and actively self-excised from the chromosome at high frequency to form an apparently non-replicative circular form. The insertion also encoded a type II restriction endonuclease and a NurA-like nuclease, whose activities were required for efficient transjugation. All these data support that TdtA belongs to a new type of Integrative and Conjugative Element which promotes the generalized and efficient transfer of genetic traits that could facilitate its co-selection among bacterial populations. PMID:28282376

  2. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    Science.gov (United States)

    Sharma, Reetu; Sastry, G Narahari

    2015-01-01

    Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

  3. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Reetu Sharma

    Full Text Available Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

  4. Functional Screening of Core Promoter Activity.

    Science.gov (United States)

    Even, Dan Y; Kedmi, Adi; Ideses, Diana; Juven-Gershon, Tamar

    2017-01-01

    The core promoter is the DNA sequence that recruits the basal transcription machinery and directs accurate initiation of transcription. It is an active contributor to gene expression that can be rationally designed to manipulate the levels of expression. Core promoter function can be analyzed using different experimental approaches. Here, we describe the qualitative and quantitative analysis of engineered core promoter functions using the EGFP reporter gene that is driven by distinct core promoters. Expression plasmids are transfected into different mammalian cell lines, and the resulting fluorescence is monitored by live cell imaging , as well as by flow cytometry. In order to verify that the transcriptional activity of the examined core promoters is indeed a function of their activity, as opposed to differences in DNA uptake, real-time quantitative PCR analysis is performed. Importantly, the described methodology for functional screening of core promoter activity has enabled the analysis of engineered potent core promoters for extended time periods.

  5. Structural basis of transcription activation.

    Science.gov (United States)

    Feng, Yu; Zhang, Yu; Ebright, Richard H

    2016-06-10

    Class II transcription activators function by binding to a DNA site overlapping a core promoter and stimulating isomerization of an initial RNA polymerase (RNAP)-promoter closed complex into a catalytically competent RNAP-promoter open complex. Here, we report a 4.4 angstrom crystal structure of an intact bacterial class II transcription activation complex. The structure comprises Thermus thermophilus transcription activator protein TTHB099 (TAP) [homolog of Escherichia coli catabolite activator protein (CAP)], T. thermophilus RNAP σ(A) holoenzyme, a class II TAP-dependent promoter, and a ribotetranucleotide primer. The structure reveals the interactions between RNAP holoenzyme and DNA responsible for transcription initiation and reveals the interactions between TAP and RNAP holoenzyme responsible for transcription activation. The structure indicates that TAP stimulates isomerization through simple, adhesive, stabilizing protein-protein interactions with RNAP holoenzyme. Copyright © 2016, American Association for the Advancement of Science.

  6. Metabolic network reconstruction, growth characterization and 13C-metabolic flux analysis of the extremophile Thermus thermophilus HB8.

    Science.gov (United States)

    Swarup, Aditi; Lu, Jing; DeWoody, Kathleen C; Antoniewicz, Maciek R

    2014-07-01

    Thermus thermophilus is an extremely thermophilic bacterium with significant biotechnological potential. In this work, we have characterized aerobic growth characteristics of T. thermophilus HB8 at temperatures between 50 and 85°C, constructed a metabolic network model of its central carbon metabolism and validated the model using (13)C-metabolic flux analysis ((13)C-MFA). First, cells were grown in batch cultures in custom constructed mini-bioreactors at different temperatures to determine optimal growth conditions. The optimal temperature for T. thermophilus grown on defined medium with glucose was 81°C. The maximum growth rate was 0.25h(-1). Between 50 and 81°C the growth rate increased by 7-fold and the temperature dependence was described well by an Arrhenius model with an activation energy of 47kJ/mol. Next, we performed a (13)C-labeling experiment with [1,2-(13)C] glucose as the tracer and calculated intracellular metabolic fluxes using (13)C-MFA. The results provided support for the constructed network model and highlighted several interesting characteristics of T. thermophilus metabolism. We found that T. thermophilus largely uses glycolysis and TCA cycle to produce biosynthetic precursors, ATP and reducing equivalents needed for cells growth. Consistent with its proposed metabolic network model, we did not detect any oxidative pentose phosphate pathway flux or Entner-Doudoroff pathway activity. The biomass precursors erythrose-4-phosphate and ribose-5-phosphate were produced via the non-oxidative pentose phosphate pathway, and largely via transketolase, with little contribution from transaldolase. The high biomass yield on glucose that was measured experimentally was also confirmed independently by (13)C-MFA. The results presented here provide a solid foundation for future studies of T. thermophilus and its metabolic engineering applications.

  7. Thermus parvatiensis RL(T) sp. nov., Isolated from a Hot Water Spring, Located Atop the Himalayan Ranges at Manikaran, India.

    Science.gov (United States)

    Dwivedi, Vatsala; Kumari, Kirti; Gupta, Sanjay Kumar; Kumari, Rekha; Tripathi, Charu; Lata, Pushp; Niharika, Neha; Singh, Amit Kumar; Kumar, Roshan; Nigam, Aeshna; Garg, Nidhi; Lal, Rup

    2015-12-01

    A Gram negative, yellow pigmented, rod shaped bacterium designated as RL(T) was isolated from a hot water spring (90-98 °C) located at Manikaran in Northern India. The isolate grows at 60-80 °C (optimum, 70 °C) and at pH 7.0-9.0 (optimum pH 7.2). Phylogenetic analysis of 16S rRNA gene sequences and levels of DNA-DNA relatedness together indicate that the new isolate represents a novel species of the genus Thermus with closest affinity to Thermus thermophilus HB8(T) (99.5 %) followed by Thermus arciformis (96.4 %). A comparative analysis of partial sequences of housekeeping genes (HKG) further revealed that strain RL(T) is a novel species belonging to the genus Thermus. The melting G+C content of strain RL(T) was calculated as 68.7 mol%. The DNA-DNA relatedness value of strain RL(T) with its nearest neighbours (>97 %) was found to be less than 70 % indicating that strain RL(T) represents a novel species of the genus Thermus. MK-8 was the predominant respiratory quinone. The presence of characteristic phospholipid and glycolipid further confirmed that strain RL(T) belongs to the genus Thermus. The predominant fatty acids of strain RL(T) were iso-C17:0 (23.67 %) and iso-C15:0 (24.50 %). The results obtained after DNA-DNA hybridization, biochemical and physiological tests clearly distinguished strain RL(T) from its closely related species. Thus, strain RL(T) represents a novel species of the genus Thermus for which the name Thermus parvatiensis is proposed (=DSM 21745(T)= MTCC 8932(T)).

  8. Thermophilic amylase from Thermus sp. isolation and its potential application for bioethanol production

    Directory of Open Access Journals (Sweden)

    Amin Fatoni

    2012-11-01

    Full Text Available Limited reserves of fossil energy stimulate researchers to explore for a new alternative energy, such as bioethanol.A thermophilic amylase producing bacterium was isolated from local hot-springs and its characteristic and potential applicationfor bioethanol production was determined. The obtained amylase was studied to determine its optimum temperature, pH,enzymatic reaction time, and substrate concentration. Tapioca waste was used as the substrate to find the potential of theamylase for degrading starch into glucose, and then the process was continued by fermentation to produce bioethanol. Theamylase producer bacterium was proposed as genus Thermus sp. The crude amylase that was obtained has the optimumtemperature of 60°C and optimum pH of 8.0, optimum substrate concentration at 10% (w/w and optimum enzymatic reactiontime of 45 minutes. These enzymes convert the starches of waste tapioca at optimum conditions, with the result of 2.9%ethanol produced from raw materials.

  9. Crystal structure of TTC0263, a thermophilic TPR protein from Thermus thermophilus HB27.

    Science.gov (United States)

    Lim, Hyosun; Kim, Kyunggon; Han, Dohyun; Oh, Jongkil; Kim, Youngsoo

    2007-08-31

    The hypothetical protein TTC0263 of Thermus thermophilus HB27 is a thermophilic tetratricopeptide repeat (TPR)-containing protein. In the present study, the TPR region (residues 26-230) was resolved at 2.5 A with R-factors of R/Rfree = 23.6%/28.6%. TTC0263 consists of 11 helices that form five TPR units. Uniquely, it contains one atypical "extended" TPR (eTPR) unit. This comprises extended helical residues near the loop region of TTC0263, such that the helical length of eTPR is longer than that of the canonical TPR sequence. In addition, the hybrid TPR domain of TTC0263 possesses oligomer-forming characteristics. TPR domains are generally involved in forming multi-subunit complexes by interacting with each other or with other subunit proteins. The dynamic structure of TTC0263 described here goes some way to explaining how TPR domains mediate the formation of multi-subunit complexes.

  10. Structure and flexibility of the thermophilic cold-shock protein of Thermus aquaticus.

    Science.gov (United States)

    Jin, Bonghwan; Jeong, Ki-Woong; Kim, Yangmee

    2014-08-29

    The thermophilic bacterium Thermus aquaticus is a well-known source of Taq polymerase. Here, we studied the structure and dynamics of the T. aquaticus cold-shock protein (Ta-Csp) to better understand its thermostability using NMR spectroscopy. We found that Ta-Csp has a five-stranded β-barrel structure with five salt bridges which are important for more rigid structure and a higher melting temperature (76 °C) of Ta-Csp compared to mesophilic and psychrophilic Csps. Microsecond to millisecond time scale exchange processes occur only at the β1-β2 surface region of the nucleic acid binding site with an average conformational exchange rate constant of 674 s(-1). The results imply that thermophilic Ta-Csp has a more rigid structure and may not need high structural flexibility to accommodate nucleic acids upon cold shock compared to its mesophile and psychrophile counterparts.

  11. The identification and quantification of phospholipids from Thermus and Meiothermus bacteria.

    Science.gov (United States)

    Lagutin, Kirill; MacKenzie, Andrew; Houghton, Karen M; Stott, Matthew B; Vyssotski, Mikhail

    2014-11-01

    Structural identities of the major phospholipid (PL-2), minor phospholipid (PL-1) and trace phospholipid (PL-0) from representative strains of the genera Thermus and Meiothermus were established. Phospholipids were quantified using phosphorus-31 nuclear magnetic resonance ((31)P-NMR). The structures of the major phospholipid (PL-2) from Thermus filiformis MOK14.7 and Meiothermus ruber WRG6.9 were identified as 2'-O-(1,2-diacyl-sn-glycero-3-phospho)-3'-O-(α-N-acetylglucosaminyl)-N-glyceroyl alkylamine (GlcNAc-PGAA) and 2'-O-(2-acylalkyldiol-1-O-phospho)-3'-O-(α-N-acetylglucosaminyl)-N-glyceroyl alkylamine (GlcNAc-diolPGAA). Interestingly, M. ruber contained only a diacyl form of GlcNAc-PGAA (87 %), while T. filiformis contained both GlcNAc-PGAA (59 %) and GlcNAc-diolPGAA (18 %). The structures of the minor phospholipid (PL-1) were established as 2'-O-(1,2-diacyl-sn-glycero-3-phospho)-3'-O-(α-glucosaminyl)-N-glyceroyl alkylamine (GlcN-PGAA, 13 %) in T. filiformis and 2'-O-(1,2-diacyl-sn-glycero-3-phospho)-3'-O-(α-galactosaminyl)-N-glyceroyl alkylamine (GalN-PGAA, 19 %) in M. ruber. This is the first reliable discovery of phosphatidylglyceroylalkylamines modified by glucosamine or galactosamine with a free amino group. No signs of diol-based phosphatidylglyceroylalkylamines were found in PL-1 phospholipids. Similar to PL-2, trace phospholipid (PL-0) from T. filiformis contained both unsubstituted diol-based phosphatidylglyceroylalkylamine (diolPGAA) and PGAA, while M. ruber contained only free PGAA. Unlike analysis using TLC, the diol form of phosphatidylglyceroylalkylamines is clearly resolved from the diacyl form via (31)P-NMR.

  12. Cerebral blood flow response to functional activation

    DEFF Research Database (Denmark)

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill

    2010-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only...

  13. Biochemical and structural characterization of quinoprotein aldose sugar dehydrogenase from Thermus thermophilus HJ6: Mutational analysis of Tyr156 in the substrate-binding site.

    Science.gov (United States)

    Kim, Han-Woo; Wang, Ji-Yeon; Lee, Ji-Yeon; Park, Ae-Kyung; Park, Hyun; Jeon, Sung-Jong

    2016-10-15

    The gene encoding a quinoprotein aldose sugar dehydrogenase (ASD) from Thermus thermophilus HJ6 (Tt_ASD) was cloned and sequenced; it comprised 1059 nucleotides encoding a protein containing 352 amino acids that had a predicted molecular mass of 38.9 kDa. The deduced amino acid sequence showed 42.9% and 33.9% identities to the ASD proteins from Pyrobaculum aerophilum and Escherichia coli, respectively. The biochemical properties of Tt_ASD were characterized. The optimum pH for the oxidation of glucose was 7.0-7.5 and the optimum temperature was 70 °C. The half-life of heat inactivation for the apoenzyme was about 25 min at 85 °C. The enzyme was highly thermostable, and the activity of the pyrroloquinoline quinone-bound holoenzyme was not lost after incubation at 85 °C for 100 min. Tt_ASD could oxidize various sugars, including hexoses, pentoses, disaccharides, and polysaccharides, in addition to alcohols. Structural analysis suggested that Tyr156 would be the substrate-binding residue. Two mutants, Y156A and Y156K, had impaired activities and affinities for all substrates and completely lost their activities for alcohols. This structural and mutational analysis of Tt_ASD demonstrates the crucial role of Tyr156 in determining substrate specificity.

  14. Functional Stability of Plasminogen Activator Inhibitor-1

    Directory of Open Access Journals (Sweden)

    Songul Yasar Yildiz

    2014-01-01

    Full Text Available Plasminogen activator inhibitor-1 (PAI-1 is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA and urokinase-type plasminogen activator (u-PA, and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT and myocardial infarction (MI. The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

  15. Functions for diverse metabolic activities in heterochromatin.

    Science.gov (United States)

    Su, Xue Bessie; Pillus, Lorraine

    2016-03-15

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes.

  16. Simulation of the PIR detector active function

    Directory of Open Access Journals (Sweden)

    Drga Rudolf

    2016-01-01

    Full Text Available The work deals with the behaviour of the PIR detector in an environment with great influence of a thermal background. It was necessary to perform simulations of the thermal behaviour of the sensor by COMSOL Multiphysics in different modes of heating the room to be able to prove that the PIR detector can function as an active detector with improved detection possibilities of intruders who would be invisible to a detector under normal circumstances. This confirms the detector’s ability to work on the principle of active detector, i.e. as transmitter and receiver of thermal radiation and evaluation of heat flux changes depending on the type of the heater and the shrouding.

  17. Overproduction of Thermus sp. Strain T2 β-Galactosidase in Escherichia coli and Preparation by Using Tailor-Made Metal Chelate Supports

    Science.gov (United States)

    Pessela, Benevides C. C.; Vian, Alejandro; Mateo, César; Fernández-Lafuente, Roberto; García, José L.; Guisán, José M.; Carrascosa, Alfonso V.

    2003-01-01

    A novel thermostable chimeric β-galactosidase was constructed by fusing a poly-His tag to the N-terminal region of the β-galactosidase from Thermus sp. strain T2 to facilitate its overexpression in Escherichia coli and its purification by immobilized metal-ion affinity chromatography (IMAC). The poly-His tag fusion did not affect the activation, kinetic parameters, and stability of the β-galactosidase. Copper-iminodiacetic acid (Cu-IDA) supports enabled the most rapid adsorption of the His-tagged enzyme, favoring multisubunit interactions, but caused deleterious effects on the enzyme stability. To improve the enzyme purification a selective one-point adsorption was achieved by designing tailor-made low-activated Co-IDA or Ni-IDA supports. The new enzyme was not only useful for industrial purposes but also has become an excellent model to study the purification of large multimeric proteins via selective adsorption on tailor-made IMAC supports. PMID:12676671

  18. Crystal structure studies of NADP+ dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain.

    Science.gov (United States)

    Kumar, S M; Pampa, K J; Manjula, M; Abdoh, M M M; Kunishima, Naoki; Lokanath, N K

    2014-06-20

    NADP(+) dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP(+) was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH's. And, small domain and clasp domain showing significant differences when compared to other IDH's of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH's. Also, helices/beta sheets are absent in the small domain, when compared to other IDH's of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit-subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.

  19. Crystal structures and ligand binding of PurM proteins from Thermus thermophilus and Geobacillus kaustophilus.

    Science.gov (United States)

    Kanagawa, Mayumi; Baba, Seiki; Watanabe, Yuzo; Nakagawa, Noriko; Ebihara, Akio; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Sampei, Gen-Ichi; Kawai, Gota

    2016-03-01

    Crystal structures of 5-aminoimidazole ribonucleotide (AIR) synthetase, also known as PurM, from Thermus thermophilus (Tt) and Geobacillus kaustophilus (Gk) were determined. For TtPurM, the maximum resolution was 2.2 Å and the space group was P21212 with four dimers in an asymmetric unit. For GkPurM, the maximum resolution was 2.2 Å and the space group was P21212 with one monomer in asymmetric unit. The biological unit is dimer for both TtPurM and GkPurM and the dimer structures were similar to previously determined structures of PurM in general. For TtPurM, ∼50 residues at the amino terminal were disordered in the crystal structure whereas, for GkPurM, the corresponding region covered the ATP-binding site forming an α helix in part, suggesting that the N-terminal region of PurM changes its conformation upon binding of ligands. FGAM binding site was predicted by the docking simulation followed by the MD simulation based on the SO4 (2-) binding site found in the crystal structure of TtPurM.

  20. Single mutations that redirect internal proton transfer in the ba3 oxidase from Thermus thermophilus.

    Science.gov (United States)

    Smirnova, Irina; Chang, Hsin-Yang; von Ballmoos, Christoph; Ädelroth, Pia; Gennis, Robert B; Brzezinski, Peter

    2013-10-08

    The ba3-type cytochrome c oxidase from Thermus thermophilus is a membrane-bound proton pump. Results from earlier studies have shown that with the aa3-type oxidases proton uptake to the catalytic site and "pump site" occurs simultaneously. However, with ba3 oxidase the pump site is loaded before proton transfer to the catalytic site because the proton transfer to the latter is slower than that with the aa3 oxidases. In addition, the timing of formation and decay of catalytic intermediates is different in the two types of oxidases. In the present study, we have investigated two mutant ba3 CytcOs in which residues of the proton pathway leading to the catalytic site as well as the pump site were exchanged, Thr312Val and Tyr244Phe. Even though ba3 CytcO uses only a single proton pathway for transfer of the substrate and "pumped" protons, the amino-acid residue substitutions had distinctly different effects on the kinetics of proton transfer to the catalytic site and the pump site. The results indicate that the rates of these reactions can be modified independently by replacement of single residues within the proton pathway. Furthermore, the data suggest that the Thr312Val and Tyr244Phe mutations interfere with a structural rearrangement in the proton pathway that is rate limiting for proton transfer to the catalytic site.

  1. Proline dehydrogenase from Thermus thermophilus does not discriminate between FAD and FMN as cofactor

    Science.gov (United States)

    Huijbers, Mieke M. E.; Martínez-Júlvez, Marta; Westphal, Adrie H.; Delgado-Arciniega, Estela; Medina, Milagros; van Berkel, Willem J. H.

    2017-01-01

    Flavoenzymes are versatile biocatalysts containing either FAD or FMN as cofactor. FAD often binds to a Rossmann fold, while FMN prefers a TIM-barrel or flavodoxin-like fold. Proline dehydrogenase is denoted as an exception: it possesses a TIM barrel-like fold while binding FAD. Using a riboflavin auxotrophic Escherichia coli strain and maltose-binding protein as solubility tag, we produced the apoprotein of Thermus thermophilus ProDH (MBP-TtProDH). Remarkably, reconstitution with FAD or FMN revealed that MBP-TtProDH has no preference for either of the two prosthetic groups. Kinetic parameters of both holo forms are similar, as are the dissociation constants for FAD and FMN release. Furthermore, we show that the holo form of MBP-TtProDH, as produced in E. coli TOP10 cells, contains about three times more FMN than FAD. In line with this flavin content, the crystal structure of TtProDH variant ΔABC, which lacks helices αA, αB and αC, shows no electron density for an AMP moiety of the cofactor. To the best of our knowledge, this is the first example of a flavoenzyme that does not discriminate between FAD and FMN as cofactor. Therefore, classification of TtProDH as an FAD-binding enzyme should be reconsidered. PMID:28256579

  2. Structure of N-formylglycinamide ribonucleotide amidotransferase II (PurL) from Thermus thermophilus HB8

    Science.gov (United States)

    Suzuki, Sakiko; Yanai, Hisaaki; Kanagawa, Mayumi; Tamura, Satoko; Watanabe, Yuzo; Fuse, Kyotaro; Baba, Seiki; Sampei, Gen-ichi; Kawai, Gota

    2012-01-01

    The crystal structure of PurL from Thermus thermophilus HB8 (TtPurL; TTHA1519) was determined in complex with an adenine nucleotide, PO4 3− and Mg2+ at 2.35 Å resolution. TtPurL consists of 29 α-helices and 28 β-strands, and one loop is disordered. TtPurL consists of four domains, A1, A2, B1 and B2, and the structures of the A1–B1 and A2–B2 domains were almost identical to each other. Although the sequence identity between TtPurL and PurL from Thermotoga maritima (TmPurL) is higher than that between TtPurL and the PurL domain of the large PurL from Salmonella typhimurium (StPurL), the secondary structure of TtPurL is much more similar to that of StPurL than to that of TmPurL. PMID:22232163

  3. Models for the a subunits of the Thermus thermophilus V/A-ATPase and Saccharomyces cerevisiae V-ATPase enzymes by cryo-EM and evolutionary covariance.

    Science.gov (United States)

    Schep, Daniel G; Zhao, Jianhua; Rubinstein, John L

    2016-03-22

    Rotary ATPases couple ATP synthesis or hydrolysis to proton translocation across a membrane. However, understanding proton translocation has been hampered by a lack of structural information for the membrane-embedded a subunit. The V/A-ATPase from the eubacterium Thermus thermophilus is similar in structure to the eukaryotic V-ATPase but has a simpler subunit composition and functions in vivo to synthesize ATP rather than pump protons. We determined the T. thermophilus V/A-ATPase structure by cryo-EM at 6.4 Å resolution. Evolutionary covariance analysis allowed tracing of the a subunit sequence within the map, providing a complete model of the rotary ATPase. Comparing the membrane-embedded regions of the T. thermophilus V/A-ATPase and eukaryotic V-ATPase from Saccharomyces cerevisiae allowed identification of the α-helices that belong to the a subunit and revealed the existence of previously unknown subunits in the eukaryotic enzyme. Subsequent evolutionary covariance analysis enabled construction of a model of the a subunit in the S. cerevisae V-ATPase that explains numerous biochemical studies of that enzyme. Comparing the two a subunit structures determined here with a structure of the distantly related a subunit from the bovine F-type ATP synthase revealed a conserved pattern of residues, suggesting a common mechanism for proton transport in all rotary ATPases.

  4. Structural asymmetry in the Thermus thermophilus RuvC dimer suggests a basis for sequential strand cleavages during Holliday junction resolution.

    Science.gov (United States)

    Chen, Luan; Shi, Ke; Yin, Zhiqi; Aihara, Hideki

    2013-01-07

    Holliday junction (HJ) resolvases are structure-specific endonucleases that cleave four-way DNA junctions (HJs) generated during DNA recombination and repair. Bacterial RuvC, a prototypical HJ resolvase, functions as homodimer and nicks DNA strands precisely across the junction point. To gain insights into the mechanisms underlying symmetrical strand cleavages by RuvC, we performed crystallographic and biochemical analyses of RuvC from Thermus thermophilus (T.th. RuvC). The crystal structure of T.th. RuvC shows an overall protein fold similar to that of Escherichia coli RuvC, but T.th. RuvC has a more tightly associated dimer interface possibly reflecting its thermostability. The binding mode of a HJ-DNA substrate can be inferred from the shape/charge complementarity between the T.th. RuvC dimer and HJ-DNA, as well as positions of sulfate ions bound on the protein surface. Unexpectedly, the structure of T.th. RuvC homodimer refined at 1.28 Å resolution shows distinct asymmetry near the dimer interface, in the region harboring catalytically important aromatic residues. The observation suggests that the T.th. RuvC homodimer interconverts between two asymmetric conformations, with alternating subunits switched on for DNA strand cleavage. This model provides a structural basis for the 'nick-counter-nick' mechanism in HJ resolution, a mode of HJ processing shared by prokaryotic and eukaryotic HJ resolvases.

  5. Electron transfer among the CuA-, heme b- and a3-centers of Thermus thermophilus cytochrome ba3

    DEFF Research Database (Denmark)

    Farver, Ole; Chen, Ying; Fee, James A

    2006-01-01

    . and Pecht, I. (2006) Rates and equilibrium of CuA to heme a electron transfer in Paracoccus denitrificans cytochrome c oxidase. Biophys. J. 90, 2131-2137]. Investigating this process in the cytochrome ba(3) of Thermus thermophilus (Tt), we now show that MNA(*) also reduces Cu(A) with a subsequent ET...... to the heme b and then to heme a(3), with first-order rate constants 11200 s(-1), and 770 s(-1), respectively. The results provide clear evidence for ET among the three spectroscopically distinguishable centers and indicate that the binuclear a(3)-Cu(B) center can be reduced in molecules containing a single...

  6. Cloning, overexpression, purification and crystallization of malate dehydrogenase from Thermus thermophilus.

    Science.gov (United States)

    Chang, Yu-Yung; Hung, Chih-Hung; Hwang, Tzann-Shun; Hsu, Chun-Hua

    2013-11-01

    Malate dehydrogenase (MDH) has been used as a conjugate for enzyme immunoassay of a wide variety of compounds, such as drugs of abuse, drugs used in repetitive therapeutic application and hormones. In consideration of the various biotechnological applications of MDH, investigations of MDH from Thermus thermophilus were carried out to further understand the properties of this enzyme. The DNA fragment containing the open reading frame of mdh was amplified from the genomic DNA of T. thermophilus and cloned into the expression vector pET21b(+). The protein was expressed in a soluble form in Escherichia coli strain BL21(DE3). Homogeneous protein was obtained using a three-step procedure consisting of thermal treatment, Ni(2+)-chelating chromatography and size-exclusion chromatography. The purified MDH was crystallized and the crystals diffracted to a resolution of 1.80 Å on the BL13C1 beamline of the National Synchrotron Radiation Research Center (NSRRC), Taiwan. The crystals belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 71.3, b = 86.1, c = 118.2 Å. The unit-cell volume of the crystal is compatible with the presence of two monomers in the asymmetric unit, with a corresponding Matthews coefficient VM of 2.52 Å(3) Da(-1) and a solvent content of 51.2%. The crystal structure of MDH has been solved by molecular replacement and is currently under refinement.

  7. Evaluation of biomass production, carotenoid level and antioxidant capacity produced by Thermus filiformis Using fractional factorial design

    Science.gov (United States)

    Mandelli, Fernanda; Yamashita, Fábio; Pereira, José L.; Mercadante, Adriana Z.

    2012-01-01

    A fractional factorial design 25–1 was used to evaluate the effect of temperature, pH, and concentrations of yeast extract, tryptone and Nitsch’s trace elements on the biomass, total carotenoids and protection against singlet oxygen by carotenoid extracts of the bacterium Thermus filiformis. In addition, the carotenoid composition was determined by high-performance liquid chromatography connected to a diode array and mass spectrometer detectors (HPLC-DAD-MS/MS). The production of biomass ranged from 0.113 to 0.658 g/L, the total carotenoid from 137.6 to 1,517.4 µg/g and the protection against singlet oxygen from 4.3 to 85.1 %. Results of the fractional factorial design showed that temperature had a negative effect on biomass production and a positive effect on carotenoid content and protection against singlet oxygen, besides, high levels of pH value, concentrations of yeast extract and tryptone had a positive effect on biomass production only at lower temperatures. The main carotenoids of T. filiformis were thermozeaxanthins. In the tested conditions, changes in the levels of the variables influenced the biomass, carotenoid production, and protection against singlet oxygen, although they did not influence the carotenoid profile. The results of this study provide a better understanding on the interactions among certain nutritional and cultivation conditions of a thermophile bacterium, Thermus filiformis, on biomass and carotenoid amounts, as well as on the antioxidant capacity. PMID:24031811

  8. PRODUCCIÓN DE α-AMILASA CON CÉLULAS LIBRES E INMOVILIZADAS DE Thermus sp.

    Directory of Open Access Journals (Sweden)

    Sarmiento VC

    2003-12-01

    Full Text Available Se compara la producción de á-amilasa termoestable a partir de almidón, empleando una cepa autóctona deThermus sp., en cultivo discontinuo con células libres e inmovilizadas en 3% p/v de alginato de sodio. Laproducción se llevó a cabo en medio PAP2 modificado por la adición de almidón de maíz a 3.024g/l. Losresultados obtenidos en el fermentador, reportaron mayor eficiencia debido a la configuración geométrica;concentración de la fuente de carbono, oxigenación y temperatura; lo que permite mejor aprovechamiento delsustrato. La máxima producción de alpha amilasa se obtuvo con células inmovilizadas en fermentador con 1lde caldo de cultivo (cultivo fluidizado, a las 24 horas de fermentación (360.97UA/min l y 149.09 de actividadespecífica, vs., 60.31UA/min l y 18.40 de actividad específica, obtenida en fermentador con 10l de volumende trabajo a las 14h. Es importante resaltar de este trabajo, que por primera vez en Colombia son utilizadascélulas inmovilizadas de Thermus sp., para la producción de alpha amilasa termoestable.

  9. Evaluation of biomass production, carotenoid level and antioxidant capacity produced by Thermus filiformis using fractional factorial design

    Directory of Open Access Journals (Sweden)

    Fernanda Mandelli

    2012-03-01

    Full Text Available A fractional factorial design 2(5-1 was used to evaluate the effect of temperature, pH, and concentrations of yeast extract, tryptone and Nitsch's trace elements on the biomass, total carotenoids and protection against singlet oxygen by carotenoid extracts of the bacterium Thermus filiformis. In addition, the carotenoid composition was determined by high-performance liquid chromatography connected to a diode array and mass spectrometer detectors (HPLC-DAD-MS/MS. The production of biomass ranged from 0.113 to 0.658 g/L, the total carotenoid from 137.6 to 1,517.4 mg/g and the protection against singlet oxygen from 4.3 to 85.1 %. Results of the fractional factorial design showed that temperature had a negative effect on biomass production and a positive effect on carotenoid content and protection against singlet oxygen, besides, high levels of pH value, concentrations of yeast extract and tryptone had a positive effect on biomass production only at lower temperatures. The main carotenoids of T. filiformis were thermozeaxanthins. In the tested conditions, changes in the levels of the variables influenced the biomass, carotenoid production, and protection against singlet oxygen, although they did not influence the carotenoid profile. The results of this study provide a better understanding on the interactions among certain nutritional and cultivation conditions of a thermophile bacterium, Thermus filiformis, on biomass and carotenoid amounts, as well as on the antioxidant capacity.

  10. High-Quality Draft Genomes from Thermus caliditerrae YIM 77777 and T. tengchongensis YIM 77401, Isolates from Tengchong, China

    Science.gov (United States)

    Mefferd, Chrisabelle C.; Zhou, En-Min; Yu, Tian-Tian; Ming, Hong; Murugapiran, Senthil K.; Huntemann, Marcel; Clum, Alicia; Pillay, Manoj; Palaniappan, Krishnaveni; Varghese, Neha; Mikhailova, Natalia; Stamatis, Dimitrios; Reddy, T. B. K.; Ngan, Chew Yee; Daum, Chris; Duffy, Kecia; Shapiro, Nicole; Markowitz, Victor; Ivanova, Natalia; Kyrpides, Nikos; Williams, Amanda J.; Woyke, Tanja

    2016-01-01

    The draft genomes of Thermus  tengchongensis YIM 77401 and T. caliditerrae YIM 77777 are 2,562,314 and 2,218,114 bp and encode 2,726 and 2,305 predicted genes, respectively. Gene content and growth experiments demonstrate broad metabolic capacity, including starch hydrolysis, thiosulfate oxidation, arsenite oxidation, incomplete denitrification, and polysulfide reduction. PMID:27125486

  11. High-Quality Draft Genomes from Thermus caliditerrae YIM 77777 and T. tengchongensis YIM 77401, Isolates from Tengchong, China.

    Science.gov (United States)

    Mefferd, Chrisabelle C; Zhou, En-Min; Yu, Tian-Tian; Ming, Hong; Murugapiran, Senthil K; Huntemann, Marcel; Clum, Alicia; Pillay, Manoj; Palaniappan, Krishnaveni; Varghese, Neha; Mikhailova, Natalia; Stamatis, Dimitrios; Reddy, T B K; Ngan, Chew Yee; Daum, Chris; Duffy, Kecia; Shapiro, Nicole; Markowitz, Victor; Ivanova, Natalia; Kyrpides, Nikos; Williams, Amanda J; Woyke, Tanja; Li, Wen-Jun; Hedlund, Brian P

    2016-04-28

    The draft genomes of Thermus  tengchongensis YIM 77401 and T. caliditerrae YIM 77777 are 2,562,314 and 2,218,114 bp and encode 2,726 and 2,305 predicted genes, respectively. Gene content and growth experiments demonstrate broad metabolic capacity, including starch hydrolysis, thiosulfate oxidation, arsenite oxidation, incomplete denitrification, and polysulfide reduction.

  12. The structures of the CutA1 proteins from Thermus thermophilus and Pyrococcus horikoshii: characterization of metal-binding sites and metal-induced assembly

    Science.gov (United States)

    Bagautdinov, Bagautdin

    2014-01-01

    CutA1 (copper tolerance A1) is a widespread cytoplasmic protein found in archaea, bacteria, plants and animals, including humans. In Escherichia coli it is implicated in divalent metal tolerance, while the mammalian CutA1 homologue has been proposed to mediate brain enzyme acetylcholinesterase activity and copper homeostasis. The X-ray structures of CutA1 from the thermophilic bacterium Thermus thermophilus (TtCutA1) with and without bound Na+ at 1.7 and 1.9 Å resolution, respectively, and from the hyperthermophilic archaeon Pyrococcus horikoshii (PhCutA1) in complex with Na+ at 1.8 Å resolution have been determined. Both are short and rigid proteins of about 12 kDa that form intertwined compact trimers in the crystal and solution. The main difference in the structures is a wide-type β-bulge on top of the TtCutA1 trimer. It affords a mechanism for lodging a single-residue insertion in the middle of β2 while preserving the interprotomer main-chain hydrogen-bonding network. The liganded forms of the proteins provide new structural information about the metal-binding sites and CutA1 assembly. The Na+–TtCutA1 structure unveils a dodecameric assembly with metal ions in the trimer–trimer interfaces and the lateral clefts of the trimer. For Na+–PhCutA1, the metal ion associated with six waters in an octahedral geometry. The structures suggest that CutA1 may contribute to regulating intracellular metal homeostasis through various binding modes. PMID:24699729

  13. Modes of Action of Acarbose Hydrolysis and Transglycosylation Catalyzed by a Thermostable Maltogenic Amylase, the Gene for Which Was Cloned from a Thermus Strain

    Science.gov (United States)

    Kim, Tae-Jip; Kim, Myo-Jeong; Kim, Byung-Cheon; Kim, Jae-Cherl; Cheong, Tae-Kyou; Kim, Jung-Wan; Park, Kwan-Hwa

    1999-01-01

    A maltogenic amylase gene was cloned in Escherichia coli from a gram-negative thermophilic bacterium, Thermus strain IM6501. The gene encoded an enzyme (ThMA) with a molecular mass of 68 kDa which was expressed by the expression vector p6xHis119. The optimal temperature of ThMA was 60°C, which was higher than those of other maltogenic amylases reported so far. Thermal inactivation kinetic analysis of ThMA indicated that it was stabilized in the presence of 10 mM EDTA. ThMA harbored both hydrolysis and transglycosylation activities. It hydrolyzed β-cyclodextrin and starch mainly to maltose and pullulan to panose. ThMA not only hydrolyzed acarbose, an amylase inhibitor, to glucose and pseudotrisaccharide (PTS) but also transferred PTS to 17 sugar acceptors, including glucose, fructose, maltose, cellobiose, etc. Structural analysis of acarbose transfer products by using methylation, thin-layer chromatography, high-performance ion chromatography, and nuclear magnetic resonance indicated that PTS was transferred primarily to the C-6 of the acceptors and at lower degrees to the C-3 and/or C-4. The transglycosylation of sugar to methyl-α-d-glucopyranoside by forming an α-(1,3)-glycosidic linkage was demonstrated for the first time by using acarbose and ThMA. Kinetic analysis of the acarbose transfer products showed that the C-4 transfer product formed most rapidly but readily hydrolyzed, while the C-6 transfer product was stable and accumulated in the reaction mixture as the main product. PMID:10103262

  14. Constructive feedforward neural networks using hermite polynomial activation functions.

    Science.gov (United States)

    Ma, Liying; Khorasani, K

    2005-07-01

    In this paper, a constructive one-hidden-layer network is introduced where each hidden unit employs a polynomial function for its activation function that is different from other units. Specifically, both a structure level as well as a function level adaptation methodologies are utilized in constructing the network. The functional level adaptation scheme ensures that the "growing" or constructive network has different activation functions for each neuron such that the network may be able to capture the underlying input-output map more effectively. The activation functions considered consist of orthonormal Hermite polynomials. It is shown through extensive simulations that the proposed network yields improved performance when compared to networks having identical sigmoidal activation functions.

  15. Computational study of putative residues involved in DNA synthesis fidelity checking in Thermus aquaticus DNA polymerase I.

    Science.gov (United States)

    Elias, Angela A; Cisneros, G Andrés

    2014-01-01

    A fidelity-checking site for DNA polymerase I has been proposed based on recent single-molecule Förster resonance energy transfer studies. The checking site is believed to ensure proper base pairing of the newly inserted nucleotide. Computational studies have been utilized to predict residues involved in this putative checking site on the Klenow and Bacillus fragments. Here, we employ energy decomposition analysis, electrostatic free energy response, and noncovalent interaction plots to identify the residues involved in the hypothesized checking site in the homologous Klenow fragment from Thermus aquaticus (Klentaq). Our results indicate multiple protein residues that show altered interactions for three mispairs compared to the correctly paired DNA dimer. Many of these residues are also conserved along A family polymerases.

  16. The effects of K+ growth conditions on the accumulation of cesium by the bacterium Thermus sp. TibetanG6

    Institute of Scientific and Technical Information of China (English)

    WANG; Hailei; KONG; Fanjing; ZHENG; Mianping

    2006-01-01

    The accumulation of cesium by the bacterium Thermus sp. TibetanG6 was examined under different K+ growth conditions. The effects of external pH and Na+ on the accumulation of cesium were also studied, and the mechanism involved was discussed. K+ regimes played an important role in the accumulation of cesium by the strain TibetanG6. The quantity of cesium accumulated (24 h) was much higher in K+-deficient regime than that in K+-sufficient regime. The pH and Na+ had different effects on the accumulation of cesium in the two K+ regimes. IR spectra analyses indicated that the biosorption is a process of homeostasis with cesium initially accumulated on the cell wall.

  17. High-quality draft genome sequence of the Thermus amyloliquefaciens type strain YIM 77409(T) with an incomplete denitrification pathway.

    Science.gov (United States)

    Zhou, En-Min; Murugapiran, Senthil K; Mefferd, Chrisabelle C; Liu, Lan; Xian, Wen-Dong; Yin, Yi-Rui; Ming, Hong; Yu, Tian-Tian; Huntemann, Marcel; Clum, Alicia; Pillay, Manoj; Palaniappan, Krishnaveni; Varghese, Neha; Mikhailova, Natalia; Stamatis, Dimitrios; Reddy, T B K; Ngan, Chew Yee; Daum, Chris; Shapiro, Nicole; Markowitz, Victor; Ivanova, Natalia; Spunde, Alexander; Kyrpides, Nikos; Woyke, Tanja; Li, Wen-Jun; Hedlund, Brian P

    2016-01-01

    Thermus amyloliquefaciens type strain YIM 77409(T) is a thermophilic, Gram-negative, non-motile and rod-shaped bacterium isolated from Niujie Hot Spring in Eryuan County, Yunnan Province, southwest China. In the present study we describe the features of strain YIM 77409(T) together with its genome sequence and annotation. The genome is 2,160,855 bp long and consists of 6 scaffolds with 67.4 % average GC content. A total of 2,313 genes were predicted, comprising 2,257 protein-coding and 56 RNA genes. The genome is predicted to encode a complete glycolysis, pentose phosphate pathway, and tricarboxylic acid cycle. Additionally, a large number of transporters and enzymes for heterotrophy highlight the broad heterotrophic lifestyle of this organism. A denitrification gene cluster included genes predicted to encode enzymes for the sequential reduction of nitrate to nitrous oxide, consistent with the incomplete denitrification phenotype of this strain.

  18. Crystallization and preliminary X-ray diffraction study of recombinant ribokinase from Thermus Species 2.9

    Science.gov (United States)

    Abramchik, Yu. A.; Timofeev, V. I.; Muravieva, T. I.; Esipov, R. S.; Kuranova, I. P.

    2016-11-01

    Ribokinase from a thermophilic strain of Thermus species 2.9 belonging to the carbohydrate ribokinase family (EC 2.7.1.15) was isolated, purified, and crystallized. The crystallization conditions were found by the vapor-diffusion technique and were then optimized to apply the capillary counter-diffusion technique. The X-ray diffraction data set was collected from the crystals, which were grown by the counter-diffusion technique, at the SPring-8 synchrotron radiation facility to 2.87 Å resolution. The crystals belong to sp. gr. P1211 and have the following unit-cell parameters: a = 81.613 Å, b = 156.132 Å, c = 87.714 Å, α = γ = 90°, β = 103.819°. The X-ray diffraction data set is suitable for determining the three-dimensional structure of the protein by the molecular-replacement method.

  19. The Deinococcus-Thermus phylum and the effect of rRNA composition on phylogenetic tree construction

    Science.gov (United States)

    Weisburg, W. G.; Giovannoni, S. J.; Woese, C. R.

    1989-01-01

    Through comparative analysis of 16S ribosomal RNA sequences, it can be shown that two seemingly dissimilar types of eubacteria Deinococcus and the ubiquitous hot spring organism Thermus are distantly but specifically related to one another. This confirms an earlier report based upon 16S rRNA oligonucleotide cataloging studies (Hensel et al., 1986). Their two lineages form a distinctive grouping within the eubacteria that deserved the taxonomic status of a phylum. The (partial) sequence of T. aquaticus rRNA appears relatively close to those of other thermophilic eubacteria. e.g. Thermotoga maritima and Thermomicrobium roseum. However, this closeness does not reflect a true evolutionary closeness; rather it is due to a "thermophilic convergence", the result of unusually high G+C composition in the rRNAs of thermophilic bacteria. Unless such compositional biases are taken into account, the branching order and root of phylogenetic trees can be incorrectly inferred.

  20. Accelerating Activation Function for 3- Satisfiability Logic Programming

    Directory of Open Access Journals (Sweden)

    Mohd Asyraf Mansor

    2016-10-01

    Full Text Available This paper presents the technique for accelerating 3-Satisfiability (3-SAT logic programming in Hopfield neural network. The core impetus for this work is to integrate activation function for doing 3-SAT logic programming in Hopfield neural network as a single hybrid network. In logic programming, the activation function can be used as a dynamic post optimization paradigm to transform the activation level of a unit (neuron into an output signal. In this paper, we proposed Hyperbolic tangent activation function and Elliot symmetric activation function. Next, we compare the performance of proposed activation functions with a conventional function, namely McCu lloch-Pitts function. In this study, we evaluate the performances between these functions through computer simulations. Microsoft Visual C++ 2013 was used as a platform for training, validating and testing of the network. We restrict our analysis to 3-Satisfiability (3-SAT clauses. Moreover, evaluations are made between these activation functions to see the robustness via aspects of global solutions, global Hamming distance, and CPU time.

  1. Preschool physical activity and functional constipation: The generation r study

    NARCIS (Netherlands)

    Driessen, L.M.; Jong, J.C.K.D.; Wijtzes, A.; Vries, S.I. de; Jaddoe, V.W.V.; Hofman, A.; Raat, H.; Moll, H.A.

    2013-01-01

    OBJECTIVES:: Decreased physical activity levels in children may partly explain the rising prevalence of functional constipation in childhood. The aim of the present study, therefore, was to examine the association between physical activity and functional constipation during the preschool period. MET

  2. Joint Health, Functional Ability and Physical Activity in Haemophilia

    NARCIS (Netherlands)

    Groen, W.G.

    2011-01-01

    In haemophilia outcome measurement has long been strongly focused on the level of body functions and structures while functional outcome and physical activity have been underrepresented. However, the past decade a shift has been made to a more total evaluation of the patients’ functional health

  3. Joint Health, Functional Ability and Physical Activity in Haemophilia

    NARCIS (Netherlands)

    Groen, W.G.

    2011-01-01

    In haemophilia outcome measurement has long been strongly focused on the level of body functions and structures while functional outcome and physical activity have been underrepresented. However, the past decade a shift has been made to a more total evaluation of the patients’ functional health stat

  4. Assessing physical function and physical activity in patients with CKD.

    Science.gov (United States)

    Painter, Patricia; Marcus, Robin L

    2013-05-01

    Patients with CKD are characterized by low levels of physical functioning, which, along with low physical activity, predict poor outcomes in those treated with dialysis. The hallmark of clinical care in geriatric practice and geriatric research is the orientation to and assessment of physical function and functional limitations. Although there is increasing interest in physical function and physical activity in patients with CKD, the nephrology field has not focused on this aspect of care. This paper provides an in-depth review of the measurement of physical function and physical activity. It focuses on physiologic impairments and physical performance limitations (impaired mobility and functional limitations). The review is based on established frameworks of physical impairment and functional limitations that have guided research in physical function in the aging population. Definitions and measures for physiologic impairments, physical performance limitations, self-reported function, and physical activity are presented. On the basis of the information presented, recommendations for incorporating routine assessment of physical function and encouragement for physical activity in clinical care are provided.

  5. Draft genome sequence of Thermus sp. strain RL, isolated from a hot water spring located atop the Himalayan ranges at Manikaran, India.

    Science.gov (United States)

    Dwivedi, Vatsala; Sangwan, Naseer; Nigam, Aeshna; Garg, Nidhi; Niharika, Neha; Khurana, Paramjit; Khurana, Jitendra P; Lal, Rup

    2012-07-01

    Thermus sp. strain RL was isolated from a hot water spring (90°C to 98°C) at Manikaran, Himachal Pradesh, India. Here we report the draft genome sequence (20,36,600 bp) of this strain. The draft genome sequence consists of 17 contigs and 1,986 protein-coding sequences and has an average G+C content of 68.77%.

  6. Cesium accumulation by bacterium Thermus sp.TibetanG7: hints for biomineralization of cesiumbearing geyserite in hot springs in Tibet, China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The bacterium Thermus sp. TibetanG7, isolated from hot springs in Tibet, China, was examined for the ability to accumulate cesium from solutions. Environmental conditions were simulated and the effects of pH, K+, Na+ and K+-regimes were then studied to determine the possible role of the bacterium in the formation of cesium-bearing geyserite around these hot springs. In despite of the inhibition of K+ and Na+, the bacterium Thermus sp. TibetanG7 revealed noticeable accumulation of cesium from solutions, with maximum accumulations of 53.49 and 40.41 μmol Cesium/g cell dry weight in Na+ and K+ inhibition experiments, respectively. The accumulation of cesium by this microorganism is rapid, with 40%―50% accumulated within the first 5 min. K+-deficient cells showed a much higher capacity of cesium accumulation compared with K+-sufficient cells. It is evident that the bacteria within the genus thermus play a significant role in the cesium assembly. The formation of cesium-bearing geyserite is also considered.

  7. Resting state brain activity and functional brain mapping

    Institute of Scientific and Technical Information of China (English)

    Zhao Xiaohu; Wang Peijun; Tang Xiaowei

    2007-01-01

    Functional brain imaging studies commonly use either resting or passive task states as their control conditions, and typically identify the activation brain region associated with a specific task by subtracting the resting from the active task conditions. Numerous studies now suggest, however, that the resting state may not reflect true mental "rest" conditions. The mental activity that occurs during"rest" might therefore greatly influence the functional neuroimaging observations that are collected through the usual subtracting analysis strategies. Exploring the ongoing mental processes that occur during resting conditions is thus of particular importance for deciphering functional brain mapping results and obtaining a more comprehensive understanding of human brain functions. In this review article, we will mainly focus on the discussion of the current research background of functional brain mapping at resting state and the physiological significance of the available neuroimaging data.

  8. Extracellular enzyme activity assay as indicator of soil microbial functional diversity and activity

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne

    2012-01-01

    Extracellular enzyme activity assay as indicator of soil microbial functional diversity and activity Niels Bohse Hendriksen, Anne Winding. Department of Environmental Science, Aarhus University, 4000 Roskilde, Denmark Soils provide numerous essential ecosystem services such as carbon cycling...... the functional diversity and activity of the microorganisms involved in decomposition processes. Their activity has been measured by the use of fluorogenic model substrates e.g. methylumbelliferyl (MUF) substrates for a number of enzymes involved in the degradation of polysacharides as cellulose, hemicellulose...

  9. Proteins as the source of physiologically and functionally active peptides

    Directory of Open Access Journals (Sweden)

    Anna Iwaniak

    2007-09-01

    Full Text Available The market of functional foods and beverages develops dynamically. Biological activities of many food components which occur naturally become an issue of many scientific and industrial interests. The structural and chemical changes occurring during the proteins processing lead to the release of bioactive peptides. Their multifunctional activity is based on their structure and other factors including e.g. hydrophobicity, charge, or microelements binding properties. This article focuses on peptides with other physiological and functional activities such as antithromobotic, antioxidative, antibacterial and antifungal, sensory, and improving those nutritional value of food.

  10. Models of neural networks with fuzzy activation functions

    Science.gov (United States)

    Nguyen, A. T.; Korikov, A. M.

    2017-02-01

    This paper investigates the application of a new form of neuron activation functions that are based on the fuzzy membership functions derived from the theory of fuzzy systems. On the basis of the results regarding neuron models with fuzzy activation functions, we created the models of fuzzy-neural networks. These fuzzy-neural network models differ from conventional networks that employ the fuzzy inference systems using the methods of neural networks. While conventional fuzzy-neural networks belong to the first type, fuzzy-neural networks proposed here are defined as the second-type models. The simulation results show that the proposed second-type model can successfully solve the problem of the property prediction for time – dependent signals. Neural networks with fuzzy impulse activation functions can be widely applied in many fields of science, technology and mechanical engineering to solve the problems of classification, prediction, approximation, etc.

  11. Cortical language activation in aphasia:a functional MRI study

    Institute of Scientific and Technical Information of China (English)

    徐晓俊; 张敏鸣; 商德胜; 汪启东; 罗本燕; 翁旭初

    2004-01-01

    Background Functional neuroimaging has been used in neurolinguistic research on normal subjects and on patients with brain damage. This study was designed to investigate the differences of the neural basis underlying language processing between normal subjects and aphasics.Methods Functional magnetic resonance imaging (fMRI) was used to map the language network in 6 normal subjects and 3 patients with aphasia who were in the stage of recovery from acute stroke. The participants performed a word generation task during multi-slice functional scanning for the measurement of signal change associated with regional neural activity induced by the task. Results In normal subjects, a distributed language network was activated. Activations were present in the frontal, temporal, parietal and occipital regions. In the patient group, however, no activation was detected in the left inferior frontal gyrus whether the patient had a lesion in the left frontal lobe or not. Two patients showed activations in some right hemisphere regions where no activation appeared in normal subjects. Conclusions fMRI with word generation task is feasible for evaluating language function in aphasic patients. Remote effect of focal lesion and functional redistribution or reorganisation can be found in aphasic patients.

  12. Physical activity and sexual function in middle-aged women

    Directory of Open Access Journals (Sweden)

    Patrícia Uchôa Leitão Cabral

    2014-02-01

    Full Text Available Objective To investigate the relationship between physical activity level and sexual function in middle-aged women. Methods A cross-sectional study with a sample of 370 middle-aged women (40-65 years old, treated at public health care facilities in a Brazilian city. A questionnaire was used containing enquiries on sociodemographic, clinical and behavioral characteristics: the International Physical Activity Questionnaire (IPAQ, short form, and the Female Sexual Function Index (FSFI. Results The average age of the women studied was 49.8 years (± 8.1, 67% of whom exhibited sexual dysfunction (FSFI ≤ 26.55. Sedentary women had a higher prevalence (78.9% of sexual dysfunction when compared to active (57.6% and moderately active (66.7% females (p = 0.002. Physically active women obtained higher score in all FSFI domains (desire, arousal, lubrication, orgasm, satisfaction and pain and total FSFI score (20.9, indicating better sexual function than their moderately active (18.8 and sedentary (15.6 counterparts (p <0.05. Conclusion Physical activity appears to influence sexual function positively in middle-aged women.

  13. Neural Network Hydrological Modelling: Linear Output Activation Functions?

    Science.gov (United States)

    Abrahart, R. J.; Dawson, C. W.

    2005-12-01

    The power to represent non-linear hydrological processes is of paramount importance in neural network hydrological modelling operations. The accepted wisdom requires non-polynomial activation functions to be incorporated in the hidden units such that a single tier of hidden units can thereafter be used to provide a 'universal approximation' to whatever particular hydrological mechanism or function is of interest to the modeller. The user can select from a set of default activation functions, or in certain software packages, is able to define their own function - the most popular options being logistic, sigmoid and hyperbolic tangent. If a unit does not transform its inputs it is said to possess a 'linear activation function' and a combination of linear activation functions will produce a linear solution; whereas the use of non-linear activation functions will produce non-linear solutions in which the principle of superposition does not hold. For hidden units, speed of learning and network complexities are important issues. For the output units, it is desirable to select an activation function that is suited to the distribution of the target values: e.g. binary targets (logistic); categorical targets (softmax); continuous-valued targets with a bounded range (logistic / tanh); positive target values with no known upper bound (exponential; but beware of overflow); continuous-valued targets with no known bounds (linear). It is also standard practice in most hydrological applications to use the default software settings and to insert a set of identical non-linear activation functions in the hidden layer and output layer processing units. Mixed combinations have nevertheless been reported in several hydrological modelling papers and the full ramifications of such activities requires further investigation and assessment i.e. non-linear activation functions in the hidden units connected to linear or clipped-linear activation functions in the output unit. There are two

  14. Experimental conditions affecting functional comparison of highly active glutathione transferases.

    Science.gov (United States)

    Fedulova, Natalia; Mannervik, Bengt

    2011-06-01

    Glutathione transferases (GSTs, EC 2.5.1.18) possess multiple functions and have potential applications in biotechnology. Direct evidence of underestimation of activity of human GST A3-3 and porcine GST A2-2 measured at submicromolar enzyme concentrations is reported here for the first time. The combination of time-dependent and enzyme concentration-dependent loss of activity and the choice of the organic solvent for substrates were found to cause irreproducibility of activity measurements of GSTs. These effects contribute to high variability of activity values of porcine GST A2-2 and human Alpha-class GSTs reported in the literature. Adsorption of GSTs to surfaces was found to be the main explanation of the observed phenomena. Several approaches to improved functional comparison of highly active GSTs are proposed.

  15. Surface functional groups and redox property of modified activated carbons

    Institute of Scientific and Technical Information of China (English)

    Zhang Xianglan; Deng Shengfu; Liu Qiong; Zhang Yan; Cheng Lei

    2011-01-01

    A series of activated carbons (ACs) were prepared using HNO3, H2O2 and steam as activation agents with the aim to introduce functional groups to carbon surface in the ACs preparation process. The effects of concentration of activation agent, activation time on the surface functional groups and redox property of ACs were characterized by Temperature Program Desorption (TPD) and Cyclic Voitammetry (CV). Results showed that lactone groups of ACs activated by HNO3 increase with activation time, and the carboxyl groups increase with the concentration of HNO3. Carbonyl/quinine groups of ACs activated by H2O2 increase with the activation time and the concentration of H2O2, although the acidic groups decrease with the concentration of H2O2. The redox property reflected by CV at 0 and 0.5 V is different with any kinds of oxygen functional groups characterized by TPD, but it is consistent with the SO2 catalytic oxidization/oxidation properties indicated by TPR.

  16. Production of rubusoside from stevioside by using a thermostable lactase from Thermus thermophilus and solubility enhancement of liquiritin and teniposide.

    Science.gov (United States)

    Nguyen, Thi Thanh Hanh; Jung, Seung-Jin; Kang, Hee-Kyoung; Kim, Young-Min; Moon, Young-Hwan; Kim, Misook; Kim, Doman

    2014-10-01

    Solubility is an important factor for achieving the desired plasma level of drug for pharmacological response. About 40% of drugs are not soluble in water in practice and therefore are slowly absorbed, which results in insufficient and uneven bioavailability and GI toxicity. Rubusoside (Ru) is a sweetener component in herbal tea and was discovered to enhance the solubility of a number of pharmaceutically and medicinally important compounds, including anticancer compounds. In this study, thirty-one hydrolyzing enzymes were screened for the conversion of stevioside (Ste) to Ru. Recombinant lactase from Thermus thermophiles which was expressed in Escherichia coli converted stevioside to rubusoside as a main product. Immobilized lactase was prepared and used for the production of rubusoside; twelve reaction cycles were repeated with 95.4% of Ste hydrolysis and 49 g L(-1) of Ru was produced. The optimum rubusoside synthesis yield was 86% at 200 g L(-1), 1200 U lactase. The purified 10% rubusoside solution showed increased water solubility of liquiritin from 0.98 mg mL(-1) to 4.70±0.12 mg mL(-1) and 0 mg mL(-1) to 3.42±0.11 mg mL(-1) in the case of teniposide.

  17. Highly conserved salt bridge stabilizes a proteinase K subfamily enzyme, Aqualysin I, from Thermus aquaticus YT-1.

    Science.gov (United States)

    Sakaguchi, Masayoshi; Osaku, Kanae; Maejima, Susumu; Ohno, Nao; Sugahara, Yasusato; Oyama, Fumitaka; Kawakita, Masao

    2014-01-01

    The proteinase K subfamily enzymes, thermophilic Aqualysin I (AQN) from Thermus aquaticus YT-1 and psychrophilic serine protease (VPR) from Vibrio sp. PA-44, have six and seven salt bridges, respectively. To understand the possible significance of salt bridges in the thermal stability of AQN, we prepared mutant proteins in which amino acid residues participating in salt bridges common to proteinase K subfamily members and intrinsic to AQN were replaced to disrupt the bridges one at a time. Disruption of a salt bridge common to proteinase K subfamily enzymes in the D183N mutant resulted in a significant reduction in thermal stability, and a massive change in the content of the secondary structure was observed, even at 70°C, in the circular dichroism (CD) analysis. These results indicate that the common salt bridge Asp183-Arg12 is important in maintaining the conformation of proteinase K subfamily enzymes and suggest the importance of proximity between the regions around Asp183 and the N-terminal region around Arg12. Of the three mutants that lack an AQN intrinsic salt bridge, D212N was more prone to unfolding at 80°C than the wild-type enzyme. Similarly, D17N and E237Q were less thermostable than the wild-type enzyme, although this may be partially due to increased autolysis. The AQN intrinsic salt bridges appear to confer additional thermal stability to this enzyme. These findings will further our understanding of the factors involved in stabilizing protein structure.

  18. Cloning, expression, purification, crystallization and preliminary X-ray crystallographic study of molybdopterin synthase from Thermus thermophilus HB8

    Energy Technology Data Exchange (ETDEWEB)

    Kanaujia, Shankar Prasad; Ranjani, Chellamuthu Vasuki [Bioinformatics Centre (Centre of Excellence in Structural Biology and Biocomputing), Indian Institute of Science, Bangalore 560 012 (India); Jeyakanthan, Jeyaraman; Ohmori, Miwa; Agari, Kazuko; Kitamura, Yoshiaki [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Baba, Seiki [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Ebihara, Akio; Shinkai, Akeo [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Kuramitsu, Seiki [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Shiro, Yoshitsugu [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Sekar, Kanagaraj, E-mail: sekar@physics.iisc.ernet.in [Bioinformatics Centre (Centre of Excellence in Structural Biology and Biocomputing), Indian Institute of Science, Bangalore 560 012 (India); Supercomputer Education and Research Centre, Indian Institute of Science, Bangalore 560 012 (India); Yokoyama, Shigeyuki, E-mail: sekar@physics.iisc.ernet.in [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Bioinformatics Centre (Centre of Excellence in Structural Biology and Biocomputing), Indian Institute of Science, Bangalore 560 012 (India)

    2007-04-01

    The molybdopterin synthase from T. thermophilus HB8 was cloned, expressed, purified and crystallized. The crystals belong to space group P2{sub 1} and diffracted to a resolution of 1.64 Å. Thermus thermophilus is a Gram-negative aerobic thermophilic eubacterium which can grow at temperatures ranging from 323 to 355 K. In addition to their importance in thermostability or adaptation strategies for survival at high temperatures, the thermostable enzymes in thermophilic organisms contribute to a wide range of biotechnological applications. The molybdenum cofactor in all three kingdoms consists of a tricyclic pyranopterin termed molybdopterin that bears the cis-dithiolene group responsible for molybdenum ligation. The crystals of molybdopterin synthase from T. thermophilus HB8 belong to the primitive monoclinic space group P2{sub 1}, with unit-cell parameters a = 33.94, b = 103.32, c = 59.59 Å, β = 101.3°. Preliminary studies and molecular-replacement calculations reveal the presence of three monomers in the asymmetric unit.

  19. Electron paramagnetic resonance studies of the soluble CuA protein from the cytochrome ba3 of Thermus thermophilus.

    Science.gov (United States)

    Karpefors, M; Slutter, C E; Fee, J A; Aasa, R; Källebring, B; Larsson, S; Vänngård, T

    1996-11-01

    The electron paramagnetic resonance (EPR) spectrum of the binuclear CuA center in the water-soluble subunit II fragment from cytochrome ba3 of Thermus thermophilus was recorded at 3.93, 9.45, and 34.03 GHz, and the EPR parameters were determined by computer simulations. The frequency and M1 dependence of the linewidth was discussed in terms of g strain superimposed on a correlation between the A and g values. The g values were found to be gx = 1.996, gy = 2.011, gz = 2.187, and the two Cu ions contribute nearly equally to the hyperfine structure, with magnitude of Ax magnitude of approximately 15 G, magnitude of Ay magnitude = 29 G, and magnitude of Az magnitude of = 28.5 G (65Cu). Theoretical CNDO/S calculations, based on the x-ray structure of the Paracoccus denitrificans enzyme, yield a singly occupied antibonding orbital in which each Cu is pi*-bonded to one S and sigma*-bonded to the other. In contrast to the equal spin distribution suggested by the EPR simulations, the calculated contributions from the Cu ions differ by a factor of 2. However, only small changes in the ligand geometry are needed to reproduce the experimental results.

  20. Pulse Radiolysis Studies of Temperature Dependent Electron Transfers among Redox Centers in ba(3)-Cytochrome c Oxidase from Thermus thermophilus

    DEFF Research Database (Denmark)

    Farver, Ole; Wherland, Scot; Antholine, William E

    2010-01-01

    in cytochrome ba(3) had no effect on the rate of this reaction whereas the II-Met160Leu Cu(A)-mutation was slower by an amount corresponding to a decreased driving force of ∼0.06 eV. The structures support the presence of a common, electron-conducting "wire" between Cu(A) and heme-a(b). The transfer......-a(b)(o) → Cu(A)(o) + heme-a(b)(r) in three structurally characterized enzymes: A-type aa(3) from Paracoccus denitrificans (PDB code 3HB3 ) and bovine heart tissue (PDB code 2ZXW ), and the B-type ba(3) from T. thermophilus (PDB codes 1EHK and 1XME ). k,T data sets were obtained with the use of pulse radiolysis...... of an electron from the low-spin heme to the high-spin heme, i.e., heme-a(b)(r) + heme-a(3)(o) → heme-a(b)(o) + heme-a(3)(r), was not observed with the A-type enzymes in our experiments but was observed with the Thermus ba(3); its Marcus parameters are λ = 1.5 eV, H(ab) = 26.6 × 10(-5) eV (2.14 cm(-1)), and β...

  1. Synthesis and Antibacterial Activity of Antibiotic-Functionalized Graphite Nanofibers

    Directory of Open Access Journals (Sweden)

    Madeline Rotella

    2015-01-01

    Full Text Available Surface functionalization of nanomaterials is an area of current investigation that supports the development of new biomaterials for applications in biology and medicine. Herein we describe the synthesis, characterization, and antibacterial properties of the first examples of antibiotic-labeled graphitic carbon nanofibers (GCNFs covalently functionalized with aminoglycoside and quinolone antibiotics. Ruthenium tetroxide oxidation of herringbone GCNFs gave higher amounts of surface carboxyl groups than previous methods. These carboxyl groups served as sites of attachment for antibiotics by acyl substitution. Bioassay of these novel, functionalized GCNFs using serial dilution and optical density methods demonstrated that antibiotic-labeled GCNFs possess significant antibacterial activity against Pseudomonas aeruginosa. The activity we observe for aminoglycoside-functionalized GCNFs suggests a membranolytic mechanism of action.

  2. Effects of functional physical activity on the maintenance of motor function in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Laís Fajersztajn

    Full Text Available Abstract It is widely known that older adults, even frail individuals, can improve their physical function using appropriately targeted exercise. Nevertheless, older adults with Alzheimer's disease (AD have been excluded from the majority of studies on exercise. The functional-task physical activity program is based on activities of daily living, and may be suited for elderly people with AD because it focuses on the maintenance and stimulation of preserved abilities. In addition, session costs are substantially reduced by adopting a group approach. Furthermore, the group approach may improve the social interaction of the demented patient. Objectives: To determine whether a functional-task physical activity program in groups can maintain motor function in elderly with AD. Methods: 10 elderly diagnosed with mild or moderate AD were assigned into one of two groups: subjects with and without intervention. The intervention consisted of a 12-week function-task physical activity program in groups. Measurements: activities of daily living (Katz and Lawton & Brody questionnaires, mobility (Timed Up and Go Test, Timed Up and Go manual Test and Timed Up and Go Cognitive Test, cognition (Mini-Mental State Examination, behavioral disturbances (Neuropsychiatric Inventory I-brief and functional balance (Berg Balance Scale. Results: A statistically significant difference between the two groups was found regarding the functional balance mean change measured by Berg scale score (p=0.046. A significant improvement of 1.60 points (95%CI[0.22;2.98] was observed in the intervention group on this scale, while the non-intervention group showed -0.40 points (95%CI[-1.78;0.98], no change. Conclusions: It is possible to treat mild and moderate Alzheimer's patients using a group approach. The functional task physical activity program was efficient in functional balance improvement and also appeared to prevent mobility decline.

  3. Structure and Structure-activity Relationship of Functional Organic Molecules

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Research theme The group is made up of junior scientists from the State Key Laboratory of Elemento-organic Chemistry, Nankai University.The scientists focus their studis on the structure and structure-activity relationship of functional organic molecules not only because it has been the basis of their research, but also because the functional study of organic compounds is now a major scientific issue for organic chemists around the world.

  4. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    Science.gov (United States)

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  5. Activated and deactivated functional brain areas in the Deqi state

    Science.gov (United States)

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46. PMID:25538761

  6. Activated and deactivated functional brain areas in the Deqi state

    OpenAIRE

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, th...

  7. Model of local temperature changes in brain upon functional activation.

    Science.gov (United States)

    Collins, Christopher M; Smith, Michael B; Turner, Robert

    2004-12-01

    Experimental results for changes in brain temperature during functional activation show large variations. It is, therefore, desirable to develop a careful numerical model for such changes. Here, a three-dimensional model of temperature in the human head using the bioheat equation, which includes effects of metabolism, perfusion, and thermal conduction, is employed to examine potential temperature changes due to functional activation in brain. It is found that, depending on location in brain and corresponding baseline temperature relative to blood temperature, temperature may increase or decrease on activation and concomitant increases in perfusion and rate of metabolism. Changes in perfusion are generally seen to have a greater effect on temperature than are changes in metabolism, and hence active brain is predicted to approach blood temperature from its initial temperature. All calculated changes in temperature for reasonable physiological parameters have magnitudes <0.12 degrees C and are well within the range reported in recent experimental studies involving human subjects.

  8. Brain Activity and Functional Connectivity Associated with Hypnosis.

    Science.gov (United States)

    Jiang, Heidi; White, Matthew P; Greicius, Michael D; Waelde, Lynn C; Spiegel, David

    2017-08-01

    Hypnosis has proven clinical utility, yet changes in brain activity underlying the hypnotic state have not yet been fully identified. Previous research suggests that hypnosis is associated with decreased default mode network (DMN) activity and that high hypnotizability is associated with greater functional connectivity between the executive control network (ECN) and the salience network (SN). We used functional magnetic resonance imaging to investigate activity and functional connectivity among these three networks in hypnosis. We selected 57 of 545 healthy subjects with very high or low hypnotizability using two hypnotizability scales. All subjects underwent four conditions in the scanner: rest, memory retrieval, and two different hypnosis experiences guided by standard pre-recorded instructions in counterbalanced order. Seeds for the ECN, SN, and DMN were left and right dorsolateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and posterior cingulate cortex (PCC), respectively. During hypnosis there was reduced activity in the dACC, increased functional connectivity between the dorsolateral prefrontal cortex (DLPFC;ECN) and the insula in the SN, and reduced connectivity between the ECN (DLPFC) and the DMN (PCC). These changes in neural activity underlie the focused attention, enhanced somatic and emotional control, and lack of self-consciousness that characterizes hypnosis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Lifetime Musical Activities and Cognitive Function of the Elderly

    Directory of Open Access Journals (Sweden)

    Alicia Nevriana

    2013-02-01

    Full Text Available Decreasing cognitive function of the elderly is one of the most common problems that might affect their quality of life. Music is an element that is believed to be able to contribute to the quality of life of the elderly. However, whether musical activities that are done throughout the life span related to cognitive function is unclear. In this research, we evaluated the association between lifetime musical activities and cognitive function. Fifty three older adults from three nursing homes in East Jakarta were selected and interviewed regarding their characteristics and lifetime musical activities. Cognitive function was also measured using Mini Mental State Examinaion (MMSE. The results of this preliminary study revealed that a possibility of an association between lifetime musical activities and cognitive function of the elderly was indicated. The result also showed that the participants who were not actively involved in musical activities during their lifetime were twice more likely to develop cognitive function impairment than the elderly who were actively involved in musical activities, after being adjusted by the characteristics. These correlational results suggest the beneficial effect of musical activities throughout the life span on cognitive functioning for the elderly. Penurunan fungsi kognitif merupakan salah satu masalah umum pada lanjut usia yang mampu memengaruhi kualitas hidup mereka. Musik merupakan sebuah elemen yang dipercaya mampu berkontribusi terhadap kualitas hidup mereka. Meski demikian, hubungan antara aktivitas musikal yang dilakukan sepanjang hidup dan fungsi kognitif lansia belum diketahui secara pasti. Pada penelitian ini, hubungan antara aktivitas musikal sepanjang hidup dan fungsi kognitif dievaluasi. Lima puluh tiga lansia penghuni panti tresna werdha di Jakarta Timur dipilih dan diwawancarai terkait karakteristik dan aktivitas musikal sepanjang hidup mereka. Fungsi kognitif juga diukur menggunakan MMSE. Hasil

  10. Neural progenitor cells regulate microglia functions and activity.

    Science.gov (United States)

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  11. Functional modifications of macrophage activity after sublethal irradiation. [Toxoplasma gondii

    Energy Technology Data Exchange (ETDEWEB)

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytes exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin.

  12. Sexual activity and functioning in women treated for gynaecological cancers.

    Science.gov (United States)

    Sekse, Ragnhild Johanne Tveit; Hufthammer, Karl Ove; Vika, Margrethe Elin

    2017-02-01

    A description and comparison of sexual activity and function in relation to various gynaecological cancer diagnoses, treatment modalities, age groups, psychological distress and health-related quality of life. Various forms of gynaecological cancer have the potential to negatively influence sexual functioning, but there are few studies that describe and compare sexual activity and functioning according to diagnosis. A descriptive cross-sectional study. The study includes 129 women from an intervention study. The questionnaires addressed sexuality, psychological distress, health-related quality of life and demographics. Disease and treatment characteristics were extracted from medical records. Close to two-thirds of the women were sexually active. However, 54% of the sexually active women reported that they were not satisfied or little satisfied with their sexual activity. About half of the women reported dryness in the vagina, and 41% reported pain and discomfort during penetration. There were no significant differences concerning pleasure and discomfort related to treatment modality, diagnoses or FIGO stage. Health personnel should make a priority of sexuality throughout a patient's cancer treatment and in the follow-up, as sexuality is a vital part of a good life. Since the patients experience relatively low satisfaction with their sexual activity and many report pain during penetration, health personnel need to be sensitive to the woman, her questions, and her needs. Of importance are also the personnel's ability to communicate and their expertise in diagnosing and treating difficulties relating to sexuality. © 2016 The Authors. Journal of Clinical Nursing Published by John Wiley & Sons Ltd.

  13. The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: the mechanism of discrimination between asparagine and aspartic acid.

    Science.gov (United States)

    Berthet-Colominas, C; Seignovert, L; Härtlein, M; Grotli, M; Cusack, S; Leberman, R

    1998-01-01

    The crystal structure of Thermus thermophilus asparaginyl-tRNA synthetase has been solved by multiple isomorphous replacement and refined at 2.6 A resolution. This is the last of the three class IIb aminoacyl-tRNA synthetase structures to be determined. As expected from primary sequence comparisons, there are remarkable similarities between the tertiary structures of asparaginyl-tRNA synthetase and aspartyl-tRNA synthetase, and most of the active site residues are identical except for three key differences. The structure at 2.65 A of asparaginyl-tRNA synthetase complexed with a non-hydrolysable analogue of asparaginyl-adenylate permits a detailed explanation of how these three differences allow each enzyme to discriminate between their respective and very similar amino acid substrates, asparagine and aspartic acid. In addition, a structure of the complex of asparaginyl-tRNA synthetase with ATP shows exactly the same configuration of three divalent cations as previously observed in the seryl-tRNA synthetase-ATP complex, showing that this a general feature of class II synthetases. The structural similarity of asparaginyl- and aspartyl-tRNA synthetases as well as that of both enzymes to the ammonia-dependent asparagine synthetase suggests that these three enzymes have evolved relatively recently from a common ancestor. PMID:9582288

  14. Synthesis and antibacterial activity of aminosugar-functionalized intercalating agents.

    Science.gov (United States)

    Shi, Wei; Marcus, Sandra L; Lowary, Todd L

    2010-01-11

    A series of previously reported amino sugar-functionalized intercalating agents, 3-14, were evaluated in two antibacterial assays (paper disk diffusion and 96-well microdilution) against Bacillus atrophaeus, ATCC 9372 and Escherichia coli, ATCC 47076. Although none of the compounds were active against this E. coli strain, several showed activity against B. atrophaeus. In anticipation of the need for larger amounts of these compounds for future structure-activity relationship studies, improved routes to 11-14 were developed. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Heated Proteins are Still Active in a Functionalized Nanoporous Support

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Baowei; Qi, Wen N.; Li, Xiaolin; Lei, Chenghong; Liu, Jun

    2013-07-08

    We report that even under the heated condition, the conformation and activity of a protein can be hoarded in a functionalized nanoporous support via non-covalent interaction, although the hoarded protein was not exhibiting the full protein activity, the protein released subsequently still maintained its native conformation and activity. Glucose oxidase (GOX) was spontaneously and largely entrapped in aminopropyl-functionalized mesoporous silica (NH2-FMS) at 20 oC via a dominant electrostatic interaction. Although FMS-GOX displayed 45% activity of the free enzyme in solution, the GOX released from FMS exhibited its 100% activity prior to the entrapment. Surprisingly, the released GOX from FMS still maintained 89% of its initial activity prior to the entrapment after FMS-GOX was incubated at 60 oC for 1 h prior to release, while the free GOX in solution lost nearly all activity under the same incubation. Intrinsic fluorescence emission of GOX and native electrophoresis demonstrated that the heating resulted in significant conformational changes and oligomeric structures of the free GOX, but FMS efficiently maintained the thermal stability of GOX therein and resisted the thermal denaturation and oligomeric aggregation.

  16. Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

    Science.gov (United States)

    Leonardsson, G; Peng, X R; Liu, K; Nordström, L; Carmeliet, P; Mulligan, R; Collen, D; Ny, T

    1995-01-01

    Several lines of indirect evidence suggest that plasminogen activation plays a crucial role in degradation of the follicular wall during ovulation. However, single-deficient mice lacking tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), or PA inhibitor type 1(PAI-1) gene function were recently found to have normal reproduction, although mice with a combined deficiency of tPA and uPA were significantly less fertile. To investigate whether the reduced fertility of mice lacking PA gene function is due to a reduced ovulation mechanism, we have determined the ovulation efficiency in 25-day-old mice during gonadotropin-induced ovulation. Our results reveal that ovulation efficiency is normal in mice with a single deficiency of tPA or uPA but reduced by 26% in mice lacking both physiological PAs. This result suggests that plasminogen activation plays a role in ovulatory response, although neither tPA nor uPA individually or in combination is obligatory for ovulation. The loss of an individual PA seems to be functionally complemented by the remaining PA but this compensation does not appear to involve any compensatory up-regulation. Our data imply that a functionally redundant mechanism for plasmin formation operates during gonadotropin-induced ovulation and that PAs together with other proteases generate the proteolytic activity required for follicular wall degradation. Images Fig. 3 Fig. 4 PMID:8618918

  17. Functional activity in patients after total hip replacement.

    Science.gov (United States)

    Pogorzała, Adam M; Stryła, Wanda; Nowakowski, Andrzej

    2012-11-08

    Osteoarthritis of hip joints is one of the most common diseases limiting social functioning of patients. Pain and mobility disorders are major problems associated with the disease. The goal of the study was to compare the efficacy of surgical treatment in a selected group of patients using a modified Harris Hip Score questionnaire including questions regarding the pain, the type of gait disorders and the functional activity. Surgical treatment helped to reduce the pain and improve the gait quality and parameters as well as functional activities associated with putting on socks and shoes, climbing stairs, sitting and using public transportation. Following conclusions were drawn after the study: Surgical treatment leads to significant reduction in hip pain. Mobility improvement was observed in most analyzed patients in early post-operative period as a consequence of hip contracture and pain being eliminated. The walking speed and distance improved significantly during the first 3 months after the surgery. All patients were satisfied with the treatment.

  18. Human brain activity with functional NIR optical imager

    Science.gov (United States)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  19. Functional fitness of older women performing physical activities

    Directory of Open Access Journals (Sweden)

    Tania Rosane Bertoldo Benedetti

    2010-02-01

    Full Text Available Aging is a natural and progressive process and physical activities have been indi-cated as a possibility to minimize its impact and, especially, to maintain the functional capacity of older adults for a longer period of time. The objective of the present study was to analyze modifications in the General Functional Fitness Index (GFFI in older adults participating in a physical activity program for a period of 10 months and to associate the results with different age strata, duration of participation in the program and modifications in physical fitness. The study was conducted on 225 older women (mean age: 69.26, sd=5.685, participating in the Physical Activity and Folk Dance Program for The Elderly of the Sports Center, Universidade Federal de Santa Catarina. Descriptive statistics, Student t-test and analysis of variance (ANOVA were used for analysis of the data. A significant difference (p< 0.01 in GFFI and in the variables agility/balance and coordination (p< 0.01 was observed between March and December 2005. Strength (p=0.323, resistance (p=0,946 and flexibility (p=0.722 did not differ significantly during the period analyzed. In addition, the group performing physical activity for more than 10 years and the group older than 80 years presented the best GFFI in the assessments. Physical activity for older adults might be an important factor to improve and/or maintain functional fitness during the process of aging.

  20. Performance on the Functional Movement Screen in older active adults

    Institute of Scientific and Technical Information of China (English)

    Ulrike H. Mitchell; A. Wayne Johnson; Pat R. Vehrs; J. Brent Feland; Sterling C. Hilton

    2016-01-01

    Background: The Functional Movement Screen (FMS™) has become increasingly popular for identifying functional limitations in basic functional movements. This exploratory and descriptive study was undertaken to confirm feasibility of performing the FMS™ in older active adults, assess prevalence of asymmetries and to evaluate the relationship between functional movement ability, age, physical activity levels and body mass index (BMI). Methods: This is an observational study;97 men (n=53) and women (n=44) between the ages of 52 and 83 participated. BMI was computed and self-reported physical activity levels were obtained. Subjects were grouped by age (5-year intervals), BMI (normal, over-weight, and obese) and sex. Each participant’s performance on the FMS™was digitally recorded for later analysis. Results: The youngest age group (50–54 years) scored highest in all seven tests and the oldest age group (75+) scored lowest in most of the tests compared to all other age groups. The subjects in the“normal weight”group performed no different than those who were in the“overweight”group;both groups performed better than the“obese”group. Of the 97 participants 54 had at least one asymmetry. The pairwise correlations between the total FMS™score and age (r=−0.531), BMI (r=−0.270), and the measure of activity level (r=0.287) were significant (p<0.01 for all). Conclusion: FMS™scores decline with increased BMI, increased age, and decreased activity level. The screen identifies range of motion-and strength-related asymmetries. The FMS™can be used to assess functional limitations and asymmetries. Future research should evaluate if a higher total FMS™score is related to fewer falls or injuries in the older population.

  1. Functional Assessment of Pharmacological Telomerase Activators in Human T Cells

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    Rita B. Effros

    2013-01-01

    Full Text Available Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.

  2. Motivational activation: a unifying hypothesis of orexin/hypocretin function.

    Science.gov (United States)

    Mahler, Stephen V; Moorman, David E; Smith, Rachel J; James, Morgan H; Aston-Jones, Gary

    2014-10-01

    Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.

  3. Extracellular Enzyme Activity assay as indicator of soil microbial functional diversity and activity

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne

    2012-01-01

    Extracellular Enzyme Activity assay as indicator of soil microbial functional diversity and activity Niels Bohse Hendriksen, Anne Winding. Department of Environmental Science, Aarhus University, 4000 Roskilde, Denmark Soil enzymes originate from a variety of organisms, notably fungi and bacteria...... and especially hydrolytic extracellular enzymes are of pivotal importance for decomposition of organic substrates and biogeochemical cycling. Their activity reflects the functional diversity and activity of the microorganisms involved in decomposition processes which are essential processes for soil functioning......, experimental conditions of extraction of enzymes from soils, buffer and pH, substrate concentration, temperature and the necessary controls were optimized and standardized. This has resulted in an optimized standard operating procedure of EEA, which are being tested as an indicator of soil functional diversity...

  4. PTEN inhibits BMI1 function independently of its phosphatase activity

    Directory of Open Access Journals (Sweden)

    Kapoor Anil

    2009-11-01

    Full Text Available Abstract Background PTEN is the second most mutated tumor suppressor gene other than p53. It suppresses tumorigenesis by dephosphorylating phosphatidylinositol (3,4,5-triphosphate (PIP3 to phosphatidylinositol (4,5-biphosphate (PIP2, thereby directly inhibiting phosphatidylinositol 3 kinase (PI3K-mediated tumorigenic activities. Consistent with this model of action, cytosolic PTEN is recruited to the plasma membrane to dephosphorylate PIP3. While nuclear PTEN has been shown to suppress tumorigenesis by governing genome integrity, additional mechanisms may also contribute to nuclear PTEN-mediated tumor suppression. The nuclear protein BMI1 promotes stem cell self-renewal and tumorigenesis and PTEN inhibits these events, suggesting that PTEN may suppress BMI1 function. Results We investigated whether PTEN inhibits BMI1 function during prostate tumorigenesis. PTEN binds to BMI1 exclusively in the nucleus. This interaction does not require PTEN's phosphatase activity, as phosphatase-deficient PTEN mutants, PTEN/C124S (CS, PTEN/G129E (GE, and a C-terminal PTEN fragment (C-PTEN excluding the catalytic domain, all associate with BMI1. Furthermore, the residues 186-286 of C-PTEN are sufficient for binding to BMI1. This interaction reduces BMI1's function. BMI1 enhances hTERT activity and reduces p16INK4A and p14ARF expression. These effects were attenuated by PTEN, PTEN(CS, PTEN(GE, and C-PTEN. Furthermore, knockdown of PTEN in DU145 cells increased hTERT promoter activity, which was reversed when BMI1 was concomitantly knocked-down, indicating that PTEN reduces hTERT promoter activity via inhibiting BMI1 function. Conversely, BMI1 reduces PTEN's ability to inhibit AKT activation, which can be attributed to its interaction with PTEN in the nucleus, making PTEN unavailable to dephosphorylate membrane-bound PIP3. Furthermore, BMI1 appears to co-localize with PTEN more frequently in clinical prostate tissue samples from patients diagnosed with PIN

  5. Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Grünwald Frank

    2007-10-01

    Full Text Available Abstract Background The arterial in line application of the leukocyte inhibition module (LIM in the cardiopulmonary bypass (CPB limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion without (group I; n = 6 or with LIM (group II; n = 6. The cardiac indices (CI and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 ± 0.31; pre: 4.05 ± 0.45 l/min/m2; p 2; p = 0.23. Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p Conclusion Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.

  6. Activated and deactivated functional brain areas in the Deqi state: A functional MRI study.

    Science.gov (United States)

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-10-25

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46.

  7. ns-μs Time-Resolved Step-Scan FTIR of ba3 Oxidoreductase from Thermus thermophilus: Protonic Connectivity of w941-w946-w927

    Science.gov (United States)

    Nicolaides, Antonis; Soulimane, Tewfik; Varotsis, Constantinos

    2016-01-01

    Time-resolved step-scan FTIR spectroscopy has been employed to probe the dynamics of the ba3 oxidoreductase from Thermus thermophilus in the ns-μs time range and in the pH/pD 6–9 range. The data revealed a pH/pD sensitivity of the D372 residue and of the ring-A propionate of heme a3. Based on the observed transient changes a model in which the protonic connectivity of w941-w946-927 to the D372 and the ring-A propionate of heme a3 is described. PMID:27690021

  8. Physically active academic lessons : Effects on physical fitness and executive functions in primary school children

    NARCIS (Netherlands)

    de Greeff, Johannes Wilhelmus

    2016-01-01

    There is increasing evidence that physical activity can improve cognitive functions of primary school children, especially the executive functions (functions that are important for goal directed cognition and behavior). Physically active academic lessons, however, do not improve executive functions

  9. Crystal structure studies of NADP{sup +} dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S.M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Pampa, K.J. [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India); Manjula, M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Abdoh, M.M.M. [Department of Physics, Faculty of Science, An-Najah National University, Nablus, West Bank, Palestine (Country Unknown); Kunishima, Naoki [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148 (Japan); Lokanath, N.K., E-mail: lokanath@physics.uni-mysore.ac.in [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India)

    2014-06-20

    Highlights: • We determined the structure of isocitrate dehydrogenase with citrate and cofactor. • The structure reveals a unique novel terminal domain involved in dimerization. • Clasp domain shows significant difference, and catalytic residues are conserved. • Oligomerization of the enzyme is quantized with subunit-subunit interactions. • Novel domain of this enzyme is classified as subfamily of the type IV. - Abstract: NADP{sup +} dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP{sup +} was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH’s. And, small domain and clasp domain showing significant differences when compared to other IDH’s of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH’s. Also, helices/beta sheets are absent in the small domain, when compared to other IDH’s of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit–subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.

  10. Independent in vitro assembly of all three major morphological parts of the 30S ribosomal subunit of Thermus thermophilus.

    Science.gov (United States)

    Agalarov, S C; Selivanova, O M; Zheleznyakova, E N; Zheleznaya, L A; Matvienko, N I; Spirin, A S

    1999-12-01

    Fragments of the 16S rRNA of Thermus thermophilus representing the 3' domain (nucleotides 890-1515) and the 5' domain (nucleotides 1-539) have been prepared by transcription in vitro. Incubation of these fragments with total 30S ribosomal proteins of T. thermophilus resulted in formation of specific RNPs. The particle assembled on the 3' RNA domain contained seven proteins corresponding to Escherichia coli ribosomal proteins S3, S7, S9, S10, S13, S14, and S19. All of them have previously been shown to interact with the 3' domain of the 16S RNA and to be localized in the head of the 30S ribosomal subunit. The particle formed on the 5' RNA domain contained five ribosomal proteins corresponding to E. coli proteins S4, S12, S17, S16, and S20. These proteins are known to be localized in the main part of the body of the 30S subunit. Both types of particle were compact and had sedimentation coefficients of 15.5 S and 13 S, respectively. Together with our recent demonstration of the reconstitution of the RNA particle representing the platform of the T. thermophilus 30S ribosomal subunit [Agalarov, S.C., Zheleznyakova, E.N., Selivanova, O.M., Zheleznaya, L.A., Matvienko, N.I., Vasiliev, V.D. & Spirin, A.S. (1998) Proc. Natl Acad. Sci. USA 95, 999-1003], these experiments establish that all three main structural lobes of the small ribosomal subunit can be reconstituted independently of each other and prepared in the individual state.

  11. Review: Production and functionality of active peptides from milk.

    Science.gov (United States)

    Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A

    2011-08-01

    In recent years, research on the production of active peptides obtained from milk and their potential functionality has grown, to a great extent. Bioactive peptides have been defined as specific protein fragments that have a positive impact on body functions or conditions, and they may ultimately have an influence on health. Individual proteins of casein or milk-derived products such as cheese and yogurt have been used as a protein source to study the isolation and activity of peptides with several applications. Currently, the milk whey waste obtained in the production of cheese also represents a protein source from which active peptides could be isolated with potential industrial applications. The active properties of milk peptides and the results found with regard to their physiological effects have led to the classification of peptides as belonging to the group of ingredients of protein nature, appropriate for use in functional foods or pharmaceutical formulations. In this study, the main peptides obtained from milk protein and the past research studies about its production and biological activities will be explained. Second, an analysis will be made on the methods to determinate the biological activities, the separation of bioactive peptides and its structure identification. All of these form the base required to obtain synthetic peptides. Finally, we explain the experimental animal and human trials done in the past years. Nevertheless, more research is required on the design and implementation of equipment for the industrial production and separation of peptides. In addition, different authors suggest that more emphasis should therefore be given to preclinical studies, proving that results are consistent and that effects are demonstrated repeatedly by several research human groups.

  12. Practice induces function-specific changes in brain activity.

    Directory of Open Access Journals (Sweden)

    Tamar R van Raalten

    Full Text Available BACKGROUND: Practice can have a profound effect on performance and brain activity, especially if a task can be automated. Tasks that allow for automatization typically involve repeated encoding of information that is paired with a constant response. Much remains unknown about the effects of practice on encoding and response selection in an automated task. METHODOLOGY: To investigate function-specific effects of automatization we employed a variant of a Sternberg task with optimized separation of activity associated with encoding and response selection by means of m-sequences. This optimized randomized event-related design allows for model free measurement of BOLD signals over the course of practice. Brain activity was measured at six consecutive runs of practice and compared to brain activity in a novel task. PRINCIPAL FINDINGS: Prompt reductions were found in the entire cortical network involved in encoding after a single run of practice. Changes in the network associated with response selection were less robust and were present only after the third run of practice. CONCLUSIONS/SIGNIFICANCE: This study shows that automatization causes heterogeneous decreases in brain activity across functional regions that do not strictly track performance improvement. This suggests that cognitive performance is supported by a dynamic allocation of multiple resources in a distributed network. Our findings may bear importance in understanding the role of automatization in complex cognitive performance, as increased encoding efficiency in early stages of practice possibly increases the capacity to otherwise interfering information.

  13. The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma

    DEFF Research Database (Denmark)

    van Beekum, Olivier; Brenkman, Arjan B; Grøntved, Lars

    2008-01-01

    The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism in adipocytes, by regulating their differentiation, maintenance, and function. The transcriptional activity of PPARgamma is dictated by the set ...

  14. ACTIVITY-BASED COST ALLOCATION AND FUNCTION ANALYZES IN TRADE

    Directory of Open Access Journals (Sweden)

    TÜNDE VERES

    2011-01-01

    Full Text Available In this paper the author is thinking about the efficiency analyzes of trading. The most important evaluation factors of trade are the sales value, volume and the margin. Of course the easiest and fastest way is to follow the market situation by the turnover but for long term thinking the sales companies need to concentrate also for efficiency. Trading activity has some functions which can deeply effect for the final result and this is the reason to calculate their clear and reliable costs is an important condition of the decision making. The author reviews the cost categories and the basic functions in trading activity to find possible ways getting reliable information.

  15. Potential therapeutic effects of functionally active compounds isolated from garlic.

    Science.gov (United States)

    Yun, Hyung-Mun; Ban, Jung Ok; Park, Kyung-Ran; Lee, Chong Kil; Jeong, Heon-Sang; Han, Sang Bae; Hong, Jin Tae

    2014-05-01

    The medicinal properties of functionally active organosulfur compounds such as allin, diallyl disulfide, S-allylmercaptocysteine, and S-trityl-L-cysteine isolated from garlic have received great attention from a large number of investigators who have studied their pharmacological effects for the treatment of various diseases. These organosulfur compounds are able to prevent for development of cancer, cardiovascular, neurological, and liver diseases as well as allergy and arthritis. There have been also many reports on toxicities and pharmacokinetics of these compounds. The aim of this study is to review a variety of experimental and clinical reports, and describe the effectiveness, toxicities and pharmacokinetics, and possible mechanisms of pharmaceutical actions of functionally active compounds isolated from garlic. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Which activation function of cooperation describes human behavior?

    CERN Document Server

    Jarynowski, Andrzej

    2016-01-01

    Properties of cooperation's probability function in Prisoner`s Dilemma have impact on evolution of game. Basic model defines that probability of cooperation depends linearly, both on the player's altruism and the co-player's reputation. I propose modification of activation function to smooth one (hyperbolic tangent with scaling parameter a, which corresponds to its shape) and observe three phases for different range of a. (1) For small a, strategies seem to randomly change in time and situation of mixed choices (one cooperates and second defects) dominate. (2) For medium a, players choose only one strategy for given period of time (the common state can switch to opposite one with some probability). (3) For large a, mixed strategy (once defect, once cooperate) is coexisting with common strategies and no change is allowed. I believe that proposed function characterizes better socio-economical phenomena and especially phase 1 and 2 contain most of human behavior.

  17. Intermediate scattering function of an anisotropic active Brownian particle

    Science.gov (United States)

    Kurzthaler, Christina; Leitmann, Sebastian; Franosch, Thomas

    2016-10-01

    Various challenges are faced when animalcules such as bacteria, protozoa, algae, or sperms move autonomously in aqueous media at low Reynolds number. These active agents are subject to strong stochastic fluctuations, that compete with the directed motion. So far most studies consider the lowest order moments of the displacements only, while more general spatio-temporal information on the stochastic motion is provided in scattering experiments. Here we derive analytically exact expressions for the directly measurable intermediate scattering function for a mesoscopic model of a single, anisotropic active Brownian particle in three dimensions. The mean-square displacement and the non-Gaussian parameter of the stochastic process are obtained as derivatives of the intermediate scattering function. These display different temporal regimes dominated by effective diffusion and directed motion due to the interplay of translational and rotational diffusion which is rationalized within the theory. The most prominent feature of the intermediate scattering function is an oscillatory behavior at intermediate wavenumbers reflecting the persistent swimming motion, whereas at small length scales bare translational and at large length scales an enhanced effective diffusion emerges. We anticipate that our characterization of the motion of active agents will serve as a reference for more realistic models and experimental observations.

  18. PIC Activation through Functional Interplay between Mediator and TFIIH.

    Science.gov (United States)

    Malik, Sohail; Molina, Henrik; Xue, Zhu

    2017-01-06

    The multiprotein Mediator coactivator complex functions in large part by controlling the formation and function of the promoter-bound preinitiation complex (PIC), which consists of RNA polymerase II and general transcription factors. However, precisely how Mediator impacts the PIC, especially post-recruitment, has remained unclear. Here, we have studied Mediator effects on basal transcription in an in vitro transcription system reconstituted from purified components. Our results reveal a close functional interplay between Mediator and TFIIH in the early stages of PIC development. We find that under conditions when TFIIH is not normally required for transcription, Mediator actually represses transcription. TFIIH, whose recruitment to the PIC is known to be facilitated by the Mediator, then acts to relieve Mediator-induced repression to generate an active form of the PIC. Gel mobility shift analyses of PICs and characterization of TFIIH preparations carrying mutant XPB translocase subunit further indicate that this relief of repression is achieved through expending energy via ATP hydrolysis, suggesting that it is coupled to TFIIH's established promoter melting activity. Our interpretation of these results is that Mediator functions as an assembly factor that facilitates PIC maturation through its various stages. Whereas the overall effect of the Mediator is to stimulate basal transcription, its initial engagement with the PIC generates a transcriptionally inert PIC intermediate, which necessitates energy expenditure to complete the process.

  19. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

    Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

  20. Electrical activity patterns and the functional maturation of the neocortex.

    Science.gov (United States)

    Kilb, Werner; Kirischuk, Sergei; Luhmann, Heiko J

    2011-11-01

    At the earliest developmental stages, sensory neocortical areas in various species reveal distinct patterns of spontaneous neuronal network activity. These activity patterns either propagate over large neocortical areas or synchronize local neuronal ensembles. In vitro and in vivo experiments indicate that these spontaneous activity patterns are generated from neuronal networks in the cerebral cortex, in subcortical structures or in the sensory periphery (retina, cochlea, whiskers). At early stages spontaneous periphery-driven and also sensory evoked activity is relayed to the developing cerebral cortex via the thalamus and the neocortical subplate, which amplifies the afferent sensory input. These early local and large-scale neuronal activity patterns influence a variety of developmental processes during corticogenesis, such as neurogenesis, apoptosis, neuronal migration, differentiation and network formation. The experimental data also indicate that disturbances in early neuronal patterns may have an impact on the development of cortical layers, columns and networks. In this article we review our current knowledge on the origin of early electrical activity patterns in neocortical sensory areas and their functional implications on shaping developing cortical networks.

  1. Assessment of strontium oxide functionalized graphene nanoflakes for enhanced photocatalytic activity: A density functional theory approach

    Energy Technology Data Exchange (ETDEWEB)

    Divya, A.; Mathavan, T., E-mail: tjmathavan@gmail.com; Asath, R. Mohamed; Benial, A. Milton Franklin [PG & Research Department of Physics, N.M.S.S.V.N College, Madurai-625019, Tamilnadu (India); Archana, J.; Hayakawa, Y. [Research Institute of Engineering, Shizuoka University (Japan)

    2016-05-23

    A series of strontium oxide functionalized graphene nanoflakes were designed and their optoelectronic properties were studied for enhanced photocatalytic activity. The efficiency of designed molecules was studied using various parameters such as HOMO-LUMO energy gap, light harvesting efficiency and exciton binding energy. The computed results show that by increasing the degree of functionalization of strontium oxide leads to lowering the band gap of hydrogen terminated graphene nanoflakes. Furthermore, the study explores the role of strontium oxide functionalization in Frontier Molecular Orbitals, ionization potential, electron affinity, exciton binding energy and light harvesting efficiency of designed molecules. The infrared and Raman spectra were simulated for pure and SrO functionalized graphene nanoflakes. The electron rich and electron deficient regions which are favorable for electrophilic and nucleophilic attacks respectively were analyzed using molecular electrostatic potential surface analysis.

  2. Extracellular Enzyme Activity assay as indicator of soil microbial functional diversity and activity

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne

    2012-01-01

    and especially hydrolytic extracellular enzymes are of pivotal importance for decomposition of organic substrates and biogeochemical cycling. Their activity reflects the functional diversity and activity of the microorganisms involved in decomposition processes which are essential processes for soil functioning...... and soil ecosystem services. The soil enzyme activity has been measured by the use of fluorogenic model substrates e.g. methylumbelliferyl (MUF) substrates for a number of enzymes involved in the degradation of polysaccharides as cellulose, hemicellulose and chitin, while degradation of proteins has been...... followed by amino-methyl-coumaric substrates (AMC). The already developed Extracellular Enzyme Activity (EEA) assay was further optimized as a microwell based assay for the activity of enzymes involved in degradation of polysaccharides and proteins. Using specific MUF and AMC substrates on European soils...

  3. Extracellular enzyme activity assay as indicator of soil microbial functional diversity and activity

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne

    2012-01-01

    of soil microbial functions is still needed. In soil, enzymes originate from a variety of organisms, notably fungi and bacteria and especially hydrolytic extracellular enzymes are of pivotal importance for decomposition of organic substrates and biogeochemical cycling. Their activity will reflect...... the functional diversity and activity of the microorganisms involved in decomposition processes. Their activity has been measured by the use of fluorogenic model substrates e.g. methylumbelliferyl (MUF) substrates for a number of enzymes involved in the degradation of polysacharides as cellulose, hemicellulose...... and chitin, while degradation of proteins has been followed by amino-methyl-coumaric substrates (AMC). Based on these fluorogenic substrates the Extracellular Enzyme Activity assay was optimized as a microwell based standardized assay for the activity of enzymes involved in degradation of polysaccharides...

  4. Functional analysis of Ficolin-3 mediated complement activation.

    Directory of Open Access Journals (Sweden)

    Estrid Hein

    Full Text Available The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA was acetylated (acBSA and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway.

  5. The β-barrel assembly machinery (BAM) is required for the assembly of a primitive S-layer protein in the ancient outer membrane of Thermus thermophilus.

    Science.gov (United States)

    Acosta, Federico; Ferreras, Eloy; Berenguer, José

    2012-11-01

    The ancient bacterial lineage Thermus spp has a primitive form of outer membrane attached to the cell wall through SlpA, a protein that shows intermediate properties between S-layer proteins and outer membrane (OM) porins. In E. coli and related Proteobacteria, porins are secreted through the BAM (β-barrel assembly machinery) pathway, whose main component is BamA. A homologue to this protein is encoded in all the Thermus spp so far sequenced, so we wondered if this pathway could be responsible for SlpA secretion in this ancient bacterial model. To analyse this hypothesis, we attempted to get mutants on this BamA(th) of T. thermophilus HB27. Knockout and deletion mutants lacking the last 10 amino acids were not viable, whereas its depletion by means of a BamA antisense RNA lead defective attachment to the cell wall of its OM-like envelope. Such defects were related to defective folding of the SlpA protein that was more sensitive to proteases than in a wild-type strain. A similar phenotype was found in mutants lacking the terminal Phe of SlpA. Further protein-protein interaction assays confirmed the existence of specific binding between SlpA and BamA(th). Taking together, these data suggest that SlpA is secreted through a BAM-like pathway in this ancestral bacterial lineage, supporting an ancient origin of this pathway before the evolution of the Proteobacteria.

  6. Cargo binding activates myosin VIIA motor function in cells.

    Science.gov (United States)

    Sakai, Tsuyoshi; Umeki, Nobuhisa; Ikebe, Reiko; Ikebe, Mitsuo

    2011-04-26

    Myosin VIIA, thought to be involved in human auditory function, is a gene responsible for human Usher syndrome type 1B, which causes hearing and visual loss. Recent studies have suggested that it can move processively if it forms a dimer. Nevertheless, it exists as a monomer in vitro, unlike the well-known two-headed processive myosin Va. Here we studied the molecular mechanism, which is currently unknown, of activating myosin VIIA as a cargo-transporting motor. Human myosin VIIA was present throughout cytosol, but it moved to the tip of filopodia upon the formation of dimer induced by dimer-inducing reagent. The forced dimer of myosin VIIA translocated its cargo molecule, MyRip, to the tip of filopodia, whereas myosin VIIA without the forced dimer-forming module does not translocate to the filopodial tips. These results suggest that dimer formation of myosin VIIA is important for its cargo-transporting activity. On the other hand, myosin VIIA without the forced dimerization module became translocated to the filopodial tips in the presence of cargo complex, i.e., MyRip/Rab27a, and transported its cargo complex to the tip. Coexpression of MyRip promoted the association of myosin VIIA to vesicles and the dimer formation. These results suggest that association of myosin VIIA monomers with membrane via the MyRip/Rab27a complex facilitates the cargo-transporting activity of myosin VIIA, which is achieved by cluster formation on the membrane, where it possibly forms a dimer. Present findings support that MyRip, a cargo molecule, functions as an activator of myosin VIIA transporter function.

  7. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  8. Insilico studies of organosulfur-functional active compounds in garlic.

    Science.gov (United States)

    Singh, Yogendra P; Singh, Ram A

    2010-01-01

    Garlic has been used medicinally since antiquity because of its antimicrobial activity, anticancer activity, antioxidant activity, ability to reduce cardiovascular diseases, improving immune functions, and antidiabetic activities and also in reducing cardiovascular diseases and improving immune functions. Recent studies identify that the wide variety of medicinal functions are attributed to the sulfur compounds present in garlic. Epidemiological observations and laboratory studies in animal models have also showed anticarcinogenic potential of organosulfur compounds of garlic. In this study, in silico analysis of organosulfur compounds is reported using the methods of theoretical chemistry to elucidate the molecular properties of garlic as it is more time and cost efficient, reduces the number of wet experiments, and offers the possibility of replacing some animal tests with suitable in silico models. The analysis of molecular descriptors defined by Lipinski has been done. The solubility of drug in water has been determined as it is of useful importance in the process of drug discovery from molecular design to pharmaceutical formulation and biopharmacy. All toxicities associated with candidate drug have been calculated. P-Glycoprotein expressed in normal tissues as a cause of drug pharmacokinetics and pharmacodynamics has been examined. Drug-plasma protein binding and volume of distribution have also been calculated. To avoid rejection of drugs, it is becoming more important to determine pK(a), absorption, polar surface area, and other physiochemical properties associated with a drug, before synthetic work is undertaken. The present in silico study is aimed at examining these compounds of garlic to evaluate its possible efficacy and toxicity under conditions of actual use in humans.

  9. Medroxyprogesterone acetate impairs human dendritic cell activation and function.

    Science.gov (United States)

    Quispe Calla, N E; Ghonime, M G; Cherpes, T L; Vicetti Miguel, R D

    2015-05-01

    Does medroxyprogesterone acetate (MPA) impair human dendritic cell (DC) activation and function? In vitro MPA treatment suppressed expression of CD40 and CD80 by human primary DCs responding to Toll-like receptor 3 (TLR3) agonist stimulation (i.e. DC activation). Moreover, this MPA-mediated decrease in CD40 expression impaired DC capacity to stimulate T cell proliferation (i.e. DC function). MPA is the active molecule in Depo-Provera(®) (DMPA), a commonly used injectable hormonal contraceptive (HC). Although DMPA treatment of mice prior to viral mucosal tissue infection impaired the capacity of DCs to up-regulate CD40 and CD80 and prime virus-specific T cell proliferation, neither DC activation marker expression nor the ability of DCs to promote T cell proliferation were affected by in vitro progesterone treatment of human DCs generated from peripheral blood monocytes. This cross-sectional study examined MPA-mediated effects on the activation and function of human primary untouched peripheral blood DCs. Human DCs isolated from peripheral blood mononuclear cells by negative immunomagnetic selection were incubated for 24 h with various concentrations of MPA. After an additional 24 h incubation with the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C), flow cytometry was used to evaluate DC phenotype (i.e. expression of CD40, CD80, CD86, and HLA-DR). In separate experiments, primary untouched human DCs were sequentially MPA-treated, poly I:C-activated, and incubated for 7 days with fluorescently labeled naïve allogeneic T cells. Flow cytometry was then used to quantify allogeneic T cell proliferation. Several pharmacologically relevant concentrations of MPA dramatically reduced CD40 and CD80 expression in human primary DCs responding to the immunostimulant poly I:C. In addition, MPA-treated DCs displayed a reduced capacity to promote allogeneic CD4(+) and CD8(+) T cell proliferation. In other DC: T cell co-cultures, the addition of antibody blocking the CD40

  10. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  11. Functional brain activation associated with working memory training and transfer.

    Science.gov (United States)

    Clark, Cameron M; Lawlor-Savage, Linette; Goghari, Vina M

    2017-09-15

    While behavioural trials of working memory (WM) training have received much attention in recent years, a lesser explored parallel approach is functional neuroimaging. A small literature has suggested a complex time course for functional activation pattern changes following WM training (i.e. not simply increasing or decreasing due to training); however, no study to date has examined such neuroplastic effects in both the training task (dual n-back) and the fluid intelligence transfer task to which the training is purported to transfer (Raven's Matrices). This study investigated neural correlates of WM training in healthy young adults randomized to six weeks of WM training, or an active control condition (processing speed training) with a pre- and post-training fMRI design. Results indicated significant reductions in activation for the WM trained group in key WM-task related areas for trained WM tasks after training compared to the processing speed active control group. The same pattern of training related decreases in activation for the WM trained group was not observed for the transfer task, which is consistent with null results for all cognitive outcomes of the present trial. The observed pattern of results suggests that repetitive practice with a complex task does indeed lead to neuroplastic processes that very likely represent the reduced demand for attentional control while sub-components of the task become more routinized with practice. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired and/or behavioural trials of WM training have returned more promising results. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Biological function of activation-induced cytidine deaminase (AID).

    Science.gov (United States)

    Kumar, Ritu; DiMenna, Lauren J; Chaudhuri, Jayanta; Evans, Todd

    2014-01-01

    Activation-induced Cytidine Deaminase (AID) is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  13. Influence of gold nanoparticles on platelets functional activity in vitro

    Science.gov (United States)

    Akchurin, Garif G.; Akchurin, George G.; Ivanov, Alexey N.; Kirichuk, Vyacheslav F.; Terentyuk, George S.; Khlebtsov, Boris N.; Khlebtsov, Nikolay G.

    2008-02-01

    Now in the leading biomedical centers of the world approved new technology of laser photothermal destruction of cancer cells using plasmon gold nanoparticles. Investigations of influence of gold nanoparticles on white rat platelets aggregative activity in vitro have been made. Platelet aggregation was investigated in platelet rich plasma (PRP) with help of laser analyzer 230 LA >, Russia). Aggregation inductor was ADP solution in terminal concentration 2.5 micromole (>, Russia). Gold nanoshells soluted in salt solution were used for experiments. Samples of PRP were incubated with 50 or 100 μl gold nanoshells solution in 5 minute, after that we made definition ADP induced platelet aggregation. We found out increase platelet function activity after incubation with nanoparticles solution which shown in maximum ADP-induced aggregation degree increase. Increase platelet function activity during intravenous nanoshells injection can be cause of thrombosis on patients. That's why before clinical application of cancer cell destruction based on laser photothermal used with plasmon gold nanoparticles careful investigations of thrombosis process and detail analyze of physiological blood parameters are very necessary.

  14. Activated and deactivated functional brain areas in the Deqi state A functional MRI study

    Institute of Scientific and Technical Information of China (English)

    Yong Huang; Tongjun Zeng; Guifeng Zhang; Ganlong Li; Na Lu; Xinsheng Lai; Yangjia Lu; Jiarong Chen

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state,as reported by physicians and subjects during acupuncture.Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint.Real-time cerebral functional MRI showed that compared with non-sensation after sham needling,true needling activated Brodmann areas 3,6,8,9,10,11,13,20,21,37,39,40,43,and 47,the head of the caudate nucleus,the parahippocampal gyrus,thalamus and red nucleus.True needling also deactivated Brodmann areas 1,2,3,4,5,6,7,9,10,18,24,31,40 and 46.

  15. Transfer function between EEG and BOLD signals of epileptic activity

    Directory of Open Access Journals (Sweden)

    Marco eLeite

    2013-01-01

    Full Text Available Simultaneous EEG-fMRI recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a heamodynamic response function to model the associated BOLD changes. Although more flexible approaches may allow a higher degree of complexity for the haemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis (ICA of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept.

  16. Functional imaging reveals movement preparatory activity in the vegetative state

    Directory of Open Access Journals (Sweden)

    Tristan A Bekinschtein

    2011-01-01

    Full Text Available The Vegetative State (VS is characterized by the absence of awareness of self or the environment and preserved autonomic functions. The diagnosis relies critically on the lack of consistent signs of purposeful behavior in response to external stimulation. Yet, given that patients with disorders of consciousness often exhibit fragmented movement patterns, voluntary actions may go unnoticed. Here we designed a simple motor paradigm that could potentially detect residual conscious awareness in VS patients with mild to severe brain damage by examining the neural correlates of motor preparation in response to verbal commands. Twenty-four patients who met the diagnostic criteria for VS were recruited for this study. Eleven of these patients showing preserved auditory evoked potentials underwent functional magnetic resonance imaging (fMRI to test for basic speech processing. Five of these patients, who showed word related activity, were included in a second fMRI study aimed at detecting functional changes in premotor cortex elicited by specific verbal instructions to move either their left or their right hand. Despite the lack of overt muscle activity, two patients out of five activated the dorsal premotor cortex contralateral to the instructed hand, consistent with movement preparation. Given that movement preparation in response to a motor command is a sign of purposeful behavior, our results are consistent with residual conscious awareness in these patients. We believe that the identification of positive results with fMRI using this simple task, may complement the clinical assessment by helping attain a more precise diagnosis in patients with disorders of consciousness.

  17. Functionalization of hydroxyl terminated polybutadiene with biologically active fluorescent molecule

    Indian Academy of Sciences (India)

    R Murali Sankar; Subhadeep Saha; K Seeni Meera; Tushar Jana

    2009-10-01

    A biologically active molecule, 2-chloro-4,6-bis(dimethylamino)-1,3,5-triazine (CBDT), has been covalently attached at the terminal carbon atoms of the hydroxyl terminated polybutadiene (HTPB) backbone. The modification of HTPB backbone by CBDT molecule does not affect the unique physico-chemical properties such as fluidity, hydroxyl value and microstructure of the parent HTPB. The formation of hydrogen bonding between the terminal hydroxyl groups and the nitrogen atoms of triazine moiety is the driving force for the terminal attachment chemistry. The functionalized HTPB (HTPB–CBDT) shows a strong fluorescence emission at 385 nm.

  18. Functional analysis of Ficolin-3 mediated complement activation

    DEFF Research Database (Denmark)

    Hein, Estrid; Honoré, Christian; Skjoedt, Mikkel-Ole

    2010-01-01

    assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition...... was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides...

  19. Active membrane having uniform physico-chemically functionalized ion channels

    Science.gov (United States)

    Gerald, II, Rex E; Ruscic, Katarina J; Sears, Devin N; Smith, Luis J; Klingler, Robert J; Rathke, Jerome W

    2012-09-24

    The present invention relates to a physicochemically-active porous membrane for electrochemical cells that purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. One dimension of the pore surface has a macroscopic length (1 nm-1000 .mu.m) and is directed parallel to the direction of an electric field, which is produced between the cathode and the anode electrodes of an electrochemical cell. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

  20. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals.

    Science.gov (United States)

    Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

    2014-01-01

    The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications.

  1. Bimanual passive movement: functional activation and inter-regional coupling.

    Science.gov (United States)

    Macaluso, Emiliano; Cherubini, Andrea; Sabatini, Umberto

    2007-01-01

    The aim of this study was to investigate intra-regional activation and inter-regional connectivity during passive movement. During fMRI, a mechanic device was used to move the subject's index and middle fingers. We assessed four movement conditions (unimanual left/right, bimanual symmetric/asymmetric), plus Rest. A conventional intra-regional analysis identified the passive stimulation network, including motor cortex, primary and secondary somatosensory cortex, plus the cerebellum. The posterior (sensory) part of the sensory-motor activation around the central sulcus showed a significant modulation according to the symmetry of the bimanual movement, with greater activation for asymmetric compared to symmetric movements. A second set of fMRI analyses assessed condition-dependent changes of coupling between sensory-motor regions around the superior central sulcus and the rest of the brain. These analyses showed a high inter-regional covariation within the entire network activated by passive movement. However, the specific experimental conditions modulated these patterns of connectivity. Highest coupling was observed during the Rest condition, and the coupling between homologous sensory-motor regions around the left and right central sulcus was higher in bimanual than unimanual conditions. These findings demonstrate that passive movement can affect the connectivity within the sensory-motor network. We conclude that implicit detection of asymmetry during bimanual movement relies on associative somatosensory region in post-central areas, and that passive stimulation reduces the functional connectivity within the passive movement network. Our findings open the possibility to combine passive movement and inter-regional connectivity as a tool to investigate the functionality of the sensory-motor system in patients with very poor mobility.

  2. Active robotic training improves locomotor function in a stroke survivor

    Directory of Open Access Journals (Sweden)

    Krishnan Chandramouli

    2012-08-01

    Full Text Available Abstract Background Clinical outcomes after robotic training are often not superior to conventional therapy. One key factor responsible for this is the use of control strategies that provide substantial guidance. This strategy not only leads to a reduction in volitional physical effort, but also interferes with motor relearning. Methods We tested the feasibility of a novel training approach (active robotic training using a powered gait orthosis (Lokomat in mitigating post-stroke gait impairments of a 52-year-old male stroke survivor. This gait training paradigm combined patient-cooperative robot-aided walking with a target-tracking task. The training lasted for 4-weeks (12 visits, 3 × per week. The subject’s neuromotor performance and recovery were evaluated using biomechanical, neuromuscular and clinical measures recorded at various time-points (pre-training, post-training, and 6-weeks after training. Results Active robotic training resulted in considerable increase in target-tracking accuracy and reduction in the kinematic variability of ankle trajectory during robot-aided treadmill walking. These improvements also transferred to overground walking as characterized by larger propulsive forces and more symmetric ground reaction forces (GRFs. Training also resulted in improvements in muscle coordination, which resembled patterns observed in healthy controls. These changes were accompanied by a reduction in motor cortical excitability (MCE of the vastus medialis, medial hamstrings, and gluteus medius muscles during treadmill walking. Importantly, active robotic training resulted in substantial improvements in several standard clinical and functional parameters. These improvements persisted during the follow-up evaluation at 6 weeks. Conclusions The results indicate that active robotic training appears to be a promising way of facilitating gait and physical function in moderately impaired stroke survivors.

  3. Bimanual passive movement: functional activation and inter-regional coupling

    Directory of Open Access Journals (Sweden)

    Emiliano Macaluso

    2007-12-01

    Full Text Available The aim of this study was to investigate intra-regional activation and inter-regional connectivity during passive movement. During fMRI, a mechanic device was used to move the subject's index and middle fingers. We assessed four movement conditions (unimanual left/right, bimanual symmetric/asymmetric, plus Rest. A conventional intra-regional analysis identified the passive stimulation network, including motor cortex, primary and secondary somatosensory cortex, plus the cerebellum. The posterior (sensory part of the sensory-motor activation around the central sulcus showed a significant modulation according to the symmetry of the bimanual movement, with greater activation for asymmetric compared to symmetric movements. A second set of fMRI analyses assessed condition-dependent changes of coupling between sensory-motor regions around the superior central sulcus and the rest of the brain. These analyses showed a high inter-regional covariation within the entire network activated by passive movement. However, the specific experimental conditions modulated these patterns of connectivity. Highest coupling was observed during the Rest condition, and the coupling between homologous sensory-motor regions around the left and right central sulcus was higher in bimanual than unimanual conditions. These findings demonstrate that passive movement can affect the connectivity within the sensory-motor network. We conclude that implicit detection of asymmetry during bimanual movement relies on associative somatosensory region in post-central areas, and that passive stimulation reduces the functional connectivity within the passive movement network. Our findings open the possibility to combine passive movement and inter-regional connectivity as a tool to investigate the functionality of the sensory-motor system in patients with very poor mobility.

  4. Functional integration of parietal lobe activity in early Alzheimer disease.

    Science.gov (United States)

    Jacobs, H I L; Van Boxtel, M P J; Heinecke, A; Gronenschild, E H B M; Backes, W H; Ramakers, I H G B; Jolles, J; Verhey, F R J

    2012-01-31

    Parietal lobe dysfunction is an important characteristic of early Alzheimer disease (AD). Functional studies have shown conflicting parietal activation patterns indicative of either compensatory or dysfunctional mechanisms. This study aimed at examining activation differences in early AD using a visuospatial task. We focused on functional characteristics of the parietal lobe and examined compensation or disconnection mechanisms by combining a fMRI task with effective connectivity measures from Granger causality mapping (GCM). Eighteen male patients with amnestic mild cognitive impairment (aMCI) and 18 male cognitively healthy older individuals were given a mental rotation task with different rotation angles. There were no behavioral group differences on the fMRI task. Separate measurements at each angle revealed widespread activation group differences. More temporal and parietal activation in the higher angle condition was observed in patients with aMCI. The parametric modulation, which identifies regions associated with increasing angle, confirmed these results. The GCM showed increased connectivity within the parietal lobe and between parietal and temporal regions in patients with aMCI. Decreased connectivity was found between the inferior parietal lobule and posterior cingulate gyrus. Connectivity patterns correlated with memory performance scores in patients with aMCI. Our results demonstrate increased effective temporoparietal connectivity in patients with aMCI, while maintaining intact behavioral performance. This might be a compensational mechanism to counteract a parietal-posterior cingulate gyrus disconnection. These findings highlight the importance of connectivity changes in the pathophysiology of AD. In addition, effective connectivity may be a promising method for evaluating interventions aimed at the promotion of compensatory mechanisms.

  5. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  6. Active robotic training improves locomotor function in a stroke survivor.

    Science.gov (United States)

    Krishnan, Chandramouli; Ranganathan, Rajiv; Kantak, Shailesh S; Dhaher, Yasin Y; Rymer, William Z

    2012-08-20

    Clinical outcomes after robotic training are often not superior to conventional therapy. One key factor responsible for this is the use of control strategies that provide substantial guidance. This strategy not only leads to a reduction in volitional physical effort, but also interferes with motor relearning. We tested the feasibility of a novel training approach (active robotic training) using a powered gait orthosis (Lokomat) in mitigating post-stroke gait impairments of a 52-year-old male stroke survivor. This gait training paradigm combined patient-cooperative robot-aided walking with a target-tracking task. The training lasted for 4-weeks (12 visits, 3 × per week). The subject's neuromotor performance and recovery were evaluated using biomechanical, neuromuscular and clinical measures recorded at various time-points (pre-training, post-training, and 6-weeks after training). Active robotic training resulted in considerable increase in target-tracking accuracy and reduction in the kinematic variability of ankle trajectory during robot-aided treadmill walking. These improvements also transferred to overground walking as characterized by larger propulsive forces and more symmetric ground reaction forces (GRFs). Training also resulted in improvements in muscle coordination, which resembled patterns observed in healthy controls. These changes were accompanied by a reduction in motor cortical excitability (MCE) of the vastus medialis, medial hamstrings, and gluteus medius muscles during treadmill walking. Importantly, active robotic training resulted in substantial improvements in several standard clinical and functional parameters. These improvements persisted during the follow-up evaluation at 6 weeks. The results indicate that active robotic training appears to be a promising way of facilitating gait and physical function in moderately impaired stroke survivors.

  7. Water-soluble, recombinant CuA-domain of the cytochrome ba3 subunit II from Thermus thermophilus.

    Science.gov (United States)

    Slutter, C E; Sanders, D; Wittung, P; Malmström, B G; Aasa, R; Richards, J H; Gray, H B; Fee, J A

    1996-03-19

    Recently, the genes of cytochrome ba3 from thermus thermophilus [Keightley, J.A., et al. (1995) J. Biol. Chem. 270, 20345-20358], a homolog of the heme-copper oxidase family, have been cloned. We report here expression of a truncated gene, encoding the copper A (CuA) domain of cytochrome ba3, that is regulated by a T7 RNA polymerase promoter in Escherichia coli. The CuA-containing domain is purified in high yields as a water-soluble, thermostable, purple-colored protein. Copper analysis by chemical assay, mass spectrometry, X-ray fluorescence, and EPR spin quantification show that this protein contains two copper ions bound in a mixed-valence state, indicating that the CuA site in cytochrome ba3, is a binuclear center. The absorption spectrum of the CuA site, free of the heme interference in cytochrome ba3, is similar to the spectra of other soluble fragments from the aa3-type oxidase of Parachccus denitrificans [Lappalainen, P., et al. (1993) J. Biol Chem. 268, 26416-26421] and the caa3-type oxidase of Bacillus subtilis [von Wachenfeldt, C. et al. (1994) FEBS Lett. 340, 109-113]. There are intense bands at 480 nm (3100 M(-1) cm(-1)) and 530 nm (3200 M(-1) cm(-1)), a band in the near -IR centered at 790 nm (1900 M(-1) cn(-1)), and a weaker band at 363 nm (1300M(-1) cm(-1)). The visible CD spectrum shows a positive-going band at 460 nm and a negative-going band at 527 nm, the opposite signs of which may result from the binuclear nature of the site. The secondary structure prediction from the far-UV CD spectrum indicates that this domain is predominantly beta-sheet, in agreement with the recent X-ray structure reported for the complete P. denitrificans cytochrome aa3 molecule [Iwata, S., et al. (1995) Nature 376, 660-669] and the engineered, purple CyoA protein [Wilmanns, M., et al. (1996) Proc. Natl Acad. Sci. U.S.A. 92, 11955-11959]. However, the thermostability of the fragment described here (Tm approximately 80 degrees C) and the stable binding of copper over a

  8. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Der-Yuan Chen

    2013-01-01

    Full Text Available Dendritic cells (DCs play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM, a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS, proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs. These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

  9. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Science.gov (United States)

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  10. β-Glucans: Relationships between Modification, Conformation and Functional Activities

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2017-02-01

    Full Text Available β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role on its biological activities. Therefore, β-glucans obtained from different sources, while sharing the same basic structures, often show different bioactivities. The basic structure and inter-molecular forces of polysaccharides can be changed by modification, which leads to the conformational transformation in solution that can directly affect bioactivity. In this review, we will first determine different ways to modify β-glucan molecules including physical methods, chemical methods, and biological methods, and then reveal the relationship of the flexible helix form of the molecule chain and the helix conformation to their bioactivities. Last, we summarize the scientific challenges to modifying β-glucan’s conformation and functional activity, and discuss its potential future development.

  11. Activities and Programs That Improve Children's Executive Functions.

    Science.gov (United States)

    Diamond, Adele

    2012-10-01

    Executive functions (EFs; e.g., reasoning, working memory, and self-control) can be improved. Good news indeed, since EFs are critical for school and job success and for mental and physical health. Various activities appear to improve children's EFs. The best evidence exists for computer-based training, traditional martial arts, and two school curricula. Weaker evidence, though strong enough to pass peer review, exists for aerobics, yoga, mindfulness, and other school curricula. Here I address what can be learned from the research thus far, including that EFs need to be progressively challenged as children improve and that repeated practice is key. Children devote time and effort to activities they love; therefore, EF interventions might use children's motivation to advantage. Focusing narrowly on EFs or aerobic activity alone appears not to be as efficacious in improving EFs as also addressing children's emotional, social, and character development (as do martial arts, yoga, and curricula shown to improve EFs). Children with poorer EFs benefit more from training; hence, training might provide them an opportunity to "catch up" with their peers and not be left behind. Remaining questions include how long benefits of EF training last and who benefits most from which activities.

  12. N7-Methylguanine at position 46 (m7G46) in tRNA from Thermus thermophilus is required for cell viability at high temperatures through a tRNA modification network.

    Science.gov (United States)

    Tomikawa, Chie; Yokogawa, Takashi; Kanai, Tamotsu; Hori, Hiroyuki

    2010-01-01

    N(7)-methylguanine at position 46 (m(7)G46) in tRNA is produced by tRNA (m(7)G46) methyltransferase (TrmB). To clarify the role of this modification, we made a trmB gene disruptant (DeltatrmB) of Thermus thermophilus, an extreme thermophilic eubacterium. The absence of TrmB activity in cell extract from the DeltatrmB strain and the lack of the m(7)G46 modification in tRNA(Phe) were confirmed by enzyme assay, nucleoside analysis and RNA sequencing. When the DeltatrmB strain was cultured at high temperatures, several modified nucleotides in tRNA were hypo-modified in addition to the lack of the m(7)G46 modification. Assays with tRNA modification enzymes revealed hypo-modifications of Gm18 and m(1)G37, suggesting that the m(7)G46 positively affects their formations. Although the lack of the m(7)G46 modification and the hypo-modifications do not affect the Phe charging activity of tRNA(Phe), they cause a decrease in melting temperature of class I tRNA and degradation of tRNA(Phe) and tRNA(Ile). (35)S-Met incorporation into proteins revealed that protein synthesis in DeltatrmB cells is depressed above 70 degrees C. At 80 degrees C, the DeltatrmB strain exhibits a severe growth defect. Thus, the m(7)G46 modification is required for cell viability at high temperatures via a tRNA modification network, in which the m(7)G46 modification supports introduction of other modifications.

  13. Inhibitory Effect of Bridged Nucleosides on Thermus aquaticus DNA Polymerase and Insight into the Binding Interactions.

    Directory of Open Access Journals (Sweden)

    Sung-Kun Kim

    Full Text Available Modified nucleosides have the potential to inhibit DNA polymerases for the treatment of viral infections and cancer. With the hope of developing potent drug candidates by the modification of the 2',4'-position of the ribose with the inclusion of a bridge, efforts were focused on the inhibition of Taq DNA polymerase using quantitative real time PCR, and the results revealed the significant inhibitory effects of 2',4'-bridged thymidine nucleoside on the polymerase. Study on the mode of inhibition revealed the competitive mechanism with which the 2',4'-bridged thymidine operates. With a Ki value of 9.7 ± 1.1 μM, the 2',4'-bridged thymidine proved to be a very promising inhibitor. Additionally, docking analysis showed that all the nucleosides including 2',4'-bridged thymidine were able to dock in the active site, indicating that the substrate analogs reflect a structural complementarity to the enzyme active site. The analysis also provided evidence that Asp610 was a key binding site for 2',4'-bridged thymidine. Molecular dynamics (MD simulations were performed to further understand the conformational variations of the binding. The root-mean-square deviation (RMSD values for the peptide backbone of the enzyme and the nitrogenous base of the inhibitor stabilized within 0.8 and 0.2 ns, respectively. Furthermore, the MD analysis indicates substantial conformational change in the ligand (inhibitor as the nitrogenous base rotated anticlockwise with respect to the sugar moiety, complemented by the formation of several new hydrogen bonds where Arg587 served as a pivot axis for binding formation. In conclusion, the active site inhibition of Taq DNA polymerase by 2',4'-bridged thymidine suggests the potential of bridged nucleosides as drug candidates.

  14. Functional neuroimaging of conversion disorder: the role of ancillary activation.

    Science.gov (United States)

    Burke, Matthew J; Ghaffar, Omar; Staines, W Richard; Downar, Jonathan; Feinstein, Anthony

    2014-01-01

    Previous functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to better define the functional neuroanatomical correlates of conversion disorder. Ten subjects meeting clinical criteria for unilateral sensory conversion disorder underwent fMRI during which a vibrotactile stimulus was applied to anesthetic and sensate areas. A block design was used with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times. Event-related group averages of the BOLD response were compared between conditions. All subjects were right-handed females, with a mean age of 41. Group analyses revealed 10 areas that had significantly greater activation (p conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder.

  15. Active chemisorption sites in functionalized ionic liquids for carbon capture.

    Science.gov (United States)

    Cui, Guokai; Wang, Jianji; Zhang, Suojiang

    2016-07-25

    Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined.

  16. Imaging brain neuronal activity using functionalized magnetonanoparticles and MRI.

    Science.gov (United States)

    Akhtari, Massoud; Bragin, Anatol; Moats, Rex; Frew, Andrew; Mandelkern, Mark

    2012-10-01

    This study explored the use of non-radioactive 2-deoxy glucose (2DG)-labeled magnetonanoparticles (MNP) and magnetic resonance imaging (MRI) to detect functional activity during rest, peripheral stimulation, and epileptic seizures, in animal models. Non-radioactive 2DG was covalently attached to magnetonanoparticles composed of iron oxide and dextran and intravenous (tail) injections were performed. 2DG-MNP was injected in resting and stimulated naïve rodents and the subsequent MRI was compared to published (14)C-2DG autoradiography data. Reproducibility and statistical significance was established in one studied model. Negative contrast enhancement (NCE) in acute seizures and chronic models of epilepsy were investigated. MRI NCE due to 2DG-MNP particles was compared to that of plain (unconjugated) MNP in one animal. NCE due to 2DG-MNP particles at 3 T, which is approved for human use, was also investigated. Histology showed presence of MNP (following intravenous injection) in the brain tissues of resting naïve animal. 2DG-MNP intraparenchymal uptake was visible on MRI and histology. The locations of NCE agreed with published results of 2DG autoradiography in resting and stimulated animals and epileptic rats. Localization of epileptogenicity was confirmed by subsequent depth-electrode EEG (iEEG). Non-radioactive 2DG-MNP can cross the blood-brain barrier (BBB) and may accurately localize areas of increased activity. Although, this proof-of-principle study involves only a limited number of animals, and much more research and quantification are necessary to demonstrate that 2DG-MNP, or MNPs conjugated with other ligands, could eventually be used to image localized cerebral function with MRI in humans, this MNP-MRI approach is potentially applicable to the use of many bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions.

  17. Preparation of functionalized and metal-impregnated activated carbon by a single-step activation method

    Science.gov (United States)

    Dastgheib, Seyed A.; Ren, Jianli; Rostam-Abadi, Massoud; Chang, Ramsay

    2014-01-01

    A rapid method to prepare functionalized and metal-impregnated activated carbon from coal is described in this paper. A mixture of ferric chloride and a sub-bituminous coal was used to demonstrate simultaneous coal activation, chlorine functionalization, and iron/iron oxides impregnation in the resulting porous carbon products. The FeCl3 concentration in the mixture, the method to prepare the FeCl3-coal mixture (solid mixing or liquid impregnation), and activation atmosphere and temperature impacted the surface area and porosity development, Cl functionalization, and iron species impregnation and dispersion in the carbon products. Samples activated in nitrogen or a simulated flue gas at 600 or 1000 °C for 1-2 min had surface areas up to ∼800 m2/g, bulk iron contents up to 18 wt%, and surface chlorine contents up to 27 wt%. Potential catalytic and adsorption application of the carbon materials was explored in catalytic wet air oxidation (CWAO) of phenol and adsorption of ionic mercury from aqueous solutions. Results indicated that impregnated activated carbons outperformed their non-impregnated counterparts in both the CWAO and adsorption tests.

  18. Estimation of spatiotemporal neural activity using radial basis function networks.

    Science.gov (United States)

    Anderson, R W; Das, S; Keller, E L

    1998-12-01

    We report a method using radial basis function (RBF) networks to estimate the time evolution of population activity in topologically organized neural structures from single-neuron recordings. This is an important problem in neuroscience research, as such estimates may provide insights into systems-level function of these structures. Since single-unit neural data tends to be unevenly sampled and highly variable under similar behavioral conditions, obtaining such estimates is a difficult task. In particular, a class of cells in the superior colliculus called buildup neurons can have very narrow regions of saccade vectors for which they discharge at high rates but very large surround regions over which they discharge at low, but not zero, levels. Estimating the dynamic movement fields for these cells for two spatial dimensions at closely spaced timed intervals is a difficult problem, and no general method has been described that can be applied to all buildup cells. Estimation of individual collicular cells' spatiotemporal movement fields is a prerequisite for obtaining reliable two-dimensional estimates of the population activity on the collicular motor map during saccades. Therefore, we have developed several computational-geometry-based algorithms that regularize the data before computing a surface estimation using RBF networks. The method is then expanded to the problem of estimating simultaneous spatiotemporal activity occurring across the superior colliculus during a single movement (the inverse problem). In principle, this methodology could be applied to any neural structure with a regular, two-dimensional organization, provided a sufficient spatial distribution of sampled neurons is available.

  19. Interaction between functional health literacy, patient activation, and glycemic control

    Directory of Open Access Journals (Sweden)

    Woodard LD

    2014-07-01

    Full Text Available LeChauncy D Woodard, Cassie R Landrum, Amber B Amspoker, David Ramsey, Aanand D Naik Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey Veterans Affairs Medical Center, and Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA Background: Functional health literacy (FHL and patient activation can impact diabetes control through enhanced diabetes self-management. Less is known about the combined effect of these characteristics on diabetes outcomes. Using brief, validated measures, we examined the interaction between FHL and patient activation in predicting glycosylated hemoglobin (HbA1c control among a cohort of multimorbid diabetic patients.Methods: We administered a survey via mail to 387 diabetic patients with coexisting ­hypertension and ischemic heart disease who received outpatient care at one regional VA medical center between November 2010 and December 2010. We identified patients with the study conditions using the International Classification of Diseases-Ninth Revision-Clinical ­Modification (ICD-9-CM diagnoses codes and Current Procedure Terminology (CPT ­procedures codes. Surveys were returned by 195 (50.4% patients. We determined patient activation levels based on participant responses to the 13-item Patient Activation Measure and FHL levels using the single-item screening question, “How confident are you filling out medical forms by yourself?” We reviewed patient medical records to assess glycemic control. We used multiple logistic regression to examine whether activation and FHL were individually or jointly related to HbA1c control.Results: Neither patient activation nor FHL was independently related to glycemic control in the unadjusted main effects model; however, the interaction between the two was significantly associated with glycemic control (odds ratio 1.05 [95% confidence

  20. Molecular cloning, sequencing and expression in Escherichia coli cells Thermus thermophilus leucyl-tRNA synthetase

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    Kovalenko O. P.

    2011-12-01

    Full Text Available Aim. Cloning and sequencing of the T. thermophilus leucyl-tRNA synthetase (LeuRSTT followed by the creation of genetically engineered construct for protein expression in E.coli cells and its purification. Methods. Searching for the LeuRSTT gene was performed by Southern blot hybridization with chromosomal DNA, where digoxigenin-labeled PCR fragments of DNA were used as probes. Results. The gene of T. thermophilus HB27 leucyl-tRNA synthetase was cloned and sequenced. The open reading frame encodes a polypeptide chain of 878 amino acid residues in length (molecular mass 101 kDa. Comparison of the amino acid sequence of T. thermophilus LeuRS with that of the enzymes from other organisms showed that LeuRSTT was a part of the group of similar enzymes of prokaryotes, formed by the proteins of protobacteriae, rickettsia and mitochondria of eukaryotes. The resulting phylogenetic tree of LeuRSs reveals dichotomous branching into two lines: prokaryotic/eukaryotic mitochondrial and arhaeal/eukaryotic cytosolic proteins. Differences between prokaryotic and arhaeal branches of the LeuRSs phylogenetic tree are primarily due to the structure of two domains of the enzyme – the editing and the C-terminal. T. thermophilus LeuRS was expressed in E. coli cells by cloning the corresponding gene into pET29b vector. Conclusions. The cloned T. thermophilus leuS gene and expressed recombinant protein will be used for structural and functional studies on LeuRSTT, including X-ray analysis of the enzyme and its mutant forms in complex with different substrates

  1. Variability in measuring (instrumental) activities of daily living functioning and functional decline in hospitalized older medical patients: a systematic review.

    NARCIS (Netherlands)

    Buurman, B.M.; Munster, B.C. van; Korevaar, J.C.; Haan, R.J. de; Rooij, S.E. de

    2011-01-01

    OBJECTIVE: To study instruments used and definitions applied in order to measure (instrumental) activities of daily living (I [ADL]) functioning and functional decline in hospitalized older medical patients. STUDY DESIGN: We systematically searched Medline, Embase, and the Cochrane Database of

  2. The Changes of Muscle Strength and Functional Activities During Aging in Male and Female Populations

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    Shih-Jung Cheng

    2014-12-01

    Conclusion: We noted that the muscle strength and functional activities were decreased earlier in female than male individuals. The decrease of functional activities during the aging process seems to be earlier than the decrease of muscle strength. It is important to implement functional activities training in addition to strengthening exercise to maintain functional levels of the geriatric population.

  3. Overexpression of a Novel Thermostable and Chloride-Tolerant Laccase from Thermus thermophilus SG0.5JP17-16 in Pichia pastoris and Its Application in Synthetic Dye Decolorization

    Science.gov (United States)

    Liu, Huiping; Cheng, Yu; Du, Bing; Tong, Chaofan; Liang, Shuli; Han, Shuangyan; Zheng, Suiping; Lin, Ying

    2015-01-01

    Laccases have been used for the decolorization and detoxification of synthetic dyes due to their ability to oxidize a wide variety of dyes with water as the sole byproduct. A putative laccase gene (LacTT) from Thermus thermophilus SG0.5JP17-16 was screened using the genome mining approach, and it was highly expressed in Pichia pastoris, yielding a high laccase activity of 6130 U/L in a 10-L fermentor. The LacTT open reading frame encoded a protein of 466 amino acid residues with four putative Cu-binding regions. The optimal pH of the recombinant LacTT was 4.5, 6.0, 7.5 and 8.0 with 2,2'-azino-bis(3-ethylbenzothazoline-6-sulfonic acid) (ABTS), syringaldazine (SGZ), guaiacol, and 2,6-dimethoxyphenol (2,6-DMP) as the substrate, respectively. The optimal temperature of LacTT was 90°C with guaiacol as the substrate. LacTT was highly stable at pH 4.0–11.0 and thermostable at 40°C–90°C, confirming that it is a pH-stable and thermostable laccase. Furthermore, LacTT also exhibited high tolerance to halides such as NaCl, NaBr and NaF, and decolorized 100%, 94%, 94% and 73% of Congo Red, Reactive Black B and Reactive Black WNN, and Remazol Brilliant Blue R, respectively. Interestingly, addition of high concentration of NaCl increased the RBBR decolorization efficiency of LacTT. These results suggest that LacTT is a good candidate for industrial applications such as dyestuff processing and degradation of dyes in textile wastewaters. PMID:25790466

  4. Crystallographic Studies of Xe And Kr Binding Within the Large Internal Cavity of Cytochrome Ba(3) From Thermus Thermophilus: Structural Analysis And Role of Oxygen Transport Channels in the Heme-Cu Oxidases

    Energy Technology Data Exchange (ETDEWEB)

    Luna, V.M.; Chen, Y.; Fee, J.A.; Stout, C.D.

    2009-05-26

    Cytochrome ba{sub 3} is a cytochrome c oxidase from the plasma membrane of Thermus thermophilus and is the preferred terminal enzyme of cellular respiration at low dioxygen tensions. Using cytochrome ba{sub 3} crystals pressurized at varying conditions under Xe or Kr gas, and X-ray data for six crystals, we identify the relative affinities of Xe and Kr atoms for as many as seven distinct binding sites. These sites track a continuous, Y-shaped channel, 18--20 {angstrom} in length, lined by hydrophobic residues, which leads from the surface of the protein where two entrance holes, representing the top of the Y, connect the bilayer to the {alpha}{sub 3}-Cu{sub B} center at the base of the Y. Considering the increased affinity of O{sub 2} for hydrophobic environments, the hydrophobic nature of the channel, its orientation within the bilayer, its connection to the active site, its uniform diameter, its virtually complete occupation by Xe, and its isomorphous presence in the native enzyme, we infer that the channel is a diffusion pathway for O{sub 2} into the dinuclear center of cytochrome ba{sub 3}. These observations provide a basis for analyzing similar channels in other oxidases of known structure, and these structures are discussed in terms of mechanisms of O{sub 2} transport in biological systems, details of CO binding to and egress from the dinuclear center, the bifurcation of the oxygen-in and water-out pathways, and the possible role of the oxygen channel in aerobic thermophily.

  5. Overexpression of a novel thermostable and chloride-tolerant laccase from Thermus thermophilus SG0.5JP17-16 in Pichia pastoris and its application in synthetic dye decolorization.

    Directory of Open Access Journals (Sweden)

    Huiping Liu

    Full Text Available Laccases have been used for the decolorization and detoxification of synthetic dyes due to their ability to oxidize a wide variety of dyes with water as the sole byproduct. A putative laccase gene (LacTT from Thermus thermophilus SG0.5JP17-16 was screened using the genome mining approach, and it was highly expressed in Pichia pastoris, yielding a high laccase activity of 6130 U/L in a 10-L fermentor. The LacTT open reading frame encoded a protein of 466 amino acid residues with four putative Cu-binding regions. The optimal pH of the recombinant LacTT was 4.5, 6.0, 7.5 and 8.0 with 2,2'-azino-bis(3-ethylbenzothazoline-6-sulfonic acid (ABTS, syringaldazine (SGZ, guaiacol, and 2,6-dimethoxyphenol (2,6-DMP as the substrate, respectively. The optimal temperature of LacTT was 90°C with guaiacol as the substrate. LacTT was highly stable at pH 4.0-11.0 and thermostable at 40°C-90°C, confirming that it is a pH-stable and thermostable laccase. Furthermore, LacTT also exhibited high tolerance to halides such as NaCl, NaBr and NaF, and decolorized 100%, 94%, 94% and 73% of Congo Red, Reactive Black B and Reactive Black WNN, and Remazol Brilliant Blue R, respectively. Interestingly, addition of high concentration of NaCl increased the RBBR decolorization efficiency of LacTT. These results suggest that LacTT is a good candidate for industrial applications such as dyestuff processing and degradation of dyes in textile wastewaters.

  6. Overexpression of a novel thermostable and chloride-tolerant laccase from Thermus thermophilus SG0.5JP17-16 in Pichia pastoris and its application in synthetic dye decolorization.

    Science.gov (United States)

    Liu, Huiping; Cheng, Yu; Du, Bing; Tong, Chaofan; Liang, Shuli; Han, Shuangyan; Zheng, Suiping; Lin, Ying

    2015-01-01

    Laccases have been used for the decolorization and detoxification of synthetic dyes due to their ability to oxidize a wide variety of dyes with water as the sole byproduct. A putative laccase gene (LacTT) from Thermus thermophilus SG0.5JP17-16 was screened using the genome mining approach, and it was highly expressed in Pichia pastoris, yielding a high laccase activity of 6130 U/L in a 10-L fermentor. The LacTT open reading frame encoded a protein of 466 amino acid residues with four putative Cu-binding regions. The optimal pH of the recombinant LacTT was 4.5, 6.0, 7.5 and 8.0 with 2,2'-azino-bis(3-ethylbenzothazoline-6-sulfonic acid) (ABTS), syringaldazine (SGZ), guaiacol, and 2,6-dimethoxyphenol (2,6-DMP) as the substrate, respectively. The optimal temperature of LacTT was 90°C with guaiacol as the substrate. LacTT was highly stable at pH 4.0-11.0 and thermostable at 40°C-90°C, confirming that it is a pH-stable and thermostable laccase. Furthermore, LacTT also exhibited high tolerance to halides such as NaCl, NaBr and NaF, and decolorized 100%, 94%, 94% and 73% of Congo Red, Reactive Black B and Reactive Black WNN, and Remazol Brilliant Blue R, respectively. Interestingly, addition of high concentration of NaCl increased the RBBR decolorization efficiency of LacTT. These results suggest that LacTT is a good candidate for industrial applications such as dyestuff processing and degradation of dyes in textile wastewaters.

  7. Bipartite functions of the CREB co-activators selectively direct alternative splicing or transcriptional activation.

    Science.gov (United States)

    Amelio, Antonio L; Caputi, Massimo; Conkright, Michael D

    2009-09-16

    The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1-MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity.

  8. Platelet function and fibrinolytic activity following distance running.

    Science.gov (United States)

    Knudsen, J B; Brodthagen, U; Gormsen, J; Jordal, R; Nørregaard-Hansen, K; Paulev, P E

    1982-11-01

    6 long distance runners from the Danish marathon elite and 6 non-runners completed test runs of 28 and 12 km, respectively. Distance runners and non-runners showed the same responses in platelet function. We found a significant decrease in ADP induced platelet aggregability, a decreased serotonin release induced by ADP and collagen and an increase in platelet factor 4 immediately following the run. The antithrombin III levels remained constant. Euglobulin lysis time was shortened (by approximately 50%) and the plasminogen levels significantly increased. The last 2 findings indicate an equal increase in fibrinolytic activity during distance running in both groups. While short term, strenuous exercise induces platelet hyperaggregation, long term distance running induces a state of exhaustion of platelet aggregation capacity.

  9. Active plasma resonance spectroscopy: A functional analytic description

    CERN Document Server

    Lapke, Martin; Mussenbrock, Thomas; Brinkmann, Ralf Peter

    2012-01-01

    The term "Active Plasma Resonance Spectroscopy" refers to a class of diagnostic methods which employ the ability of plasmas to resonate on or near the plasma frequency. The basic idea dates back to the early days of discharge physics: An signal in the GHz range is coupled to the plasma via an electrical probe; the spectral response is recorded, and then evaluated with a mathematical model to obtain information on the electron density and other plasma parameters. In recent years, the concept has found renewed interest as a basis of industry compatible plasma diagnostics. This paper analyzes the diagnostics technique in terms of a general description based on functional analytic (or Hilbert Space) methods which hold for arbitrary probe geometries. It is shown that the response function of the plasma-probe system can be expressed as a matrix element of the resolvent of an appropriately defined dynamical operator. A specialization of the formalism for a symmetric probe desing is given, as well as an interpreation...

  10. Functional metabolomics reveals novel active products in the DHA metabolome

    Directory of Open Access Journals (Sweden)

    Masakazu eShinohara

    2012-04-01

    Full Text Available Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA. Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered (AT forms of protectins. The new oxygenated DHEA derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.

  11. Active plasma resonance spectroscopy: a functional analytic description

    Science.gov (United States)

    Lapke, M.; Oberrath, J.; Mussenbrock, T.; Brinkmann, R. P.

    2013-04-01

    The term ‘active plasma resonance spectroscopy’ denotes a class of diagnostic methods which employ the ability of plasmas to resonate on or near the plasma frequency. The basic idea dates back to the early days of discharge physics: a signal in the GHz range is coupled to the plasma via an electrical probe; the spectral response is recorded, and then evaluated with a mathematical model to obtain information on the electron density and other plasma parameters. In recent years, the concept has found renewed interest as a basis of industry compatible plasma diagnostics. This paper analyzes the diagnostic technique in terms of a general description based on functional analytic (or Hilbert Space) methods which hold for arbitrary probe geometries. It is shown that the response function of the plasma-probe system can be expressed as a matrix element of the resolvent of an appropriately defined dynamical operator. A specialization of the formalism to a symmetric probe design is given, as well as an interpretation in terms of a lumped circuit model consisting of series resonance circuits. We present ideas for an optimized probe design based on geometric and electrical symmetry.

  12. Sexual function, activity, and satisfaction among women receiving maintenance hemodialysis.

    Science.gov (United States)

    Mor, Maria K; Sevick, Mary Ann; Shields, Anne Marie; Green, Jamie A; Palevsky, Paul M; Arnold, Robert M; Fine, Michael J; Weisbord, Steven D

    2014-01-01

    Past studies that demonstrated that sexual dysfunction is common among women receiving chronic hemodialysis did not distinguish sexual dysfunction/difficulty from sexual inactivity. This study sought to differentiate these in order to elucidate the prevalence of true "sexual dysfunction" in this population. As part of a clinical trial of symptom management strategies in patients receiving chronic hemodialysis, female sexual function was prospectively assessed monthly for 6 months and quarterly thereafter using the Female Sexual Function Index, to which questions were added differentiating sexual dysfunction/difficulty from sexual inactivity. Beginning in month 7, patients were asked three questions about sexual activity, difficulty, and satisfaction monthly. Of the women enrolled in the clinical trial,125 participants completed 1721 assessments between 2009 and 2011. Scores on 574 of 643 (89%) quarterly Female Sexual Function Index assessments were consistent with sexual dysfunction, due largely to sexual inactivity, which was reported on 525 (82%) quarterly assessments. When reported (n=1663), the most frequently described reasons for sexual inactivity were lack of interest in sex (n=715; 43%) and lack of a partner (n=647; 39%), but rarely sexual difficulty (n=36; 2%). When reported (n=1582), women were moderately to very satisfied with their sexual life on 1020 (64%) assessments and on 513 of 671 (76%) assessments in which lack of interest was cited as a reason for sexual inactivity. Women indicated an interest in learning about the causes of and treatment for sexual dysfunction on just 5% of all assessments. Although many women receiving chronic hemodialysis are sexually inactive, few describe sexual difficulty. Most, including those with a lack of interest in sex, are satisfied with their sexual life and few wish to learn about treatment options. These findings suggest that true sexual dysfunction is uncommon in this population and that treatment opportunities

  13. Metaproteomics provides functional insight into activated sludge wastewater treatment.

    Directory of Open Access Journals (Sweden)

    Paul Wilmes

    Full Text Available BACKGROUND: Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR. METHODOLOGY/PRINCIPAL FINDINGS: A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism "Candidatus Accumulibacter phosphatis". When EBPR failed, the sludge was dominated by tetrad-forming alpha-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from "Candidatus Accumulibacter phosphatis" and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid beta oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. CONCLUSIONS/SIGNIFICANCE: Importantly, this study provides direct evidence linking the metabolic activities of "Accumulibacter" to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models.

  14. Functional composition and antioxidant activities of eight Moroccan date frui

    Directory of Open Access Journals (Sweden)

    Eimad dine Tariq Bouhlali

    2017-07-01

    Full Text Available The aim of this study was to determine the functional composition and antioxidant activities of eight major date fruit varieties grown in Morocco. The analysis shows that date fruit contains a high amount of sugar (66.03–83.05% DW but a low content of fat (0.218–0.363% DW and protein (2.2–3.45% DW. Among the eight studied minerals potassium, calcium and magnesium were the predominant. Moreover, the niacin is the major B vitamin of all analyzed varieties. The total phenolic content was found between 331.86 and 537.07 mg GAE/100 g DW, the flavonoid between 68.88 and 208.53 mg of RE/100 g DW and condensed tannins between 57.56 and 92.141 mg CE/100 g DW, the antioxidant activity ranged between 383.90 and 846.94 μmol TE/100 g DW for ABTS, 6.255 and 2.046 g of date/l for DPPHIC50 and 406.614 and 860.89 μmol TE/100 g DW for FRAP assays. The results suggest that date fruit, which is good source of vital nutrients and antioxidant, is an extensive and varied field.

  15. Metaproteomics Provides Functional Insight into Activated Sludge Wastewater Treatment

    Science.gov (United States)

    Wilmes, Paul; Wexler, Margaret; Bond, Philip L.

    2008-01-01

    Background Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR). Methodology/Principal Findings A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism “Candidatus Accumulibacter phosphatis”. When EBPR failed, the sludge was dominated by tetrad-forming α-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from “Candidatus Accumulibacter phosphatis” and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid β oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. Conclusions/Significance Importantly, this study provides direct evidence linking the metabolic activities of “Accumulibacter” to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models. PMID:18392150

  16. Interaction of Thermus thermophilus, ArsC enzyme and gold nanoparticles naked-eye assays speciation between As(III) and As(V)

    Science.gov (United States)

    Politi, Jane; Spadavecchia, Jolanda; Fiorentino, Gabriella; Antonucci, Immacolata; Casale, Sandra; De Stefano, Luca

    2015-10-01

    The thermophilic bacterium Thermus thermophilus HB27 encodes chromosomal arsenate reductase (TtArsC), the enzyme responsible for resistance to the harmful effects of arsenic. We report on adsorption of TtArsC onto gold nanoparticles for naked-eye monitoring of biomolecular interaction between the enzyme and arsenic species. Synthesis of hybrid biological-metallic nanoparticles has been characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-vis), dynamic light scattering (DLS) and phase modulated infrared reflection absorption (PM-IRRAS) spectroscopies. Molecular interactions have been monitored by UV-vis and Fourier transform-surface plasmon resonance (FT-SPR). Due to the nanoparticles’ aggregation on exposure to metal salts, pentavalent and trivalent arsenic solutions can be clearly distinguished by naked-eye assay, even at 85 μM concentration. Moreover, the assay shows partial selectivity against other heavy metals.

  17. Suppressive Activity of Quercetin on Periostin Functions In Vitro.

    Science.gov (United States)

    Irie, Shinji; Kashiwabara, Misako; Yamada, Asako; Asano, Kazuhito

    2016-01-01

    Periostin, a 90-kDa extracellular matrix protein, has been attracting attention as a novel biomarker of airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although oral administration of quercetin to patients with AR can favorably modify the clinical condition of this disease, the influence of quercetin on periostin functions is not well understood. The present study was, therefore, undertaken to examine the influence of quercetin on the production of both periostin and periostin-induced eosinophil chemoattractants from human nasal epithelial cells (HNEpC) in vitro. HNEpC were stimulated with 15.0 ng/ml interleukin (IL)-4 in the absence or presence of quercetin for 72 h. Periostin levels in the culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Addition of 4.0 μM quercetin into cell cultures suppressed periostin production from HNEpC that was induced by IL-4 stimulation through inhibitation of signal transducer and activator of transcription 6 (STAT6) activation. We then examined whether quercetin could inhibit production of the periostin-induced eosinophil chemoattractants, regulated on activation, normal T-cell expressed and secreted (RANTES) and eotaxin, from HNEpC. HNEpC were stimulated with 2.0 ng/ml periostin in the absence or presence of quercetin for 72 h. RANTES and eotaxin levels in culture supernatants were examined using ELISA. Treatment of HNEpC with quercetin at a concentration of 4.0 μM suppressed the ability of cells to produce RANTES and eotaxin. This suppression was mediated through suppression of activation of the transcription factor nuclear factor-kappa B (NF-κB) p65, as measured using ELISA, and of chemokine mRNA expression, as measured using reverse transcriptase-polymerase chain reaction (RT-PCR). These results strongly suggest that quercetin suppresses the production of both periostin and periostin-induced eosinophil chemoattractants from HNEpC and results in improvement of the

  18. Shoulder muscle activity and function in common shoulder rehabilitation exercises.

    Science.gov (United States)

    Escamilla, Rafael F; Yamashiro, Kyle; Paulos, Lonnie; Andrews, James R

    2009-01-01

    , posterior tilt and ER. The serratus anterior also helps stabilize the medial border and inferior angle of the scapular, preventing scapular IR (winging) and anterior tilt. If normal scapular movements are disrupted by abnormal scapular muscle firing patterns, weakness, fatigue, or injury, the shoulder complex functions less efficiency and injury risk increases. Scapula position and humeral rotation can affect injury risk during humeral elevation. Compared with scapular protraction, scapular retraction has been shown to both increase subacromial space width and enhance supraspinatus force production during humeral elevation. Moreover, scapular IR and scapular anterior tilt, both of which decrease subacromial space width and increase impingement risk, are greater when performing scaption with IR ('empty can') compared with scaption with ER ('full can'). There are several exercises in the literature that exhibit high to very high activity from the rotator cuff, deltoids and scapular muscles, such as prone horizontal abduction at 100 degrees abduction with ER, flexion and abduction with ER, 'full can' and 'empty can', D1 and D2 diagonal pattern flexion and extension, ER and IR at 0 degrees and 90 degrees abduction, standing extension from 90-0 degrees , a variety of weight-bearing upper extremity exercises, such as the push-up, standing scapular dynamic hug, forward scapular punch, and rowing type exercises. Supraspinatus activity is similar between 'empty can' and 'full can' exercises, although the 'full can' results in less risk of subacromial impingement. Infraspinatus and subscapularis activity have generally been reported to be higher in the 'full can' compared with the 'empty can', while posterior deltoid activity has been reported to be higher in the 'empty can' than the 'full can'.

  19. Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging.

    Science.gov (United States)

    Umanskaya, Alisa; Santulli, Gaetano; Xie, Wenjun; Andersson, Daniel C; Reiken, Steven R; Marks, Andrew R

    2014-10-21

    Age-related skeletal muscle dysfunction is a leading cause of morbidity that affects up to half the population aged 80 or greater. Here we tested the effects of increased mitochondrial antioxidant activity on age-dependent skeletal muscle dysfunction using transgenic mice with targeted overexpression of the human catalase gene to mitochondria (MCat mice). Aged MCat mice exhibited improved voluntary exercise, increased skeletal muscle specific force and tetanic Ca(2+) transients, decreased intracellular Ca(2+) leak and increased sarcoplasmic reticulum (SR) Ca(2+) load compared with age-matched wild type (WT) littermates. Furthermore, ryanodine receptor 1 (the sarcoplasmic reticulum Ca(2+) release channel required for skeletal muscle contraction; RyR1) from aged MCat mice was less oxidized, depleted of the channel stabilizing subunit, calstabin1, and displayed increased single channel open probability (Po). Overall, these data indicate a direct role for mitochondrial free radicals in promoting the pathological intracellular Ca(2+) leak that underlies age-dependent loss of skeletal muscle function. This study harbors implications for the development of novel therapeutic strategies, including mitochondria-targeted antioxidants for treatment of mitochondrial myopathies and other healthspan-limiting disorders.

  20. PWM-Statcom system additionally having active filter function

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, K.; Kojima, H.; Yamamoto, I.; Hasegawa, M. [Chubu Univ., Kasugai Aichi (Japan); Ando, K. [Nitto Kogyo Corp., Nagakute, Aichi (Japan)

    2006-07-01

    The harmonic characteristics of static synchronous compensators (Statcom) were discussed with particular reference to the difference between symmetrical and asymmetrical modulation strategies that influence a quality of output waveform. The asymmetrical modulation strategy is the better approach in higher power factor applications such as alternating current (AC) motor drives. It was noted that in cases requiring a passive filter with a very large scale Statcom, a symmetrical modulation strategy is superior. Therefore, in this study, a symmetrical modulation was preferred for a neutral point clamped (NPC) pulse width modulation (PWM) inverter. Due to switching in a limited narrow frequency band, such output harmonics can be eliminated using a simple passive filter and harmonics such as the fifth and the seventh, can be suppressed using the proposed Statcom scheme in which the feedback signals for the fifth and seventh harmonics are injected into the Statcom. Using these feedback signals, the harmonics in the power system were significantly reduced. This result was also confirmed by simulation. It was concluded that, in addition to the proper operation of the Statcom, it is possible to perform an active filtering function . 10 refs., 1 tab., 9 figs.

  1. Cardiopulmonary bypass reduces peripheral microvascular contractile function by inhibition of mitogen-activated protein kinase activity.

    Science.gov (United States)

    Khan, Tanveer A; Bianchi, Cesario; Araujo, Eugenio G; Ruel, Marc; Voisine, Pierre; Li, Jianyi; Liddicoat, John R; Sellke, Frank W

    2003-08-01

    Mitogen-activated protein kinases (MAPK) have been implicated in pathophysiologic responses to cardiopulmonary bypass (CPB). MAPK are deactivated by phosphatases, such as MAPK phosphatase-1 (MKP-1). We hypothesized that MAPK mediate peripheral microvascular contractile dysfunction caused by CPB in humans. Skeletal muscle was harvested before and after CPB. Protein levels of MKP-1 and activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 were measured. MKP-1 gene expression was measured. Peripheral microvessel responses to vasopressors were studied by videomicroscopy. Contractile function also was measured after MAPK inhibition with PD98059 (ERK1/2) and SB203580 (p38). ERK1/2, p38, and MKP-1 were localized by immunohistochemistry and in situ hybridization. ERK1/2 and p38 activity was decreased in peripheral tissue after CPB. MKP-1 was increased after CPB. Contractile responses of peripheral arterioles to phenylephrine and vasopressin were decreased after CPB. Microvessel reactivity also was reduced after treatment with PD98059 and SB203580. ERK1/2, p38, and MKP-1 localized to peripheral arterioles in tissue sections. CPB reduces ERK1/2 and p38 activity in peripheral tissue, potentially by MKP-1. Contractile responses of peripheral arterioles to phenylephrine and vasopressin are dependent on ERK1/2 and p38 and are decreased after CPB. These results suggest that alterations in MAPK pathways in part regulate peripheral microvascular dysfunction after CPB in humans.

  2. Canid progesterone receptors lack activation function 3 domain-dependent activity.

    Science.gov (United States)

    Gracanin, Ana; van Wolferen, Monique E; Sartorius, Carol A; Brenkman, Arjan B; Schoonen, Willem G; Mol, Jan A

    2012-12-01

    Progesterone regulates multiple behavioral, physiological, and pathological aspects of female reproductive biology through its two progesterone receptors (PRs), PR-B and the truncated PR-A. PR-B is necessary for mammary gland development in mice and, compared with PR-A, is overall a stronger transactivator of target genes due to an additional activation function 3 (AF3) domain. In dogs, known for their high sensitivity to progesterone-induced mammary cancer, the PR-B function was studied. Canine PR (cPR)-B appeared to contain multiple mutations within AF3 core sequence motifs and lacks N-terminal ligand-independent posttranslational modifications. Consequently, cPR-B has a weak transactivation potential on progesterone-responsive mouse mammary tumor virus-luc and progesterone response element 2-luc reporters transiently transfected in hamster, human, or canine cells and also on known target genes FKBP5 and SGK in doxycycline-inducible, stable transfected cPR-B in canine mammary cells. The cPR-B function was restored to the level of human PR-B by the replacement of canine AF3 domain with the human one. The lack of AF3 domain-dependent transcriptional activity was unique for canids (gray wolf, red fox, and raccoon dog) and not present in closely related caniform species (brown bear, gray seal, and domestic ferret). Despite the limited transactivation potential, canids develop normal mammary glands and frequently mammary tumors. Therefore, these results question the role of PR-B in breast cancer development and may explain unique features of canid reproduction.

  3. Restoration of landscape function: Reserves or active management?

    Science.gov (United States)

    A.B. Carey

    2003-01-01

    A 20-year program of research suggests that old-growth forests are ecologically unique and highly valued by people, that naturally young forests with legacies from old forests sustain many, if not all, the higher organisms associated with old growth, but that many managed forests are impoverished in species. Thus, restoring landscape function entails restoring function...

  4. Long-term functional outcome of patients with longitudinal radial deficiency : cross-sectional evaluation of function, activity and participation

    NARCIS (Netherlands)

    Holtslag, Irene; van Wijk, Iris; Hartog, Hermien; van der Molen, Aebele Mink; van der Sluis, Corry

    2013-01-01

    Purpose: To evaluate all functional aspects of patients with longitudinal radial dysplasia and to clarify the relationship between body functions on the one hand and limitations in activity and participation on the other hand. Methods: Thirty-one arms of seventeen adult patients with longitudinal ra

  5. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment

    NARCIS (Netherlands)

    Angevaren, Maaike; Aufdemkampe, Geert; Verhaar, H. J. J.; Aleman, A.; Vanhees, Luc

    2008-01-01

    Background Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function. Studies in which activity, f

  6. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment

    NARCIS (Netherlands)

    Angevaren, Maaike; Aufdemkampe, Geert; Verhaar, H. J. J.; Aleman, A.; Vanhees, Luc

    2008-01-01

    Background Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function. Studies in which activity,

  7. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

    DEFF Research Database (Denmark)

    Efsen, Eva; Saermark, Torben; Hansen, Alastair

    2011-01-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue...... and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies......-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity...

  8. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

    DEFF Research Database (Denmark)

    Efsen, Eva; Saermark, Torben; Hansen, Alastair

    2011-01-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue...... and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies......-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity...

  9. Electrocatalytic Activity and Selectivity - a Density Functional Theory Study

    DEFF Research Database (Denmark)

    Karamad, Mohammadreza

    the isolated sites that are active for CO2 reduction and surrounded by inactive elements towards both hydrogen evolution reaction (HER) and CO2 reduction to direct the selectivity towards favorable products. In the next step, using this concept we screen for suitable catalysts. Our screening includes viii both......-catalysts towards two appealing electrochemical reactions: 1)electroreduction of CO2 to hydrocarbons and alcohols, and 2) electrochemical production of hydrogen peroxide, i.e. H2O2, from its elements i.e. H2 and O2. The thesis is divided into three parts: In the first part, electro-catalytic activity of different...... site concept to tune the activity and selectivity for oxygen reduction towards H2O2 production. We screen for new catalysts that exhibit both high catalytic activity and selectivity by constructing activity volcano plots for ORR towards water and H2O2. Moreover, the stability of these catalysts...

  10. Executive Functions and Motor Ability Contribute to Children's Participation in Daily Activities

    Science.gov (United States)

    Rosenberg, Limor; Jacobi, Shani; Bart, Orit

    2017-01-01

    Executive functions are crucial for efficient daily functioning. However, the contribution of executive functions to the participation in daily life activities of children, have been inadequately studied. The study aimed to examine the unique contribution of executive functions, beyond motor ability, to the diversity and independence of children's…

  11. Associations between daily physical activity and executive functioning in primary school-aged children

    NARCIS (Netherlands)

    van der Niet, Anneke G.; Smith, Joanne; Scherder, Erik J. A.; Oosterlaan, Jaap; Hartman, Esther; Visscher, Chris

    2015-01-01

    Objectives: While there is some evidence that aerobic fitness is positively associated with executive functioning in children, evidence for a relation between children's daily physical activity and their executive functioning is limited. The objective was to examine associations between objectively

  12. Functional modulation of AMP-activated protein kinase by cereblon.

    Science.gov (United States)

    Lee, Kwang Min; Jo, Sooyeon; Kim, Hyunyoung; Lee, Jongwon; Park, Chul-Seung

    2011-03-01

    Mutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation. The ectopic expression of CRBN reduces phosphorylation of AMPK α1 and, thus, inhibits the enzyme in a nutrient-independent manner. Moreover, AMPK α1 can be potently activated by suppressing endogenous CRBN using CRBN-specific small hairpin RNAs. Thus, CRBN may act as a negative modulator of the AMPK signaling pathway in vivo.

  13. Prioritising Marketing Activities in Different Types of Marketing Functions

    DEFF Research Database (Denmark)

    Martensen, Anne; Mouritsen, Jan

    2017-01-01

    are not equally important to practise. Moreover, all roles are not equally important to all marketing functions, but depend on the marketing function's unique starting point. Since MFs differ, relevant investments in marketing roles also differ, making it beneficial to prioritise them. However, management......Marketing functions (MFs) differ in how they practise marketing roles. The purpose of this article is to differentiate between MFs that practice marketing roles in a particular manner and then study how these different types of MFs differ with regard to the marketing roles’ effect on business...... performance (BP) and top management's respect. An empirical survey identifies four types of MFs: (1) the broad spectrum; (2) the hesitant; (3) the traditional and (4) the market-creating. Findings show that for each of the four types, the effect of investing in a particular role varies: all roles...

  14. Supercritical CO2 extraction of functional compounds from Spirulina and their biological activity

    National Research Council Canada - National Science Library

    K.G, Mallikarjun Gouda; K, Udaya Sankar; R, Sarada; G.A, Ravishankar

    2015-01-01

    Supercritical carbon dioxide (SCCO2) extraction and fractionation of Spirulina platensis was carried out to obtain functional compounds with antioxidant, antimicrobial and enzyme inhibitory activities...

  15. FUNCTIONALITY OF STUDENTS WITH PHYSICAL DEFICIENCY IN WRITING AND COMPUTER USE ACTIVITIES

    National Research Council Canada - National Science Library

    Fernanda Matrigani Mercado Gutierres de Queiroz; Lígia Maria Presumido Braccialli

    2017-01-01

    ... in: Describe the functionality of students with physical disabilities, in the Multifunctional Resource Rooms, for activities of writing and computer use, according to the perception of the teachers...

  16. A bidirectional relationship between physical activity and executive function in older adults.

    Science.gov (United States)

    Daly, Michael; McMinn, David; Allan, Julia L

    2014-01-01

    Physically active lifestyles contribute to better executive function. However, it is unclear whether high levels of executive function lead people to be more active. This study uses a large sample and multi-wave data to identify whether a reciprocal association exists between physical activity and executive function. Participants were 4555 older adults tracked across four waves of the English Longitudinal Study of Aging. In each wave executive function was assessed using a verbal fluency test and a letter cancelation task and participants reported their physical activity levels. Fixed effects regressions showed that changes in executive function corresponded with changes in physical activity. In longitudinal multilevel models low levels of physical activity led to subsequent declines in executive function. Importantly, poor executive function predicted reductions in physical activity over time. This association was found to be over 50% larger in magnitude than the contribution of physical activity to changes in executive function. This is the first study to identify evidence for a robust bidirectional link between executive function and physical activity in a large sample of older adults tracked over time.

  17. System-functional approach in enterprise''s innovation activity management

    OpenAIRE

    Olikh, L.; Maslyukivska, А.

    2012-01-01

    The article is devoted to the problems of forming management system of enterprise innovation activity. The authors pick out the enterprise's innovation subsystem main parts and generalize management functions' realization in the context of its innovation activity management.

  18. Prioritising Marketing Activities in Different Types of Marketing Functions

    DEFF Research Database (Denmark)

    Martensen, Anne; Mouritsen, Jan

    2016-01-01

    Marketing functions (MFs) differ in how they practise marketing roles. The purpose of this article is to differentiate between MFs that practice marketing roles in a particular manner and then study how these different types of MFs differ with regard to the marketing roles’ effect on business per...

  19. Functional analysis of Ficolin-3 mediated complement activation

    DEFF Research Database (Denmark)

    Hein, Estrid; Honoré, Christian; Skjoedt, Mikkel-Ole;

    2010-01-01

    The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating...

  20. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    Science.gov (United States)

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  1. A Flexible Domain-Domain Hinge Promotes an Induced-fit Dominant Mechanism for the Loading of Guide-DNA into Argonaute Protein in Thermus thermophilus

    KAUST Repository

    Zhu, Lizhe

    2016-02-24

    Argonaute proteins (Ago) are core components of the RNA Induced Silencing Complex (RISC) that load and utilize small guide nucleic acids to silence mRNAs or cleave foreign DNAs. Despite the essential role of Ago in gene regulation and defense against virus, the molecular mechanism of guide-strand loading into Ago remains unclear. We explore such a mechanism in the bacterium Thermus thermophilus Ago (TtAgo), via a computational approach combining molecular dynamics, bias-exchange metadynamics, and protein-DNA docking. We show that apo TtAgo adopts multiple closed states that are unable to accommodate guide-DNA. Conformations able to accommodate the guide are beyond the reach of thermal fluctuations from the closed states. These results suggest an induced-fit dominant mechanism for guide-strand loading in TtAgo, drastically different from the two-step mechanism for human Ago 2 (hAgo2) identified in our previous study. Such a difference between TtAgo and hAgo2 is found to mainly originate from the distinct rigidity of their L1-PAZ hinge. Further comparison among known Ago structures from various species indicates that the L1-PAZ hinge may be flexible in general for prokaryotic Agos but rigid for eukaryotic Agos. © 2016 American Chemical Society.

  2. The reduction rates of DEPC-modified mutant Thermus thermophilus Rieske proteins differ when there is a negative charge proximal to the cluster.

    Science.gov (United States)

    Karagas, Nicholas E; Jones, Christie N; Osborn, Deborah J; Dzierlenga, Anika L; Oyala, Paul; Konkle, Mary E; Whitney, Emily M; David Britt, R; Hunsicker-Wang, Laura M

    2014-10-01

    Rieske and Rieske-type proteins are electron transport proteins involved in key biological processes such as respiration, photosynthesis, and detoxification. They have a [2Fe-2S] cluster ligated by two cysteines and two histidines. A series of mutations, L135E, L135R, L135A, and Y158F, of the Rieske protein from Thermus thermophilus has been produced which probe the effects of the neighboring residues, in the second sphere, on the dynamics of cluster reduction and the reactivity of the ligating histidines. These properties were probed using titrations and modifications with diethyl pyrocarbonate (DEPC) at various pH values monitored using UV-Visible and circular dichroism spectrophotometry. These results, along with results from EPR studies, provide information on ligating histidine modification and rate of reduction of each of the mutant proteins. L135R, L135A, and Y158F react with DEPC similarly to wild type, resulting in modified protein with a reduced [2Fe-2S] cluster in 15 h under the same conditions. Thus, the negative charge slows down the rate of reduction and provides an explanation as to why negatively charged residues are rarely, if ever, found in the equivalent position of other Rieske and Rieske-type proteins.

  3. Direct electrochemistry of dinuclear Cu{sub A} fragment from cytochrome c oxidase of Thermus thermophilus at surfactant modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Rajbongshi, Jitumani [Department of Chemistry, Gauhati University, Guwahati 14 (India); Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, Maharashtra 5 (India); Das, Diganta Kumar [Department of Chemistry, Gauhati University, Guwahati 14 (India); Mazumdar, Shyamalava, E-mail: shyamal@tifr.res.i [Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, Maharashtra 5 (India)

    2010-05-01

    Cytochrome c oxidase is ubiquitous enzyme involved in the terminal step of respiratory electron transfer process. The unique binuclear copper center containing bis-dithiolato bridges form a valance delocalized [Cu{sup 1.5+}-Cu{sup 1.5+}] state of the metal center located at the subunit II of cytochrome c oxidase. This metal center acts as the electron entry site of the enzyme and accepts electrons from cytochrome c. Direct electrochemistry of this binuclear copper center containing the water soluble protein obtained by genetically truncating the membrane bound part of the subunit II from Thermus thermophilus was achieved by favorable orientation of the protein on glassy carbon electrode surface promoting efficient electron transfer in the presence of various surfactants. Very reproducible, Nernstian responses are obtained with Cu{sub A}. The redox potential and the electrochemical response were enhanced prominently in case of cationic surfactant CTAB indicating that the nature of the surfactant has a significant effect on the microenvironment of the protein-electrode interface. The results have been used to understand the mechanism of electron transfer from cytochrome c to the copper center during the enzymatic reaction.

  4. A Flexible Domain-Domain Hinge Promotes an Induced-fit Dominant Mechanism for the Loading of Guide-DNA into Argonaute Protein in Thermus thermophilus.

    Science.gov (United States)

    Zhu, Lizhe; Jiang, Hanlun; Sheong, Fu Kit; Cui, Xuefeng; Gao, Xin; Wang, Yanli; Huang, Xuhui

    2016-03-17

    Argonaute proteins (Ago) are core components of the RNA Induced Silencing Complex (RISC) that load and utilize small guide nucleic acids to silence mRNAs or cleave foreign DNAs. Despite the essential role of Ago in gene regulation and defense against virus, the molecular mechanism of guide-strand loading into Ago remains unclear. We explore such a mechanism in the bacterium Thermus thermophilus Ago (TtAgo), via a computational approach combining molecular dynamics, bias-exchange metadynamics, and protein-DNA docking. We show that apo TtAgo adopts multiple closed states that are unable to accommodate guide-DNA. Conformations able to accommodate the guide are beyond the reach of thermal fluctuations from the closed states. These results suggest an induced-fit dominant mechanism for guide-strand loading in TtAgo, drastically different from the two-step mechanism for human Ago 2 (hAgo2) identified in our previous study. Such a difference between TtAgo and hAgo2 is found to mainly originate from the distinct rigidity of their L1-PAZ hinge. Further comparison among known Ago structures from various species indicates that the L1-PAZ hinge may be flexible in general for prokaryotic Ago's but rigid for eukaryotic Ago's.

  5. Discovery and characterization of RecA protein of thermophilic bacterium Thermus thermophilus MAT72 phage Tt72 that increases specificity of a PCR-based DNA amplification.

    Science.gov (United States)

    Stefanska, Aleksandra; Kaczorowska, Anna-Karina; Plotka, Magdalena; Fridjonsson, Olafur H; Hreggvidsson, Gudmundur O; Hjorleifsdottir, Sigridur; Kristjansson, Jakob K; Dabrowski, Slawomir; Kaczorowski, Tadeusz

    2014-07-20

    The recA gene of newly discovered Thermus thermophilus MAT72 phage Tt72 (Myoviridae) was cloned and overexpressed in Escherichia coli. The 1020-bp gene codes for a 339-amino-acid polypeptide with an Mr of 38,155 which shows 38.7% positional identity to the E. coli RecA protein. When expressed in E. coli, the Tt72 recA gene did not confer the ability to complement the ultraviolet light (254nm) sensitivity of an E. coli recA mutant. Tt72 RecA protein has been purified with good yield to catalytic and electrophoretic homogeneity using a three-step chromatography procedure. Biochemical characterization indicated that the protein can pair and promote ATP-dependent strand exchange reaction resulting in formation of a heteroduplex DNA at 60°C under conditions otherwise optimal for E. coli RecA. When the Tt72 RecA protein was included in a standard PCR-based DNA amplification reaction, the specificity of the PCR assays was significantly improved by eliminating non-specific products.

  6. Functional analysis of Ficolin-3 mediated complement activation

    DEFF Research Database (Denmark)

    Hein, Estrid; Honoré, Christian; Skjoedt, Mikkel-Ole

    2010-01-01

    The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating...... on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound...... the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway....

  7. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort;

    2012-01-01

    of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII...

  8. Management with willow short rotation coppice increase the functional gene diversity and functional activity of a heavy metal polluted soil.

    Science.gov (United States)

    Xue, K; van Nostrand, J D; Vangronsveld, J; Witters, N; Janssen, J O; Kumpiene, J; Siebielec, G; Galazka, R; Giagnoni, L; Arenella, M; Zhou, J-Z; Renella, G

    2015-11-01

    We studied the microbial functional diversity, biochemical activity, heavy metals (HM) availability and soil toxicity of Cd, Pb and Zn contaminated soils, kept under grassland or short rotation coppice (SRC) to attenuate the risks associated with HM contamination and restore the soil ecological functions. Soil microbial functional diversity was analyzed by the GeoChip, a functional gene microarray containing probes for genes involved in nutrient cycling, metal resistance and stress response. Soil under SRC showed a higher abundance of microbial genes involved in C, N, P and S cycles and resistance to various HM, higher microbial biomass, respiration and enzyme activity rates, and lower HM availability than the grassland soil. The linkages between functional genes of soil microbial communities and soil chemical properties, HM availability and biochemical activity were also investigated. Soil toxicity and N, P and Pb availability were important factors in shaping the microbial functional diversity, as determined by CCA. We concluded that in HM contaminated soils the microbial functional diversity was positively influenced by SRC management through the reduction of HM availability and soil toxicity increase of nutrient cycling. The presented results can be important in predicting the long term environmental sustainability of plant-based soil remediation.

  9. Functional neuroimaging of conversion disorder: The role of ancillary activation

    Directory of Open Access Journals (Sweden)

    Matthew J. Burke, MD

    2014-01-01

    Conclusions: Sensory conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder.

  10. Functionally charged nanosize particles differentially activate BV2 microglia.

    Science.gov (United States)

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Nanosize (860-950 nm) spherical polystyrene microparticles (SPM) were coated with carboxyl (COOH-) or dimethyl amino (CH3)2-N- groups to give a net negative or p...

  11. Emergent Public Spaces: Generative Activities on Function Interpolation

    Science.gov (United States)

    Carmona, Guadalupe; Dominguez, Angeles; Krause, Gladys; Duran, Pablo

    2011-01-01

    This study highlights ways in which generative activities may be coupled with network-based technologies in the context of teacher preparation to enhance preservice teachers' cognizance of how their own experience as students provides a blueprint for the learning environments they may need to generate in their future classrooms. In this study, the…

  12. Self-Assembling Protein Nanostructures - Towards Active Functionality

    Science.gov (United States)

    2011-04-22

    to this scaffold. These active nanoscaffolds were also embedded in permeable films and grown from surfaces. In the case of organophosphorous ...quaternary structure, amyloid fibril, organophosphorous hydrolase, enzyme Juliet Gerrard University of Canterbury 20 Kirkwood Ave Ilam 8041 - REPORT... organophosphorous hydrolase, a significant increase in thermal stability was observed. Two papers were published in Biotechnology Progress and a new

  13. Selenium glutathione peroxidase activities and thyroid functions in human individuals

    Science.gov (United States)

    Bellisola, G.; Calza Contin, M.; Ceccato, D.; Cinque, G.; Francia, G.; Galassini, S.; Liu, N. Q.; Lo Cascio, C.; Moschini, G.; Sussi, P. L.

    1996-04-01

    At least two enzymes are involved in metabolism of thyroid hormones. GSHPx protects thyrocyte from high H 2O 2 levels that are required for iodination of prohormones to form T4 in thyroid cell. Type I iodothyronine 5'-deiodinase (5'-D) catalyzes the deiodination of L-thyroxin (T4) to the biologically active thyroid hormone 3,3'-5-triiodothyronine (T 3) in liver, in kidney and in thyroid tissues. Circulating thyroid hormones, plasma Se levels, GSHPx activities in platelets and in plasma were investigated in 29 human individuals with increased thyroid mass. PIXE was applied to measure Se in 1 ml of plasma because we supposed patients were in a marginal carential status for Se. Plasma Se concentrations were compared with those of normal individuals. Correlation studies between plasma Se level and both GSHPx activities were carried out as well as between platelets and plasma GSHPx activities to verify the hypothesis of a marginal Se deficiency in patients. Significance of circulating thyroid hormones levels will be discussed.

  14. XPS of nitrogen-containing functional groups on activated carbon

    NARCIS (Netherlands)

    Jansen, R.J.J.; Bekkum, van H.

    1995-01-01

    XPS is used to study the binding energy of the Cls, Nls and Ols photoelectrons of surface groups on several nitrogen-containing activated carbons. Specific binding energies are assigned to amide (399.9 eV). lactam and imidc (399.7 eV). pyridine (398.7 eV), pyrrole (400.7 eV), alkylamine. secondary a

  15. Functional and catalytic active sites prediction and docking analysis ...

    African Journals Online (AJOL)

    Bioinformatics

    2015-07-01

    Jul 1, 2015 ... industrially important azo dyes such as the molecular weight, molecular ... et al., 2010). The software possesses structure-based method to predict active sites in proteins based on a Difference of Gaussian (DoG) approach ...

  16. Etk/Bmx activation modulates barrier function in epithelial cells.

    Science.gov (United States)

    Hamm-Alvarez, S F; Chang, A; Wang, Y; Jerdeva, G; Lin, H H; Kim, K J; Ann, D K

    2001-06-01

    Etk/Bmx is a member of the Tec family of cytoplasmic non-receptor tyrosine kinases known to express in epithelial cells. We demonstrate herein that Etk activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypoxic (1% O(2)) exposure, the TER and equivalent active ion transport rate (I(eq)) were reduced to <5% of the normoxia control in Pa-4 cells, whereas both TER and I(eq) were maintained at comparable and 60% levels, respectively, relative to their normoxic controls in cells with Etk activation. Moreover, Pa-4 cells exhibited an abundant actin stress fiber network with a diffuse distribution of beta-catenin at the cell periphery. By contrast, Etk-activated cells displayed a redistribution of actin to an exclusively peripheral network, with a discrete band of beta-catenin also concentrated at the cell periphery, and an altered occludin distribution profile. On the basis of these findings, we propose that Etk may be a novel regulator of epithelial junctions during physiological and pathophysiological conditions.

  17. Folding of Aggregated Proteins to Functionally Active Form

    Science.gov (United States)

    2006-06-01

    in Cn5 were reformed with a total protein yield of 87% and 100% recovery of activity [34]. Artificial chaperone-assisted refolding This method...typically formed using a mixture of reduced/oxidizedCurrent Opinion in Biotechnology 2006, 17:367–372 370 Protein technologiesglutathione, and glycerol

  18. EFFECT OF ELECTROACUPUNCTURE ON GASTRIC FUNCTIONAL ACTIVITY IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    王景杰; 黄裕新; 王键; 邱建勇

    2001-01-01

    Subjective: To investigate the mechanisms of electroacupuncture (EA) in regulating the gastric activity in rats. Methods: 64 SD rats were randomly divided into group A and B, both of which were further divided into EA subgroup a and b (n = 8×2), sciatotomy + EA subgroup a and b ( n = 8×2), vagotomy + EA subgroup a and b (n = 8×2) and control subgroup a and b (n = 8×2). Rats of the 4 subgroups of group A were used for observing changes of c-fos expression, while those of the 4 subgroups of group B used for analyzing changes of electrogastrogram (EGG). Left Zusanli (ST 36) was punctured and stimulated for 30 min using a 6805-A EA Therapeutic Apparatus by setting the parameters as intermittent waves, frequency of 50 Hz and strength of 20 V. Changes of c-fos expression in the nucleus of tractus solitarius (NTS) and dorsal motor nucleus of vagus (DMV) of the medullary bulb were detected by using immunohistochemical method and the effect of EA on EGG using electrophysiological method in 846-mixture anesthetized rats. Results: After EA of Zusanli(ST 36), the expression of c-fos in NTS and DMV changed significantly and marked changes were observed in the gastric electro-activity. Conclusion: Electro-acupuncture can regulate gastric activity by activating neurons of NTS and DMV.

  19. Twist1 activity thresholds define multiple functions in limb development.

    Science.gov (United States)

    Krawchuk, Dayana; Weiner, Shoshana J; Chen, You-Tzung; Lu, Benson C; Costantini, Frank; Behringer, Richard R; Laufer, Ed

    2010-11-01

    The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1(-/-) embryos die at midgestation. However, studies on early limb buds found that Twist1(-/-) mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity.

  20. Spatial Correlation Function of the Chandra Selected Active Galactic Nuclei

    Science.gov (United States)

    Yang, Y.; Mushotzky, R. F.; Barger, A. J.; Cowie, L. L.

    2006-01-01

    We present the spatial correlation function analysis of non-stellar X-ray point sources in the Chandra Large Area Synoptic X-ray Survey of Lockman Hole Northwest (CLASXS). Our 9 ACIS-I fields cover a contiguous solid angle of 0.4 deg(exp 2) and reach a depth of 3 x 10(exp -15) erg/square cm/s in the 2-8 keV band. We supplement our analysis with data from the Chandra Deep Field North (CDFN). The addition of this field allows better probe of the correlation function at small scales. A total of 233 and 252 sources with spectroscopic information are used in the study of the CLASXS and CDFN fields respectively. We calculate both redshift-space and projected correlation functions in co-moving coordinates, averaged over the redshift range of 0.1 tau(sub 0 = 8.1(sup +1.2 sub -2.2) Mpc, and gamma = 2.1 +/- 0.5 for the CLASXS field, and tau(sub 0) = 5.8(sup +.1.0 sub -1.5) Mpc, gamma = 1.38(sup +0.12 sub -0.14 for the CDFN field. By comparing the real- and redshift-space correlation functions in the combined CLASXS and CDFN samples, we are able to estimate the redshift distortion parameter Beta = 0.4 +/- 0.2 at an effective redshift z = 0.94. We compare the correlation functions for hard and soft spectra sources in the CLASXS field and find no significant difference between the two groups. We have also found that the correlation between X-ray luminosity and clustering amplitude is weak, which, however, is fully consistent with the expectation using the simplest relations between X-ray luminosity, black hole mass, and dark halo mass. We study the evolution of the AGN clustering by dividing the samples into 4 redshift bins over 0.1 Mpcestimate the evolution of the bias, and find that the bias increases rapidly with redshift (b(z = 0.45) = 0.95 +/- 0.15 and b(z = 2.07) = 3.03 +/- 0.83): The typical mass of the dark matter halo derived from the bias estimates show little change with redshift. The average halo mass is found to be log (M(sub halo)/M(sun))approximates 12.1. Subject

  1. A two-host fosmid system for functional screening of (meta)genomic libraries from extreme thermophiles.

    Science.gov (United States)

    Angelov, Angel; Mientus, Markus; Liebl, Susanne; Liebl, Wolfgang

    2009-05-01

    A new cloning system is described, which allows the construction of large-insert fosmid libraries in Escherichia coli and the transfer of the recombinant libraries to the extreme thermophile Thermus thermophilus via natural transformation. Libraries are established in the thermophilic host by site-specific chromosomal insertion of the recombinant fosmids via single crossover or double crossover recombination at the T. thermophilus pyr locus. Comparative screening of a fosmid library constructed from genomic DNA from the thermophilic spirochaete, Spirochaeta thermophila, for clones expressing thermoactive xylanase activity revealed that 50% of the fosmids that conferred xylanase activity upon the corresponding T. thermophilus transformants did not give rise to xylanase-positive E. coli clones, indicating that significantly more S. thermophila genes are functionally expressed in T. thermophilus than in E. coli. The novel T. thermophilus host/vector system may be of value for the construction and functional screening of recombinant DNA libraries from individual thermophilic or extremely thermophilic organisms as well as from complex metagenomes isolated from thermophilic microbial communities.

  2. Active plasma resonance spectroscopy: A functional analytic description

    OpenAIRE

    Lapke, Martin; Oberrath, Jens; Mussenbrock, Thomas; Brinkmann, Ralf Peter

    2012-01-01

    The term "Active Plasma Resonance Spectroscopy" refers to a class of diagnostic methods which employ the ability of plasmas to resonate on or near the plasma frequency. The basic idea dates back to the early days of discharge physics: An signal in the GHz range is coupled to the plasma via an electrical probe; the spectral response is recorded, and then evaluated with a mathematical model to obtain information on the electron density and other plasma parameters. In recent years, the concept h...

  3. Contributions to Design of Actuators functioning with Nitinol Active Springs

    Directory of Open Access Journals (Sweden)

    Daniel Amariei

    2015-07-01

    Full Text Available The paper presents the research results achieved in order to perform a comparison regarding the influence of natural and forced cooling process applied to the Nitinol active springs inside a linear motion actuator. SMAs offer attractive potentials such as reversible strains of several percent, generation of high recovery stresses and high power / weight ratios. The actuator behavior was simulated first with SolidWorks and experimentally tested for results validation.

  4. Structure, functions, and activities of a research support informatics section.

    Science.gov (United States)

    Murray, Michael D; Smith, Faye E; Fox, Joanne; Teal, Evgenia Y; Kesterson, Joseph G; Stiffler, Troy A; Ambuehl, Roberta J; Wang, Jane; Dibble, Maria; Benge, Dennis O; Betley, Leonard J; Tierney, William M; McDonald, Clement J

    2003-01-01

    The authors describe a research group that supports the needs of investigators seeking data from an electronic medical record system. Since its creation in 1972, the Regenstrief Medical Records System has captured and stored more than 350 million discrete coded observations on two million patients. This repository has become a central data source for prospective and retrospective research. It is accessed by six data analysts--working closely with the institutional review board--who provide investigators with timely and accurate data while protecting patient and provider privacy and confidentiality. From January 1, 1999, to July 31, 2002, data analysts tracked their activities involving 47,559 hours of work predominantly for physicians (54%). While data retrieval (36%) and analysis (25%) were primary activities, data analysts also actively collaborated with researchers. Primary objectives of data provided to investigators were to address disease-specific (35.4%) and drug-related (12.2%) questions, support guideline implementation (13.1%), and probe various aspects of clinical epidemiology (5.7%). Outcomes of these endeavors included 117 grants (including 300,000 US dollars per year salary support for data analysts) and 139 papers in peer-reviewed journals by investigators who rated the support provided by data analysts as extremely valuable.

  5. Functionalized Activated Carbon Derived from Biomass for Photocatalysis Applications Perspective

    Directory of Open Access Journals (Sweden)

    Samira Bagheri

    2015-01-01

    Full Text Available This review highlighted the developments of safe, effective, economic, and environmental friendly catalytic technologies to transform lignocellulosic biomass into the activated carbon (AC. In the photocatalysis applications, this AC can further be used as a support material. The limits of AC productions raised by energy assumption and product selectivity have been uplifted to develop sustainable carbon of the synthesis process, where catalytic conversion is accounted. The catalytic treatment corresponding to mild condition provided a bulk, mesoporous, and nanostructure AC materials. These characteristics of AC materials are necessary for the low energy and efficient photocatalytic system. Due to the excellent oxidizing characteristics, cheapness, and long-term stability, semiconductor materials have been used immensely in photocatalytic reactors. However, in practical, such conductors lead to problems with the separation steps and loss of photocatalytic activity. Therefore, proper attention has been given to develop supported semiconductor catalysts and certain matrixes of carbon materials such as carbon nanotubes, carbon microspheres, carbon nanofibers, carbon black, and activated carbons have been recently considered and reported. AC has been reported as a potential support in photocatalytic systems because it improves the transfer rate of the interface charge and lowers the recombination rate of holes and electrons.

  6. Nanoscale friction as a function of activation energies

    Science.gov (United States)

    Chong, W. W. F.; Rahnejat, H.

    2015-12-01

    Understanding the scale-dependence of friction is increasingly viewed as a critical quest. With progressively thinner films, mixed and boundary regimes of lubrication have become commonplace. Therefore, at the micro-scale a greater need for mitigating friction is desired in order to improve operational efficiency of many machines and mechanisms. Furthermore, there is a growing tendency to use low friction hard wear-resistant advanced coatings to guard against wear. In parallel, there has been much attention paid to lubricant rheology and formulation. However, only in recent times there has been an emerging view of lubricant-surface combination as a system. In this perspective it is essential to relate the observed and measured friction at component level to the underlying interactions in micro/nano-scales. This is the approach in this paper. Observed phenomenon at micro-scale are related back to the activation energies of lubricant-surface system, providing in particular results for surface modified Ni-SiC coated specimen in combination with formulated lubricants, the combination of which represent the lubricant-surface system of choice in cylinders of high performance race engine. The nano-scale conjunction of an AFM tip with lubricated surface-engineered specimen, subjected to various conjunctional loading and sliding kinematics is investigated. It is shown that the measured frictional characteristics can be adequately described in terms of activation energies in line with the Eyring’s thermal activation model for cases of fairly smooth asperity tip contact conjunctions.

  7. Variability in measuring (instrumental) activities of daily living functioning and functional decline in hospitalized older medical patients: a systematic review.

    Science.gov (United States)

    Buurman, Bianca M; van Munster, Barbara C; Korevaar, Johanna C; de Haan, Rob J; de Rooij, Sophia E

    2011-06-01

    To study instruments used and definitions applied in order to measure (instrumental) activities of daily living (I [ADL]) functioning and functional decline in hospitalized older medical patients. We systematically searched Medline, Embase, and the Cochrane Database of Systematic Reviews from 1990 to January 2010. Articles were included if they (1) focused on acute hospitalization for medical illness in older patients; (2) described the instrument used to measure functioning; and (3) outlined the clinical definition of functional decline. Two reviewers independently extracted data. In total, 28 studies were included in this review. Five different instruments were used to measure functioning: the Katz ADL index, the IADL scale of Lawton and Brody, the Barthel index, Functional Independence Measure, and Care Needs Assessment. Item content and scoring between and within the instruments varied widely. The minimal amount for decline, as defined by the authors, referred to a decrease in functioning between 2.4% and 20.0%. This review shows there is a large variability in measuring (I)ADL functioning of older hospitalized patients and a large range of clinical definitions of functional decline. These conceptual and clinimetric barriers hamper the interpretation and comparison of functional outcome data of epidemiological and clinical studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Variability in measuring (instrumental) activities of daily living functioning and functional decline in hospitalized older medical patients: a systematic review.

    OpenAIRE

    Buurman, B. M.; van Munster, B.C.; Korevaar, J. C.; de Haan, R. J.; de Rooij, S. E.

    2011-01-01

    OBJECTIVE: To study instruments used and definitions applied in order to measure (instrumental) activities of daily living (I [ADL]) functioning and functional decline in hospitalized older medical patients. STUDY DESIGN: We systematically searched Medline, Embase, and the Cochrane Database of Systematic Reviews from 1990 to January 2010. Articles were included if they (1) focused on acute hospitalization for medical illness in older patients; (2) described the instrument used to measure func...

  9. Application of a novel functional gene microarray to probe the functional ecology of ammonia oxidation in nitrifying activated sludge.

    Directory of Open Access Journals (Sweden)

    Michael D Short

    Full Text Available We report on the first study trialling a newly-developed, functional gene microarray (FGA for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively. FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples - an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems.

  10. Physical activity, motor function, and white matter hyperintensity burden in healthy older adults.

    Science.gov (United States)

    Fleischman, Debra A; Yang, Jingyun; Arfanakis, Konstantinos; Arvanitakis, Zoe; Leurgans, Sue E; Turner, Arlener D; Barnes, Lisa L; Bennett, David A; Buchman, Aron S

    2015-03-31

    To test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia. Total daily activity (exercise and nonexercise physical activity) was measured for up to 11 days with actigraphy (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia participating in the Rush Memory and Aging Project. Eleven motor performances were summarized into a previously described global motor score. WMH volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with total WMH volume as the predictor and global motor score as the outcome. Terms for total daily physical activity and its interaction with WMH volume were then added to the model. Higher WMH burden was associated with lower motor function (p = 0.006), and total daily activity was positively associated with motor function (p = 0.002). Total daily activity modified the association between WMH and motor function (p = 0.007). WMH burden was not associated with motor function in persons with high activity (90th percentile). By contrast, higher WMH burden remained associated with lower motor function in persons with average (50th percentile; estimate = -0.304, slope = -0.133) and low (10th percentile; estimate = -1.793, slope = -0.241) activity. Higher levels of physical activity may reduce the effect of WMH burden on motor function in healthy older adults. © 2015 American Academy of Neurology.

  11. SysML model of exoplanet archive functionality and activities

    Science.gov (United States)

    Ramirez, Solange

    2016-08-01

    The NASA Exoplanet Archive is an online service that serves data and information on exoplanets and their host stars to help astronomical research related to search for and characterization of extra-solar planetary systems. In order to provide the most up to date data sets to the users, the exoplanet archive performs weekly updates that include additions into the database and updates to the services as needed. These weekly updates are complex due to interfaces within the archive. I will be presenting a SysML model that helps us perform these update activities in a weekly basis.

  12. Twist1 activity thresholds define multiple functions in limb development

    OpenAIRE

    Krawchuk, Dayana; Weiner, Shoshana J; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional...

  13. Determination of Activation Functions in A Feedforward Neural Network by using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Oğuz ÜSTÜN

    2009-03-01

    Full Text Available In this study, activation functions of all layers of the multilayered feedforward neural network have been determined by using genetic algorithm. The main criteria that show the efficiency of the neural network is to approximate to the desired output with the same number nodes and connection weights. One of the important parameter to determine this performance is to choose a proper activation function. In the classical neural network designing, a network is designed by choosing one of the generally known activation function. In the presented study, a table has been generated for the activation functions. The ideal activation function for each node has been chosen from this table by using the genetic algorithm. Two dimensional regression problem clusters has been used to compare the performance of the classical static neural network and the genetic algorithm based neural network. Test results reveal that the proposed method has a high level approximation capacity.

  14. Functional magnetic resonance imaging evaluation of visual cortex activation in patients with anterior visual pathway lesions

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Song; Guohua Wang; Tong Zhang; Lei Feng; Peng An; Yueli Zhu

    2012-01-01

    The aim of this study was to examine the secondary visual cortex functional disorder in patients with glaucoma and large pituitary adenoma by functional magnetic resonance imaging, and to determine the correlation between visual field defect and primary visual cortex activation. Results showed that single eye stimulation resulted in bilateral visual cortex activation in patients with glaucoma or large pituitary adenoma. Compared with the normal control group, the extent and intensity of visual cortex activation was decreased after left and right eye stimulation, and functional magnetic resonance imaging revealed a correlation between visual field defects and visual cortex activation in patients with glaucoma and large pituitary adenoma. These functional magnetic resonance imaging data suggest that anterior optic pathway lesions can cause secondary functional disorder of the visual cortex, and that visual defects are correlated with visual cortex activation.

  15. Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies

    DEFF Research Database (Denmark)

    Løkkegaard, Annemette; Herz, Damian M; Haagensen, Brian N;

    2016-01-01

    . Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia-related alterations in task-related activity....... Hum Brain Mapp 37:547-557, 2016. © 2015 Wiley Periodicals, Inc....

  16. Feelings of well being in elderly people: relationship to physical activity and physical function.

    Science.gov (United States)

    Garatachea, Nuria; Molinero, Olga; Martínez-García, Raquel; Jiménez-Jiménez, Rodrigo; González-Gallego, Javier; Márquez, Sara

    2009-01-01

    The aim of the research was to investigate in a sample of Spanish elderly whether measures of physical activity and physical function are related to feelings of well being, and whether level of dependence is a moderator in the relation of well being, physical activity and physical function. The sample was a cohort of 151 elderly people (89 women and 62 men, aged 60-98 years) from the North of Spain. Participants completed surveys including demographic characteristics, and measures of physical activity (Yale Physical Activity Survey, YPAS), instrumental activities of daily living (Barthel Index, BI) and well being (Psychological Well Being Scale, from Spanish: Escala de Bienestar Psicológico=EBP). Components of the physical function were measured by the Senior Fitness Test (SFT). Upper and lower body strength, dynamic balance, aerobic endurance, self-reported weekly energy expenditure and physical activity total time were significantly correlated with both Material and Subjective well being. All components of physical function were significantly impaired in dependent subjects when compared to independent individuals of the same sex and physical activity category. Significant differences were also observed in Subjective well being among less active dependent or independent individuals. In conclusion, physical function and physical activity are related to feelings of well being, and results emphasize the positive functional and psychological effects of physical activity in dependent subjects.

  17. Functionally diverse biotin-dependent enzymes with oxaloacetate decarboxylase activity.

    Science.gov (United States)

    Lietzan, Adam D; St Maurice, Martin

    2014-02-15

    Biotin-dependent enzymes catalyze carboxylation, decarboxylation and transcarboxylation reactions that participate in the primary metabolism of a wide range of organisms. In all cases, the overall reaction proceeds via two half reactions that take place in physically distinct active sites. In the first half-reaction, a carboxyl group is transferred to the 1-N' of a covalently tethered biotin cofactor. The tethered carboxybiotin intermediate subsequently translocates to a second active site where the carboxyl group is either transferred to an acceptor substrate or, in some bacteria and archaea, is decarboxylated to biotin and CO2 in order to power the export of sodium ions from the cytoplasm. A homologous carboxyltransferase domain is found in three enzymes that catalyze diverse overall reactions: carbon fixation by pyruvate carboxylase, decarboxylation and sodium transport by the biotin-dependent oxaloacetate decarboxylase complex, and transcarboxylation by transcarboxylase from Propionibacterium shermanii. Over the past several years, structural data have emerged which have greatly advanced the mechanistic description of these enzymes. This review assembles a uniform description of the carboxyltransferase domain structure and catalytic mechanism from recent studies of pyruvate carboxylase, oxaloacetate decarboxylase and transcarboxylase, three enzymes that utilize an analogous carboxyltransferase domain to catalyze the biotin-dependent decarboxylation of oxaloacetate.

  18. Graves' disease: thyroid function and immunologic activity

    Energy Technology Data Exchange (ETDEWEB)

    Gossage, A.A.R.; Crawley, J.C.W.; Copping, S.; Hinge, D.; Himsworth, R.L.

    1982-11-01

    Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of (/sup 9/-9..mu..Tc)pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity - TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p<0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

  19. Graves' disease: thyroid function and immunologic activity

    Energy Technology Data Exchange (ETDEWEB)

    Gossage, A.A.; Crawley, J.C.; Copping, S.; Hinge, D.; Himsworth, R.L.

    1982-11-01

    Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of (/sup 99m/Tc)pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

  20. Executive Functions in Learning Processes: Do They Benefit from Physical Activity?

    Science.gov (United States)

    Barenberg, Jonathan; Berse, Timo; Dutke, Stephan

    2011-01-01

    As executive functions play an essential role in learning processes, approaches capable of enhancing executive functioning are of particular interest to educational psychology. Recently, the hypothesis has been advanced that executive functioning may benefit from changes in neurobiological processes induced by physical activity. The present…

  1. Executive Functions in Learning Processes: Do They Benefit from Physical Activity?

    Science.gov (United States)

    Barenberg, Jonathan; Berse, Timo; Dutke, Stephan

    2011-01-01

    As executive functions play an essential role in learning processes, approaches capable of enhancing executive functioning are of particular interest to educational psychology. Recently, the hypothesis has been advanced that executive functioning may benefit from changes in neurobiological processes induced by physical activity. The present…

  2. Physical activity and obesity mediate the association between childhood motor function and adolescents’ academic achievement

    OpenAIRE

    Kantomaa, Marko T.; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2012-01-01

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people’s cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, pre...

  3. Altered activity and functional connectivity of superior temporal gyri in anxiety disorders: A functional magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xiaohu; Xi, Qian; Wang, Peijun; Li, Chunbo [Tong Ji Hospital of Tong Ji University, Shanghai (China); He, Hongjian [Bio-X lab, Dept. of Physics, Zhe Jiang University, Hangzhou (China)

    2014-08-15

    The prior functional MRI studies have demonstrated significantly abnormal activity in the bilateral superior temporal gyrus (STG) of anxiety patients. The purpose of the current investigation was to determine whether the abnormal activity in these regions was related to a loss of functional connectivity between these regions. Ten healthy controls and 10 anxiety patients underwent noninvasive fMRI while actively listening to emotionally neutral words alternated by silence (Task 1) or threat-related words (Task 2). The participants were instructed to silently make a judgment of each word's valence (i.e., unpleasant, pleasant, or neutral). A coherence analysis was applied to the functional MRI data to examine the functional connectivity between the left and the right STG, which was selected as the primary region of interest on the basis of our prior results. The data demonstrated that the anxiety patients exhibited significantly increased activation in the bilateral STG than the normal controls. The functional connectivity analysis indicated that the patient group showed significantly decreased degree of connectivity between the bilateral STG during processing Task 2 compared to Task 1 (t = 2.588, p = 0.029). In addition, a significantly decreased connectivity was also observed in the patient group compared to the control group during processing Task 2 (t = 2.810, p = 0.012). Anxiety patients may exhibit increased activity of the STG but decreased functional connectivity between the left and right STG, which may reflect the underlying neural abnormality of anxiety disorder, and this will provide new insights into this disease.

  4. Sympathetic activation and baroreflex function during intradialytic hypertensive episodes.

    Directory of Open Access Journals (Sweden)

    Dvora Rubinger

    Full Text Available BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI and systolic blood pressure (SBP were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS in the low (LF and high (HF frequency ranges were assessed using the complex demodulation technique (CDM. Intradialytic hypertensive episodes were associated with an increased (n = 45 or decreased (n = 17 heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes

  5. The Complex Association between Religious Activities and Functional Limitations in Older Adults

    Science.gov (United States)

    Hybels, Celia F.; Blazer, Dan G.; George, Linda K.; Koenig, Harold G.

    2012-01-01

    Purpose of the Study: To examine the longitudinal associations between 3 dimensions of religious involvement--religious attendance, use of religious media, and private religious activities--and 3 domains of functional status--limitations in basic activities of daily living (ADL), instrumental activities of daily living (IADL), and mobility in…

  6. Activation and Function of iNKT and MAIT Cells.

    Science.gov (United States)

    Chandra, Shilpi; Kronenberg, Mitchell

    2015-01-01

    Over the last two decades, it has been established that peptides are not the only antigens recognized by T lymphocytes. Here, we review information on two T lymphocyte populations that recognize nonpeptide antigens: invariant natural killer T cells (iNKT cells), which respond to glycolipids, and mucosal associated invariant T cells (MAIT cells), which recognize microbial metabolites. These two populations have a number of striking properties that distinguish them from the majority of T cells. First, their cognate antigens are presented by nonclassical class I antigen-presenting molecules; CD1d for iNKT cells and MR1 for MAIT cells. Second, these T lymphocyte populations have a highly restricted diversity of their T cell antigen receptor α chains. Third, these cells respond rapidly to antigen or cytokine stimulation by producing copious amounts of cytokines, such as IFNγ, which normally are only made by highly differentiated effector T lymphocytes. Because of their response characteristics, iNKT and MAIT cells act at the interface of innate and adaptive immunity, participating in both types of responses. In this review, we will compare these two subsets of innate-like T cells, with an emphasis on the various ways that lead to their activation and their participation in antimicrobial responses.

  7. How do case managers spend time on their functions and activities?

    Science.gov (United States)

    You, Emily Chuanmei; Dunt, David; Doyle, Colleen

    2016-04-02

    Case management has been a widely accepted approach to practice in various care settings. This study aimed to explore how community aged care case managers allocated their time to case management functions, how frequently they performed specific case management activities, and what factors influenced the frequency of their activities. The study involved 154 survey participants, or 17.1% of the target case managers in the State of Victoria, Australia. Key information collected included participants' socio-demographic characteristics, proportions of time allocated to six core case management functions, and frequency ratings of 41 specific activities within seven case management functions. Ordinal regression analyses were performed to determine significant factors associated with participants' frequency ratings of their activities. Participants allocated the largest proportion of time to care coordination (22.0%), and the smallest proportion of time to outcome evaluation (8.0%). Over 70% of the participants assigned high frequency ratings to 31 of the 41 case management activities. The remaining ten activities, including all four outcome evaluation activities, three needs assessment activities, one care planning activity, one care coordination activity, and one general functions-related activity were less commonly performed very frequently. The regression analyses indicated that some case manager and client factors were significantly associated with frequency ratings of nine of the ten activities aforementioned. The two main findings of the regression analyses were: First, emphasising achieving more case management goals was significantly associated with higher frequency of three outcome evaluation activities; second, longer work experience was significantly associated with higher frequency of one care coordination activity and one outcome evaluation activity. The frequent performance of most case management activities and relative absence of factors influencing their

  8. The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

    Directory of Open Access Journals (Sweden)

    Laura eChaddock-Heyman

    2013-03-01

    Full Text Available This study used functional magnetic resonance imaging (fMRI to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ minutes of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control.

  9. Physical activity as an indicator of predictive functional disability in elderly.

    Science.gov (United States)

    Virtuoso Júnior, Jair Sindra; Tribess, Sheilla; Paulo, Thais Reis Silva De; Martins, Cristiane Alves; Romo-Perez, Vicente

    2012-01-01

    To analyze the time spent on physical activity in female and male individuals as a predictor of the absence of functional disability in older adults, a cross-sectional study was conducted with 624 individuals. Receiver Operating Characteristic curves (ROC) were constructed and compared to areas of physical activity by gender and the absence of functional disability. We identified cutoffs of physical activity (minutes / week) to predict the absence of functional disability (CI 95%). It was found that there is a higher area under the ROC curve for the time spent on physical activities in females. It was observed that 280 minutes / week (women) or 410 minutes / week (men) were the best cutoff points for predicting the absence of functional disability. Time spent on physical activity practices can serve as an important indicator to sort priority groups for certain interventions.

  10. Social Activity and Cognitive Functioning Over Time: A Coordinated Analysis of Four Longitudinal Studies

    Directory of Open Access Journals (Sweden)

    Cassandra L. Brown

    2012-01-01

    Full Text Available Social activity is typically viewed as part of an engaged lifestyle that may help mitigate the deleterious effects of advanced age on cognitive function. As such, social activity has been examined in relation to cognitive abilities later in life. However, longitudinal evidence for this hypothesis thus far remains inconclusive. The current study sought to clarify the relationship between social activity and cognitive function over time using a coordinated data analysis approach across four longitudinal studies. A series of multilevel growth models with social activity included as a covariate is presented. Four domains of cognitive function were assessed: reasoning, memory, fluency, and semantic knowledge. Results suggest that baseline social activity is related to some, but not all, cognitive functions. Baseline social activity levels failed to predict rate of decline in most cognitive abilities. Changes in social activity were not consistently associated with cognitive functioning. Our findings do not provide consistent evidence that changes in social activity correspond to immediate benefits in cognitive functioning, except perhaps for verbal fluency.

  11. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    Directory of Open Access Journals (Sweden)

    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  12. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

    Science.gov (United States)

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-07-02

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  13. A neuron model with trainable activation function (TAF) and its MFNN supervised learning

    Institute of Scientific and Technical Information of China (English)

    吴佑寿; 赵明生

    2001-01-01

    This paper addresses a new kind of neuron model, which has trainable activation function (TAF) in addition to only trainable weights in the conventional M-P model. The final neuron activation function can be derived from a primitive neuron activation function by training. The BP like learning algorithm has been presented for MFNN constructed by neurons of TAF model. Several simulation examples are given to show the network capacity and performance advantages of the new MFNN in comparison with that of conventional sigmoid MFNN.

  14. The effect of physical activity and motivation on function in ankylosing spondylitis: a cohort study.

    Science.gov (United States)

    Brophy, Sinead; Cooksey, Roxanne; Davies, Helen; Dennis, Michael S; Zhou, Shang-Ming; Siebert, Stefan

    2013-06-01

    Exercise is reported to improve function for people with ankylosing spondylitis (AS) but it is not clear if this effect is causal or if patients with milder disease find it easier to exercise. This study examines the effect of exercise and motivation to exercise on function, while controlling for disease severity. Participants who were members of an existing AS cohort were asked about physical activity, motivation to exercise, function, and disease severity. Path analysis on STATA was used to examine the correlation between factors associated with function at time of exercise and with function after 3 months of follow-up. The response rate to the questionnaire was 88% (326/371). Improvement in function was greatest for people with higher physical activity levels and those who were more motivated to exercise-this was especially the case for patients with the most severe disease activity. The effect of motivation to exercise not only had a direct effect on function, but also an indirect effect of improving activity levels thereby improving both current and future function. People with high intrinsic motivation (driven by pleasure) had the greatest benefit to activity and function. Exercise does improve function, especially for those with severe disease. In addition, motivation alone improves function as much as exercising itself. Therefore, interventions targeting motivation to exercise would have as much effect on improving function as interventions offering exercise opportunities. In addition, any intervention that both improves motivation and increases opportunities to exercise would have a 2-fold influence on function. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Interspecies activity correlations reveal functional correspondence between monkey and human brain areas.

    Science.gov (United States)

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A; Vanduffel, Wim

    2012-02-05

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. For cases in which functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assessed similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by temporal correlation. Using natural vision data, we revealed regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models.

  16. Functional analysis of the Tat trans activator of human immunodeficiency virus type 2.

    OpenAIRE

    Fenrick, R; Malim, M H; Hauber, J; Le, S.Y.; Maizel, J; Cullen, B R

    1989-01-01

    The trans-activator (Tat) proteins of the related but distinct type 1 and type 2 human immunodeficiency viruses (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation of this observation, suggested by computer analysis of potential RNA secondary structures within the viral trans-activation response (TAR) elements, is that HIV-2 Tat requires the presentation of two viral RNA stem-loop sequences for full activity whereas HIV-1 Tat is maximally active upon presenta...

  17. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    Science.gov (United States)

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

  18. Identifying active functionalities on few-layered graphene catalysts for oxidative dehydrogenation of isobutane.

    Science.gov (United States)

    Dathar, Gopi Krishna Phani; Tsai, Yu-Tung; Gierszal, Kamil; Xu, Ye; Liang, Chengdu; Rondinone, Adam J; Overbury, Steven H; Schwartz, Viviane

    2014-02-01

    The general consensus in the studies of nanostructured carbon catalysts for oxidative dehydrogenation (ODH) of alkanes to olefins is that the oxygen functionalities generated during synthesis and reaction are responsible for the catalytic activity of these nanostructured carbons. Identification of the highly active oxygen functionalities would enable engineering of nanocarbons for ODH of alkanes. Few-layered graphenes were used as model catalysts in experiments to synthesize reduced graphene oxide samples with varying oxygen concentrations, to characterize oxygen functionalities, and to measure the activation energies for ODH of isobutane. Periodic density functional theory calculations were performed on graphene nanoribbon models with a variety of oxygen functionalities at the edges to calculate their thermal stability and to model reaction mechanisms for ODH of isobutane. Comparing measured and calculated thermal stability and activation energies leads to the conclusion that dicarbonyls at the zigzag edges and quinones at armchair edges are appropriately balanced for high activity, relative to other model functionalities considered herein. In the ODH of isobutane, both dehydrogenation and regeneration of catalytic sites are relevant at the dicarbonyls, whereas regeneration is facile compared with dehydrogenation at quinones. The catalytic mechanism involves weakly adsorbed isobutane reducing functional oxygen and leaving as isobutene, and O2 in the feed, weakly adsorbed on the hydrogenated functionality, reacting with that hydrogen and regenerating the catalytic sites.

  19. Mutations in the catalytic loop HRD motif alter the activity and function of Drosophila Src64.

    Directory of Open Access Journals (Sweden)

    Taylor C Strong

    Full Text Available The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele.

  20. Evaluation of the functional activity of activated sludge from local waste water treatment plant in the Arctic region

    Directory of Open Access Journals (Sweden)

    Il'inskiy V. V.

    2017-03-01

    Full Text Available The paper considers characteristics of the activated sludge in the local wastewater treatment plant (LWTP and its ability to purify fully domestic sewage water in the Far North. Biochemical process of destruction of organic pollutants is influenced by a microbial complex functioning in aeration tanks. Taking into account climatic conditions of the region where the organic matter degradation processes are slowed, and lack of control over the operation, efficiency and occupational safety of LWTPs, it seems to be important to study the physiological characteristics of the bacteria used in bioremediation, and their ability to maximize the purifying domestic sewage in the Arctic region. Undue intervention in the biosphere systems leads to disruption of the balance of internal and external ecosystems communications. The goal of research is studying structural determination and functioning of activated sludge bacteriocenosis of LWTP TOPAS-5 (GK "Topol-ECO" in certain physical and chemical conditions of the habitat, and establishing completeness of cleaning process in this treatment plant. The paper considers the structure (quantitative and qualitative composition and function of LWTP activated sludge bacteriocenosis functioning in the Arctic region. The estimation of the activated sludge of full waste water treatment process of the LWTP has been given. The research's results have allowed to identify and determine the bacterial count of physiological groups of microorganisms purified domestic sewage; to isolate from activated sludge the bioflocculant-producing microorganisms' on the experimental medium; to evaluate efficiency of LWTP work in the Arctic region

  1. Physical activity in the elderly is associated with improved executive function and processing speed

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Verdelho, Ana; Madureira, Sofia;

    2015-01-01

    OBJECTIVES: Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes...... or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: β: 0.39, 95......-up scores, executive function remained significant (β: 0.11, 95% CI: 0-0.22, p = 0.04). CONCLUSION: Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present...

  2. Measuring everyday functional competence using the Rasch assessment of everyday activity limitations (REAL) item bank

    NARCIS (Netherlands)

    Oude Voshaar, Martijn A.H.; Ten Klooster, Peter M.; Vonkeman, Harald E.; van de Laar, Mart A.F.J.

    2017-01-01

    Objective: Traditional patient-reported physical function instruments often poorly differentiate patients with mild-to-moderate disability. We describe the development and psychometric evaluation of a generic item bank for measuring everyday activity limitations in outpatient populations. Study

  3. Children with profound intellectual and multiple disabilities : the effects of functional movement activities

    NARCIS (Netherlands)

    van der Putten, A; Vlaskamp, C; Reynders, K; Nakken, H

    2005-01-01

    Objective: To determine the effect of functional movement activities within the MOVE ( Mobility Opportunities Via Education) curriculum on the independence of children with profound intellectual and multiple disabilities. Subjects: Forty-four children with profound intellectual and multiple disabili

  4. Differences in physical functioning between relatively active and passive patients with Chronic Fatigue Syndrome.

    NARCIS (Netherlands)

    Vos-Vromans, D.C.; Huijnen, I.P.; Koke, A.J.; Seelen, H.A.; Knottnerus, J.A.; Smeets, R.J.P.

    2013-01-01

    OBJECTIVE: According to the Cognitive behavioral therapy (CBT) protocol for patients with Chronic Fatigue Syndrome (CFS), therapists are advised to categorize patients in relatively active and passive patients. However, evidence to support the differences in physical functioning between these subgro

  5. A new kind of neuron model with a tunable activation function and its applications

    Institute of Scientific and Technical Information of China (English)

    吴佑寿; 赵明生; 丁晓青

    1997-01-01

    A new neuron model with a tunable activation function, denoted by the TAF model, and its application are addressed. The activation function as well as the connection weights of the neuron model can be adjusted in the training process The two-spiral problem was used as an example to show how to deduce the adjustable activation function required, and how to construct and train the network by the use of the a priori knowledge of the problem. Due to the incorporation of constraints known a priori into the activation function, many novel aspects are revealed, such as small network size, fast learning and good performances. It is believed that the introduction of the new neuron model will pave a new way in ANN studies.

  6. Second-Order Perturbation Theory for Generalized Active Space Self-Consistent-Field Wave Functions.

    Science.gov (United States)

    Ma, Dongxia; Li Manni, Giovanni; Olsen, Jeppe; Gagliardi, Laura

    2016-07-12

    A multireference second-order perturbation theory approach based on the generalized active space self-consistent-field (GASSCF) wave function is presented. Compared with the complete active space (CAS) and restricted active space (RAS) wave functions, GAS wave functions are more flexible and can employ larger active spaces and/or different truncations of the configuration interaction expansion. With GASSCF, one can explore chemical systems that are not affordable with either CASSCF or RASSCF. Perturbation theory to second order on top of GAS wave functions (GASPT2) has been implemented to recover the remaining electron correlation. The method has been benchmarked by computing the chromium dimer ground-state potential energy curve. These calculations show that GASPT2 gives results similar to CASPT2 even with a configuration interaction expansion much smaller than the corresponding CAS expansion.

  7. Chronic regulation of colonic epithelial secretory function by activation of G protein-coupled receptors.

    LENUS (Irish Health Repository)

    Toumi, F

    2011-02-01

    Enteric neurotransmitters that act at G protein-coupled receptors (GPCRs) are well known to acutely promote epithelial Cl(-) and fluid secretion. Here we examined if acute GPCR activation might have more long-term consequences for epithelial secretory function.

  8. Multistability and Instability of Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.

    Science.gov (United States)

    Nie, Xiaobing; Zheng, Wei Xing

    2015-11-01

    In this paper, we discuss the coexistence and dynamical behaviors of multiple equilibrium points for recurrent neural networks with a class of discontinuous nonmonotonic piecewise linear activation functions. It is proved that under some conditions, such n -neuron neural networks can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable, based on the contraction mapping theorem and the theory of strict diagonal dominance matrix. The investigation shows that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibrium points and more locally stable equilibrium points than the ones with continuous Mexican-hat-type activation function or discontinuous two-level activation functions. An illustrative example with computer simulations is presented to verify the theoretical analysis.

  9. ORGANIZATION AS A MANAGEMENT FUNCTION IN THE ACTIVITY OF TRADE COMPANIES

    Directory of Open Access Journals (Sweden)

    Bretan Florin-Ioan

    2013-01-01

    Full Text Available Organizational system is a set of methods, procedures and techniques used in the management of organization function of the production process. It has as main functions methodological and logistical support creation of the functional act. Generally, systems, methods and management functions trigger the assembly of the developed activities by the managed system in order to establish and achieve the aims of commercial enterprises. In most cases, the management is done by exercising a range of functions including the organization of enterprises in Maramures County, Romania.

  10. Organization as a management function in the activity of trade companies

    Directory of Open Access Journals (Sweden)

    Bretan Florin-Ioan

    2013-01-01

    Full Text Available Organizational system is a set of methods, procedures and techniques used in the management of organization function of the production process. It has as main functions methodological and logistical support creation of the functional act. Generally, systems, methods and management functions trigger the assembly of the developed activities by the managed system in order to establish and achieve the aims of commercial enterprises. In most cases, the management is done by exercising a range of functions including the organization of enterprises in Maramures County, Romania.

  11. Muscle activity during functional coordination training: implications for strength gain and rehabilitation

    DEFF Research Database (Denmark)

    Jørgensen, Marie Birk; Andersen, Lars Louis; Kirk, Niels

    2010-01-01

    The purpose of this study was to evaluate if different types, body positions, and levels of progression of functional coordination exercises can provide sufficiently high levels of muscle activity to improve strength of the neck, shoulder, and trunk muscles. Nine untrained women were familiarized...... training can be performed with a muscle activity sufficient for strength gain. Functional coordination training may therefore be a good choice for prevention or rehabilitation of musculoskeletal pain or injury in the neck, shoulder, or trunk muscles....

  12. [14C]deoxyglucose labelling of functional activity in the cephalopod central nervous system.

    Science.gov (United States)

    Novicki, A; Messenger, J B; Budelmann, B U; Terrell, M L; Kadekaro, M

    1992-07-22

    For the first time, the [14C]deoxyglucose radioautographic technique has been successfully used to map physiological activity in cephalopod brains. In unilaterally blinded octopus and cuttlefish, the optic lobe of the deprived side showed a decreased uptake of the labelled tracer. This suggests that the uptake is related to functional activity. The potential of the [14C]deoxyglucose technique as a powerful tool in studying the functional organization of cephalopod brains is discussed.

  13. Experiences of Habitual Physical Activity in Maintaining Roles and Functioning among Older Adults: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Hadeel Halaweh

    2016-01-01

    Full Text Available Physically active older adults have reduced risk of functional restrictions and role limitations. Several aspects may interrelate and influence habitual physical activity (PA. However, older adults’ own perspectives towards their PA need to be addressed. The aim of this study was to explore the experiences of habitual physical activity in maintaining roles and functioning among older adult Palestinians ≥60 years. Data were collected through in-depth interviews based on a narrative approach. Seventeen participants were recruited (aged 64–84 years. Data were analyzed using a narrative interpretative method. Findings. Three central narratives were identified, “keep moving, stay healthy,” “social connectedness, a motive to stay active,” and “adapting strategies to age-related changes.” Conclusion. Habitual physical activity was perceived as an important factor to maintain functioning and to preserve active roles in older adults. Walking was the most prominent pattern of physical activity and it was viewed as a vital tool to maintain functioning among the older adults. Social connectedness was considered as a contributing factor to the status of staying active. To adapt the process of age-related changes in a context to stay active, the participants have used different adapting strategies, including protective strategy, awareness of own capabilities, and modifying or adopting new roles.

  14. Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin.

    Science.gov (United States)

    Friis, Stine; Madsen, Daniel H; Bugge, Thomas H

    2016-02-01

    The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth. Prostasin is found in two forms in the epidermis: a one-chain zymogen and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin. Interestingly, these mutant mice displayed normal interfollicular epidermal development and postnatal survival, but had defects in whisker and pelage hair formation. These findings identify two distinct in vivo functions of epidermal prostasin: a function in the interfollicular epidermis, not requiring activation site cleavage, that can be mediated by the zymogen-locked version of prostasin and a proteolysis-dependent function of activated prostasin in hair follicles, dependent on zymogen conversion by matriptase.

  15. Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg

    DEFF Research Database (Denmark)

    Mortensen, S P; Nyberg, Michael; Winding, K;

    2012-01-01

    and exercise hyperaemia in the leg and whether ATP signalling is altered by ageing and physical activity. Leg haemodynamics, interstitial [ATP] and P2Y(2) receptor content was determined in eight young (23 ± 1 years), eight lifelong sedentary elderly (66 ± 2 years) and eight lifelong active elderly (62 ± 2...... not alter the vasodilator response to ATP infusion in any of the three groups. Plasma [noradrenaline] increased more during tyramine infusion in both elderly groups compared to young (P physically active lifestyle can maintain an intact functional sympatholysis during exercise......Ageing is associated with an impaired ability to modulate sympathetic vasoconstrictor activity (functional sympatholysis) and a reduced exercise hyperaemia. The purpose of this study was to investigate whether a physically active lifestyle can offset the impaired functional sympatholysis...

  16. Activation of brain areas following ankle dorsiflexion versus plantar flexion Functional magnetic resonance imaging verification

    Institute of Scientific and Technical Information of China (English)

    Tianyu Jiang; Weiping Wu; Xinglin Wang; Changshui Weng; Qiuhua Wang; Yanmei Guo

    2012-01-01

    Changes in activated areas of the brain during ankle active dorsiflexion and ankle active plantar flexion were observed in six healthy subjects using functional magnetic resonance imaging.Excited areas of ankle active dorsiflexion involved the bilateral primary motor area and the primary somatosensory area, as well as the bilateral supplementary sensory area, the primary visual area, the right second visual area, and the vermis of cerebellum.Excited areas of ankle active plantar flexion included the ipsilateral supplementary motor area, the limbic system, and the contralateral corpus striatum.Fine movements of the cerebral cortex control the function of the ankle dorsiflexion to a larger extent than ankle plate flexion, and the function of ankle plate flexion is more controlled by the subcortical area.

  17. A novel pattern mining approach for identifying cognitive activity in EEG based functional brain networks.

    Science.gov (United States)

    Thilaga, M; Vijayalakshmi, R; Nadarajan, R; Nandagopal, D

    2016-06-01

    The complex nature of neuronal interactions of the human brain has posed many challenges to the research community. To explore the underlying mechanisms of neuronal activity of cohesive brain regions during different cognitive activities, many innovative mathematical and computational models are required. This paper presents a novel Common Functional Pattern Mining approach to demonstrate the similar patterns of interactions due to common behavior of certain brain regions. The electrode sites of EEG-based functional brain network are modeled as a set of transactions and node-based complex network measures as itemsets. These itemsets are transformed into a graph data structure called Functional Pattern Graph. By mining this Functional Pattern Graph, the common functional patterns due to specific brain functioning can be identified. The empirical analyses show the efficiency of the proposed approach in identifying the extent to which the electrode sites (transactions) are similar during various cognitive load states.

  18. Physical activity and obesity mediate the association between childhood motor function and adolescents’ academic achievement

    Science.gov (United States)

    Kantomaa, Marko T.; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-01

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people’s cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents’ academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents’ academic achievement via physical inactivity (B = –0.023, 95% confidence interval = –0.031, –0.015) and obesity (B = –0.025, 95% confidence interval = –0.039, –0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents’ academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement. PMID:23277558

  19. Sedentary behavior and physical activity are independently related to functional fitness in older adults.

    Science.gov (United States)

    Santos, Diana A; Silva, Analiza M; Baptista, Fátima; Santos, Rute; Vale, Susana; Mota, Jorge; Sardinha, Luís B

    2012-12-01

    The last decades of life have been traditionally viewed as a time of inevitable disease and frailty. Sedentary living and physical activity may influence capacity to perform activities that are needed to maintain physical independence in daily living. A total of 117 males and 195 females, aged 65-103years, were assessed for physical activity and sedentary time with accelerometers and for functional fitness with the Senior Fitness Test battery. Based on the individual scores for each fitness item, a Z-score was created. Associations between functional fitness with sedentary time and moderate-to-vigorous physical activity (MVPA) were analyzed. A negative association was found between the composite Z-score for functional fitness and the sedentary time, even adjusting for MVPA and other confounders. On the other hand, MVPA was positively associated with the composite Z-score for functional fitness, independently of the sedentary time. In conclusion elderly who spend more time in physical activity or less time in sedentary behaviors exhibit improved functional fitness and other confounders. The results reinforce the importance of promoting both the reduction of sedentary behaviors and the increase of MVPA in this age group, as it may interfere at older ages in order to preserve functional fitness and performance of daily functioning tasks.

  20. Physical activity and obesity mediate the association between childhood motor function and adolescents' academic achievement.

    Science.gov (United States)

    Kantomaa, Marko T; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-29

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.

  1. Alterations in Brain Activation During Cognitive Empathy Are Related to Social Functioning in Schizophrenia

    Science.gov (United States)

    Smith, Matthew J.; Schroeder, Matthew P.; Abram, Samantha V.; Goldman, Morris B.; Parrish, Todd B.; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L.; Csernansky, John G.; Breiter, Hans C.

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response. PMID:24583906

  2. Dynamical Behaviors of Multiple Equilibria in Competitive Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.

    Science.gov (United States)

    Nie, Xiaobing; Zheng, Wei Xing

    2016-03-01

    This paper addresses the problem of coexistence and dynamical behaviors of multiple equilibria for competitive neural networks. First, a general class of discontinuous nonmonotonic piecewise linear activation functions is introduced for competitive neural networks. Then based on the fixed point theorem and theory of strict diagonal dominance matrix, it is shown that under some conditions, such n -neuron competitive neural networks can have 5(n) equilibria, among which 3(n) equilibria are locally stable and the others are unstable. More importantly, it is revealed that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibria and locally stable equilibria than the ones with other activation functions, such as the continuous Mexican-hat-type activation function and discontinuous two-level activation function. Furthermore, the 3(n) locally stable equilibria given in this paper are located in not only saturated regions, but also unsaturated regions, which is different from the existing results on multistability of neural networks with multiple level activation functions. A simulation example is provided to illustrate and validate the theoretical findings.

  3. The Geriatric Hand: Correlation of Hand-Muscle Function and Activity Restriction in Elderly

    Science.gov (United States)

    Incel, Nurgul Arinci; Sezgin, Melek; As, Ismet; Cimen, Ozlem Bolgen; Sahin, Gunsah

    2009-01-01

    On the basis of the importance of hand manipulation in activities of daily living (ADL), deterioration of hand function because of various factors reduces quality and independence of life of the geriatric population. The aim of this study was to identify age-induced changes in manual function and to quantify the correlations between hand-muscle…

  4. Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

    Science.gov (United States)

    Sidtis, John J.

    2007-01-01

    Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

  5. Functional level, physical activity and wellbeing in nursing home residents in three Nordic countries

    DEFF Research Database (Denmark)

    Grönstedt, Helena; Hellström, Karin; Bergland, Astrid

    2011-01-01

    The main aim of this study was to describe physical and cognitive function and wellbeing among nursing home residents in three Nordic countries. A second aim was to compare groups of differing ages, levels of dependency in daily life activities (ADL), degree of fall-related self-efficacy, wellbeing...... and cognitive function....

  6. Outcome after 40 years with rheumatoid arthritis: a prospective study of function, disease activity and mortality

    NARCIS (Netherlands)

    Minaur, Nicola J.; Jacoby, Richard K.; Cosh, John A.; Taylor, Gordon; Rasker, Hans J.

    2004-01-01

    In an inception cohort of 100 patients with rheumatoid arthritis (RA) we studied course and outcome after 40 years, regarding function, disease activity, cause and age of death, and prognostic factors. Function, joint count, erythrocyte sedimentation rate (ESR), hemoglobin (Hb), rheumatoid factor

  7. Physical activity and executive functions in the elderly with mild cognitive impairment

    NARCIS (Netherlands)

    Scherder, EJA; Van Paasschen, J; Deijen, JB; Van der Knokke, S; Orlebeke, JFK; Burgers, [No Value; Devriese, PP; Swaab, DF; Sergeant, JA

    2005-01-01

    The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. S

  8. Physical activity and executive functions in the elderly with mild cognitive impairment.

    NARCIS (Netherlands)

    Scherder, E.J.A.; Paasschen, J. van; Deijen, J.-B.; Knokke, S. van der; Orlebeke, J.F.K.; Burgers, I.; DeVriesse, P.-P.; Swaab, D.F.; Sergeant, J.A.

    2005-01-01

    The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. S

  9. Functional near-infrared spectroscopy (fNIRS) of brain function during active balancing using a video game system.

    Science.gov (United States)

    Karim, Helmet; Schmidt, Benjamin; Dart, Dwight; Beluk, Nancy; Huppert, Theodore

    2012-03-01

    Functional near-infrared spectroscopy (fNIRS) is a portable, non-invasive, brain imaging technology that uses low levels of non-ionizing light to record changes in cerebral blood flow in the brain through optical sensors placed on the surface of the scalp. These signals are recorded via flexible fiber optic cables, which allow neuroimaging experiments to be conducted on participants while performing tasks such as standing or walking. FNIRS has the potential to provide new insights into the evolution of brain activation during ambulatory motor learning tasks and standing tasks to probe balance and vestibular function. In this study, a 32 channel fNIRS system was used to record blood flow changes in the frontal, motor, sensory, and temporal cortices during active balancing associated with playing a video game simulating downhill skiing (Nintendo Wii™; Wii-fit™). Using fNIRS, we found activation of superior temporal gyrus, which was modulated by the difficulty of the balance task. This region had been previously implicated in vestibular function from other animal and human studies. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. The effect of physical activity and motivation on function in ankylosing spondylitis: a cohort study

    OpenAIRE

    Brophy, Sinead; Cooksey, Roxanne; Davies, Helen; Michael S Dennis; Zhou, Shang-Ming; Siebert, Stefan

    2013-01-01

    OBJECTIVES: Exercise is reported to improve function for people with ankylosing spondylitis (AS) but it is not clear if this effect is causal or if patients with milder disease find it easier to exercise. This study examines the effect of exercise and motivation to exercise on function, while controlling for disease severity.\\ud \\ud METHODS: Participants who were members of an existing AS cohort were asked about physical activity, motivation to exercise, function, and disease severity. Path a...

  11. Transcriptional coactivator CIITA, a functional homolog of TAF1, has kinase activity.

    Science.gov (United States)

    Soe, Katherine C; Devaiah, Ballachanda N; Singer, Dinah S

    2013-11-01

    The Major Histocompatibility Complex (MHC) class II transactivator (CIITA) mediates activated immune responses and its deficiency results in the Type II Bare Lymphocyte Syndrome. CIITA is a transcriptional co-activator that regulates γ-interferon-activated transcription of MHC class I and class II genes. It is also a functional homolog of TAF1, a component of the general transcription factor complex TFIID. TAF1 and CIITA both possess intrinsic acetyltransferase (AT) activity that is required for transcription initiation. In response to induction by γ-interferon, CIITA and it's AT activity bypass the requirement for TAF1 AT activity. TAF1 also has kinase activity that is essential for its function. However, no similar activity has been identified for CIITA thus far. Here we report that CIITA, like TAF1, is a serine-threonine kinase. Its substrate specificity parallels, but does not duplicate, that of TAF1 in phosphorylating the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF and histone H2B. Like TAF1, CIITA autophosphorylates, affecting its interaction with TAF7. Additionally, CIITA phosphorylates histone H2B at Ser36, a target of TAF1 that is required for transcription during cell cycle progression and stress response. However, unlike TAF1, CIITA also phosphorylates all the other histones. The identification of this novel kinase activity of CIITA further clarifies its role as a functional homolog of TAF1 which may operate during stress and γ-IFN activated MHC gene transcription.

  12. Functional Specificity of the Visual Word Form Area: General Activation for Words and Symbols but Specific Network Activation for Words

    Science.gov (United States)

    Reinke, Karen; Fernandes, Myra; Schwindt, Graeme; O'Craven, Kathleen; Grady, Cheryl L.

    2008-01-01

    The functional specificity of the brain region known as the Visual Word Form Area (VWFA) was examined using fMRI. We explored whether this area serves a general role in processing symbolic stimuli, rather than being selective for the processing of words. Brain activity was measured during a visual 1-back task to English words, meaningful symbols…

  13. Surface binding sites in carbohydrate active enzymes: An emerging picture of structural and functional diversity

    DEFF Research Database (Denmark)

    Svensson, Birte; Cockburn, Darrell

    2013-01-01

    Carbohydrate active enzymes, particularly those that are active on polysaccharides, are often found associated with carbohydrate binding modules (CBMs), which can play several roles in supporting enzyme function, such as localizing the enzyme to the substrate. However, the presence of CBMs...

  14. Relation of Physical Activity to Memory Functioning in Older Adults: The Memory Workout Program.

    Science.gov (United States)

    Rebok, George W.; Plude, Dana J.

    2001-01-01

    The Memory Workout, a CD-ROM program designed to help older adults increase changes in physical and cognitive activity influencing memory, was tested with 24 subjects. Results revealed a significant relationship between exercise time, exercise efficacy, and cognitive function, as well as interest in improving memory and physical activity.…

  15. IMPORTANCE OF ACTIVATED CARBON'S OXYGEN SURFACE FUNCTIONAL GROUPS ON ELEMENTAL MERCURY ADSORPTION

    Science.gov (United States)

    The effect of varying physical and chemical properties of activated carbons on adsorption of elemental mercury [Hg(0)] was studied by treating two activated carbons to modify their surface functional groups and pore structures. Heat treatment (1200 K) in nitrogen (N2), air oxidat...

  16. Targeting complement activation in brain-dead donors improves renal function after transplantation

    NARCIS (Netherlands)

    Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G.; Ploeg, Rutger J.; Yard, Benito A.; Seelen, Marc A.

    2011-01-01

    Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function afte

  17. Participation in Daily Activities of Young Adults with High Functioning Autism Spectrum Disorder

    Science.gov (United States)

    McCollum, Mary; LaVesser, Patti; Berg, Christine

    2016-01-01

    Young adults with an autism spectrum disorder (ASD) struggle to assume adult roles. This research assessed the feasibility of using the Adolescent and Young Adult Activity Card Sort (AYA-ACS) with emerging adults with high functioning ASD. Two phases were utilized during this research: (1) comparing the activity participation reported by emerging…

  18. Activities of daily living, instrumental activities for daily living and predictors of functional capacity of older men in Jamaica

    Directory of Open Access Journals (Sweden)

    Paul Andrew Bourne

    2009-09-01

    Full Text Available Background: An extensive search of the literature found no studies that have examined functional capacity [Activities of Daily Living (ADL and Instrumental Activities for Daily Living (I ADL] of Jamaican older men as well as factors that determine their functional capacity. Aims: The current study examines 1 ADL, 2 (I ADL, 3 self-reported health status, 4 functional capacity, and 5 factors that determine functional capacity of older men. Methods and Method: Stratified multistage probability sampling technique was used to draw a sample of 2,000 55+ year men. A132-item questionnaire was used to collect the data. Descriptive statistics provide background information on the sample, cross tabulations were used to examine non-metric variables and logistic regression provides a model of predictors of functional capacity. Result: Fifty-five percent of sample indicated good current health status. Four percent was mostly satisfied with life; 21.7% had moderate dependence; 77.1% had high dependence (i.e. independence; 1.2% had low dependence; 21.9% were ages 75 years and older; 35.6% were ages 65 to 74 years and 42.6% reported ages 55 to 64 years. Functional capacity can be determined by church attendance (β=0.245; 95% CI: 0.264, 1.291; social support (β=0.129; 95% CI: 0.129, 0.258, area of residence (β=-0.060; 95% CI: -0.427, -0.061 and lastly by age of respondents. Conclusion: Ageing in explains deterioration in their (I ADL, suggesting the challenges of ageing men’s independence. More rural men were rarely satisfied with life; but more of them had a greater functional capacity than urban men. Depression was found to negatively relate to functional capacity, and church attendees had a greater functional status than non-attendees

  19. EMG analysis of peroneal and tibialis anterior muscle activity prior to foot contact during functional activities.

    Science.gov (United States)

    McLoda, T A; Hansen, A J; Birrer, D A

    2004-06-01

    The purpose of this investigation was to determine the pre-activity of the tibialis anterior (TA), peroneus longus (PL), and peroneus brevis (PB) prior to foot contact during three conditions. Twenty-six subjects (age 22 +/- 2 yrs; 15 male, 11 female) with no lower extremity injuries reported for data collection. Data were collected from each subject's dominant leg using surface electromyography (EMG). EMG electrodes were applied over the test muscles using a standard protocol. A heel-toe strike transducer was affixed to the bottom of the subject's shoe. The subject completed two randomized trials of walking on a treadmill (5.6 kph), jogging on a treadmill (9.3 kph) and drop landing from a 38 cm box. Isometric reference positions (IRPs) were recorded for the TA, PL, and PB. Muscle data were normalized to IRPs and the average processed EMG for the 200 ms prior to heel strike during walking and jogging and prior to toe strike when dropping from the box was used for analysis. A one-way repeated measures MANOVA was used to detect differences in pre-activity of the muscles between the three conditions. Univariate tests were used to determine differences for each muscle and Tukey's was applied post hoc to determine individual effect differences. The MANOVA revealed significant differences among the three conditions (F2.50 = 10.770; P < .0005). Average TA activity was significantly higher during jogging (Tukey's; P < .0005). Significant differences existed between each condition for the TA. Average PL and PB activity was significantly higher when drop landing (Tukey's; P < .0005). There was no significant difference between walking and jogging for the PL and PB. The amount of muscle pre-activity occurring before heel or toe strike provides useful information for the examination of reaction times to unexpected inversion during dynamic activities.

  20. Psychopathological and Functional Correlates of Behavioral Activation and Avoidance in Schizophrenia

    OpenAIRE

    Depp, Colin A; Cardenas, Veronica; Harris, Sara; Vahia, Ipsit V.; Thomas L. Patterson; Mausbach, Brent T.

    2011-01-01

    Behavioral activation and avoidance are well studied in depression, yet the relationship of these constructs to symptoms, cognitive ability and functioning in schizophrenia is poorly understood. In a sample of 73 middle-aged and older outpatients with schizophrenia (mean age=50.3, sd=6.3), we examined the relationship of the Activation and Avoidance subscales of the Behavioral Activation for Depression Scale with measures of psychopathology (Positive and Negative Symptoms, Depression), global...

  1. Psychometric Evaluation of the Physical Activity Enjoyment Scale in Adults with Functional Limitations.

    Science.gov (United States)

    Murrock, Carolyn J; Bekhet, Abir; Zauszniewski, Jaclene A

    2016-01-01

    Enjoyment is an important construct for understanding physical activity participation, and it has not been examined in adults with functional limitations. This secondary analysis reported the reliability and validity of the Physical Activity Enjoyment Scale (PACES) in a convenience sample of 40 adults with functional limitations. The participants completed the PACES, Center for Epidemiological Studies Depression Scale (CES-D), and the Late Life Function and Disability Instrument (LLFDI) prior to beginning a 12-week feasibility dance intervention study. Results indicated reliability as Cronbach's alpha was .95 and mean inter-item correlation was .52. To further support reliability, homogeneity of the instrument was evaluated using item-to-total scale correlations. Homogeneity was supported as all items had corrected item-to-total correlations greater than .30. For validity, the PACES was significantly related to only the Physical Function component of the LLFDI (r = .38, p = .02), but not the CES-D. Exploratory factor analysis revealed a 3-factor structure that accounted for 73.76% of the variance. This feasibility intervention dance study represented the first attempt to examine the psychometric properties of the PACES in adults with functional limitations. The findings demonstrate support for the scale's reliability and validity among adults with functional limitations. Results are informative as further psychometric testing of the PACES is recommended using randomized clinical trials with larger sample sizes. Enjoyment for physical activity is an important construct for understanding physical activity participation in adults with functional limitations.

  2. An application of multilayer neural network on hepatitis disease diagnosis using approximations of sigmoid activation function

    Directory of Open Access Journals (Sweden)

    Onursal Çetin

    2015-06-01

    Full Text Available Objective: Implementation of multilayer neural network (MLNN with sigmoid activation function for the diagnosis of hepatitis disease. Methods: Artificial neural networks (ANNs are efficient tools currently in common use for medical diagnosis. In hardware based architectures activation functions play an important role in ANN behavior. Sigmoid function is the most frequently used activation function because of its smooth response. Thus, sigmoid function and its close approximations were implemented as activation function. The dataset is taken from the UCI machine learning database. Results: For the diagnosis of hepatitis disease, MLNN structure was implemented and Levenberg Morquardt (LM algorithm was used for learning. Our method of classifying hepatitis disease produced an accuracy of 91.9% to 93.8% via 10 fold cross validation. Conclusion: When compared to previous work that diagnosed hepatitis disease using artificial neural networks and the identical data set, our results are promising in order to reduce the size and cost of neural network based hardware. Thus, hardware based diagnosis systems can be developed effectively by using approximations of sigmoid function.

  3. Halogenated and isosteric cytisine derivatives with increased affinity and functional activity at nicotinic acetylcholine receptors.

    Science.gov (United States)

    Fitch, Richard W; Kaneko, Yumika; Klaperski, Paul; Daly, John W; Seitz, Gunther; Gündisch, Daniela

    2005-02-15

    A series of pyridone ring-modified derivatives of (7R,9S)-(-)-cytisine were evaluated for affinity and functional activity at neuromuscular alpha1beta1gammadelta, ganglionic alpha3beta4, and central neuronal alpha4beta2 subtypes of nicotinic receptors. Halogenation at the 3-position improved affinity and functional activity, while substitution at the 5-position led to modest decreases in both, and disubstitution led to near abolition of functional activities and could be correlated with the electron-withdrawing ability of the halogen. Subtype selectivities of the halogenated derivatives were altered relative to cytisine in a substitution-dependent manner. Caulophylline methiodide was less potent than cytisine, but retained significant activity. Thiocytisine was relatively weak in potency and efficacy, but was significantly selective for the alpha4beta2 subtype.

  4. Temporal lobe functional activity and connectivity in young adult APOE e4 carriers

    Science.gov (United States)

    Dennis, Nancy A.; Browndyke, Jeffrey N.; Stokes, Jared; Need, Anna; Burke, James R.; Welsh-Bohmer, Kathleen A.; Cabeza, Roberto

    2009-01-01

    Background To determine if the APOE e4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTL) during successful memory encoding in young adults. Methods Twenty-four healthy young adults, twelve carriers and twelve non-carriers of the APOE e4 allele, were scanned in a subsequent memory paradigm, using event-related functional magnetic resonance imaging (fMRI). The neuroanatomical correlates of successful encoding were measured as greater neural activity for subsequently remembered versus forgotten task items, or in short, encoding success activity (ESA). Group differences in ESA within the MTL, as well as whole brain functional connectivity with the MTL, were assessed. Results In the absence of demographic or performance differences, APOE e4 allele carriers exhibited greater bilateral MTL activity relative to the non-carriers to accomplish the same encoding task. Additionally, while e4 carriers demonstrated greater functional connectivity of ESA-related MTL activity with the posterior cingulate (PCC) and other peri-limbic regions, overall connectivity reductions were found across anterior and posterior cortices. Conclusions These results suggest that the APOE e4 allele may influence not only functional activations within the MTL, but functional connectivity of the MTL to other regions implicated in memory encoding. Enhanced functional connectivity of the MTL with the PCC in young adult e4 carriers suggests that APOE may be expressed early in brain regions known to be involved in Alzheimer's disease long before late-onset dementia is a practical risk or consideration. It is also possible that these functional connectivity differences reflect pleiotropic effects of APOE during early development. PMID:19744893

  5. Application of neural networks with orthogonal activation functions in control of dynamical systems

    Science.gov (United States)

    Nikolić, Saša S.; Antić, Dragan S.; Milojković, Marko T.; Milovanović, Miroslav B.; Perić, Staniša Lj.; Mitić, Darko B.

    2016-04-01

    In this article, we present a new method for the synthesis of almost and quasi-orthogonal polynomials of arbitrary order. Filters designed on the bases of these functions are generators of generalised quasi-orthogonal signals for which we derived and presented necessary mathematical background. Based on theoretical results, we designed and practically implemented generalised first-order (k = 1) quasi-orthogonal filter and proved its quasi-orthogonality via performed experiments. Designed filters can be applied in many scientific areas. In this article, generated functions were successfully implemented in Nonlinear Auto Regressive eXogenous (NARX) neural network as activation functions. One practical application of the designed orthogonal neural network is demonstrated through the example of control of the complex technical non-linear system - laboratory magnetic levitation system. Obtained results were compared with neural networks with standard activation functions and orthogonal functions of trigonometric shape. The proposed network demonstrated superiority over existing solutions in the sense of system performances.

  6. Prospective study of physical activity and physical function in early old age.

    Science.gov (United States)

    Hillsdon, Melvyn M; Brunner, Eric J; Guralnik, Jack M; Marmot, Michael G

    2005-04-01

    In the elderly, higher levels of physical function have consistently been associated with higher levels of physical activity. In this study, we test the hypothesis that physical activity earlier in the life course preserves high physical function over an extended period of time, before the onset of major age-related declines in physical function. A cohort study with an average of 8.8 years of follow-up (1991-1993 to 2001). Logistic regression analyses were conducted adjusting for long-standing illness, baseline physical function, smoking, body mass index, and employment grade. Participants were 6398 London-based civil servants aged 39 to 63 years at baseline, 90% of whom were working. The main outcome measure was physical function measured by the Short Form (SF-36) General Health Survey. Relatively fit and healthy, mainly working, middle-aged men and women who were physically active at recommended levels, were more likely to report high physical function at follow-up, compared to their sedentary counterparts (odds ratio 1.63, 95% confidence interval 1.32-2.00). The association between initial level of physical activity and high physical function at follow-up remained after adjustment for baseline level of physical function and the presence of long-standing illness. Participation in a physically active lifestyle during mid-life appears to be critical to the maintenance of high physical function in those who are fit and well enough to work and do or do not report any long-standing illness.

  7. Mass Functions of the Active Black Holes in Distant Quasars from the Sloan Digital Sky Survey Data Release 3

    DEFF Research Database (Denmark)

    Vestergaard, Marianne; Fan, X.; Tremonti, C. A.

    2007-01-01

    We present the mass functions of actively accreting supermassive black holes over the redshift range 0.3......We present the mass functions of actively accreting supermassive black holes over the redshift range 0.3...

  8. Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.

    Directory of Open Access Journals (Sweden)

    Basavaraju G Sanganahalli

    Full Text Available Mitochondrial Ca(2+ uptake, central to neural metabolism and function, is diminished in aging whereas enhanced after acute/sub-acute traumatic brain injury. To develop relevant translational models for these neuropathologies, we determined the impact of perturbed mitochondrial Ca(2+ uptake capacities on intrinsic brain activity using clinically relevant markers. From a multi-compartment estimate of probable baseline Ca(2+ ranges in the brain, we hypothesized that reduced or enhanced mitochondrial Ca(2+ uptake capacity would decrease or increase spontaneous neuronal activity respectively. As resting state fMRI-BOLD fluctuations and stimulus-evoked BOLD responses have similar physiological origins [1] and stimulus-evoked neuronal and hemodynamic responses are modulated by mitochondrial Ca(2+ uptake capacity [2], [3] respectively, we tested our hypothesis by measuring hemodynamic fluctuations and spontaneous neuronal activities during normal and altered mitochondrial functional states. Mitochondrial Ca(2+ uptake capacity was perturbed by pharmacologically inhibiting or enhancing the mitochondrial Ca(2+ uniporter (mCU activity. Neuronal electrical activity and cerebral blood flow (CBF fluctuations were measured simultaneously and integrated with fMRI-BOLD fluctuations at 11.7T. mCU inhibition reduced spontaneous neuronal activity and the resting state functional connectivity (RSFC, whereas mCU enhancement increased spontaneous neuronal activity but reduced RSFC. We conclude that increased or decreased mitochondrial Ca(2+ uptake capacities lead to diminished resting state modes of brain functional connectivity.

  9. Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor γ (PPARγ activation function 1 (AF1 domain.

    Directory of Open Access Journals (Sweden)

    Rolf Diezko

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ is a ligand-activated nuclear receptor regulating adipogenesis, glucose homeostasis and inflammatory responses. The activity of PPARγ is controlled by post-translational modifications including SUMOylation and phosphorylation that affects its biological and molecular functions. Several important aspects of PPARγ SUMOylation including SUMO isoform-specificity and the impact of ligand binding on SUMOylation remain unresolved or contradictory. Here, we present a comprehensive study of PPARγ1 SUMOylation. We show that PPARγ1 can be modified by SUMO1 and SUMO2. Mutational analyses revealed that SUMOylation occurs exclusively within the N-terminal activation function 1 (AF1 domain predominantly at lysines 33 and 77. Ligand binding to the C-terminal ligand-binding domain (LBD of PPARγ1 reduces SUMOylation of lysine 33 but not of lysine 77. SUMOylation of lysine 33 and lysine 77 represses basal and ligand-induced activation by PPARγ1. We further show that lysine 365 within the LBD is not a target for SUMOylation as suggested in a previous report, but it is essential for full LBD activity. Our results suggest that PPARγ ligands negatively affect SUMOylation by interdomain communication between the C-terminal LBD and the N-terminal AF1 domain. The ability of the LBD to regulate the AF1 domain may have important implications for the evaluation and mechanism of action of therapeutic ligands that bind PPARγ.

  10. Toward the processing speed theory of activities of daily living in healthy aging: normative data of the Functional Activities Questionnaire.

    Science.gov (United States)

    Bezdicek, Ondrej; Stepankova, Hana; Martinec Novakova, Lenka; Kopecek, Miloslav

    2016-04-01

    The aim of this study was to describe an instrumental activities of daily living (IADL) measure: Functional Activities Questionnaire (FAQ), which is often used in clinical settings as a self- or informant-based measure of IADL. However, the FAQ's relationship with age or education in healthy aging has not been investigated. FAQ and a neuropsychological battery were administered to old and very old Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders. FAQ is significantly dependent on age and education, but not gender. Younger subjects and those with higher education have the lowest scores in the FAQ and show a higher degree of functional independence. FAQ moderately correlates with speed of processing, visual-perceptual and executive functions measures (Trail Making Tests, Stroop Test) and depressive symptoms, but not with episodic memory (WMS-III logical memory). We present normative percentile values for different age groups from 60 to 96 years of age. The present study shows conclusively that IADL measures, such as FAQ, should not be used without appropriate normative data, especially in very old adults. Thus, it has the ability to differentiate functional dependence due to age-related decline from neurodegenerative disease.

  11. Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus.

    Science.gov (United States)

    Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

    2014-11-04

    A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.

  12. Detection of cortical activities on eye movement using functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Masaki; Kawai, Kazushige; Kitahara, Kenji [Jikei Univ., Tokyo (Japan). School of Medicine; Soulie, D.; Cordoliani, Y.S.; Iba-Zizen, M.T.; Cabanis, E.A.

    1997-11-01

    Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann`s areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann`s areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement. (author)

  13. Developmental changes in motor cortex activity as infants develop functional motor skills.

    Science.gov (United States)

    Nishiyori, Ryota; Bisconti, Silvia; Meehan, Sean K; Ulrich, Beverly D

    2016-09-01

    Despite extensive research examining overt behavioral changes of motor skills in infants, the neural basis underlying the emergence of functional motor control has yet to be determined. We used functional near-infrared spectroscopy (fNIRS) to record hemodynamic activity of the primary motor cortex (M1) from 22 infants (11 six month-olds, 11 twelve month-olds) as they reached for an object, and stepped while supported over a treadmill. Based on the developmental systems framework, we hypothesized that as infants increased goal-directed experience, neural activity shifts from a diffused to focal pattern. Results showed that for reaching, younger infants showed diffuse areas of M1 activity that became focused by 12 months. For elicited stepping, younger infants produced much less M1 activity which shifted to diffuse activity by 12 months. Thus, the data suggest that as infants gain goal-directed experience, M1 activity emerges, initially showing a diffuse area of activity, becoming refined as the behavior stabilizes. Our data begin to document the cortical activity underlying early functional skill acquisition.

  14. Continuous monitoring of functional activities using wearable, wireless gyroscope and accelerometer technology.

    Science.gov (United States)

    Wagenaar, Robert C; Sapir, Inbal; Zhang, Yuting; Markovic, Stacey; Vaina, Lucia M; Little, Thomas D C

    2011-01-01

    The development of functional activity monitors (FAMs) will allow rehabilitation researchers and clinicians to evaluate treatment efficacy, to monitor compliance to exercise instructions, and to provide real time feedback in the treatment of movement disorders during the performance of daily activities. The purpose of the present study was to develop and test a small sized wearable FAM system comprised of three sensors positioned on the sternum and both thighs, wireless Bluetooth transmission capability to a smartphone, and computationally efficient activity detection algorithms for the accurate detection of functional activities. Each sensor was composed of a tri-axial accelerometer and a tri-axial gyroscope. Computationally efficient activity recognition algorithms were developed, using a sliding window of 1 second, the variability of the tilt angle time series and power spectral analysis. In addition, it includes a decision tree that identifies postures such as sitting, standing and lying, walking at comfortable, slow and fast speeds, transitions between these functional activities (e.g, sit-to-stand and stand-to-sit), activity duration and step frequency. In a research lab setting the output of the FAM system, video recordings and a 3D motion analysis system were compared in 10 healthy young adults. The results show that the agreement between the FAM system and the video recordings ranged from 98.10% to 100% for all postures, transfers and walking periods. There were no significant differences in activity durations and step frequency between measurement instruments.

  15. Coupling between neuronal activity and microcirculation: implications for functional brain imaging.

    Science.gov (United States)

    Vanzetta, Ivo; Grinvald, Amiram

    2008-04-01

    In the neocortex, neurons with similar response properties are often clustered together in column-like structures, giving rise to what has become known as functional architecture-the mapping of various stimulus feature dimensions onto the cortical sheet. At least partially, we owe this finding to the availability of several functional brain imaging techniques, both post-mortem and in-vivo, which have become available over the last two generations, revolutionizing neuroscience by yielding information about the spatial organization of active neurons in the brain. Here, we focus on how our understanding of such functional architecture is linked to the development of those functional imaging methodologies, especially to those that image neuronal activity indirectly, through metabolic or haemodynamic signals, rather than directly through measurement of electrical activity. Some of those approaches allow exploring functional architecture at higher spatial resolution than others. In particular, optical imaging of intrinsic signals reaches the striking detail of approximately 50 mum, and, together with other methodologies, it has allowed characterizing the metabolic and haemodynamic responses induced by sensory-evoked neuronal activity. Here, we review those findings about the spatio-temporal characteristics of neurovascular coupling and discuss their implications for functional brain imaging, including position emission tomography, and non-invasive neuroimaging techniques, such as funtional magnetic resonance imaging, applicable also to the human brain.

  16. Cortical activation during clock reading as a quadratic function of dementia state.

    Science.gov (United States)

    Saur, Ralf; Milian, Monika; Erb, Michael; Eschweiler, Gerhard W; Grodd, Wolfgang; Leyhe, Thomas

    2010-01-01

    In patients with Alzheimer's disease (AD), neuroimaging studies have demonstrated decreased brain activation, while increased activation was detected in patients with mild cognitive impairment (MCI). It can be hypothesized that increased cerebral activity seen in patients with MCI reflects neural compensation at the beginning of neurodegenerative processes. Later, as patients develop AD, neural integrity is increasingly impaired. This is accompanied by decreased neural activation. In this study we examined cognitive performance and functional magnetic resonance imaging activation on a Clock Reading task (CRT) and a Spatial Control task (SCT) in healthy controls, patients with MCI, and patients with early AD. Correlations between neural-functional activation and cognitive state, measured by the Mini Mental Status Examination, were determined using rank, linear and quadratic correlation models. It could be shown that CRT, in comparison to SCT, specifically activates brain regions in the ventral visual stream and precuneus known to be involved in conceptual processing and spatial imagery. The correlation between brain activity and cognitive state followed a quadratic rather than a linear pattern in several brain regions, including the lingual gyrus, cuneus, and precuneus. The strongest brain activity was found in patients with MCI and less severely impaired early AD subjects. These findings support the hypothesis that patients in early stages of dementia compensate for neuronal loss by the recruitment of additional neural resources reflected by increased neural activation, as measured by the blood oxygen level-dependent signal.

  17. Hydrodynamics-Based Functional Forms of Activity Metabolism: A Case for the Power-Law Polynomial Function in Animal Swimming Energetics

    OpenAIRE

    Anthony Papadopoulos

    2009-01-01

    The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metaboli...

  18. INVESTIGETING THE EFFECTS OF STANDING TRAINING ON BODY FUNCTIONS AND ACTIVITY FOR NONAMBULATORY CHILDREN WITH MYELOMENINGOCELE

    Directory of Open Access Journals (Sweden)

    Ozge Cankaya

    2017-09-01

    Full Text Available Background: It was indicated in many studies that verticalization have positive effects such as preventing fractures,regulating cardiopulmonary functions, increasing the head control, and the facilitation of postural muscles in pediatric patients, however, no study showing the effect of supported standing in patients with myelomeningocele on body functions and activity was encountered. The aim of this study is to examine the effects of structured supported standing training in children with myelomeningocele on body functions and activity according to ICF-CY. Methods: Twenty-five children with MMC aged between 3 and 17, who were divided into two groups-SST and control. The supported standing training was given to supported standing group 2 hours a day for 8 weeks in addition to the routine physical therapy program. Body functions were assessed with the Trunk Impairment Scale, and activity levels were assessed with the Gross Motor Function Measurement-88 and Pediatric Functional Independence Measurement at the beginning of the study, at the end of 8 weeks and at the end of 12 weeks from beginning. Results: The results of the structured supported standing training program during 8 weeks showed that children’s body functions and activity increased statistically significantly in SST group (p0.05. Conclusion: The results show that supported standing training effects the body functions and activity positively. It is recommended to educate the families for the supported standing training to be added to the routine physiotherapy and rehabilitation program for children with MMC and continue the training at home.

  19. Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis

    Science.gov (United States)

    2012-01-01

    Introduction The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs. Methods Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression. Results Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index. Conclusions

  20. New biotechnological perspectives of a NADH oxidase variant from Thermus thermophilus HB27 as NAD+-recycling enzyme

    Directory of Open Access Journals (Sweden)

    Rocha-Martín Javier

    2011-11-01

    Full Text Available Abstract Background The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD+ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD+. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds. Results The NADH-oxidase (NOX presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80°C under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37°C. The hyperactivated form presented a high specific activity (37.5 U/mg at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme. The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols. Conclusion We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations.

  1. Regulation of pumping function of the heart in developing body under changing regimens of motor activity.

    Science.gov (United States)

    Vafina, E Z; Abzalov, R A; Abzalov, N I; Nikitin, A S; Gulyakov, A A

    2014-06-01

    We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia.

  2. FUNCTIONAL PROFILE OF ACTIVE OLDER ADULTS WITH LOW BACK PAIN, ACCORDING TO THE ICF

    Directory of Open Access Journals (Sweden)

    Andersom Ricardo Fréz

    Full Text Available ABSTRACT Introduction: The International Classification of Functioning, Disability and Health (ICF considers multiples aspects of functionality. It is believed that this tool can help to classify the functionality of older adults with low back pain (LBP . Objectives: To describe the functionality of active older adults with LBP according to the ICF. Methods: A transversal study was conducted using the brief ICF core set for low back pain, to establish functional profiles of 40 older adults. The ICF categories were considered valid when ≥20% of participants showed some disability. Results: Thirty-two of the 35 categories of the brief ICF core set could be considered representative of the sample. Conclusion: The brief ICF core set for LBP results demonstrated that this classification system is representative for describing the functional profile of the sample.

  3. Sexual activity and function assessment in middle-aged Chinese women using the female sexual function index.

    Science.gov (United States)

    Zhang, Caiyun; Cui, Liping; Zhang, Lizhi; Shi, Chang; Zang, Hong

    2017-06-01

    To assess sexual activity, sexual function, and their correlation with vaginal maturation status among middle-aged Chinese women. A cross-sectional study with comparisons across age groups was carried out. In all, 120 women aged 45 to 60 years were recruited into three groups: 45 to 50 (youngest group), 51 to 55 (intermediate group), and 56 to 60 years old (eldest group). Sexual function was assessed through the Female Sexual Function Index (FSFI); vaginal maturation status was determined through the Vaginal Maturation Index (VMI) and pH value. Sexual activity was recorded with self-administered questionnaires. Low sexual frequency was present in a higher proportion of women, but sexual distress was identified within a lower proportion of women in the eldest group. The total FSFI score was significantly lower in the eldest group than in the youngest and intermediate groups (P VMI (P VMI was positively correlated with the total FSFI score, the domain score for sexual desire, and lubrication (r = 0.26, 0.25, 0.34; P < 0.05, 0.05, 0.01), but the opposite associations were demonstrated for pH value (r = -0.47, -0.37, -0.38; P < 0.01, respectively), especially with vaginal pain (r = -0.44, P < 0.01). Among middle-aged Chinese women, sexual desire is lower in 56 to 60-year-old women, compared with those aged 45 to 55 years, whereas vaginal dryness and dyspareunia become more prevalent with age. Importantly, sexual function is associated with vaginal maturation status in women at midlife.

  4. Paid Work and Physical Activity Preserve Functional Capacity in Elderly People

    Directory of Open Access Journals (Sweden)

    Lariane Mortean Ono MMSc

    2015-09-01

    Full Text Available Objective: To investigate the prevalence and association between functional disability and health conditions in elderly people. Method: A cross-sectional, population-based study with 1,705 elderly residents in urban region of Florianópolis, Brazil, from September 2009 to July 2010. The functional disability was classified according to the difficulty in accomplishing six basic activities of daily living. The crude and adjusted multinomial logistic regression was used to identify the associated factors. Results: The prevalence of mild functional disability was 38.9%, and it was positively associated with being female, older age, reporting four or more chronic diseases, overweight, and negative self-perception of health. High education and income, having paid work, and being physically active in leisure activities reduced the chance of presenting it. The prevalence of moderate/severe disability was 11.7% and positively associated with older age, presence of depressive symptoms, four or more chronic diseases, and negative self-perception of health. High education, paid work, and being physically active in leisure activities also reduced the chance of presenting moderate/severe disability. Conclusion: Being gainfully employed, having a high level of education, and being physically active in their leisure time reduced the chance of presenting disability. The negative self-perception of health was the factor that most increased the chance of presenting functional disability.

  5. Paid Work and Physical Activity Preserve Functional Capacity in Elderly People

    Science.gov (United States)

    Ono, Lariane Mortean; Schneider, Ione Jayce Ceola; Confortin, Susana Cararo; d’Orsi, Eleonora

    2015-01-01

    Objective: To investigate the prevalence and association between functional disability and health conditions in elderly people. Method: A cross-sectional, population-based study with 1,705 elderly residents in urban region of Florianópolis, Brazil, from September 2009 to July 2010. The functional disability was classified according to the difficulty in accomplishing six basic activities of daily living. The crude and adjusted multinomial logistic regression was used to identify the associated factors. Results: The prevalence of mild functional disability was 38.9%, and it was positively associated with being female, older age, reporting four or more chronic diseases, overweight, and negative self-perception of health. High education and income, having paid work, and being physically active in leisure activities reduced the chance of presenting it. The prevalence of moderate/severe disability was 11.7% and positively associated with older age, presence of depressive symptoms, four or more chronic diseases, and negative self-perception of health. High education, paid work, and being physically active in leisure activities also reduced the chance of presenting moderate/severe disability. Conclusion: Being gainfully employed, having a high level of education, and being physically active in their leisure time reduced the chance of presenting disability. The negative self-perception of health was the factor that most increased the chance of presenting functional disability. PMID:28138470

  6. Paid Work and Physical Activity Preserve Functional Capacity in Elderly People

    Directory of Open Access Journals (Sweden)

    Lariane Mortean Ono MMSc

    2015-09-01

    Full Text Available Objective: To investigate the prevalence and association between functional disability and health conditions in elderly people. Method: A cross-sectional, population-based study with 1,705 elderly residents in urban region of Florianópolis, Brazil, from September 2009 to July 2010. The functional disability was classified according to the difficulty in accomplishing six basic activities of daily living. The crude and adjusted multinomial logistic regression was used to identify the associated factors. Results: The prevalence of mild functional disability was 38.9%, and it was positively associated with being female, older age, reporting four or more chronic diseases, overweight, and negative self-perception of health. High education and income, having paid work, and being physically active in leisure activities reduced the chance of presenting it. The prevalence of moderate/severe disability was 11.7% and positively associated with older age, presence of depressive symptoms, four or more chronic diseases, and negative self-perception of health. High education, paid work, and being physically active in leisure activities also reduced the chance of presenting moderate/severe disability. Conclusion: Being gainfully employed, having a high level of education, and being physically active in their leisure time reduced the chance of presenting disability. The negative self-perception of health was the factor that most increased the chance of presenting functional disability.

  7. Intrinsic muscle strength and voluntary activation of both lower limbs and functional performance after stroke.

    Science.gov (United States)

    Horstman, Astrid M; Beltman, Marijke J; Gerrits, Karin H; Koppe, Peter; Janssen, Thomas W; Elich, Peter; de Haan, Arnold

    2008-07-01

    The objective of this study was to assess the nature of muscle weakness in both legs after stroke compared with able-bodied control individuals and to examine whether there is a relationship between the degree of muscle weakness and coactivation of knee extensors and flexors as well as voluntary activation capacity of knee extensors of both paretic and non-paretic legs and indices of functional performance. Maximal voluntary isometric torques of knee extensors (MVCe) and flexors (MVCf) were determined in 14 patients (bilaterally) and 12 able-bodied controls. Simultaneous measurements were made of torque and surface EMG from agonist and antagonist muscles. Coactivation was calculated. Supramaximal triplets were evoked with electrical stimulation to estimate maximal torque capacity and degree of voluntary activation of knee extensors. MVCs, activation and coactivation parameters were correlated to scores of seven functional performance tests. MVCe, MVCf and voluntary activation were lower in paretic lower limb (PL) compared with both non-paretic lower limb (NL) and control. Besides, all these parameters of NL were also lower than control. Electrically evoked torque capacity of knee extensors of PL was about 60% of both NL and control, which were not significantly different from each other. Strong significant correlations between strength, as well as voluntary activation, and functional performance were found. Coactivation did not correlate well with functional performance. Thus, whereas for NL activation failure can explain weakness, for PL both activation failure and reduced intrinsic torque capacity are responsible for the severe weakness. Activation capacity and muscle strength correlated strongly to functional performance, while coactivation did not.

  8. Premature sperm activation and defective spermatogenesis caused by loss of spe-46 function in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Wei-Siang Liau

    Full Text Available Given limited resources for motility, sperm cell activation must be precisely timed to ensure the greatest likelihood of fertilization. Like those of most species, the sperm of C. elegans become active only after encountering an external signaling molecule. Activation coincides with spermiogenesis, the final step in spermatogenesis, when the spherical spermatid undergoes wholesale reorganization to produce a pseudopod. Here, we describe a gene involved in sperm activation, spe-46. This gene was identified in a suppressor screen of spe-27(it132ts, a sperm-expressed gene whose product functions in the transduction of the spermatid activation signal. While spe-27(it132ts worms are sterile at 25°C, the spe-46(hc197I; spe-27(it132tsIV double mutants regain partial fertility. Single nucleotide polymorphism mapping, whole genome sequencing, and transformation rescue were employed to identify the spe-46 coding sequence. It encodes a protein with seven predicted transmembrane domains but with no other predicted functional domains or homology outside of nematodes. Expression is limited to spermatogenic tissue, and a transcriptional GFP fusion shows expression corresponds with the onset of the pachytene stage of meiosis. The spe-46(hc197 mutation bypasses the need for the activation signal; mutant sperm activate prematurely without an activation signal in males, and mutant males are sterile. In an otherwise wild-type genome, the spe-46(hc197 mutation induces a sperm defective phenotype. In addition to premature activation, spe-46(hc197 sperm exhibit numerous defects including aneuploidy, vacuolization, protruding spikes, and precocious fusion of membranous organelles. Hemizygous worms [spe-46(hc197/mnDf111] are effectively sterile. Thus, spe-46 appears to be involved in the regulation of spermatid activation during spermiogenesis, with the null phenotype being an absence of functional sperm and hypomorphic phenotypes being premature spermatid activation

  9. On the construction of CASCI-type wave functions for very large active spaces

    CERN Document Server

    Boguslawski, Katharina; Reiher, Markus

    2011-01-01

    We present an efficient procedure to construct configuration-interaction-type electronic wave functions of molecular systems that require very large active spaces for a qualitatively correct description of their electronic structure. Our procedure is based on the density-matrix renormalization group algorithm that provides the necessary information in terms of the eigenstates of the reduced density matrices to calculate the coefficient of any basis state in the many-particle Hilbert space of the molecular system under study. Since the dimension of the Hilbert space scales factorially with the size of the active space, a sophisticated Monte Carlo sampling routine has been implemented that constructs an accurate representation of the electronic wave function. We emphasize that our sampling routine can also construct complete-active-space configuration-interaction-type wave functions from any other type of tensor network states, such as the complete-graph tensor network states or the correlator product states.

  10. PREX1 Protein Function Is Negatively Regulated Downstream of Receptor Tyrosine Kinase Activation by p21-activated Kinases (PAKs).

    Science.gov (United States)

    Barrows, Douglas; He, John Z; Parsons, Ramon

    2016-09-16

    Downstream of receptor tyrosine kinase and G protein-coupled receptor (GPCR) stimulation, the phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchange factor (PREX) family of guanine nucleotide exchange factors (GEFs) activates Rho GTPases, leading to important roles for PREX proteins in numerous cellular processes and diseases, including cancer. PREX1 and PREX2 GEF activity is activated by the second messengers PIP3 and Gβγ, and further regulation of PREX GEF activity occurs by phosphorylation. Stimulation of receptor tyrosine kinases by neuregulin and insulin-like growth factor 1 (IGF1) leads to the phosphorylation of PREX1; however, the kinases that phosphorylate PREX1 downstream of these ligands are not known. We recently reported that the p21-activated kinases (PAKs), which are activated by GTP-bound Ras-related C3 botulinum toxin substrate 1 (Rac1), mediate the phosphorylation of PREX2 after insulin receptor activation. Here we show that certain phosphorylation events on PREX1 after insulin, neuregulin, and IGF1 treatment are PAK-dependent and lead to a reduction in PREX1 binding to PIP3 Like PREX2, PAK-mediated phosphorylation also negatively regulates PREX1 GEF activity. Furthermore, the onset of PREX1 phosphorylation was delayed compared with the phosphorylation of AKT, supporting a model of negative feedback downstream of PREX1 activation. We also found that the phosphorylation of PREX1 after isoproterenol and prostaglandin E2-mediated GPCR activation is partially PAK-dependent and likely also involves protein kinase A, which is known to reduce PREX1 function. Our data point to multiple mechanisms of PREX1 negative regulation by PAKs within receptor tyrosine kinase and GPCR-stimulated signaling pathways that have important roles in diseases such as diabetes and cancer.

  11. An investigation of the relationship between activation of a social cognitive neural network and social functioning.

    Science.gov (United States)

    Pinkham, Amy E; Hopfinger, Joseph B; Ruparel, Kosha; Penn, David L

    2008-07-01

    Previous work examining the neurobiological substrates of social cognition in healthy individuals has reported modulation of a social cognitive network such that increased activation of the amygdala, fusiform gyrus, and superior temporal sulcus are evident when individuals judge a face to be untrustworthy as compared with trustworthy. We examined whether this pattern would be present in individuals with schizophrenia who are known to show reduced activation within these same neural regions when processing faces. Additionally, we sought to determine how modulation of this social cognitive network may relate to social functioning. Neural activation was measured using functional magnetic resonance imaging with blood oxygenation level dependent contrast in 3 groups of individuals--nonparanoid individuals with schizophrenia, paranoid individuals with schizophrenia, and healthy controls--while they rated faces as either trustworthy or untrustworthy. Analyses of mean percent signal change extracted from a priori regions of interest demonstrated that both controls and nonparanoid individuals with schizophrenia showed greater activation of this social cognitive network when they rated a face as untrustworthy relative to trustworthy. In contrast, paranoid individuals did not show a significant difference in levels of activation based on how they rated faces. Further, greater activation of this social cognitive network to untrustworthy faces was significantly and positively correlated with social functioning. These findings indicate that impaired modulation of neural activity while processing social stimuli may underlie deficits in social cognition and social dysfunction in schizophrenia.

  12. Figural memory performance and functional magnetic resonance imaging activity across the adult lifespan.

    Science.gov (United States)

    Jamadar, Sharna; Assaf, Michal; Jagannathan, Kanchana; Anderson, Karen; Pearlson, Godfrey D

    2013-01-01

    We examined performance and functional magnetic resonance imaging activity in participants (n = 235) aged 17-81 years on a nonverbal recognition memory task, figural memory. Reaction time, error rate, and response bias measures indicated that the youngest and oldest participants were faster, made fewer errors, and showed a more conservative response bias than participants in the median age ranges. Encoding and Recognition phases activated a distributed bilateral network encompassing prefrontal, subcortical, lateral, and medial temporal and occipital regions. Activation during Encoding phase did not correlate with age. During Recognition, task-related activation for correctly identified targets (Hit-Targets) correlated linearly positively with age; nontask related activity correlated negative quadratically with age. During correctly identified distractors (Hit-Distractors) activity in task-related regions correlated positive linearly with age, nontask activity showed positive and negative quadratic relationships with age. Missed-Targets activity did not correlate with age. We concluded that figural memory performance and functional magnetic resonance imaging activity during Recognition but not Encoding was affected both by continued maturation of the brain in the early 20s and compensatory recruitment of additional brain regions during recognition memory in old age.

  13. Active life in old age. Combining measures of functional ability and social participation

    DEFF Research Database (Denmark)

    Avlund, K; Holstein, B E; Mortensen, Erik Lykke

    1999-01-01

    . SUBJECTS: A random sample of 75-year-old people who were invited to participate in the study (participation rate: 89, n = 477). MAIN OUTCOME MEASURE: ALC is a combination of two dichotomized variables: functional ability (dependent vs not dependent of help) and social participation (low vs. high). RESULTS......This paper describes a new measure of Active Life Expectancy, called Active Life Classification (ALC) in which the criterion for successful aging is a combination of good functional ability and high social participation. OBJECTIVES: 1) to describe the distribution of ALC among 75-year-old men...... were associated with ALC. CONCLUSIONS: It is an advantage to combine functional ability and social participation in the description of quality of life in old age, as 1) a high social participation may compensate for a poor functional ability, and vice versa, 2) the combined measure is meaningful...

  14. Urokinase plasminogen activator receptor: a functional integrator of extracellular proteolysis, cell adhesion, and signal transduction.

    Science.gov (United States)

    Ferraris, Gian Maria Sarra; Sidenius, Nicolai

    2013-06-01

    The urokinase plasminogen activator receptor (uPAR) is a cell surface receptor involved in a multitude of physiologic and pathologic processes. uPAR regulates simultaneously a branch of the plasminogen activator system and modulates cell adhesion and intracellular signaling by interacting with extracellular matrix components and signaling receptors. The multiple uPAR functions are deeply interconnected, and their integration determines the effects that uPAR expression triggers in different contexts. The proteolytic function of uPAR affects both the signaling and the adhesive functions of the receptor, whereas these latter two are closely interconnected. This review focuses on the molecular mechanisms that connect and mutually regulate the different uPAR functions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Estimating time-correlation functions by sampling and unbiasing dynamically activated events

    CERN Document Server

    Athènes, Manuel; Jourdan, Thomas; 10.1063/1.4766458

    2012-01-01

    Transition path sampling is a rare-event method that estimates state-to-state timecorrelation functions in many-body systems from samples of short trajectories. In this framework, it is proposed to bias the importance function using the lowest Jacobian eigenvalue moduli along the dynamical trajectory. A lowest eigenvalue modulus is related to the lowest eigenvalue of the Hessian matrix and is evaluated here using the Lanczos algorithm as in activation-relaxation techniques. This results in favoring the sampling of activated trajectories and enhancing the occurrence of the rare reactive trajectories of interest, those corresponding to transitions between locally stable states. Estimating the time-correlation functions involves unbiasing the sample of simulated trajectories which is done using the multi-state Bennett acceptance ratio (MBAR) method. To assess the performance of our procedure, we compute the time-correlation function associated with the migration of a vacancy in {\\alpha}-iron. The derivative of t...

  16. Functional Based Adaptive and Fuzzy Sliding Controller for Non-Autonomous Active Suspension System

    Science.gov (United States)

    Huang, Shiuh-Jer; Chen, Hung-Yi

    In this paper, an adaptive sliding controller is developed for controlling a vehicle active suspension system. The functional approximation technique is employed to substitute the unknown non-autonomous functions of the suspension system and release the model-based requirement of sliding mode control algorithm. In order to improve the control performance and reduce the implementation problem, a fuzzy strategy with online learning ability is added to compensate the functional approximation error. The update laws of the functional approximation coefficients and the fuzzy tuning parameters are derived from the Lyapunov theorem to guarantee the system stability. The proposed controller is implemented on a quarter-car hydraulic actuating active suspension system test-rig. The experimental results show that the proposed controller suppresses the oscillation amplitude of the suspension system effectively.

  17. Family Functioning: Associations with Weight Status, Eating Behaviors, and Physical Activity in Adolescents

    Science.gov (United States)

    Berge, Jerica M.; Wall, Melanie; Larson, Nicole; Loth, Katie A.; Neumark-Sztainer, Dianne

    2012-01-01

    Purpose This paper examines the relationship between family functioning (e.g. communication, closeness, problem solving, behavioral control) and adolescent weight status and relevant eating and physical activity behaviors. Methods Data are from EAT 2010 (Eating and Activity in Teens), a population-based study that assessed eating and activity among socioeconomically and racially/ethnically diverse youth (n = 2,793). Adolescents (46.8% boys, 53.2% girls) completed anthropometric assessments and surveys at school in 2009–2010. Multiple linear regression was used to test the relationship between family functioning and adolescent weight, dietary intake, family meal patterns, and physical activity. Additional regression models were fit to test for interactions by race/ethnicity. Results For adolescent girls, higher family functioning was associated with lower body mass index z-score and percent overweight, less sedentary behavior, higher intake of fruits and vegetables, and more frequent family meals and breakfast consumption. For adolescent boys, higher family functioning was associated with more physical activity, less sedentary behavior, less fast food consumption, and more frequent family meals and breakfast consumption. There was one significant interaction by race/ethnicity for family meals; the association between higher family functioning and more frequent family meals was stronger for non-white boys compared to white boys. Overall, strengths of associations tended to be small with effect sizes ranging from - 0.07 to 0.31 for statistically significant associations. Conclusions Findings suggest that family functioning may be protective for adolescent weight and weight-related health behaviors across all race/ethnicities, although assumptions regarding family functioning in the homes of overweight children should be avoided given small effect sizes. PMID:23299010

  18. Diversity of Dominant Bacterial Taxa in Activated Sludge Promotes Functional Resistance following Toxic Shock Loading

    KAUST Repository

    Saikaly, Pascal

    2010-12-14

    Examining the relationship between biodiversity and functional stability (resistance and resilience) of activated sludge bacterial communities following disturbance is an important first step towards developing strategies for the design of robust biological wastewater treatment systems. This study investigates the relationship between functional resistance and biodiversity of dominant bacterial taxa by subjecting activated sludge samples, with different levels of biodiversity, to toxic shock loading with cupric sulfate (Cu[II]), 3,5-dichlorophenol (3,5-DCP), or 4-nitrophenol (4-NP). Respirometric batch experiments were performed to determine the functional resistance of activated sludge bacterial community to the three toxicants. Functional resistance was estimated as the 30 min IC50 or the concentration of toxicant that results in a 50% reduction in oxygen utilization rate compared to a referential state represented by a control receiving no toxicant. Biodiversity of dominant bacterial taxa was assessed using polymerase chain reaction-terminal restriction fragment length polymorphism (PCR-T-RFLP) targeting the 16S ribosomal RNA (16S rRNA) gene. Statistical analysis of 30 min IC50 values and PCR-T-RFLP data showed a significant positive correlation (P<0.05) between functional resistance and microbial diversity for each of the three toxicants tested. To our knowledge, this is the first study showing a positive correlation between biodiversity of dominant bacterial taxa in activated sludge and functional resistance. In this system, activated sludge bacterial communities with higher biodiversity are functionally more resistant to disturbance caused by toxic shock loading. © 2010 Springer Science+Business Media, LLC.

  19. Task-modulated activation and functional connectivity of the temporal and frontal areas during speech comprehension.

    Science.gov (United States)

    Yue, Q; Zhang, L; Xu, G; Shu, H; Li, P

    2013-05-01

    There is general consensus in the literature that a distributed network of temporal and frontal brain areas is involved in speech comprehension. However, how active versus passive tasks modulate the activation and the functional connectivity of the critical brain areas is not clearly understood. In this study, we used functional magnetic resonance imaging (fMRI) to identify intelligibility and task-related effects in speech comprehension. Participants performed a semantic judgment task on normal and time-reversed sentences, or passively listened to the sentences without making an overt response. The subtraction analysis demonstrated that passive sentence comprehension mainly engaged brain areas in the left anterior and posterior superior temporal sulcus and middle temporal gyrus (aSTS/MTG and pSTS/MTG), whereas active sentence comprehension recruited bilateral frontal regions in addition to the aSTS/MTG and pSTS/MTG regions. Functional connectivity analysis revealed that during passive sentence comprehension, the left aSTS/MTG was functionally connected with the left Heschl's gyrus (HG) and bilateral superior temporal gyrus (STG) but no area was functionally connected with the left pSTS/MTG; during active sentence comprehension, however, both the left aSTS/MTG and pSTS/MTG were functionally connected with bilateral superior temporal and inferior frontal areas. While these results are consistent with the view that the ventral stream of the temporo-frontal network subserves semantic processing, our findings further indicate that both the activation and the functional connectivity of the temporal and frontal areas are modulated by task demands. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Physical activity and mortality related to obesity and functional status in older adults in Spain.

    Science.gov (United States)

    Balboa-Castillo, Teresa; Guallar-Castillón, Pilar; León-Muñoz, Luz M; Graciani, Auxiliadora; López-García, Esther; Rodríguez-Artalejo, Fernando

    2011-01-01

    Older people who increase or maintain their physical activity have lower mortality than those who remain sedentary. This could result from a lower body weight and a better functional status that allow to be more active. However, this explanation would be unlikely if the benefits of physical activity on mortality were seen also in older people with obesity or functional limitations. This study examined the association between change in leisure-time physical activity (LTPA) and mortality in older adults, and whether this association varied with obesity and functional limitations. Data were taken from a prospectively follow-up study of 2732 people representative of the Spanish population aged ≥60 years. Changes in LTPA from 2001 to 2003 were linked to all-cause mortality from 2003 to 2009. Analyses were performed in 2010 with Cox models adjusted for the main confounders, and were stratified by obesity and functional limitations. Compared with people who were continually sedentary from 2001 to 2003, those who increased their LTPA had 34% lower mortality (hazard ratio [HR]=0.66, 95% CI=0.52, 0.84), and those who were continually active had 45% lower mortality (HR=0.55; 95% CI=0.43, 0.70). These results did not vary in analyses stratified by obesity and functional limitations. Increasing or maintaining LTPA is associated with greater longevity in older adults, even those with obesity or functional limitations. Given the high frequency of these disorders, the current results suggest that most older adults can benefit from an active lifestyle. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Cardiomyocytes with disrupted CFTR function require CaMKII and Ca(2+)-activated Cl(-) channel activity to maintain contraction rate.

    Science.gov (United States)

    Sellers, Zachary M; De Arcangelis, Vania; Xiang, Yang; Best, Philip M

    2010-07-01

    The physiological role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiomyocytes remains unclear. Using spontaneously beating neonatal ventricular cardiomyocytes from wild-type (WT) or CFTR knockout (KO) mice, we examined the role of CFTR in the modulation of cardiomyocyte contraction rate. Contraction rates of spontaneously beating myocytes were captured by video imaging. Real-time changes in intracellular ([Ca(2+)](i)) and protein kinase A (PKA) activity were measured by fura-2 and fluorescence resonance energy transfer, respectively. Acute inhibition of CFTR in WT cardiomyocytes using the CFTR inhibitor CFTR(inh)-172 transiently inhibited the contraction rate. By contrast, cardiomyocytes from CFTR KO mice displayed normal contraction rates. Further investigation revealed that acute inhibition of CFTR activity in WT cardiomyocytes activated L-type Ca(2+) channels, leading to a transient increase of [Ca(2+)](i) and inhibition of PKA activity. Additionally, we found that contraction rate normalization following acute CFTR inhibition in WT cardiomyocytes or chronic deletion in cardiomyocytes from CFTR KO mice requires the activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and Ca(2+)-activated Cl(-) channels (CaCC) because simultaneous addition of myristoylated-autocamtide-2-related inhibitory peptide or niflumic acid and CFTR(inh)-172 to WT cardiomyocytes or treatment of cardiomyoctes from CFTR KO mice with these agents caused sustained attenuation of contraction rates. Our results demonstrate that regulation of cardiomyocyte contraction involves CFTR. They also reveal that activation of CaMKII and CaCC compensates for loss of CFTR function. Increased dependence on CaMKII upon loss of CFTR function might leave cystic fibrosis patients at increased risk of heart dysfunction and disease.

  2. Cardiomyocytes with disrupted CFTR function require CaMKII and Ca2+-activated Cl− channel activity to maintain contraction rate

    Science.gov (United States)

    Sellers, Zachary M; De Arcangelis, Vania; Xiang, Yang; Best, Philip M

    2010-01-01

    The physiological role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiomyocytes remains unclear. Using spontaneously beating neonatal ventricular cardiomyocytes from wild-type (WT) or CFTR knockout (KO) mice, we examined the role of CFTR in the modulation of cardiomyocyte contraction rate. Contraction rates of spontaneously beating myocytes were captured by video imaging. Real-time changes in intracellular ([Ca2+]i) and protein kinase A (PKA) activity were measured by fura-2 and fluorescence resonance energy transfer, respectively. Acute inhibition of CFTR in WT cardiomyocytes using the CFTR inhibitor CFTRinh-172 transiently inhibited the contraction rate. By contrast, cardiomyocytes from CFTR KO mice displayed normal contraction rates. Further investigation revealed that acute inhibition of CFTR activity in WT cardiomyoctyes activated L-type Ca2+ channels, leading to a transient increase of [Ca2+]i and inhibition of PKA activity. Additionally, we found that contraction rate normalization following acute CFTR inhibition in WT cardiomyocytes or chronic deletion in cardiomyocytes from CFTR KO mice requires the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and Ca2+-activated Cl− channels (CaCC) because simultaneous addition of myristoylated-autocamtide-2-related inhibitory peptide or niflumic acid and CFTRinh-172 to WT cardiomyocytes or treatment of cardiomyoctes from CFTR KO mice with these agents caused sustained attenuation of contraction rates. Our results demonstrate that regulation of cardiomyocyte contraction involves CFTR. They also reveal that activation of CaMKII and CaCC compensates for loss of CFTR function. Increased dependence on CaMKII upon loss of CFTR function might leave cystic fibrosis patients at increased risk of heart dysfunction and disease. PMID:20442264

  3. Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model.

    Science.gov (United States)

    Sershen, Henry; Hashim, Audrey; Dunlop, David S; Suckow, Raymond F; Cooper, Tom B; Javitt, Daniel C

    2016-02-01

    Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol(®)) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor NaB (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level, arguing against a DAAO

  4. Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model

    Science.gov (United States)

    Sershen, Henry; Hashim, Audrey; Dunlop, David S.; Suckow, Raymond F.; Cooper, Tom B.; Javitt, Daniel C.

    2016-01-01

    Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol®) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor sodium benzoate (NaB) (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level

  5. Mitochondrial function provides instructive signals for activation-induced B-cell fates.

    OpenAIRE

    Jang, Kyoung-Jin; Mano, Hiroto; Aoki, Koji; Hayashi, Tatsunari; Muto, Akihiko; Nambu, Yukiko; Takahashi, Katsu; Itoh, Katsuhiko; Taketani, Shigeru; Stephen L Nutt; Igarashi, Kazuhiko; Shimizu, Akira; Sugai, Manabu

    2015-01-01

    During immune reactions, functionally distinct B-cell subsets are generated by stochastic processes, including class-switch recombination (CSR) and plasma cell differentiation (PCD). In this study, we show a strong association between individual B-cell fates and mitochondrial functions. CSR occurs specifically in activated B cells with increased mitochondrial mass and membrane potential, which augment mitochondrial reactive oxygen species (mROS), whereas PCD occurs in cells with decreased mit...

  6. Effect of computerized cognitive rehabilitation program on cognitive function and activities of living in stroke patients

    OpenAIRE

    Yoo, Chanuk; Yong, Mi-hyun; Chung, Jaeyeop; Yang, YeongAe

    2015-01-01

    [Purpose] The objective of this study was to examine the effect of cognitive rehabilitation using a computer on cognitive function and activities of daily living in stroke patients presenting impairment of cognitive function. [Subjects] Forty-six stroke patients were divided into two groups (a training group and control group) through random assignment. [Methods] The training group received rehabilitation therapy and an additional computerized cognitive rehabilitation program using The RehaCo...

  7. The fast neutron fluence and the activation detector activity calculations using the effective source method and the adjoint function

    Energy Technology Data Exchange (ETDEWEB)

    Hep, J.; Konecna, A.; Krysl, V.; Smutny, V. [Calculation Dept., Skoda JS plc, Orlik 266, 31606 Plzen (Czech Republic)

    2011-07-01

    This paper describes the application of effective source in forward calculations and the adjoint method to the solution of fast neutron fluence and activation detector activities in the reactor pressure vessel (RPV) and RPV cavity of a VVER-440 reactor. Its objective is the demonstration of both methods on a practical task. The effective source method applies the Boltzmann transport operator to time integrated source data in order to obtain neutron fluence and detector activities. By weighting the source data by time dependent decay of the detector activity, the result of the calculation is the detector activity. Alternatively, if the weighting is uniform with respect to time, the result is the fluence. The approach works because of the inherent linearity of radiation transport in non-multiplying time-invariant media. Integrated in this way, the source data are referred to as the effective source. The effective source in the forward calculations method thereby enables the analyst to replace numerous intensive transport calculations with a single transport calculation in which the time dependence and magnitude of the source are correctly represented. In this work, the effective source method has been expanded slightly in the following way: neutron source data were performed with few group method calculation using the active core calculation code MOBY-DICK. The follow-up neutron transport calculation was performed using the neutron transport code TORT to perform multigroup calculations. For comparison, an alternative method of calculation has been used based upon adjoint functions of the Boltzmann transport equation. Calculation of the three-dimensional (3-D) adjoint function for each required computational outcome has been obtained using the deterministic code TORT and the cross section library BGL440. Adjoint functions appropriate to the required fast neutron flux density and neutron reaction rates have been calculated for several significant points within the RPV

  8. [Functional status, self-rated health and level of physical activity of patients with osteoarthritis].

    Science.gov (United States)

    Val Jiménez, Carmen Llanos; López-Torres Hidalgo, Jesús; García Atienza, Eva María; Navarro Ruiz, María Soledad; Hernández Cerón, Inmaculada; Moreno de la Rosa, Lorena

    2017-04-01

    To describe the functional status and self-rated health of patients with osteoarthritis (OA) in Primary Care, and checking their relationship with the level of physical activity and sociodemographic characteristics. Study of prevalence and cross association. Primary Care Clinics. Adult patients with a diagnosis of OA in any joint in their clinical records. Out of a total of 487 selected, 346 (71.0%) took part in the study. Functional capacity (WOMAC scale), self-rated quality of life (EuroQol- 5D questionnaire), physical activity (IPAQ questionnaire), number of affected joints, pain level, and sociodemographic characteristics. A mean score of 30.2 (SD: 20.8; CI 95% CI: 28.0 to 32.4) was obtained on the WOMAC scale, with pain, stiffness, and functional capacity scores of 6.5 (SD: 4.8), 1.9 (SD: 2.0), and 21.7 (SD: 15.7), respectively. The score showed a linear trend (P<.001) compared to the level of physical activity, being 41.1 (SD: 19.9) in inactive subjects, 24.3 (SD: 18.7) in subjects with moderate activity, and 22.3 (SD: 19.8) in subjects with intense activity. In the multiple linear regression, the score on the WOMAC scale, as well as that obtained in self-rated health status, maintained their association with physical activity level after adjusting for sociodemographic variables and the number of affected joints. In patients with OA, pain and functional capacity are the most affected dimensions. Functional status and self-rated health status are higher in active patients, regardless of the number of joints affected and their demographic characteristics. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  9. Bioactive Components and Functional Properties of Biologically Activated Cereal Grains: A Bibliographic Review.

    Science.gov (United States)

    Singh, Arashdeep; Sharma, Savita

    2015-10-14

    Whole grains provide energy, nutrients, fibres and bioactive compounds that may synergistically contribute to their protective effects. A wide range of these compounds is affected by germination. While some compounds, such as β-glucans are degraded, others, like antioxidants and total phenolics are increased by means of biological activation of grains. The water and oil absorption capacity as well as emulsion and foaming capacity of biologically activated grains are also improved. Application of biological activation of grains is of emerging interest, which may significantly enhance the nutritional, functional and bioactive content of grains, as well as improve palatability of grain foods in a natural way. Therefore, biological activation of cereals can be a way to produce food grains enriched with health promoting compounds and enhanced functional attributes.

  10. Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Yakunina, Natalia; Nam, Eui-Cheol [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Otolaryngology, School of Medicine, Chuncheon, Kangwon-do (Korea, Republic of); Kim, Tae Su [Kangwon National University Hospital, Department of Otolaryngology, Chuncheon (Korea, Republic of); Kim, Sam Soo [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Radiology, School of Medicine, Chuncheon (Korea, Republic of)

    2014-07-15

    The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR = 8 s) was used. In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders. (orig.)

  11. Home and Community Environmental Features, Activity Performance, and Community Participation among Older Adults with Functional Limitations

    OpenAIRE

    2012-01-01

    This paper describes relationships among home and community environmental features, activity performance in the home, and community participation potential to support aging in place. A subset of data on older adults with functional limitations ( = 1 2 2 ), sixty three (63) with mobility and 59 with other limitations, were utilized in this study from a larger project's subject pool. Results showed significant and positive correlations between environmental barriers, activity dependence and d...

  12. Relationship of phosphatidylinositol bisphosphate hydrolysis to calcium mobilization and functional activation in fluoride-treated neutrophils.

    OpenAIRE

    English, D.; Debono, D J; Gabig, T G

    1987-01-01

    Sodium fluoride (20 mM) effected rapid hydrolysis of phosphatidylinositol bisphosphate (PIP2) in human neutrophils. Intracellular free Ca2+ levels increased after PIP2 hydrolysis but before respiratory burst activation. Both the increase in intracellular free Ca2+ levels and the extent of functional activation were dependent on the availability of extracellular Ca2+. The rate of F(-)-stimulated PIP2 hydrolysis, however, was not affected when the rise in cytosolic Ca2+ was severely limited by ...

  13. Hydrodynamics-based functional forms of activity metabolism: a case for the power-law polynomial function in animal swimming energetics.

    Directory of Open Access Journals (Sweden)

    Anthony Papadopoulos

    Full Text Available The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined.

  14. Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2016-01-01

    Full Text Available Sirtuin type 1 (SIRT1 belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs, as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP. The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1.

  15. Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function

    Science.gov (United States)

    Wang, Yi; Liang, Xinying; Chen, Yaqi; Zhao, Xiaoping

    2016-01-01

    Sirtuin type 1 (SIRT1) belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs), as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP). The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1. PMID:26981165

  16. Balance, autonomy and functional independence of active and sedentary elderly: a preliminary study

    Directory of Open Access Journals (Sweden)

    Arthur Matheus da Silva

    2016-01-01

    Full Text Available Both the body balance (BB, as the functional autonomy (FA and the level of functional independence (FI of 10 sedentary elderly (GI were evaluated and compared to related data in 10 active elderly (GII, all of the health program family in Araxá-MG, after signing the informed consent, were submitted to the evaluation tests of the EC, the AF and the NIF, besides the identification of BMI. Although body overweight and equal NIF between both the EC and AF were significantly higher in GII than in GI, we concluded that the practice of therapeutic exercise promotes functional health in the elderly.  

  17. Covalent binding of hyper-activated Rhizomucor miehei lipase (RML) on hetero-functionalized siliceous supports.

    Science.gov (United States)

    Garmroodi, Maryam; Mohammadi, Mehdi; Ramazani, Ali; Ashjari, Maryam; Mohammadi, Javad; Sabour, Behrouz; Yousefi, Maryam

    2016-05-01

    Physical adsorption onto hydrophobic supports has proven to be an effective way to improve the activity of lipases. Covalent binding, on the other hand, enhances the active lifetime of the immobilized biocatalysts. To combine the benefits of adsorption and covalent binding, immobilization of RML on new hetero-functional supports are reported. For this, chemical modification of silica and silica mesoporous nanoparticles was performed by the simultaneous use of two coupling linkers; Octyltriethoxysilane (OTES) for hydrophobic interaction and glycidoxypropyltrimethoxylsilane (GPTMS) for covalent linkage of RML. Altering the GPTMS/OTES ratio makes possible to have different amount of octyl and epoxy groups on the supports. The results showed that immobilization of RML on octyl-functionalized supports produces specific activity almost 1.5-2 folds greater than the specific activity of the free enzyme. The observed hyper-activation decreased with increasing epoxy groups on the supports confirming the enhancement of covalent nature of the attachment. Leaching experiment was also confirmed positive effect of the presence of epoxy groups on the supports. Regarding the specific activity of the immobilized preparations and desorption percentages of RML from each support, the most suitable carrier obtains from the functionalization of the supports in presence of GPTMS and OTES in the ratio of 1:1.

  18. Clinical studies of brain functional images by motor activation using single photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Masahiro [Gifu Univ. (Japan). School of Medicine

    1998-09-01

    Thirty participants (10 normal controls; group A, 5 patients with brain tumors located near central sulcus without hemiparesis; group B, 10 patients with brain tumors located near central sulcus with hemiparesis; group C, and 5 patients with brain tumors besides the central regions with hemiparesis; group D) were enrolled. The images were performed by means of split-dose method with {sup 99m}Tc-ECD at rest condition (SPECT 1) and during hand grasping (SPECT 2). The activation SPECT were obtained by subtracting SPECT 1 from SPECT 2, and the functional mapping was made by the strict registration of the activation SPECT with 3D MRI. To evaluate the changes of CBF (%{Delta}CBF) of the sensorimotor and supplementary motor areas on the functional mapping, ratio of the average counts of SPECT 1 and SPECT 2 was calculated and statistically compared. The functional activation paradigms caused a significant increase of CBF in the sensorimotor area contra-lateral to the stimulated hand, although the sensorimotor area and the central sulcus in groups B and C were dislocated, compared with hemisphere of non-tumor side. The sensorimotor area ipsi-lateral to the stimulated hand could be detected in almost of all subjects. The supplementary motor area could be detected in all subjects. In group A, the average %{Delta}CBF were up 24.1{+-}4.3% in the contra-lateral sensorimotor area, and 22.3{+-}3.6% in the supplementary motor area, respectively. The average %{Delta}CBF in the contra-lateral sensorimotor area of group D was significantly higher than that of group A. The brain functional mapping by motor activation using SPECT could localize the area of cortical motor function in normal volunteers and patients with brain tumors. The changes of regional CBF by activation SPECT precisely assess the cortical motor function even in patients with brain tumors located near central sulcus. (K.H.)

  19. Task control signals in pediatric Tourette syndrome show evidence of immature and anomalous functional activity

    Directory of Open Access Journals (Sweden)

    Jessica A Church

    2009-11-01

    Full Text Available Tourette Syndrome (TS is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008. A prior resting-state functional connectivity MRI (rs-fcMRI analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e. correlations outside the typical developmental range limited to the adaptive control network (Church et al., 2009. The present study used functional MRI (fMRI to study brain activity related to adaptive control (by studying start-cues signals, and to task-maintenance (by studying signals sustained across a task set. Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue activity will be altered in TS, including activity inconsistent with typical development (“anomalous”. Second, group differences found in task maintenance (i.e., sustained activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents

  20. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review.

    Science.gov (United States)

    Tipping, Claire J; Harrold, Meg; Holland, Anne; Romero, Lorena; Nisbet, Travis; Hodgson, Carol L

    2017-02-01

    Early active mobilisation and rehabilitation in the intensive care unit (ICU) is being used to prevent the long-term functional consequences of critical illness. This review aimed to determine the effect of active mobilisation and rehabilitation in the ICU on mortality, function, mobility, muscle strength, quality of life, days alive and out of hospital to 180 days, ICU and hospital lengths of stay, duration of mechanical ventilation and discharge destination, linking outcomes with the World Health Organization International Classification of Function Framework. A PRISMA checklist-guided systematic review and meta-analysis of randomised and controlled clinical trials. Fourteen studies of varying quality including a total of 1753 patients were reviewed. Active mobilisation and rehabilitation had no impact on short- or long-term mortality (p > 0.05). Meta-analysis showed that active mobilisation and rehabilitation led to greater muscle strength (body function) at ICU discharge as measured using the Medical Research Council Sum Score (mean difference 8.62 points, 95% confidence interval (CI) 1.39-15.86), greater probability of walking without assistance (activity limitation) at hospital discharge (odds ratio 2.13, 95% CI 1.19-3.83), and more days alive and out of hospital to day 180 (participation restriction) (mean difference 9.69, 95% CI 1.7-17.66). There were no consistent effects on function, quality of life, ICU or hospital length of stay, duration of mechanical ventilation or discharge destination. Active mobilisation and rehabilitation in the ICU has no impact on short- and long-term mortality, but may improve mobility status, muscle strength and days alive and out of hospital to 180 days. CRD42015029836.

  1. Direct and indirect effects of nutritional status, physical function and cognitive function on activities of daily living in Japanese older adults requiring long-term care.

    Science.gov (United States)

    Kamo, Tomohiko; Nishida, Yuusuke

    2014-10-01

    To identify the direct and indirect effects of nutritional status, physical function, and cognitive function on activities of daily living in Japanese older adults requiring long-term care. In total, 179 participants aged ≥ 65 years who were eligible for long-term care insurance (mean age 85.5 ± 7.8 years) were recruited for this study. Nutritional status (Mini Nutritional Assessment, Short Form) and physical function (Short Physical Performance Battery) were examined. Activities of daily living, cognitive function and frailty were assessed using the Barthel Index, Mini-Mental State Examination and Clinical Frailty Scale, respectively. Path analysis was used to determine relationships between these factors and the activities of daily living. For Japanese older adults requiring long-term care, pathways were modeled for nutritional status, physical function and the activities of daily living. The total effect of nutritional status was 0.516 (Pnutritional status through physical function on the activities of daily living was 0.458 (Pnutritional status on activities of daily living was observed (b=0.058, P=0.258). The present study identified the complex pathway from nutritional status to the activities of daily living through physical function in aged Japanese people requiring long-term care. These findings suggest that maintaining good nutritional status and nutritional support might delay physical function decline, and prolong the activities of daily living. © 2013 Japan Geriatrics Society.

  2. Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities.

    Science.gov (United States)

    Tsalkova, Tamara; Blumenthal, Donald K; Mei, Fang C; White, Mark A; Cheng, Xiaodong

    2009-08-28

    Epac2 is a member of the family of exchange proteins directly activated by cAMP (Epac). Our previous studies suggest a model of Epac activation in which cAMP binding to the enzyme induces a localized "hinge" motion that reorients the regulatory lobe relative to the catalytic lobe without inducing large conformational changes within individual lobes. In this study, we identified the location of the major hinge in Epac2 by normal mode motion correlation and structural alignment analyses. Targeted mutagenesis was then performed to test the functional importance of hinge bending for Epac activation. We show that substitution of the conserved residue phenylalanine 435 with glycine (F435G) facilitates the hinge bending and leads to a constitutively active Epac2 capable of stimulating nucleotide exchange in the absence of cAMP. In contrast, substitution of the same residue with a bulkier side chain, tryptophan (F435W), impedes the hinge motion and results in a dramatic decrease in Epac2 catalytic activity. Structural parameters determined by small angle x-ray scattering further reveal that whereas the F435G mutant assumes a more extended conformation in the absence of cAMP, the F435W mutant is incapable of adopting the fully extended and active conformation in the presence of cAMP. These findings demonstrate the importance of hinge motion in Epac activation. Our study also suggests that phenylalanine at position 435 is the optimal size side chain to keep Epac closed and inactive in the absence of cAMP while still allowing the proper hinge motion for full Epac extension and activation in the presence of cAMP.

  3. AMPK up-activation reduces motility and regulates other functions of boar spermatozoa.

    Science.gov (United States)

    Hurtado de Llera, A; Martin-Hidalgo, D; Gil, M C; Garcia-Marin, L J; Bragado, M J

    2015-01-01

    We recently demonstrated that AMPK inhibition in spermatozoa regulates motility, plasma membrane organization, acrosome integrity and mitochondrial membrane potential. As AMPK activity varies in different energy conditions induced by sperm environment, this work investigates the functional effects of AMPK activation in boar spermatozoa. Spermatozoa were incubated under non-stimulating (TBM) or Ca(2+) and [Formula: see text]-stimulating (TCM) media in the presence/absence of AMPK activator, A769662, for different times. AMPK activity, evaluated as Thr(172) phosphorylation by western blot, is effectively increased by A769662 in spermatozoa. AMPK activation significantly reduces the percentage of motile spermatozoa under Ca(2+) and/or [Formula: see text]-stimulating conditions. Moreover, AMPK activation in spermatozoa incubated in TBM or TCM significantly reduces curvilinear VCL, straight-line VSL and average VAP velocities, which subsequently lead to a significant decrease in the percentage of rapid spermatozoa (VAP > 80 μm/s). The effect of AMPK activation on motility is intensified by the absence of BSA in the incubation medium. AMPK activation for a short time prevents the decline in cell viability and in the sperm population displaying high mitochondrial membrane potential which is induced by Ca(2+) and [Formula: see text]. Sustained (24 h) AMPK activation under TBM or TCM significantly increases both lipid disorganization and phosphatidylserine externalization in the sperm plasma membrane, and diminishes the acrosome membrane integrity. In summary, AMPK activation modifies essential sperm processes such as motility, viability, mitochondrial membrane potential, acrosome membrane integrity, and organization and fluidity of plasma membrane. As these spermatozoa processes are required under different environmental conditions when transiting through the female reproductive tract to achieve fertilization, we conclude that balanced levels of AMPK activity are

  4. Covalent organic polymer functionalization of activated carbon surfaces through acyl chloride for environmental clean-up

    DEFF Research Database (Denmark)

    Mines, Paul D.; Thirion, Damien; Uthuppu, Basil

    2017-01-01

    Nanoporous networks of covalent organic polymers (COPs) are successfully grafted on the surfaces of activated carbons, through a series of surface modification techniques, including acyl chloride formation by thionyl chloride. Hybrid composites of activated carbon functionalized with COPs exhibit...... a core-shell formation of COP material grafted to the outer layers of activated carbon. This general method brings features of both COPs and porous carbons together for target-specific environmental remediation applications, which was corroborated with successful adsorption tests for organic dyes...

  5. Structural and functional brain changes related to different types of physical activity across the life span.

    Science.gov (United States)

    Voelcker-Rehage, Claudia; Niemann, Claudia

    2013-11-01

    Physical activity has been shown to improve cognitive functioning. Research has largely focused on cognitive facilitation by cardiovascular exercise in older adults. Only few studies have investigated younger age groups or other types of physical activity. In this paper we review and summarize common results found in recent studies of metabolic (i.e. cardiovascular and resistance) and coordinative exercise. Findings from human motor learning are utilized to complement results on coordinative exercise. Results show that both types of exercise affect the brain differently. We propose possible mechanisms by which physical activity facilitates cognitive performance by briefly reviewing microscopic structural changes in animal research. Lastly, we highlight open research questions.

  6. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation.

    Science.gov (United States)

    Gallo, Cristina; Dallaglio, Katiuscia; Bassani, Barbara; Rossi, Teresa; Rossello, Armando; Noonan, Douglas M; D'Uva, Gabriele; Bruno, Antonino; Albini, Adriana

    2016-09-13

    Angiogenesis, a process characterized by the formation of new blood vessels from pre-existing ones, is a crucial step in tumor growth and dissemination. Recently, increased attention has been addressed to the ability of flavonoids to prevent cancer by suppressing angiogenesis, strategy that we named "angioprevention". Several natural compounds exert their anti-tumor properties by activating 5' adenosine monophosphate-activated protein kinase (AMPK), a key regulator of metabolism in cancer cells. Drugs with angiopreventive activities, in particular metformin, regulate AMPK in endothelial cells. Here we investigated the involvement of AMPK in the anti-angiogenic effects of xanthohumol (XN), the major prenylated flavonoid of the hop plant, and mechanisms of action. The anti-angiogenic activity of XN was more potent than epigallocatechin-3-gallate (EGCG). Treatment of endothelial cells with XN led to increased AMPK phosphorylation and activity. Functional studies using biochemical approaches confirmed that AMPK mediates XN anti-angiogenic activity. AMPK activation by XN was mediated by CAMMKβ, but not LKB1. Analysis of the downstream mechanisms showed that XN-induced AMPK activation reduced nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation. Finally, AKT pathway was inactivated by XN as part of its anti-angiogenic activity, but independently from AMPK, suggesting that these two signaling pathways proceed autonomously. Our study dissects the molecular mechanism by which XN exerts its potent anti-angiogenic activity, pointing out AMPK as a crucial signal transducer.

  7. Dimerization of matrix metalloproteinase-2 (MMP-2): functional implication in MMP-2 activation.

    Science.gov (United States)

    Koo, Bon-Hun; Kim, Yeon Hyang; Han, Jung Ho; Kim, Doo-Sik

    2012-06-29

    Matrix metalloproteinase-2 (MMP-2) functions in diverse biological processes through the degradation of extracellular and non-extracellular matrix molecules. Because of its potential for tissue damage, there are several ways to regulate MMP-2 activity, including gene expression, compartmentalization, zymogen activation, and enzyme inactivation by extracellular inhibitors. Enzyme regulation through zymogen activation is important for the regulation of MMP-2 activity. In our previous studies, we showed that thrombin directly cleaved the propeptide of MMP-2 at specific sites for enzyme activation. We also demonstrated that heparan sulfate was required for thrombin-mediated activation of pro-MMP-2 by binding to thrombin, presumably through conformational changes at the active site of the enzyme. This suggests a regulatory mechanism for thrombin-mediated activation of pro-MMP-2. In this study, we found that MMP-2 formed a reduction-sensitive homodimer in a controlled manner and that Ca(2+) ion was essential for homodimerization of MMP-2. Homodimerization was not associated with protein kinase C-mediated phosphorylation of MMP-2. MMP-2 formed a homodimer through an intermolecular disulfide bond between Cys(102) and the neighboring Cys(102). Homodimerization of MMP-2 enhanced thrombin-mediated activation of pro-MMP-2. Moreover, the MMP-2 homodimer could cleave a small peptide substrate without removal of the propeptide. Taken together, our experimental data suggest a novel regulatory mechanism for pro-MMP-2 activation that is modulated through homodimerization of MMP-2.

  8. Control interfaces to actively support the arm function of men with Duchenne Muscular Dystrophy

    NARCIS (Netherlands)

    Lobo Prat, Joan

    2016-01-01

    Adults with DMD can benefit from active arm supports that augment their residual functional capabilities. However, intuitively controlled and fully actuated arm supports are currently not commercially available and adults with DMD are limited to use external robotic arms which contribute to the disu

  9. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    Energy Technology Data Exchange (ETDEWEB)

    Lonsdale, H.K.; Wamser, C.C.

    1990-04-17

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  10. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    Science.gov (United States)

    Lonsdale, Harold K.; Wamser, Carl C.

    1988-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membanes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanime derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  11. A goal activation approach to the study of executive function : An application to antisaccade tasks

    NARCIS (Netherlands)

    Nieuwenhuis, S; Broerse, A; Nielen, MMA; de Jong, R

    2004-01-01

    We argue that a general control process, responsible for the activation and maintenance of task goals, is central to the concept of executive function. Failures of this process can become manifest as goal neglect: disregard of a task requirement even though it has been understood (Duncan, 1995). We

  12. Temperamental activation and inhibition associated with autonomic function in preadolescents. The TRAILS study

    NARCIS (Netherlands)

    Dietrich, Andrea; Riese, Harriette; van Roon, Arie M.; Minderaa, Ruud B.; Oldehinkel, Albertine J.; Neeleman, Jan; Rosmalen, Judith G. M.

    2009-01-01

    We investigated the temperamental traits high-intensity pleasure (temperamental activation) and shyness (temperamental inhibition) in relation to autonomic function as measured by heart rate (HR), respiratory sinus arrhythmia (RSA), and baroreflex sensitivity (BRS) in 938 10-13-year-old preadolescen

  13. Synergistic effect between defect sites and functional groups on the hydrolysis of cellulose over activated carbon.

    Science.gov (United States)

    Foo, Guo Shiou; Sievers, Carsten

    2015-02-01

    The chemical oxidation of activated carbon by H2 O2 and H2 SO4 is investigated, structural and chemical modifications are characterized, and the materials are used as catalysts for the hydrolysis of cellulose. Treatment with H2 O2 enlarges the pore size and imparts functional groups such as phenols, lactones, and carboxylic acids. H2 SO4 treatment targets the edges of carbon sheets primarily, and this effect is more pronounced with a higher temperature. Adsorption isotherms demonstrate that the adsorption of oligomers on functionalized carbon is dominated by van der Waals forces. The materials treated chemically are active for the hydrolysis of cellulose despite the relative weakness of most of their acid sites. It is proposed that a synergistic effect between defect sites and functional groups enhances the activity by inducing a conformational change in the glucan chains if they are adsorbed at defect sites. This activates the glycosidic bonds for hydrolysis by in-plane functional groups. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Functional decline from age 80 to 85: Influence of preceding changes in tiredness in daily activities

    DEFF Research Database (Denmark)

    Avlund, K.; Pedersen, Agnes Nadelmann; Schroll, M.

    2003-01-01

    County. Tiredness in daily activities was measured at age 75 and 80 by a validated scale. Changes in tiredness from age 75 to 80: 1) Sustained no tiredness, 2) not tired-tired, 3) tired-not tired, 4) sustained tiredness. Functional decline from age 80 to 85:1) Sustained no need of help; 2) need of help...

  15. Functional decline from age 80 to 85: influence of preceding changes in tiredness in daily activities

    DEFF Research Database (Denmark)

    Avlund, Kirsten; Pedersen, Agnes N; Schroll, Marianne

    2003-01-01

    County. Tiredness in daily activities was measured at age 75 and 80 by a validated scale. Changes in tiredness from age 75 to 80: 1) Sustained no tiredness, 2) not tired-tired, 3) tired-not tired, 4) sustained tiredness. Functional decline from age 80 to 85:1) Sustained no need of help; 2) need of help...

  16. The function of the earth observing system - Data information system Distributed Active Archive Centers

    Science.gov (United States)

    Lapenta, C. C.

    1992-01-01

    The functionality of the Distributed Active Archive Centers (DAACs) which are significant elements of the Earth Observing System Data and Information System (EOSDIS) is discussed. Each DAAC encompasses the information management system, the data archival and distribution system, and the product generation system. The EOSDIS DAACs are expected to improve the access to earth science data set needed for global change research.

  17. Statin Use and Functional Outcome after Tissue Plasminogen Activator Treatment in Acute Ischaemic Stroke

    NARCIS (Netherlands)

    Miedema, I; Uyttenboogaart, M; Koopman, K; De Keyser, J; Luijckx, G J

    2010-01-01

    Background: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients prior on statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional ou

  18. 24-Hour motor activity and autonomic cardiac functioning in major depressive disorder

    NARCIS (Netherlands)

    A.C. Volkers (Anita)

    2002-01-01

    textabstractThe studies of this thesis concern the spontaneous pattern of motor activity and autonomic cardiac functioning in major depressive disorder. The main purpose of the studies was to obtain insight in the psychomotor and autonomic cardiac dysfunction in depression by investigating the 24-ho

  19. Differential Item Functioning Analysis of the 2003-04 NHANES Physical Activity Questionnaire

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-01-01

    Using differential item functioning (DIF) analyses, this study examined whether there were any DIF items in the National Health and Nutrition Examination Survey (NHANES) physical activity (PA) questionnaire. A subset of adult data from the 2003-04 NHANES study (n = 3,083) was used. PA items related to respondents' occupational, transportation,…

  20. Fast Back-Propagation Learning Using Steep Activation Functions and Automatic Weight

    Science.gov (United States)

    Tai-Hoon Cho; Richard W. Conners; Philip A. Araman

    1992-01-01

    In this paper, several back-propagation (BP) learning speed-up algorithms that employ the ãgainä parameter, i.e., steepness of the activation function, are examined. Simulations will show that increasing the gain seemingly increases the speed of convergence and that these algorithms can converge faster than the standard BP learning algorithm on some problems. However,...

  1. Simultaneous EMG-Functional MRI Recordings Can Directly Relate Hyperkinetic Movements to Brain Activity

    NARCIS (Netherlands)

    van Rootselaar, Anne-Fleur; Maurits, Natasha M.; Renken, Remco; Koelman, Johannes H. T. M.; Hoogduin, Johannes M.; Leenders, Klaus L.; Tijssen, Marina A. J.

    2008-01-01

    Objective: To apply and validate the use of electromyogram (EMG) recorded during functional magnetic resonance imaging (fMRI) in patients with movement disorders, to directly relate involuntary movements to brain activity. Methods: Eight "familial cortical myoclonic tremor with epilepsy" (FCMTE) pat

  2. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities

    Science.gov (United States)

    We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypoth...

  3. A Double-Blind Atropine Trial for Active Learning of Autonomic Function

    Science.gov (United States)

    Fry, Jeffrey R.; Burr, Steven A.

    2011-01-01

    Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to…

  4. Differential Item Functioning Analysis of the 2003-04 NHANES Physical Activity Questionnaire

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-01-01

    Using differential item functioning (DIF) analyses, this study examined whether there were any DIF items in the National Health and Nutrition Examination Survey (NHANES) physical activity (PA) questionnaire. A subset of adult data from the 2003-04 NHANES study (n = 3,083) was used. PA items related to respondents' occupational, transportation,…

  5. Mutation specific functions of EGFR result in a mutation-specific downstream pathway activation

    NARCIS (Netherlands)

    L. Eraslan-Erdem (Lale); Y. Gao; N.K. Kloosterhof (Nanne); Y. Atlasi (Yaser); J.A.A. Demmers (Jeroen); A. Sacchetti (Andrea); J.M. Kros (Johan); P.A.E. Sillevis Smitt (Peter); J.G.J.V. Aerts (Joachim); P.J. French (Pim)

    2015-01-01

    markdownabstractBackground: Epidermal growth factor receptor (EGFR) is frequently mutated in various types of cancer. Although all oncogenic mutations are considered activating, different tumour types have different mutation spectra. It is possible that functional differences underlie this tumour-ty

  6. Poor Vision, Functioning, and Depressive Symptoms: A Test of the Activity Restriction Model

    Science.gov (United States)

    Bookwala, Jamila; Lawson, Brendan

    2011-01-01

    Purpose: This study tested the applicability of the activity restriction model of depressed affect to the context of poor vision in late life. This model hypothesizes that late-life stressors contribute to poorer mental health not only directly but also indirectly by restricting routine everyday functioning. Method: We used data from a national…

  7. Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue metabolic activity.

    Science.gov (United States)

    Zvintzou, Evangelia; Lhomme, Marie; Chasapi, Stella; Filou, Serafoula; Theodoropoulos, Vassilis; Xapapadaki, Eva; Kontush, Anatol; Spyroulias, George; Tellis, Constantinos C; Tselepis, Alexandros D; Constantinou, Caterina; Kypreos, Kyriakos E

    2017-09-01

    APOC3 is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to preexisting particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype. However, the roles of APOC3 in HDL functionality and adipose tissue metabolic activity remain unknown. Therefore, here we investigated the direct effects of APOC3 expression on HDL structure and function, as well as white adipose tissue (WAT) and brown adipose tissue (BAT) metabolic activity. C57BL/6 mice were infected with an adenovirus expressing human APOC3 or a recombinant attenuated control adenovirus expressing green fluorescent protein and blood and tissue samples were collected at 5 days postinfection. HDL was then analyzed for its apolipoprotein and lipid composition and particle functionality. Additionally, purified mitochondria from BAT and WAT were analyzed for uncoupling protein 1, cytochrome c (Cytc), and Cytc oxidase subunit 4 protein levels as an indirect measure of their metabolic activity. Serum metabolomic analysis was performed by NMR. Combined, our data show that APOC3 modulates HDL structure and function, while it selectively promotes BAT metabolic activation. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  8. Atrial conduction times and left atrium mechanical functions in patients with active acromegaly.

    Science.gov (United States)

    Ilter, A; Kırış, A; Kaplan, Ş; Kutlu, M; Şahin, M; Erem, C; Civan, N; Kangül, F

    2015-03-01

    The aim of this study was to evaluate atrial electromechanical delay (EMD), P wave dispersion (Pwd), and left atrial (LA) mechanical functions in patients with active acromegaly. Twenty-three patients with active acromegaly and 27 age- and sex-matched controls were included in this study. All atrial electromechanical interval parameters (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) were measured from mitral lateral annulus, mitral septal annulus, and right ventricular tricuspid annulus by tissue Doppler imaging. LA volumes were measured by the disk method in the apical four-chamber view and were indexed to the body surface area. Mechanical function parameters of LA were calculated. Pwd was performed by 12-lead electrocardiograms. Atrial electromechanical intervals (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) and Pwd were similar between patients with acromegaly and control subjects (all p > 0.05). LA volumes (maximum, minimum, and presystolic) and LA mechanical functions were not significantly different between the groups (all p > 0.05). Additionally, serum levels of growth hormone and insulin-like growth factor-1 were not correlated with atrial electromechanical parameters and LA mechanical functions. Atrial electrical conduction times were not prolonged and LA mechanical functions were not impaired in patients with active acromegaly compared with controls. And the prevalence of supraventricular arrhythmia risk may not increase in this population.

  9. Mode of action and functional significance of 7alpha-hydroxypregnenolone stimulating locomotor activity

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi

    2011-08-01

    Full Text Available Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507alpha and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7alpha-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.

  10. Tamoxifen and its active metabolites inhibit dopamine transporter function independently of the estrogen receptors.

    Science.gov (United States)

    Mikelman, Sarah R; Guptaroy, Bipasha; Gnegy, Margaret E

    2017-04-01

    As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [(3) H]dopamine uptake into human DAT (hDAT)-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake. Importantly, we demonstrate that the effects of tamoxifen and its metabolites on the DAT occur independently of its activity as selective estrogen receptor modulators. This work suggests that tamoxifen is inhibiting DAT function through a previously unidentified mechanism. © 2017 International Society for Neurochemistry.

  11. Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans.

    Science.gov (United States)

    Grigoleit, Jan-Sebastian; Oberbeck, J Reiner; Lichte, Philipp; Kobbe, Philipp; Wolf, Oliver T; Montag, Thomas; del Rey, Adriana; Gizewski, Elke R; Engler, Harald; Schedlowski, Manfred

    2010-11-01

    Systemic immune activation occurring together with release of peripheral cytokines can affect behavior and the functioning of the central nervous system (CNS). However, it remains unknown whether and to what extent cognitive functions like memory and attention are affected during transient immune activation. We employed a human endotoxemia model and standardized neuropsychological tests to assess the cognitive effects of an experimental inflammation in two groups of 12 healthy young men before and after intravenous injection of lipopolysaccharide (LPS, Escherichia coli, 0.4 ng/kg) or physiological saline. Endotoxin administration caused a profound transient physiological response with elevations in body temperature, number of circulating neutrophils, and increases in plasma cytokine levels [interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α], and concentrations of norepinephrine, ACTH and cortisol. However, these changes in immune and neuroendocrine parameters were not associated with alterations of memory performance, selective attention or executive functions. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Multistability of complex-valued neural networks with discontinuous activation functions.

    Science.gov (United States)

    Liang, Jinling; Gong, Weiqiang; Huang, Tingwen

    2016-12-01

    In this paper, based on the geometrical properties of the discontinuous activation functions and the Brouwer's fixed point theory, the multistability issue is tackled for the complex-valued neural networks with discontinuous activation functions and time-varying delays. To address the network with discontinuous functions, Filippov solution of the system is defined. Through rigorous analysis, several sufficient criteria are obtained to assure the existence of 25(n) equilibrium points. Among them, 9(n) points are locally stable and 16(n)-9(n) equilibrium points are unstable. Furthermore, to enlarge the attraction basins of the 9(n) equilibrium points, some mild conditions are imposed. Finally, one numerical example is provided to illustrate the effectiveness of the obtained results.

  13. Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells.

    Science.gov (United States)

    Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

    2014-08-01

    Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.

  14. A new era for functional labeling of neurons: activity-dependent promoters have come of age

    Directory of Open Access Journals (Sweden)

    Takashi eKawashima

    2014-04-01

    Full Text Available Genetic labeling of neurons with a specific response feature is an emerging technology for precise dissection of brain circuits that are functionally heterogeneous at the single-cell level. While immediate early gene mapping has been widely used for decades to identify brain regions which are activated by external stimuli, recent characterization of the promoter and enhancer elements responsible for neuronal activity-dependent transcription have opened new avenues for live imaging of active neurons. Indeed, these advancements provided the basis for a growing repertoire of novel experiments to address the role of active neuronal networks in cognitive behaviors. In this review, we summarize the current literature on the usage and development of activity-dependent promoters and discuss the future directions of this expanding new field.

  15. Chicken mannose-binding lectin function in relation to antibacterial activity towards Salmonella enterica

    DEFF Research Database (Denmark)

    Ulrich-Lynge, Sofie Louise; Dalgaard, Tina Sørensen; Norup, Liselotte Rothmann;

    2015-01-01

    ) serotypes B, C1 and D was investigated by flow cytometry, and Staphylococcus aureus (S. aureus) was used for comparison. For S. enterica the C1 serotypes were the only group to exhibit binding to cMBL. Furthermore, functional studies of the role of cMBL in phagocytosis and complement activation were...... performed. Spiking with cMBL had a dose-dependent effect on the HD11 phagocytic activity of S. enterica subsp. enterica serovar Montevideo, and a more pronounced effect in a carbohydrate competitive assay. This cMBL dose dependency of opsonophagocytic activity by HD11 cells was not observed for S. aureus....... No difference in complement-dependent bactericidal activity in serum with high or low cMBL concentrations was found for S. Montevideo. On the other hand, serum with high concentrations of cMBL exhibited a greater bactericidal activity to S. aureus than serum with low concentrations of cMBL. The results...

  16. Autonomic functions and their relations with disease activity in ankylosing spondylitis.

    Science.gov (United States)

    Gunay, Tuba; Yilmaz, Ozlem; Bodur, Hatice

    2012-01-01

    To evaluate the autonomic functions in patients with ankylosing spondylitis (AS) by means of clinical and electrophysiological tests, to compare the data with those of healthy individuals and to investigate the relationship with the disease activity. 32 asymptomatic AS patients and 30 healthy controls were included in the study. Parasympathetic functions were evaluated clinically with heart rate variability (HRV) and electrophysiologically with R-R interval variation (RRIV). Sympathetic functions were evaluated clinically with diastolic blood pressure response to isometric exercise (DBP) and electrophysiologically with sympathetic skin response (SSR). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score -C (ASDAS-C) were used to estimate the disease activity. HRV and RRIV was significantly lower in patients with AS when compared to controls, and in patients with BASDAI greater or equal to 4 when compared to the patients with BASDAI less than 4. There was no difference between the AS and the control groups and between the groups with BASDAI greater or equal to 4 and BASDAI less than 4 for DBP. Although there was no difference for SSR between AS and the control groups, SSR latency was significantly longer and SSR amplitude was significantly smaller in the group with BASDAI greater or equal to 4 when compared to the group with BASDAI less than 4. Our results indicate a parasympathetic dysfunction in AS patients, however the sympathetic system seems to be affected when the disease activity is increased. Patients with AS even they are asymptomatic must be investigated for autonomic dysfunction.

  17. Activation detection in functional near-infrared spectroscopy by wavelet coherence

    Science.gov (United States)

    Zhang, Xin; Yu, Jian; Zhao, Ruirui; Xu, Wenting; Niu, Haijing; Zhang, Yujin; Zuo, Nianming; Jiang, Tianzi

    2015-01-01

    Functional near-infrared spectroscopy (fNIRS) detects hemodynamic responses in the cerebral cortex by transcranial spectroscopy. However, measurements recorded by fNIRS not only consist of the desired hemodynamic response but also consist of a number of physiological noises. Because of these noises, accurately detecting the regions that have an activated hemodynamic response while performing a task is a challenge when analyzing functional activity by fNIRS. In order to better detect the activation, we designed a multiscale analysis based on wavelet coherence. In this method, the experimental paradigm was expressed as a binary signal obtained while either performing or not performing a task. We convolved the signal with the canonical hemodynamic response function to predict a possible response. The wavelet coherence was used to investigate the relationship between the response and the data obtained by fNIRS at each channel. Subsequently, the coherence within a region of interest in the time-frequency domain was summed to evaluate the activation level at each channel. Experiments on both simulated and experimental data demonstrated that the method was effective for detecting activated channels hidden in fNIRS data.

  18. Active components of common traditional Chinese medicine decoctions have antioxidant functions.

    Science.gov (United States)

    Guo, K J; Xu, S F; Yin, P; Wang, W; Song, X Z; Liu, F H; Xu, J Q; Zoccarato, I

    2011-10-01

    Many traditional Chinese medicine (TCM) decoctions are proven to have multiple functions in animal production. These decoctions are seldom recognized by the international scientific community because the mechanisms of action are not clearly elucidated. According to TCM theory, Cortex Phellodendri (COP), Rhizoma Atractylodes (RA), Agastache Rugosa (AR), and Gypsum Fibrosum (GF) can be used to formulate a medicinal compound that prevents or cures animal disease caused by heat stress. The aim of this research was to study the regulatory functions of the active components of TCM and to elucidate the effects of different TCM decoctions on antioxidant activity and lipid peroxide content, using in vitro and in vivo models of heat stress. For in vitro experiments, intestinal crypt-like epithelial cell line-6 (IEC-6) cells were employed to evaluate the effects of the active components of COP, RA, AR, and GF. For in vivo experiments, forty-eight 2-mo-old Chinese experimental mini-pigs (7.20 ± 0.02 kg) were randomly assigned to 4 groups: a normal-temperature group (NTG); a high-temperature group (HTG); HTG treated with COP, RA, AR, and GF (1:1:1:1, TCM1); and HTG treated with COP, RA, AR, and GF (1:1:1:0.5, TCM2). Results showed that the active components of the COP, RA, AR, and GF increased (P active components increased (P activities, and glutathione content, and decreased (P activities, and malondialdehyde content in porcine jejunum treated with TCM1 and TCM2 were not different (P > 0.05) from those seen in the NTG and were better (P active components of common TCM decoctions have antioxidant functions.

  19. A novel mode of ferric ion coordination by the periplasmic ferric ion-binding subunit FbpA of an ABC-type iron transporter from Thermus thermophilus HB8.

    Science.gov (United States)

    Wang, Shipeng; Ogata, Misaki; Horita, Shoichiro; Ohtsuka, Jun; Nagata, Koji; Tanokura, Masaru

    2014-01-01

    Crystal structures of FbpA, the periplasmic ferric ion-binding protein of an iron-uptake ABC transporter, from Thermus thermophilus HB8 (TtFbpA) have been solved in apo and ferric ion-bound forms at 1.8 and 1.7 Å resolution, respectively. The latter crystal structure shows that the bound ferric ion forms a novel six-coordinated complex with three tyrosine side chains, two bicarbonates and a water molecule in the metal-binding site. The results of gel-filtration chromatography and dynamic light scattering show that TtFbpA exists as a monomer in solution regardless of ferric ion binding and that TtFbpA adopts a more compact conformation in the ferric ion-bound state than in the apo state in solution.

  20. Structure-activity relationship of memapsin 2: implications on physiological functions and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xiaoman Li; Lin Hong; Kathleen Coughlan; Liang Wang; Liu Cao; Jordan Tang

    2013-01-01

    Memapsin 2 (BACE1,β-secretase),a membrane aspartic protease,functions in the cleavage of the type Ⅰ transmembrane protein,β-amyloid precursor protein (APP),leading to the production of amyloid β (Aβ) in the brain.Since Aβ is closely associated with the pathogenesis of Alzheimer's disease,understanding the biological function,particularly the catalytic activities of memapsin 2,would assist in a better understanding of the disease and the development of its inhibitors.The transmembrane and cytosolic domains of memapsin 2 function in cellular transport and localization,which are important regulatory mechanisms for its activity.The catalytic ectodomain contains a long substrate cleft that is responsible for substrate recognition,specificity,and peptide bond hydrolysis.The substrate cleft accommodates 11 residues of the substrate in separate binding subsites.Besides APP,a number of membrane proteins have been reported to be substrates of memapsin 2.The elucidation for the specificity of these subsites and the amino acid sequences surrounding the memapsin 2 cleavage site in these proteins has led to the establishment of a predictive model that can quantitatively estimate the efficiency of cleavage for any potential substrates.Such tools may be employed for future studies of memapsin 2 about its biological function.Herein,we review the current knowledge on the structure-function relationship of memapsin 2 and its relationship in the biological function.

  1. p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo.

    Science.gov (United States)

    Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Stefanini, Lucia; Schatzberg, Daphne; Cifuni, Stephen M; Bergmeier, Wolfgang; Wagner, Denisa D

    2010-03-01

    Platelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-alpha and GPV. We recently demonstrated that tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37 degrees C or 22 degrees C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets.

  2. Activation of Melatonin Signaling Promotes β-Cell Survival and Function.

    Science.gov (United States)

    Costes, Safia; Boss, Marti; Thomas, Anthony P; Matveyenko, Aleksey V

    2015-05-01

    Type 2 diabetes mellitus (T2DM) is characterized by pancreatic islet failure due to loss of β-cell secretory function and mass. Studies have identified a link between a variance in the gene encoding melatonin (MT) receptor 2, T2DM, and impaired insulin secretion. This genetic linkage raises the question whether MT signaling plays a role in regulation of β-cell function and survival in T2DM. To address this postulate, we used INS 832/13 cells to test whether activation of MT signaling attenuates proteotoxicity-induced β-cell apoptosis and through which molecular mechanism. We also used nondiabetic and T2DM human islets to test the potential of MT signaling to attenuate deleterious effects of glucotoxicity and T2DM on β-cell function. MT signaling in β-cells (with duration designed to mimic typical nightly exposure) significantly enhanced activation of the cAMP-dependent signal transduction pathway and attenuated proteotoxicity-induced β-cell apoptosis evidenced by reduced caspase-3 cleavage (∼40%), decreased activation of stress-activated protein kinase/Jun-amino-terminal kinase (∼50%) and diminished oxidative stress response. Activation of MT signaling in human islets was shown to restore glucose-stimulated insulin secretion in islets exposed to chronic hyperglycemia as well as in T2DM islets. Our data suggest that β-cell MT signaling is important for the regulation of β-cell survival and function and implies a preventative and therapeutic potential for preservation of β-cell mass and function in T2DM.

  3. Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

    Science.gov (United States)

    Peinado, Alejandro; Abrams, Charles K

    2015-01-01

    Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying

  4. EFFECTS OF LONG-TERM PHYSICAL ACTIVITY ON CARDIAC STRUCTURE AND FUNCTION: A TWIN STUDY

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    Urho M.Kujala

    2009-12-01

    Full Text Available Previous studies have shown that athletic training or other physical activity causes structural and functional adaptations in the heart, but less is known how long-term physical activity affects heart when genetic liability and childhood environment are taken into account. The aim of this study was to investigate the effects of long-term physical activity vs. inactivity on cardiac structure and function in twin pairs discordant for physical activity for 32 years. Twelve same-sex twin pairs (five monozygotic and seven dizygotic, 50-67 years were studied as a part of the TWINACTIVE study. Discordance in physical activity was initially determined in 1975 and it remained significant throughout the follow-up. At the end of the follow-up in 2007, resting echocardiographic and electrocardiographic measurements were performed. During the follow-up period, the active co-twins were on average 8.2 (SD 4.0 MET hours/day more active than their inactive co-twins (p < 0.001. At the end of the follow-up, resting heart rate was lower in the active than inactive co-twins [59 (SD 5 vs. 68 (SD 10 bpm, p=0.03]. The heart rate-corrected QT interval was similar between the co-twins. Also, there was a tendency for left ventricular mass per body weight to be greater and T wave amplitude in lead II to be higher in the active co-twins (18% and 15%, respectively, p=0.08 for both. Similar trends were found for both monozygotic and dizygotic twin pairs. In conclusion, the main adaptation to long- term physical activity is lowered resting heart rate, even after partially or fully controlling for genetic liability and childhood environment

  5. Linking Activity and Function to Ecosystem Dynamics in a Coastal Bacterioplankton Community

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    Scott Michael Gifford

    2014-04-01

    Full Text Available For bacterial communities containing hundreds to thousands of distinct populations, connecting functional processes and environmental dynamics at high taxonomic resolution has remained challenging. Here we use the expression of ribosomal proteins (%RP as a proxy for in situ activity of 200 taxa within 20 metatranscriptomic samples in a coastal ocean time series encompassing both seasonal variability and diel dynamics. %RP patterns grouped the taxa into seven activity clusters with distinct profiles in functional gene expression and correlations with environmental gradients. Clusters 1-3 had their highest potential activity in the winter and fall, and included some of the most active taxa, while Clusters 4-7 had their highest potential activity in the spring and summer. Cluster 1 taxa were characterized by gene expression for motility and complex carbohydrate degradation (dominated by Gammaproteobacteria and Bacteroidetes, and Cluster 2 taxa by transcription of genes for amino acid and aromatic compound metabolism and aerobic anoxygenic phototrophy (Roseobacter. Other activity clusters were enriched in transcripts for proteorhodopsin and methylotrophy (Cluster 4; SAR11 and methylotrophs, photosynthesis and attachment (Clusters 5 and 7; Synechococcus, picoeukaryotes, Verucomicrobia, and Planctomycetes, and sulfur oxidation (Cluster 7; Gammaproteobacteria. The seasonal patterns in activity were overlain, and sometimes obscured, by large differences in %RP over shorter day-night timescales. Seventy-eight taxa, many of them heterotrophs, had a higher %RP activity index during the day than night, indicating strong diel activity at this coastal site. Emerging from these taxonomically- and time-resolved estimates of in situ microbial activity are predictions of specific ecological groupings of microbial taxa in a dynamic coastal environment.

  6. Associations between neuromuscular function and levels of physical activity differ for boys and girls during puberty.

    Science.gov (United States)

    Rudroff, Thorsten; Kelsey, Megan M; Melanson, Edward L; McQueen, Matthew B; Enoka, Roger M

    2013-08-01

    To compare the associations between neuromuscular performance and anthropometric characteristics with habitual levels of physical activity in boys and girls during the initial stages of puberty. In a cross-sectional study of 72 healthy children (39 boys and 33 girls) ranging in age from 8 to 14 years, sex differences in anthropometric and motor performance characteristics were compared at 3 Tanner stages (T1-T3). Outcome variables included dual-energy x-ray absorptiometry measurements of body composition, assessments of neuromuscular function, and levels of physical activity (steps/day) measured by accelerometry. Physical activity was lower in girls than boys at T2 and T3, but there was no sex difference at T1. Physical activity increased with Tanner stage for boys but did not differ between Tanner stages in girls. Physical activity at each Tanner stage was strongly associated (R(2) > 0.85) with neuromuscular characteristics for both boys and girls, but percentage of body fat also was associated with physical activity for T3 girls. The attenuated gains in neuromuscular function experienced by girls in early stages of puberty were strongly associated with lower levels of physical activity, whereas the increase in physical activity exhibited by boys was mostly related to increases in the strength and endurance of leg muscles. Because sedentary activity is a known contributor to the development of obesity and type 2 diabetes in youth, this study helps to identify possible contributors to decreases in physical activity in young girls and provides potential targets for early intervention. Copyright © 2013 Mosby, Inc. All rights reserved.

  7. Inhibition of water activated by far infrared functional ceramics on proliferation of hepatoma cells.

    Science.gov (United States)

    Zhang, Dongmei; Liang, Jinsheng; Ding, Yan; Meng, Junping; Zhang, Guangchuan

    2014-05-01

    Rare earth (RE)/tourmaline composite materials prepared by the precipitation method are added to the ceramic raw materials at a certain percentage and sintered into RE functional ceramics with high far infrared emission features. Then the far infrared functional ceramics are used to interact with water. The influence of the ceramics on the physical parameters of water is investigated, and the effect of the activated water on the growth of Bel-7402 hepatoma cells cultured in vitro is further studied. The results indicate that, compared with the raw water, the water activated by the ceramics can inhibit the proliferation of hepatoma cells, with statistical probability P ceramics has a higher concentration of H+, which decreases the potential difference across the cell membrane to release the apoptosis inducing factor (AIF). After entering the cells, the activated water stimulates the mitochondria to produce immune substances that lead tumor cells to apoptosis.

  8. Regulation of myelin genes implicated in psychiatric disorders by functional activity in axons

    Directory of Open Access Journals (Sweden)

    Philip R Lee

    2009-06-01

    Full Text Available Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between cortical regions carrying out higher level cognitive functions. Myelination can be altered by impulse activity in axons and by environmental experience. Psychiatric illness is treated by psychotherapy, behavioral modification, and drugs affecting neurotransmission, raising the possibility that myelinating glia may not only contribute to such disorders, but that activity-dependent effects on myelinating glia could provide one of the cellular mechanisms contributing to the therapeutic effects of these treatments. This review examines evidence showing that genes and gene networks important for myelination can be regulated by functional activity in axons.

  9. Thio-sugar motif of functional CARB-pharmacophore for antineoplastic activity. Part 2.

    Science.gov (United States)

    Witczak, Zbigniew J; Sarnik, Joanna; Czubatka, Anna; Forma, Ewa; Poplawski, Tomasz

    2014-12-15

    Diverse functionalized representatives of (1-4)-S-thiodisaccharides, 6-9 were synthesized and assessed for cytotoxicity and apoptosis against human cancer cell lines (A549, LoVo, MCF-7 and HeLa). The FCP 6 was more active against MCF-7 cells (i.e., an estrogen-dependent breast cancer line), whereas other (1-4)-S-thiodisaccharides showed strongest activity against A549 cells (i.e., a lung adenocarcinoma line). We propose to use a concept of functional 'CARB-pharmacophores' when evaluating a potential for the compounds' general antineoplastic activity. Future studies will determine the reasons for cell-type specificity of these compounds. The thio-sugar motif appears to be a promising lead for future developments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. A reaction mode of carbene-catalysed aryl aldehyde activation and induced phenol OH functionalization

    Science.gov (United States)

    Chen, Xingkuan; Wang, Hongling; Doitomi, Kazuki; Ooi, Chong Yih; Zheng, Pengcheng; Liu, Wangsheng; Guo, Hao; Yang, Song; Song, Bao-An; Hirao, Hajime; Chi, Yonggui Robin

    2017-05-01

    The research in the field of asymmetric carbene organic catalysis has primarily focused on the activation of carbon atoms in non-aromatic scaffolds. Here we report a reaction mode of carbene catalysis that allows for aromatic aldehyde activation and remote oxygen atom functionalization. The addition of a carbene catalyst to the aldehyde moiety of 2-hydroxyl aryl aldehyde eventually enables dearomatization and remote OH activation. The catalytic process generates a type of carbene-derived intermediate with an oxygen atom as the reactive centre. Inexpensive achiral urea co-catalyst works cooperatively with the carbene catalyst, leading to consistent enhancement of the reaction enantioselectivity. Given the wide presence of aromatic moieties and heteroatoms in natural products and synthetic functional molecules, we expect our reaction mode to significantly expand the power of carbene catalysis in asymmetric chemical synthesis.

  11. In vitro culture of functionally active buffalo hepatocytes isolated by using a simplified manual perfusion method.

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    Santanu Panda

    Full Text Available In farm animals, there is no suitable cell line available to understand liver-specific functions. This has limited our understanding of liver function and metabolism in farm animals. Culturing and maintenance of functionally active hepatocytes is difficult, since they survive no more than few days. Establishing primary culture of hepatocytes can help in studying cellular metabolism, drug toxicity, hepatocyte specific gene function and regulation. Here we provide a simple in vitro method for isolation and short-term culture of functionally active buffalo hepatocytes.Buffalo hepatocytes were isolated from caudate lobes by using manual enzymatic perfusion and mechanical disruption of liver tissue. Hepatocyte yield was (5.3 ± 0.66×107 cells per gram of liver tissue with a viability of 82.3 ± 3.5%. Freshly isolated hepatocytes were spherical with well contrasted border. After 24 hours of seeding onto fibroblast feeder layer and different extracellular matrices like dry collagen, matrigel and sandwich collagen coated plates, hepatocytes formed confluent monolayer with frequent clusters. Cultured hepatocytes exhibited typical cuboidal and polygonal shape with restored cellular polarity. Cells expressed hepatocyte-specific marker genes or proteins like albumin, hepatocyte nuclear factor 4α, glucose-6-phosphatase, tyrosine aminotransferase, cytochromes, cytokeratin and α1-antitrypsin. Hepatocytes could be immunostained with anti-cytokeratins, anti-albumin and anti α1-antitrypsin antibodies. Abundant lipid droplets were detected in the cytosol of hepatocytes using oil red stain. In vitro cultured hepatocytes could be grown for five days and maintained for up to nine days on buffalo skin fibroblast feeder layer. Cultured hepatocytes were viable for functional studies.We developed a convenient and cost effective technique for hepatocytes isolation for short-term culture that exhibited morphological and functional characteristics of active hepatocytes

  12. Changes in everyday function among individuals with psychometrically defined Mild Cognitive Impairment in the ACTIVE Study

    Science.gov (United States)

    Wadley, Virginia G.; Crowe, Michael; Marsiske, Michael; Cook, Sarah E.; Unverzagt, Frederick W.; Rosenberg, Adrienne L.; Rexroth, Daniel

    2007-01-01

    Objectives. Because many individuals with Mild Cognitive Impairment (MCI) will progress to a dementia diagnosis, this population is at high risk for losing functional independence. We examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of MCI. Design. We utilized data from the longitudinal, multi-site Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which allowed for post-hoc classification of MCI status at baseline using psycho metric definitions for amnestic MCI, non-amnestic MCI, multi-domain MCI, and no MCI. Setting. Six U.S. cities. Participants. 2832 volunteers (mean age 74 years; 26% African American) living independently, recruited from senior housing, community centers, and hospitals and clinics. Measurements. Mixed effect models examined changes in self-reported instrumental and basic activities of daily living (IADLs and ADLs) from the MDS Home Care Interview in 2,358 participants over a three-year period. Results. In models for IADL performance, IADL difficulty, and a Daily Functioning Composite, there was a significant time by MCI classification interaction for each MCI subtype, indicating that all MCI groups showed faster rates of decline in everyday function relative to cognitively normal participants with no MCI. Conclusion. Results demonstrate the importance of MCI as a clinical entity that not only predicts progression to dementia but also predicts functional declines in activities that are key to autonomy and quality of life. MCI classification guidelines should allow for functional changes in MCI, and clinicians should monitor for such changes. Preservation of function may serve as a meaningful outcome for intervention efforts. PMID:17661957

  13. Cognitive activity, cognitive function, and brain diffusion characteristics in old age.

    Science.gov (United States)

    Arfanakis, Konstantinos; Wilson, Robert S; Barth, Christopher M; Capuano, Ana W; Vasireddi, Anil; Zhang, Shengwei; Fleischman, Debra A; Bennett, David A

    2016-06-01

    The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p = 0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics.

  14. Physical Activity and Physical Function in Individuals Post-bariatric Surgery

    Science.gov (United States)

    Josbeno, Deborah A.; Kalarchian, Melissa; Sparto, Patrick J.; Otto, Amy D.; Jakicic, John M.

    2016-01-01

    Background A better understanding of the physical activity behavior of individuals who undergo bariatric surgery will enable the development of effective post-surgical exercise guidelines and interventions to enhance weight loss outcomes. This study characterized the physical activity profile and physical function of 40 subjects 2–5 years post-bariatric surgery and examined the association between physical activity, physical function, and weight loss after surgery. Methods Moderate-to-vigorous intensity physical activity (MVPA) was assessed with the BodyMedia SenseWear® Pro (SWPro) armband, and physical function (PF) was measured using the physical function subscale of the 36-Item Short Form Health Survey instrument (SF-36PF). Height and weight were measured. Results Percent of excess weight loss (%EWL) was associated with MVPA (r = 0.44, p = 0.01) and PF (r = 0.38, p = 0.02); MVPA was not associated with PF (r = 0.24, p = 0.14). Regression analysis demonstrated that MVPA was associated with %EWL (β = 0.38, t = 2.43, p = 0.02). Subjects who participated in ≥150 min/week of MVPA had a greater %EWL (68.2 ± 19, p = 0.01) than those who participated in activities. However, the lack of an association between PF and MVPA suggests that a higher level of PF does not necessarily correspond to a higher level of MVPA participation. Thus, the barriers to adoption of a more physically active lifestyle may not be fully explained by the subjects’ physical limitations. Further understanding of this relationship is needed for the development of post-surgical weight loss guidelines and interventions. PMID:21153567

  15. Functional electrical stimulation early after stroke improves lower limb motor function and ability in activities of daily living.

    Science.gov (United States)

    You, Guoqing; Liang, Huiying; Yan, Tiebin

    2014-01-01

    Functional electrical stimulation (FES) to patients early after stroke has been proved to improve walking ability. The effects on abilities in activities of daily living (ADL) are not clear. To investigate the effectiveness of FES in improving lower limb function and ability in ADL of early stroke patients. Thirty-seven stroke patients were randomly allocated to standard rehabilitation (SR) group (n = 18), and FES group with FES and SR (n = 19). SR included 60 minutes each for physiotherapy and occupational therapy. FES was delivered for 30 min to induce ankle dorsiflexion and eversion. Treatments were 5 days per week for 3 weeks. Evaluations including the composite spasticity scale (CSS), lower-extremity subscale of Fugl-Myer Assessment (FMA), postural assessment scale for stroke patients (PASS), Berg Balance Scale (BBS), and modified Barthel Index (MBI) assessed before treatment, after 2 and 3 week treatment respectively. After 2 week treatment, FES group showed a significant reduction of CSS and improvements of FMA, MBI and PASS. After 3 week treatment, FES group showed a further reduction of CSS and also improvement of FMA, MBI and BBS as well. FES on the paretic lower limbs early after stroke improved the mobility and ability in ADL.

  16. Physical activity and cognitive function in individuals over 60 years of age: a systematic review

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    Carvalho A

    2014-04-01

    Full Text Available Ashley Carvalho,1,2 Irene Maeve Rea,2 Tanyalak Parimon,3,4 Barry J Cusack3,51Department of Public Health, 2School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Northern Ireland, UK; 3Research and Development Service, Veterans Affairs Medical Center, Boise, ID, USA; 4Division of Pulmonary and Critical Care Medicine, 5Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USABackground: It is unclear whether physical activity in later life is beneficial for maintenance of cognitive function. We performed a systematic review examining the effects of exercise on cognitive function in older individuals, and present possible mechanisms whereby physical activity may improve cognition.Methods: Sources consisted of PubMed, Medline, CINAHL, the Cochrane Controlled Trials Register, and the University of Washington, School of Medicine Library Database, with a search conducted on August 15, 2012 for publications limited to the English language starting January 1, 2000. Randomized controlled trials including at least 30 participants and lasting at least 6 months, and all observational studies including a minimum of 100 participants for one year, were evaluated. All subjects included were at least 60 years of age.Results: Twenty-seven studies met the inclusion criteria. Twenty-six studies reported a positive correlation between physical activity and maintenance or enhancement of cognitive function. Five studies reported a dose-response relationship between physical activity and cognition. One study showed a nonsignificant correlation.Conclusion: The preponderance of evidence suggests that physical activity is beneficial for cognitive function in the elderly. However, the majority of the evidence is of medium quality with a moderate risk of bias. Larger randomized controlled trials are needed to clarify the association between exercise and cognitive function and to determine

  17. The Antifungal Activity of Functionalized Chitin Nanocrystals in Poly (Lactid Acid Films

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    Asier M. Salaberria

    2017-05-01

    Full Text Available As, in the market, poly (lactic acid (PLA is the most used polymer as an alternative to conventional plastics, and as functionalized chitin nanocrystals (CHNC can provide structural and bioactive properties, their combination sounds promising in the preparation of functional nanocomposite films for sustainable packaging. Chitin nanocrystals were successfully modified via acylation using anhydride acetic and dodecanoyl chloride acid to improve their compatibility with the matrix, PLA. The nanocomposite films were prepared by extrusion/compression approach using different concentrations of both sets of functionalized CHNC. This investigation brings forward that both sets of modified CHNC act as functional agents, i.e., they slightly improved the hydrophobic character of the PLA nanocomposite films, and, very importantly, they also enhanced their antifungal activity. Nonetheless, the nanocomposite films prepared with the CHNC modified with dodecanoyl chloride acid presented the best properties.

  18. Platelet activation, function, and reactivity in atherosclerotic carotid artery stenosis: a systematic review of the literature.

    LENUS (Irish Health Repository)

    Kinsella, J A

    2012-09-27

    An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion. Platelet biomarkers have the potential to improve our understanding of the pathogenesis of vascular events in this patient population. A detailed systematic review was performed to collate all available data on ex vivo platelet activation and platelet function\\/reactivity in patients with carotid stenosis. Two hundred thirteen potentially relevant articles were initially identified; 26 manuscripts met criteria for inclusion in this systematic review. There was no consistent evidence of clinically informative data from urinary or soluble blood markers of platelet activation in patients with symptomatic moderate or severe carotid stenosis who might be considered suitable for carotid intervention. Data from flow cytometry studies revealed evidence of excessive platelet activation in patients in the early, sub-acute, or late phases after transient ischemic attack or stroke in association with moderate or severe carotid stenosis and in asymptomatic moderate or severe carotid stenosis compared with controls. Furthermore, pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis. Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis. Larger longitudinal studies assessing platelet activation status with flow cytometry and platelet function\\/reactivity in symptomatic vs. asymptomatic carotid stenosis are warranted to improve our understanding of the mechanisms responsible for transient ischemic attack or stroke.

  19. The brain of opera singers: experience-dependent changes in functional activation.

    Science.gov (United States)

    Kleber, B; Veit, R; Birbaumer, N; Gruzelier, J; Lotze, M

    2010-05-01

    Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

  20. Functional activation in the cerebellum during working memory and simple speech tasks.

    Science.gov (United States)

    Durisko, Corrine; Fiez, Julie A

    2010-01-01

    Verbal working memory is the ability to temporarily store and manipulate verbal information. This study tested the predictions of a neuroanatomical model of how the cerebellum contributes to verbal working memory (Desmond et al., 1997). In this model, a large bilateral region in the superior cerebellum is associated with articulatory rehearsal and a right-lateralized region in the inferior cerebellum is associated with the correction of errors within the working memory system. The Desmond et al. (1997) model was based on neuroimaging findings using item recognition tasks and comparisons between working memory and covert rehearsal tasks, whereas in this functional magnetic resonance imaging (fMRI) study we used a delayed serial recall (DSR) task because it relies more heavily on articulatory rehearsal, and our comparison tasks included both overt and covert speech tasks. Our results provide some support for the Desmond et al. (1997) model. In particular, we found multiple activation foci within the superior and inferior sectors of the cerebellum and evidence that these regions show different patterns of activation across working memory and speech tasks. However, the specific patterns of activation were not fully consistent with those reported by Desmond et al. (1997). Namely, our results indicate that activation in the superior sector should be functionally subdivided into a medial focus involved in speech processing and a lateral focus more specific to verbal working memory; the results also indicate that activation in the inferior sector is not uniquely right lateralized. These complex findings speak to the need for future studies to consider the speech-motor aspects of tasks, to investigate the functional significance of adjacent peaks of activation within large regions of cerebellar activation, and to use analysis procedures that support regional distinctions through direct statistical tests. Such studies would help to refine our understanding of how the

  1. Normalization of voltage-sensitive dye signal with functional activity measures.

    Directory of Open Access Journals (Sweden)

    Kentaroh Takagaki

    Full Text Available In general, signal amplitude in optical imaging is normalized using the well-established DeltaF/F method, where functional activity is divided by the total fluorescent light flux. This measure is used both directly, as a measure of population activity, and indirectly, to quantify spatial and spatiotemporal activity patterns. Despite its ubiquitous use, the stability and accuracy of this measure has not been validated for voltage-sensitive dye imaging of mammalian neocortex in vivo. In this report, we find that this normalization can introduce dynamic biases. In particular, the DeltaF/F is influenced by dye staining quality, and the ratio is also unstable over the course of experiments. As methods to record and analyze optical imaging signals become more precise, such biases can have an increasingly pernicious impact on the accuracy of findings, especially in the comparison of cytoarchitechtonic areas, in area-of-activation measurements, and in plasticity or developmental experiments. These dynamic biases of the DeltaF/F method may, to an extent, be mitigated by a novel method of normalization, DeltaF/DeltaF(epileptiform. This normalization uses as a reference the measured activity of epileptiform spikes elicited by global disinhibition with bicuculline methiodide. Since this normalization is based on a functional measure, i.e. the signal amplitude of "hypersynchronized" bursts of activity in the cortical network, it is less influenced by staining of non-functional elements. We demonstrate that such a functional measure can better represent the amplitude of population mass action, and discuss alternative functional normalizations based on the amplitude of synchronized spontaneous sleep-like activity. These findings demonstrate that the traditional DeltaF/F normalization of voltage-sensitive dye signals can introduce pernicious inaccuracies in the quantification of neural population activity. They further suggest that normalization

  2. Data Fusion Using Different Activation Functions in Artificial Neural Networks for Vehicular Navigation

    Directory of Open Access Journals (Sweden)

    MALLESWARAN M,

    2010-12-01

    Full Text Available Global positioning System (GPS and Inertial Navigation System (INS data can be integrated together to provide a reliable navigation. GPS/INS data integration provides reliable navigation solutions by overcoming each of their shortcomings, including signal blockage for GPS and increase in position errors with time for INS. This paper aims to provide GPS/INS data integration utilizing Artificial Neural Network (ANN architecture. This architecture is based on Feed Forward Neural Networks, which generally includes Radial Basis Function (RBF neural network and Back Propagation neural network (BPN. These are systematic methods for training multi-layer artificial networks. The BPN-ANN and RBF-ANN modules are trained to predict the INS position error and provide accurate positioning of the moving vehicle. This paper also compares performance of theGPS/INS data integration system by using different activation function like Bipolar Sigmoidal Function (BPSF, Binary Sigmoidal Function (BISF, Hyperbolic Tangential Function (HTF and Gaussian Function (GF in BPN-ANN and using Gaussian function in RBF-ANN.

  3. Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity

    Science.gov (United States)

    Ji, Gong-Jun; Liao, Wei; Yu, Yang; Miao, Huan-Huan; Feng, Yi-Xuan; Wang, Kai; Feng, Jian-Hua; Zang, Yu-Feng

    2016-01-01

    Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS. PMID:27799898

  4. Transient receptor potential vanilloid 2 function regulates cardiac hypertrophy via stretch-induced activation.

    Science.gov (United States)

    Koch, Sheryl E; Mann, Adrien; Jones, Shannon; Robbins, Nathan; Alkhattabi, Abdullah; Worley, Mariah C; Gao, Xu; Lasko-Roiniotis, Valerie M; Karani, Rajiv; Fulford, Logan; Jiang, Min; Nieman, Michelle; Lorenz, John N; Rubinstein, Jack

    2017-03-01

    Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps. Wild-type animals served as control for all experiments. Expression and localization of TRPV2 was investigated in wild-type cardiac samples. Changes in cardiac function were measured in vivo via echocardiography and invasive catheterization. Molecular changes, including protein and real-time PCR markers of hypertrophy, were measured in addition to myocyte size. TRPV2 is significantly upregulated in wild-type mice after TAC, though not in response to beta-adrenergic or angiotensin stimulation. TAC-induced stretch stimulus caused an upregulation of TRPV2 in the sarcolemmal membrane. The absence of functional TRPV2 resulted in significantly reduced left ventricular hypertrophy after TAC, though not in response to beta-adrenergic or angiotensin stimulation. The decreased development of hypertrophy was not associated with significant deterioration of cardiac function. We conclude that TRPV2 function, as a stretch-activated channel, regulates the development of cardiomyocyte hypertrophy in response to increased afterload.

  5. Comparison of TMS-induced arm activation and upper limb functional tests in hemiparetic stroke

    Directory of Open Access Journals (Sweden)

    Tarkka Ina M.

    2013-01-01

    Full Text Available Stroke has a major impact in the total cost of healthcare in the Western world as stroke is the most common cause of long-term disability [1]. In attempts to enhance motor recovery after stroke effective treatment strategies have been developed in recent years. Appropriate evaluation of the intervention programs requires comprehensive and accurate assessment of the residual abnormal function. In the present study we compare two well-known clinical functional scoring tests developed for the assessment of hemiparetic upper limb function due to stroke and navigated transcranial magnetic stimulation (nTMS, which measures involuntary target muscle response to cortical stimulation. The aim is to investigate the equivalence of these methods and thus add objective evidence of the limb function to strengthen evidence-based practice. In addition to functional tests, four muscles of both arms were studied in twenty chronic stroke patients. Those patients without motor evoked potentials (MEP to nTMS in the affected upper limb had significantly lower total score in Action Research Arm Test and Wolf Motor Function Test and longer performance time than those patients with MEP. Patients, in whom MEP in each of the four target muscles was elicitable, had better than average scores in clinical functional tests while patients, in whom no MEP was elicitable in any target muscle, had worse than average scores. Transcranial magnetic stimulation adds crucial information when clinical assessment based on voluntary activation by command is challenging, e.g. in patients suffering from cognitive deficits.

  6. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  7. Probability-Based Diagnostic Imaging Technique Using Error Functions for Active Structural Health Monitoring

    Directory of Open Access Journals (Sweden)

    Rahim Gorgin,

    2014-07-01

    Full Text Available This study presents a novel probability-based diagnostic imaging (PDI technique using error functions for active structural health monitoring (SHM. To achieve this, first the changes between baseline and current signals of each sensing path are measured, and by taking the root mean square of such changes, the energy of the scattered signal at different times can be calculated. Then, for different pairs of signal acquisition paths, an error function based on the energy of the scattered signals is introduced. Finally, the resultant error function is fused to the final estimation of the probability of damage presence in the monitoring area. As for applications, developed methods were employed to various damage identification cases, including cracks located in regions among an active sensor network with different configurations (pulse-echo and pitch-catch, and holes located in regions outside active network sensors with pitch-catch configuration. The results identified using experimental Lamb wave signals at different central frequencies corroborated that the developed PDI technique using error functions is capable of monitoring structural damage, regardless of its shape, size and location. The developed method doesn’t need direct interpretation of overlaid and dispersed lamb wave components for damage identification and can monitor damage located anywhere in the structure. These bright advantages, qualify the above presented PDI method for online structural health monitoring.

  8. Activated protein C: A regulator of human skin epidermal keratinocyte function.

    Science.gov (United States)

    McKelvey, Kelly; Jackson, Christopher John; Xue, Meilang

    2014-05-26

    Activated protein C (APC) is a physiological anticoagulant, derived from its precursor protein C (PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor (EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

  9. Association between physical activity in daily life and pulmonary function in adult smokers

    Directory of Open Access Journals (Sweden)

    Miriane Lilian Barboza

    2016-04-01

    Full Text Available Objective: To determine whether the level of physical activity in daily life (PADL is associated with pulmonary function in adult smokers. Methods: We selected 62 adult smokers from among the participants of an epidemiological study conducted in the city of Santos, Brazil. The subjects underwent forced spirometry for pulmonary function assessment. The level of PADL was assessed by the International Physical Activity Questionnaire and triaxial accelerometry, the device being used for seven days. The minimum level of PADL, in terms of quantity and intensity, was defined as 150 min/week of moderate to vigorous physical activity. Correlations between the studied variables were tested with Pearson's or Spearman's correlation coefficient, depending on the distribution of the variables. We used linear multiple regression in order to analyze the influence of PADL on the spirometric variables. The level of significance was set at 5%. Results: Evaluating all predictors, corrected for confounding factors, and using pulmonary function data as outcome variables, we found no significant associations between physical inactivity, as determined by accelerometry, and spirometric indices. The values for FVC were lower among the participants with arterial hypertension, and FEV1/FVC ratios were lower among those with diabetes mellitus. Obese participants and those with dyslipidemia presented with lower values for FVC and FEV1. Conclusions: Our results suggest that there is no consistent association between physical inactivity and pulmonary function in adult smokers. Smoking history should be given special attention in COPD prevention strategies, as should cardiovascular and metabolic comorbidities.

  10. Targeting complement activation in brain-dead donors improves renal function after transplantation.

    Science.gov (United States)

    Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G; Ploeg, Rutger J; Yard, Benito A; Seelen, Marc A

    2011-05-01

    Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function after transplantation. Brain death (BD) was induced in Fisher rats by inflation of an epidurally placed balloon catheter and ventilated for 6h. BD animals were treated with soluble complement receptor 1 (sCR1) 1h before or 1h after BD. Kidney transplantation was performed and 7 days after transplantation animals were sacrificed. Plasma creatinine and urea were measured at days 0, 1, 3, 5 and 7 after transplantation. Renal function was significantly better at day 1 after transplantation in recipients receiving a sCR1 pre-treated donor kidney compared to recipients of a non-treated donor graft. Also treatment with sCR1, 1h after the diagnosis of BD, resulted in a better renal function after transplantation. Gene expression of IL-6, IL-1beta and TGF-beta were significantly lower in renal allografts recovered from treated donors. This study shows that targeting complement activation, during BD in the donor, leads to an improved renal function after transplantation in the recipient.

  11. Activated protein C: A regulator of human skin epidermal keratinocyte function

    Institute of Scientific and Technical Information of China (English)

    Kelly; McKelvey; Christopher; John; Jackson; Meilang; Xue

    2014-01-01

    Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC’s function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

  12. Treatment of Patella Alta with Taping, Exercise, Mobilization, and Functional Activity Modification: A Case Report

    Science.gov (United States)

    Harris-Hayes, Marcie

    2014-01-01

    Study Design Case report. Background Knee pain associated with patella alta (PA) can limit involvement in sport or work activities and prevent an individual from performing basic functional tasks. This case report describes the use of patellar taping to treat an individual with PA. Case Description The patient was a 56 year-old female with bilateral knee pain associated with PA. The focus of treatment was to decrease pain during functional activities by using tape to correct patella alignment. The patient was also instructed on specific exercises and mobilizations. The primary outcome measure was the ADL subscale of the Knee Outcome Survey (ADL-KOS). Outcomes Initially, the patient scored a 50 on the ADL-KOS and rated her function at 30% of normal. She demonstrated symptom improvement when tape was applied appropriately and was, therefore, instructed in tape application. At discharge, the patient scored a 56 on the ADL-KOS and rated her function at 70% of normal. Discussion This case demonstrates the effective use of a taping method for the treatment of pain associated with PA. Taping appears to be a safe, conservative, and cost efficient measure to manage symptoms and to improve activity tolerance in this patient. PMID:21721996

  13. Pain-inducing imagery as a function of hypnotisability and of the activity of Gray's Behavioral Inhibition/Activation Systems.

    Science.gov (United States)

    Santarcangelo, Enrica L; Varanini, Maurizio; Paoletti, Giulia; Castellani, Eleonora; Palombo, Carlo; Carli, Giancarlo

    2013-12-17

    The aim of the study was to test the efficacy of pain imagery as a function of hypnotisability and of the activity of Behavioral Inhibition/Activation Systems. Questionnaires of imagery abilities (Betts) for the visual, cutaneous and organic modalities, absorption in cognitive tasks (TAS), proneness to inhibit stressful/painful experience/seek out positive experiences (BIS BAS), trait anxiety (STAI-Y2) and psychological well-being (PWB) were administered to 21 subjects with high hypnotisability (highs) and 21 subjects with low hypnotisability (lows). Self-reports of pain intensity and of neutral tactile perception were collected during imagery of nociceptive (Pain) and neutral tactile stimulation (NT). ECG and skin conductance were recorded. Highs exhibited greater imagery abilities, absorption, Behavioral Inhibition System Activity and psychological well-being with respect to lows. They reported lower scores of pain intensity than of tactile perception, while in lows Pain and NT scores did not differ. However, controlling for BAS, but not for BIS, revealed differences in the efficacy of pain imagery between highs and lows. Heart rate decreased in both tasks and groups; heart rate variability and skin conductance did not change significantly during imageries. Our findings suggest that the Behavioral Inhibition/Activation Systems interact with imagery abilities reducing the efficacy of pain imagery and prompt investigation of possible similar interactions in the modulation of physically induced experimental pain and of chronic pain in the general population.

  14. Functional capacity, physical activity, and quality of life in hypoxemic patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Saglam M

    2015-02-01

    Full Text Available Melda Saglam,1 Naciye Vardar-Yagli,1 Sema Savci,2 Deniz Inal-Ince,1 Ebru Calik Kutukcu,1 Hülya Arikan,1 Lutfi Coplu3 1Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey; 2School of Physiotherapy and Rehabilitation, Dokuz Eylul University, Izmir, Turkey; 3Department of Chest Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey Background: The risk of hypoxemia increases with the progression of chronic obstructive pulmonary disease (COPD and the deterioration of pulmonary function. The aim of this study was to compare functional capacity, physical activity, and quality of life in hypoxemic and non-hypoxemic patients with COPD.Methods: Thirty-nine COPD patients (mean age: 62.0±7.03 years were included in this study. Arterial blood gas tensions were measured, and patients were divided into two groups according to oxygen partial pressure (PaO2, the hypoxemic COPD (PaO2 <60 mmHg (n=18, and the control (PaO2 ≥60 mmHg (n=21 groups. Functional exercise capacity was evaluated using the 6-minute walk test (6MWT. Oxygen saturation, dyspnea, and fatigue perception were measured before and after the 6MWT. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ and an accelerometer. Quality of life was assessed using the St George’s Respiratory Questionnaire (SGRQ.Results: The number of emergency visits and hospitalizations were higher in hypoxemic patients (P<0.05. Lung function parameters, 6MWT distance, exercise oxygen saturation, IPAQ total score, and energy expenditure during daily life were significantly lower, but percentage of maximum heart rate reached during the 6MWT was significantly higher, in hypoxemic COPD patients than in controls (P<0.05.Conclusion: Hypoxemia has a profound effect on functional capacity and physical activity in patients with COPD. Keywords: COPD, hypoxemia, 6-minute walk test

  15. Homology to peptide pattern for annotation of carbohydrate-active enzymes and prediction of function.

    Science.gov (United States)

    Busk, P K; Pilgaard, B; Lezyk, M J; Meyer, A S; Lange, L

    2017-04-12

    Carbohydrate-active enzymes are found in all organisms and participate in key biological processes. These enzymes are classified in 274 families in the CAZy database but the sequence diversity within each family makes it a major task to identify new family members and to provide basis for prediction of enzyme function. A fast and reliable method for de novo annotation of genes encoding carbohydrate-active enzymes is to identify conserved peptides in the curated enzyme families followed by matching of the conserved peptides to the sequence of interest as demonstrated for the glycosyl hydrolase and the lytic polysaccharide monooxygenase families. This approach not only assigns the enzymes to families but also provides functional prediction of the enzymes with high accuracy. We identified conserved peptides for all enzyme families in the CAZy database with Peptide Pattern Recognition. The conserved peptides were matched to protein sequence for de novo annotation and functional prediction of carbohydrate-active enzymes with the Hotpep method. Annotation of protein sequences from 12 bacterial and 16 fungal genomes to families with Hotpep had an accuracy of 0.84 (measured as F1-score) compared to semiautomatic annotation by the CAZy database whereas the dbCAN HMM-based method had an accuracy of 0.77 with optimized parameters. Furthermore, Hotpep provided a functional prediction with 86% accuracy for the annotated genes. Hotpep is available as a stand-alone application for MS Windows. Hotpep is a state-of-the-art method for automatic annotation and functional prediction of carbohydrate-active enzymes.

  16. The relation of childhood physical activity and aerobic fitness to brain function and cognition: a review.

    Science.gov (United States)

    Khan, Naiman A; Hillman, Charles H

    2014-05-01

    Physical inactivity has been shown to increase the risk for several chronic diseases across the lifespan. However, the impact of physical activity and aerobic fitness on childhood cognitive and brain health has only recently gained attention. The purposes of this article are to: 1) highlight the recent emphasis for increasing physical activity and aerobic fitness in children's lives for cognitive and brain health; 2) present aspects of brain development and cognitive function that are susceptible to physical activity intervention; 3) review neuroimaging studies examining the cross-sectional and experimental relationships between aerobic fitness and executive control function; and 4) make recommendations for future research. Given that the human brain is not fully developed until the third decade of life, preadolescence is characterized by changes in brain structure and function underlying aspects of cognition including executive control and relational memory. Achieving adequate physical activity and maintaining aerobic fitness in childhood may be a critical guideline to follow for physical as well as cognitive and brain health.

  17. Altered cortical activation during action observation in amyotrophic lateral sclerosis patients: a parametric functional MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Li, Haiqing; Li, Yuxin; Yin, Bo; Tang, Weijun; Yu, Xiangrong; Geng, Daoying [Huashan Hospital, Department of Radiology, Fudan University, Shanghai (China); Chen, Yan [Fudan University, Department of Neurology, Huashan Hospital, Shanghai (China); Huang, Weiyuan [People' s Hospital of Hainan Province, Department of Radiology, Haikou, Hainan Province (China); Zhang, Biyun [Nanjing University of Traditional Chinese Medicine, Department of radiotherapy, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2015-09-15

    To investigate functional cerebral abnormalities in patients with amyotrophic lateral sclerosis (ALS) using functional magnetic resonance imaging (fMRI) during action observation. Thirty patients with ALS and 30 matched healthy controls underwent fMRI with an experimental paradigm while observing a video of repetitive flexion-extension of the fingers at three frequency levels or three complexity levels, alternated with periods of a static hand. A parametric analysis was applied to determine the effects of each of the two factors. Action observation activated similar neural networks as the research on execution of action in the ALS patients and healthy subjects in several brain regions related to the mirror-neuron system (MNS). In the ALS patients, in particular, the dorsal lateral premotor cortex (dPMC), inferior parietal gyrus (IPG), and SMA, were more activated compared with the activation in the controls. Increased activation within the primary motor cortex (M1), dPMC, inferior frontal gyrus (IFG), and superior parietal gyrus (SPG) mainly correlated with hand movement frequency/complexity in the videos in the patients compared with controls. The findings indicated an ongoing compensatory process occurring within the higher order motor-processing system of ALS patients, likely to overcome the loss of function. (orig.)

  18. Cortical activation during finger tapping in thyroid dysfunction: A functional magnetic resonance imaging study

    Indian Academy of Sciences (India)

    S Khushu; S Senthil Kumaran; T Sekhri; R P Tripathi; P C Jain; V Jain

    2006-12-01

    Thyroid dysfunction is associated with attention deficit and impairment of the motor system (muscle weakness and fatigue). This paper investigates possible motor function deficit in thyroid patients, compared to the controls. Functional MRI studies (fMRI) were carried out in five hypo and five hyperthyroid patients and six healthy volunteers. Whole brain imaging was performed using echo planar imaging (EPI) technique, on a 1.5T whole body MR system (Siemens Magnetom Vision). The task paradigm consisted of 8 cycles of active and reference phases of 6 measurements each, with right index finger tapping at a rate of 120 taps/min. Post-processing was performed using statistical parametric mapping on a voxel-by-voxel basis using SPM99. Clusters of activation were found in the contralateral hemisphere in primary somatomotor area (M1), supplementary motor area (SMA), somatosensory, auditory receptive and integration areas, inferior temporal lobe, thalamus and cerebellum. Increased clusters of activation were observed in M1 in thyroid subjects as compared to controls and with bilateral activation of the primary motor cortex in two hyperthyroid patients. The results are explained in terms of increased functional demands in thyroid patients compared to volunteers for the execution of the same task.

  19. Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants.

    Directory of Open Access Journals (Sweden)

    Özlem Demir

    2011-10-01

    Full Text Available The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain ("cancer mutants". Activity can be restored by second-site suppressor mutations ("rescue mutants". This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD, without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC metric was strongly correlated (r(2 = 0.77 with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i p53 cancer mutants were more flexible than wild-type protein, (ii second-site rescue mutations decreased the flexibility of cancer mutants, and (iii negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants.

  20. Effects of selective REM sleep deprivation on prefrontal gamma activity and executive functions.

    Science.gov (United States)

    Corsi-Cabrera, M; Rosales-Lagarde, A; del Río-Portilla, Y; Sifuentes-Ortega, R; Alcántara-Quintero, B

    2015-05-01

    Given that the dorsolateral prefrontal cortex is involved in executive functions and is deactivated and decoupled from posterior associative regions during REM sleep, that Gamma temporal coupling involved in information processing is enhanced during REM sleep, and that adult humans spend about 90 min of every 24h in REM sleep, it might be expected that REM sleep deprivation would modify Gamma temporal coupling and have a deteriorating effect on executive functions. We analyzed EEG Gamma activity and temporal coupling during implementation of a rule-guided task before and after REM sleep deprivation and its effect on verbal fluency, flexible thinking and selective attention. After two nights in the laboratory for adaptation, on the third night subjects (n=18) were randomly assigned to either selective REM sleep deprivation effectuated by awakening them at each REM sleep onset or, the same number of NREM sleep awakenings as a control for unspecific effects of sleep interruptions. Implementation of abstract rules to guide behavior required greater activation and synchronization of Gamma activity in the frontopolar regions after REM sleep reduction from 20.6% at baseline to just 3.93% of total sleep time. However, contrary to our hypothesis, both groups showed an overall improvement in executive task performance and no effect on their capacity to sustain selective attention. These results suggest that after one night of selective REM sleep deprivation executive functions can be compensated by increasing frontal activation and they still require the participation of supervisory control by frontopolar regions.

  1. Cancer prevention, aerobic capacity, and physical functioning in survivors related to physical activity: a recent review

    Directory of Open Access Journals (Sweden)

    Matthew S Wiggins

    2010-06-01

    Full Text Available Matthew S Wiggins1, Emily M Simonavice21Department of Kinesiology, University of Wisconsin-Eau Claire, Eau Claire, WI, USA; 2Florida State University, Tallahassee, FL, USAAbstract: According to recent published reports, over 12 million new cases of cancer were estimated worldwide for 2007. Estimates from 2008 predict that cancer will account for 22.8% of all deaths in the US. Another report stated 50% to 75% of cancer deaths in the US are related to smoking, poor dietary choices, and physical inactivity. A 2004 report indicated obesity and/or a sedentary lifestyle increases the risk of developing several types of cancer. Conversely, several large-scale cohort studies point to the positive relationship between physical activity and a reduction in cancer risk. In addition, research over the last few years has clearly shown cardiorespiratory benefits, increases in quality of life (QOL, and increases in physical functioning for cancer survivors who engage in exercise programs. Thus, the purpose of this review is to highlight three areas related to cancer and physical activity. First, information concerning the prevention of cancer through physical activity</