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Sample records for inactive arylsulphatase mutants

  1. Isolation and characterization of the pig endometrial arylsulphatase A.

    PubMed Central

    Rahi, H; Srivastava, P N

    1983-01-01

    The pig endometrial arylsulphatase A was purified 3322-fold to a specific activity of 150 mumol/min per mg. The purification involved (NH4)2SO4 fractionation, chromatography on concanavalin A-Sepharose and DEAE-Sepharose, gel filtrations on Sephadex G-200 at pH 7.4 and 5, and a new preparative gel-electrophoresis technique. The homogeneous enzyme is a glycoprotein containing 20% carbohydrate. The purified enzyme has Mr about 120 000 and it contains subunits of Mr 63 000. The pig endometrial arylsulphatase A shows many properties in common with those of arylsulphatases A purified from other sources. The similarities include their low isoelectric points, the anomalous time-activity relationships, multi-pH optima, inhibition by SO3(2-), SO4(2-), phosphate ions, metal ions and nucleoside phosphates, pH- and ionic-strength-dependent polymerization and amino acid composition. PMID:6136269

  2. Active-site mutants of beta-lactamase: use of an inactive double mutant to study requirements for catalysis.

    PubMed

    Dalbadie-McFarland, G; Neitzel, J J; Richards, J H

    1986-01-28

    We have studied the catalytic activity and some other properties of mutants of Escherichia coli plasmid-encoded RTEM beta-lactamase (EC 3.5.2.6) with all combinations of serine and threonine residues at the active-site positions 70 and 71. (All natural beta-lactamases have conserved serine-70 and threonine-71.) From the inactive double mutant Ser-70----Thr, Thr-71----Ser [Dalbadie-McFarland, G., Cohen, L. W., Riggs, A. D., Morin, C., Itakura, K., & Richards, J. H. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 6409-6413], an active revertant, Thr-71----Ser (i.e., residue 70 in the double mutant had changed from threonine to the serine conserved at position 70 in the wild-type enzyme), was isolated by an approach that allows identification of active revertants in the absence of a background of wild-type enzyme. This mutant (Thr-71----Ser) has about 15% of the catalytic activity of wild-type beta-lactamase. The other possible mutant involving serine and threonine residues at positions 70 and 71 (Ser-70----Thr) shows no catalytic activity. The primary nucleophiles of a serine or a cysteine residue [Sigal, I. S., Harwood, B. G., & Arentzen, R. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 7157-7160] at position 70 thus seem essential for enzymatic activity. Compared to wild-type enzyme, all three mutants show significantly reduced resistance to proteolysis; for the active revertant (Thr-71----Ser), we have also observed reduced thermal stability and reduced resistance to denaturation by urea.

  3. A cDNA clone for human glucosamine-6-sulphatase reveals differences between arylsulphatases and non-arylsulphatases.

    PubMed Central

    Robertson, D A; Freeman, C; Morris, C P; Hopwood, J J

    1992-01-01

    Glucosamine-6-sulphatase is an exo-hydrolase required for the lysosomal degradation of heparan sulphate and keratan sulphate. Deficiency of glucosamine-6-sulphatase activity leads to the lysosomal storage of the glycosaminoglycan, heparan sulphate and the monosaccharide sulphate N-acetylglucosamine 6-sulphate and the autosomal recessive genetic disorder mucopolysaccharidosis type IIID. Glucosamine-6-sulphatase can be classified as a non-arylsulphatase since, relative to arylsulphatase B, it shows negligible activity toward 4-methylumbelliferyl sulphate. We have isolated human cDNA clones and derived amino acid sequence coding for the entire glucosamine-6-sulphatase protein. The predicted sequence has 552 amino acids with a leader peptide of 36 amino acids and contains 13 potential N-glycosylation sites, of which it is likely that 10 are used. Glucosamine-6-sulphatase shows strong sequence similarity to other sulphatases such as the family of arylsulphatases, although the degree of similarity is not as high as that between members of the arylsulphatase family. This pattern of inter- and intra-family similarity delineates regions and amino acid residues that may be critical for sulphatase function and substrate specificity. PMID:1463457

  4. Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant.

    PubMed

    Moe, Elin; Rollo, Filipe; Silveira, Célia M; Sezer, Murat; Hildebrandt, Peter; Todorovic, Smilja

    2018-01-05

    Endonuclease III is a Fe-S containing bifunctional DNA glycosylase which is involved in the repair of oxidation damaged DNA. Here we employ surface enhanced IR spectroelectrochemistry and electrochemistry to study the enzyme from the highly radiation- and desiccation-resistant bacterium Deinococcus radiodurans (DrEndoIII2). The experiments are designed to shed more light onto specific parameters that are currently proposed to govern damage search and recognition by endonucleases III. We demonstrate that electrostatic interactions required for the redox activation of DrEndoIII2 may result in high electric fields that alter its structural and thermodynamic properties. Analysis of inactive DrEndoIII2 (K132A/D150A double mutant) interacting with undamaged DNA, and the active enzyme interacting with damaged DNA also indicate that the electron transfer is modulated by subtle differences in the protein-DNA complex. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Inactivity periods and postural change speed can explain atypical postural change patterns of Caenorhabditis elegans mutants.

    PubMed

    Fukunaga, Tsukasa; Iwasaki, Wataru

    2017-01-19

    With rapid advances in genome sequencing and editing technologies, systematic and quantitative analysis of animal behavior is expected to be another key to facilitating data-driven behavioral genetics. The nematode Caenorhabditis elegans is a model organism in this field. Several video-tracking systems are available for automatically recording behavioral data for the nematode, but computational methods for analyzing these data are still under development. In this study, we applied the Gaussian mixture model-based binning method to time-series postural data for 322 C. elegans strains. We revealed that the occurrence patterns of the postural states and the transition patterns among these states have a relationship as expected, and such a relationship must be taken into account to identify strains with atypical behaviors that are different from those of wild type. Based on this observation, we identified several strains that exhibit atypical transition patterns that cannot be fully explained by their occurrence patterns of postural states. Surprisingly, we found that two simple factors-overall acceleration of postural movement and elimination of inactivity periods-explained the behavioral characteristics of strains with very atypical transition patterns; therefore, computational analysis of animal behavior must be accompanied by evaluation of the effects of these simple factors. Finally, we found that the npr-1 and npr-3 mutants have similar behavioral patterns that were not predictable by sequence homology, proving that our data-driven approach can reveal the functions of genes that have not yet been characterized. We propose that elimination of inactivity periods and overall acceleration of postural change speed can explain behavioral phenotypes of strains with very atypical postural transition patterns. Our methods and results constitute guidelines for effectively finding strains that show "truly" interesting behaviors and systematically uncovering novel gene

  6. Comparison of arylsulphatases from Eimeria tenella (parasite) and chicken caecum (host).

    PubMed

    Farooqui, A A; Hanson, W L

    1987-02-15

    Chicken caecal arylsulphatase was purified 700-fold by (NH4)2SO4 fractionation, concanavalin A-Sepharose and cyclic AMP-Sepharose chromatographies. The purified enzyme was a glycoprotein of Mr 97,000. It hydrolysed p-nitrocatechol sulphate, cerebroside 3-sulphate and ascorbic acid 2-sulphate and was strongly inhibited by Na2SO4 (Ki = 50 microM) and Na3PO4 (Ki = 20 microM). Arylsulphatase from Eimeria tenella sporozoites was purified 28-fold by (NH4)2SO4 fractionation. Arylsulphatase of E. tenella sporozoites was not a glycoprotein. It had an Mr of 49,000. It was inhibited by Na2SO4 (Ki = 300 microM), sodium phosphate (Ki = 90 microM) and heparin. It hydrolysed ascorbic acid 2-sulphate, but cerebroside 3-sulphate was not desulphated. The kinetic parameters of chicken caecal arylsulphatase were different from those of the E. tenella enzyme.

  7. Inactive enzymatic mutant proteins (phosphoglycerate mutase and enolase) as sugar binders for ribulose-1,5-bisphosphate regeneration reactors.

    PubMed

    De, Debojyoti; Dutta, Debajyoti; Kundu, Moloy; Mahato, Sourav; Schiavone, Marc T; Chaudhuri, Surabhi; Giri, Ashok; Gupta, Vidya; Bhattacharya, Sanjoy K

    2005-02-02

    BACKGROUND: Carbon dioxide fixation bioprocess in reactors necessitates recycling of D-ribulose1,5-bisphosphate (RuBP) for continuous operation. A radically new close loop of RuBP regenerating reactor design has been proposed that will harbor enzyme-complexes instead of purified enzymes. These reactors will need binders enabling selective capture and release of sugar and intermediate metabolites enabling specific conversions during regeneration. In the current manuscript we describe properties of proteins that will act as potential binders in RuBP regeneration reactors. RESULTS: We demonstrate specific binding of 3-phosphoglycerate (3PGA) and 3-phosphoglyceraldehyde (3PGAL) from sugar mixtures by inactive mutant of yeast enzymes phosphoglycerate mutase and enolase. The reversibility in binding with respect to pH and EDTA has also been shown. No chemical conversion of incubated sugars or sugar intermediate metabolites were found by the inactive enzymatic proteins. The dissociation constants for sugar metabolites are in the micromolar range, both proteins showed lower dissociation constant (Kd) for 3-phosphoglycerate (655-796 muM) compared to 3-phosphoglyceraldehyde (822-966 muM) indicating higher affinity for 3PGA. The proteins did not show binding to glucose, sucrose or fructose within the sensitivity limits of detection. Phosphoglycerate mutase showed slightly lower stability on repeated use than enolase mutants. CONCLUSIONS: The sugar and their intermediate metabolite binders may have a useful role in RuBP regeneration reactors. The reversibility of binding with respect to changes in physicochemical factors and stability when subjected to repeated changes in these conditions are expected to make the mutant proteins candidates for in-situ removal of sugar intermediate metabolites for forward driving of specific reactions in enzyme-complex reactors.

  8. Inactive enzymatic mutant proteins (phosphoglycerate mutase and enolase) as sugar binders for ribulose-1,5-bisphosphate regeneration reactors

    PubMed Central

    De, Debojyoti; Dutta, Debajyoti; Kundu, Moloy; Mahato, Sourav; Schiavone, Marc T; Chaudhuri, Surabhi; Giri, Ashok; Gupta, Vidya; Bhattacharya, Sanjoy K

    2005-01-01

    Background Carbon dioxide fixation bioprocess in reactors necessitates recycling of D-ribulose1,5-bisphosphate (RuBP) for continuous operation. A radically new close loop of RuBP regenerating reactor design has been proposed that will harbor enzyme-complexes instead of purified enzymes. These reactors will need binders enabling selective capture and release of sugar and intermediate metabolites enabling specific conversions during regeneration. In the current manuscript we describe properties of proteins that will act as potential binders in RuBP regeneration reactors. Results We demonstrate specific binding of 3-phosphoglycerate (3PGA) and 3-phosphoglyceraldehyde (3PGAL) from sugar mixtures by inactive mutant of yeast enzymes phosphoglycerate mutase and enolase. The reversibility in binding with respect to pH and EDTA has also been shown. No chemical conversion of incubated sugars or sugar intermediate metabolites were found by the inactive enzymatic proteins. The dissociation constants for sugar metabolites are in the micromolar range, both proteins showed lower dissociation constant (Kd) for 3-phosphoglycerate (655–796 μM) compared to 3-phosphoglyceraldehyde (822–966 μM) indicating higher affinity for 3PGA. The proteins did not show binding to glucose, sucrose or fructose within the sensitivity limits of detection. Phosphoglycerate mutase showed slightly lower stability on repeated use than enolase mutants. Conclusions The sugar and their intermediate metabolite binders may have a useful role in RuBP regeneration reactors. The reversibility of binding with respect to changes in physicochemical factors and stability when subjected to repeated changes in these conditions are expected to make the mutant proteins candidates for in-situ removal of sugar intermediate metabolites for forward driving of specific reactions in enzyme-complex reactors. PMID:15689239

  9. Arylsulphatase activity and sulphate content in relation to crop rotation and fertilization of soil

    NASA Astrophysics Data System (ADS)

    Siwik-Ziomek, Anetta; Lemanowicz, Joanna; Koper, Jan

    2016-07-01

    The aim of the study was to investigate the effect of varying rates of FYM (0, 20, 40, 60 Mg ha-1) and nitrogen N0, N1, N2, and N3 on the content of sulphate sulphur (VI) and the activity of arylsulphatase, which participates in the transformations of this element in Haplic Luvisol. The study report is based on a long-term field experiment with two different crop rotations: A - recognized as exhausting the humus from soil and B - recognized as enriching the soil with humus. During the cultivation of the plants, the soil was sampled four times from corn and a red clover cultivar and grass. The FYM fertilization rate for which the highest arylsulphatase activity and the content of sulphates were identified was 60 Mg ha-1. An inhibitory effect of high rates (90 and 135 kg N ha-1) of ammonium nitrate on the arylsulphatase activity was also observed. A significant correlation between the content of carbon, nitrogen, and sulphates and the arylsulphatase activity was recorded. The investigation on the effect of combined application of farmyard manure and mineral nitrogen fertilization on the activity of arylsulphatase participating in the sulphur cycling was launched to examine the problem in detail.

  10. A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation

    PubMed Central

    Sehrawat, Sharvan; Koenig, Paul-Albert; Kirak, Oktay; Schlieker, Christian; Fankhauser, Manuel

    2013-01-01

    Antigen presenting cells (APCs) that express a catalytically inactive version of the deubiquitylase YOD1 (YOD1-C160S) present exogenous antigens more efficiently to CD8+ T cells, both in vitro and in vivo. Compared with controls, immunization of YOD1-C160S mice led to greater expansion of specific CD8+ T cells and showed improved control of infection with a recombinant γ-herpes virus, MHV-68, engineered to express SIINFEKL peptide, the ligand for the ovalbumin-specific TCR transgenic OT-I cells. Enhanced expansion of specific CD8+ T cells was likewise observed on infection of YOD1-C160S mice with a recombinant influenza A virus expressing SIINFEKL. YOD1-C160S APCs retained antigen longer than did control APCs. Enhanced cross-presentation by YOD1-C160S APCs was transporter associated with antigen processing (TAP1)–independent but sensitive to inclusion of inhibitors of acidification and of the proteasome. The activity of deubiquitylating enzymes may thus help control antigen-specific CD8+ T-cell responses during immunization. PMID:23243279

  11. Loss of the malignant phenotype of human neuroblastoma cells by a catalytically inactive dominant-negative hTERT mutant.

    PubMed

    Samy, Mona; Gattolliat, Charles-Henry; Pendino, Frédéric; Hillion, Josette; Nguyen, Eric; Bombard, Sophie; Douc-Rasy, Sétha; Bénard, Jean; Ségal-Bendirdjian, Evelyne

    2012-11-01

    Telomerase, a ribonucleoprotein complex mainly composed of the reverse transcriptase catalytic subunit (human telomerase reverse transcriptase, hTERT) and the RNA component (hTR), is a key enzyme of cancer progression. That aggressive stage 4-neuroblastoma expressed high levels of telomerase activity, whereas favorable tumors had no or little telomerase expression and activity, prompted us to investigate the role of this enzyme in this tumor model of altered proliferation, neuronal differentiation, and apoptosis. A human MYCN-amplified neuroblastoma cell line (IGR-N-91) was engineered to stably express either the normal hTERT protein (WT-hTERT) or a catalytically inactive dominant-negative mutant of this protein (DN-hTERT). We showed that DN-hTERT expression inhibited the endogenous hTERT in the malignant neuroblasts without telomere shortening nor loss of in vitro proliferative capacity. Importantly, DN-hTERT expression induced major changes in cell morphology of neuroblasts that switched them from a neuronal to a substrate adherent phenotype, which was more prone to apoptosis and lost their tumorigenic properties in nude mice. These biologic effects arose from modifications in the expression of genes involved in both apoptosis and neuroblastoma biology. Taken together these results highlighted the functional relevance of noncanonical functions of hTERT in the determination of neuroblast cell fate. Therefore, our results envision new therapeutic strategies for metastatic neuroblastoma therapeutic management. ©2012 AACR.

  12. Structure prediction of the EcoRV DNA methyltransferase based on mutant profiling, secondary structure analysis, comparison with known structures of methyltransferases and isolation of catalytically inactive single mutants.

    PubMed

    Jeltsch, A; Sobotta, T; Pingoud, A

    1996-05-01

    The EcoRV DNA methyltransferase (M.EcoRV) is an alpha-adenine methyltransferase. We have used two different programs to predict the secondary structure of M.EcoRV. The resulting consensus prediction was tested by a mutant profiling analysis. 29 neutral mutations of M.EcoRV were generated by five cycles of random mutagenesis and selection for active variants to increase the reliability of the prediction and to get a secondary structure prediction for some ambiguously predicted regions. The predicted consensus secondary structure elements could be aligned to the common topology of the structures of the catalytic domains of M.HhaI and M.TaqI. In a complementary approach we have isolated nine catalytically inactive single mutants. Five of these mutants contain an amino acid exchange within the catalytic domain of M.EcoRV (Val2-Ala, Lys81Arg, Cys192Arg, Asp193Gly, Trp231Arg). The Trp231Arg mutant binds DNA similarly to wild-type M.EcoRV, but is catalytically inactive. Hence this mutant behaves like a bona fide active site mutant. According to the structure prediction, Trp231 is located in a loop at the putative active site of M.EcoRV. The other inactive mutants were insoluble. They contain amino acid exchanges within the conserved amino acid motifs X, III or IV in M.EcoRV confirming the importance of these regions.

  13. Identification of photo-inactive phytochrome A in etiolated seedlings and photo-active phytochrome B in green leaves of the aurea mutant of tomato.

    PubMed

    Sharma, R; López-Juez, E; Nagatani, A; Furuya, M

    1993-12-01

    The contents of spectrophotometrically measurable phytochrome A (PhyA) and phytochrome B (PhyB) and the corresponding immunochemically detectable apoproteins (PHYA and PHYB) were examined in dark- and light-grown tissues of the aurea mutant of tomato and its wild-type (WT). The amount of PHYA in etiolated aurea seedlings was found to be about 20% of that in the WT; this PHYA showed no photo-reversible changes in absorbance, no downregulation of the level of PHYA in light-grown seedlings, and no differential proteolysis of Pr and Pfr species in vitro which was seen in the case of the WT. By contrast, the amount of PHYB in aurea seedlings was not significantly different from that in WT seedlings. Phytochrome isolated from green leaves of the aurea mutant and purified by ion-exchange chromatography showed a red/far-red reversible spectral change, and its elution profile during chromatography was essentially similar to that of PHYB. The results indicate that aurea is a mutant that is deficient in photoactive PhyA at the etiolated stage, when it contains a spectrally inactive PHYA. However, the mutant contains spectrally active PhyB in its green tissue as does the WT.

  14. Frequency of the arylsulphatase A pseudodeficiency allele in the Spanish population.

    PubMed

    Chabás, A; Castellvi, S; Bayés, M; Balcells, S; Grinberg, D; Vilageliu, L; Marfany, G; Lissens, W; Gonzàlez-Duarte, R

    1993-12-01

    Pseudodeficiency in arylsulphatase A (ASA) is a relatively frequent condition in healthy individuals. It produces a reduction in enzyme activity similar to that found in metachromatic leukodystrophy (MLD). Unambiguous discrimination between the two conditions cannot be achieved through conventional enzyme activity assays. A PCR method has been developed which detects the pseudodeficiency (pd) allele using a single pair of primers encompassing the mutation site and hair follicles as the source of DNA. The frequency of this allele in the Spanish population has been evaluated and correlations between different genotypes and ASA activity levels have been established. Ten out of 55 individuals were heterozygous for the ASA pd allele, while two were homozygous. The allele frequency was thus 12.7%.

  15. Development of a robust scintillation proximity assay for protein tyrosine phosphatase 1B using the catalytically inactive (C215S) mutant.

    PubMed

    Skorey, K I; Kennedy, B P; Friesen, R W; Ramachandran, C

    2001-04-15

    Protein tyrosine phosphatases are a class of enzymes that function to modulate tyrosine phosphorylation of cellular proteins and play an essential role in regulating cell function. PTP1B has been implicated in the negative regulation of the insulin signaling pathway by dephosphorylating the activated insulin receptor. Inhibiting this phosphatase and preventing the insulin-receptor downregulation has been suggested as a target for the treatment of Type II diabetes. A high-throughput screen for inhibitors of PTP1B was developed using a scintillation proximity assay (SPA) with GST-- or FLAG--PTP1B((1-320)) and a potent [(3)H]-tripeptide inhibitor. The problem of interference from extraneous oxidizing and alkylating agents which react with the cysteine active-site nucleophile was overcome by the use of the catalytically inactive C215S form of the native enzyme (GST--PTP1B(C215S)). The GST--PTP1B was linked to the protein A scintillation bead via GST antibody. The radiolabeled inhibitor when bound to the enzyme gave a radioactive signal that was competed away by the unknown competitive compounds. Further utility of PTP1B(C215S) was demonstrated by mixing in the same well both the catalytically inactive GST--PTP1B(C215S) and the catalytically active FLAG--CD45 with an inhibitor. Both a binding and kinetic assay was then performed in the same 96-well plate with the inhibition results determined for the PTP1B(C215S) (binding assay) and CD45 (activity assay). In this way inhibitors could be differentiated between the two phosphatases under identical assay conditions in one 96-well assay plate. The use of a mutant to reduce interference in a binding assay and compare with activity assays is also amenable for most cysteine active-site proteases.

  16. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A.

    PubMed

    Ogris, E; Du, X; Nelson, K C; Mak, E K; Yu, X X; Lane, W S; Pallas, D C

    1999-05-14

    Carboxymethylation of proteins is a highly conserved means of regulation in eukaryotic cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is reversibly methylated at its carboxyl terminus by specific methyltransferase and methylesterase enzymes which have been purified, but not cloned. Carboxymethylation affects PP2A activity and varies during the cell cycle. Here, we report that substitution of glutamine for either of two putative active site histidines in the PP2A C subunit results in inactivation of PP2A and formation of stable complexes between PP2A and several cellular proteins. One of these cellular proteins, herein named protein phosphatase methylesterase-1 (PME-1), was purified and microsequenced, and its cDNA was cloned. PME-1 is conserved from yeast to human and contains a motif found in lipases having a catalytic triad-activated serine as their active site nucleophile. Bacterially expressed PME-1 demethylated PP2A C subunit in vitro, and okadaic acid, a known inhibitor of the PP2A methylesterase, inhibited this reaction. To our knowledge, PME-1 represents the first mammalian protein methylesterase to be cloned. Several lines of evidence indicate that, although there appears to be a role for C subunit carboxyl-terminal amino acids in PME-1 binding, amino acids other than those at the extreme carboxyl terminus of the C subunit also play an important role in PME-1 binding to a catalytically inactive mutant.

  17. Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages.

    PubMed Central

    Muschol, Nicole; Matzner, Ulrich; Tiede, Stephan; Gieselmann, Volkmar; Ullrich, Kurt; Braulke, Thomas

    2002-01-01

    The transfer of macrophage-secreted arylsulphatase A (ASA) to enzyme-deficient brain cells is part of the therapeutic concept of bone marrow transplantation in lysosomal storage diseases. Here we have investigated this transfer in vitro. The uptake of (125)I-labelled recombinant human ASA purified from ASA-overexpressing mouse embryonic fibroblasts deficient for mannose 6-phosphate (M6P) receptors in a mouse ASA-deficient astroglial cell line was completely inhibited by M6P. In contrast, when ASA-deficient astroglial cells were incubated with secretions of [(35)S]methionine-labelled human macrophages or mouse microglia, containing various lysosomal enzymes, neither ASA nor cathepsin D (CTSD) were detected in acceptor cells. Co-culturing of metabolically labelled macrophages with ASA-deficient glial cells did not result in an M6P-dependent transfer of ASA or CTSD between these two cell types. In secretions of [(33)P]phosphate-labelled macrophages no or weakly phosphorylated ASA and CTSD precursor polypeptides were found, whereas both intracellular and secreted ASA from ASA-overexpressing baby hamster kidney cells displayed (33)P-labelled M6P residues. Finally, the uptake of CTSD from secretions of [(35)S]methionine-labelled macrophages in rat hepatocytes was M6P-independent. These data indicated that lysosomal enzymes secreted by human macrophages or a mouse microglial cell line cannot be endocytosed by brain cells due to the failure to equip newly synthesized lysosomal enzymes with the M6P recognition marker efficiently. The data suggest that other mechanisms than the proposed M6P-dependent secretion/recapture of lysosomal enzymes might be responsible for therapeutic effects of bone marrow transplantation in the brain. PMID:12296771

  18. Protonation state of Asp (Glu)-85 regulates the purple-to-blue transition in bacteriorhodopsin mutants Arg-82----Ala and Asp-85----Glu: The blue form is inactive in proton translocation

    SciTech Connect

    Subramaniam, S.; Marti, T.; Khorana, H.G. )

    1990-02-01

    Previous studies with site-specific mutants of bacteriorhodopsin have demonstrated that replacement of Asp-85 or Arg-82 affects the absorption spectrum. Between pH 5.5 and 7, the Asp-85----Glu and Arg-82----Ala mutants exist in a pH-dependent equilibrium between purple (lambda max approximately 550/540 nm) and blue (lambda max approximately 600/590 nm) forms of the pigment. Measurement of proton transport as a function of wavelength in reconstituted vesicles shows that proton-pumping activities for the above mutants reside exclusively in their respective purple species. For both mutants, formation of the blue form with decreasing pH is accompanied by loss of proton transport activity. The Asp-85----Asn mutant displays a blue chromophore (lambda max approximately 588 nm), is inactive in proton translocation from pH 5 to 7.5, and shows no transition to the purple form. In contrast, the Asp-212----Asn mutant is purple (lambda max approximately 555 nm) and shows no transition to a blue chromophore with decreasing pH. The experiments suggest that (i) the pKa of the purple-to-blue transition is directly influenced by the pKa of the carboxylate at residue 85 and (ii) the relative strengths of interaction between the protonated Schiff base, Asp-85, Asp-212, and Arg-82 make a major contribution to the regulation of color and function of bacteriorhodopsin.

  19. Protonation state of Asp (Glu)-85 regulates the purple-to-blue transition in bacteriorhodopsin mutants Arg-82----Ala and Asp-85----Glu: the blue form is inactive in proton translocation.

    PubMed

    Subramaniam, S; Marti, T; Khorana, H G

    1990-02-01

    Previous studies with site-specific mutants of bacteriorhodopsin have demonstrated that replacement of Asp-85 or Arg-82 affects the absorption spectrum. Between pH 5.5 and 7, the Asp-85----Glu and Arg-82----Ala mutants exist in a pH-dependent equilibrium between purple (lambda max approximately 550/540 nm) and blue (lambda max approximately 600/590 nm) forms of the pigment. Measurement of proton transport as a function of wavelength in reconstituted vesicles shows that proton-pumping activities for the above mutants reside exclusively in their respective purple species. For both mutants, formation of the blue form with decreasing pH is accompanied by loss of proton transport activity. The Asp-85----Asn mutant displays a blue chromophore (lambda max approximately 588 nm), is inactive in proton translocation from pH 5 to 7.5, and shows no transition to the purple form. In contrast, the Asp-212----Asn mutant is purple (lambda max approximately 555 nm) and shows no transition to a blue chromophore with decreasing pH. The experiments suggest that (i) the pKa of the purple-to-blue transition is directly influenced by the pKa of the carboxylate at residue 85 and (ii) the relative strengths of interaction between the protonated Schiff base, Asp-85, Asp-212, and Arg-82 make a major contribution to the regulation of color and function of bacteriorhodopsin.

  20. Simian Virus 40-Based Replication of Catalytically Inactive Human Immunodeficiency Virus Type 1 Integrase Mutants in Nonpermissive T Cells and Monocyte-Derived Macrophages

    PubMed Central

    Lu, Richard; Nakajima, Noriko; Hofmann, Wolfgang; Benkirane, Monsef; Teh-Jeang, Kuan; Sodroski, Joseph; Engelman, Alan

    2004-01-01

    Integrase function is required for retroviral replication in most instances. Although certain permissive T-cell lines support human immunodeficiency virus type 1 (HIV-1) replication in the absence of functional integrase, most cell lines and primary human cells are nonpermissive for integrase mutant growth. Since unintegrated retroviral DNA is lost from cells following cell division, we investigated whether incorporating a functional origin of DNA replication into integrase mutant HIV-1 might overcome the block to efficient gene expression and replication in nonpermissive T-cell lines and primary cells. Whereas the Epstein-Barr virus (EBV) origin (oriP) did little to augment expression from an integrase mutant reporter virus in EBV nuclear antigen 1-expressing cells, simian virus 40 (SV40) oriT dramatically enhanced integrase mutant infectivity in T-antigen (Tag)-expressing cells. Incorporating oriT into the nef position of a full-length, integrase-defective virus strain yielded efficient replication in Tag-expressing nonpermissive Jurkat T cells without reversion to an integration-competent genotype. Adding Tag to integrase mutant-oriT viruses yielded 11.3-kb SV40-HIV chimeras that replicated in Jurkat cells and primary monocyte-derived macrophages. Real-time quantitative PCR analyses of Jurkat cell infections revealed that amplified copies of unintegrated DNA likely contributed to SV40-HIV integrase mutant replication. SV40-based HIV-1 integrase mutant replication in otherwise nonpermissive cells suggests alternative approaches to standard integrase-mediated retroviral gene transfer strategies. PMID:14694097

  1. Expression of a Catalytically Inactive Mutant Form of Glutathione Peroxidase 4 (Gpx4) Confers a Dominant-negative Effect in Male Fertility*

    PubMed Central

    Ingold, Irina; Aichler, Michaela; Yefremova, Elena; Roveri, Antonella; Buday, Katalin; Doll, Sebastian; Tasdemir, Adrianne; Hoffard, Nils; Wurst, Wolfgang; Walch, Axel; Ursini, Fulvio; Friedmann Angeli, José Pedro; Conrad, Marcus

    2015-01-01

    The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with a targeted mutation of the active site selenocysteine of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4−/− embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breeding and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoa midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mitochondrial Gpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared with selenocysteine at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Because the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and as a structural protein, tightly controlled expression of functional Gpx4 emerges as a key for full male fertility. PMID:25922076

  2. Expression of a Catalytically Inactive Mutant Form of Glutathione Peroxidase 4 (Gpx4) Confers a Dominant-negative Effect in Male Fertility.

    PubMed

    Ingold, Irina; Aichler, Michaela; Yefremova, Elena; Roveri, Antonella; Buday, Katalin; Doll, Sebastian; Tasdemir, Adrianne; Hoffard, Nils; Wurst, Wolfgang; Walch, Axel; Ursini, Fulvio; Friedmann Angeli, José Pedro; Conrad, Marcus

    2015-06-05

    The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with a targeted mutation of the active site selenocysteine of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4(-/-) embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breeding and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoa midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mitochondrial Gpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared with selenocysteine at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Because the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and as a structural protein, tightly controlled expression of functional Gpx4 emerges as a key for full male fertility.

  3. Defining the enzyme binding domain of a ribonuclease III processing signal. Ethylation interference and hydroxyl radical footprinting using catalytically inactive RNase III mutants.

    PubMed Central

    Li, H; Nicholson, A W

    1996-01-01

    Ethylation interference and hydroxyl radical footprinting were used to identify substrate ribose-phosphate backbone sites that interact with the Escherichia coli RNA processing enzyme, ribonuclease III. Two RNase III mutants were employed, which bind substrate in vitro similarly as wild-type enzyme, but lack detectable phosphodiesterase activity. Specifically, altering glutamic acid at position 117 to lysine or alanine uncouples substrate binding from cleavage. The two substrates examined are based on the bacteriophage T7 R1.1 RNase III processing signal. One substrate, R1.1 RNA, undergoes accurate single cleavage at the canonical site, while a close variant, R1.1[WC-L] RNA, undergoes coordinate double cleavage. The interference and footprinting patterns for each substrate (i) overlap, (ii) exhibit symmetry and (iii) extend approximately one helical turn in each direction from the RNase III cleavage sites. Divalent metal ions (Mg2+, Ca2+) significantly enhance substrate binding, and confer stronger protection from hydroxyl radicals, but do not significantly affect the interference pattern. The footprinting and interference patterns indicate that (i) RNase III contacts the sugar-phosphate backbone; (ii) the RNase III-substrate interaction spans two turns of the A-form helix; and (iii) divalent metal ion does not play an essential role in binding specificity. These results rationalize the conserved two-turn helix motif seen in most RNase III processing signals, and which is necessary for optimal processing reactivity. In addition, the specific differences in the footprint and interference patterns of the two substrates suggest why RNase III catalyzes the coordinate double cleavage of R1.1[WC-L] RNA, and dsRNA in general, while catalyzing only single cleavage of R1.1 RNA and related substrates in which the scissle bond is within an asymmetric internal loop. Images PMID:8635475

  4. Structure of solvation water around the active and inactive regions of a type III antifreeze protein and its mutants of lowered activity

    NASA Astrophysics Data System (ADS)

    Grabowska, Joanna; Kuffel, Anna; Zielkiewicz, Jan

    2016-08-01

    Water molecules from the solvation shell of the ice-binding surface are considered important for the antifreeze proteins to perform their function properly. Herein, we discuss the problem whether the extent of changes of the mean properties of solvation water can be connected with the antifreeze activity of the protein. To this aim, the structure of solvation water of a type III antifreeze protein from Macrozoarces americanus (eel pout) is investigated. A wild type of the protein is used, along with its three mutants, with antifreeze activities equal to 54% or 10% of the activity of the native form. The solvation water of the ice-binding surface and the rest of the protein are analyzed separately. To characterize the structure of solvation shell, parameters describing radial and angular characteristics of the mutual arrangement of the molecules were employed. They take into account short-distance (first hydration shell) or long-distance (two solvation shells) effects. The obtained results and the comparison with the results obtained previously for a hyperactive antifreeze protein from Choristoneura fumiferana lead to the conclusion that the structure and amino acid composition of the active region of the protein evolved to achieve two goals. The first one is the modification of the properties of the solvation water. The second one is the geometrical adjustment of the protein surface to the specific crystallographic plane of ice. Both of these goals have to be achieved simultaneously in order for the protein to perform its function properly. However, they seem to be independent from one another in a sense that very small antifreeze activity does not imply that properties of water become different from the ones observed for the wild type. The proteins with significantly lower activity still modify the mean properties of solvation water in a right direction, in spite of the fact that the accuracy of the geometrical match with the ice lattice is lost because of the

  5. Spectroscopic studies of the copper sites in wild-type pseudomonas stutzeri N sub 2 O reductase and in an inactive protein isolated from a mutant deficient in copper-site biosynthesis

    SciTech Connect

    Dooley, D.M.; McGuirl, M.A.; Rosenzweig, A.C.; Landin, J.A. ); Scott, R.A. ); Zumft, W.G. ); Devlin, F.; Stephens, P.J. )

    1991-07-24

    The results of studies of circular dichroism, magnetic circular dichroism, and x-ray absorption and fluorescence spectroscopy used to further characterize the copper sites in native N{sub 2}O reductase and in a mutant protein isolated from a strain deficient in the biosynthesis of the N{sub 2}O reductase copper sites that contains only 2 copper ions/protein molecule, are reported herein. Both magnetic circular dichroism and x-ray absorption (Cu K-edge and EXADS) data are consistent with the presence of (on average) one Cu{sub A}-type site per protein in the mutant N{sub 2}O reductase. Comparisons of the near-infrared circular dichroism spectra of the oxidized native and mutant N{sub 2}O reductases suggest that transitions at 7,200 and 9,500 cm{sup {minus}1} in the native enzyme are associated with copper sites other than the Cu{sub A}-type sites. These are the first electronic spectral features that can be attributed to non-Cu-type sites in N{sub 2}O reductase. The near-infrared bands are believed to be significantly less intense in preparations of N{sub 2}O reductase that display lower specific activities. Several electronic transitions are resolved in the circular and magnetic circular dichroism spectra of dithionite-reduced N{sub 2}O reductase. Notably a near-infrared band is observed in the circular dichroism spectrum at 8,200 cm{sup {minus}1}. Theories are presented to explain the reported data. 29 refs., 8 figs., 1 tab.

  6. Exercise Responses after Inactivity

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    1986-01-01

    The exercise response after bed rest inactivity is a reduction in the physical work capacity and is manifested by significant decreases in oxygen uptake. The magnitude of decrease in maximal oxygen intake V(dot)O2max is related to the duration of confinement and the pre-bed-rest level of aerobic fitness; these relationships are relatively independent of age and gender. The reduced exercise performance and V(dot)O2max following bed rest are associated with various physiological adaptations including reductions in blood volume, submaximal and maximal stroke volume, maximal cardiac output, sceletal muscle tone and strength, and aerobic enzyme capacities, as well as increases in venous compliance and submaximal and maximal heart rate. This reduction in physiological capacity can be partially restored by specific countermeasures that provide regular muscular activity or orhtostatic stress or both during the bed rest exposure. The understanding of these physiological and physical responses to exercise following bed rest inactivity has important implications for the solution to safety and health problems that arise in clinical medicine, aerospace medicine, sedentary living, and aging.

  7. Exercise Responses after Inactivity

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    1986-01-01

    The exercise response after bed rest inactivity is a reduction in the physical work capacity and is manifested by significant decreases in oxygen uptake. The magnitude of decrease in maximal oxygen intake V(dot)O2max is related to the duration of confinement and the pre-bed-rest level of aerobic fitness; these relationships are relatively independent of age and gender. The reduced exercise performance and V(dot)O2max following bed rest are associated with various physiological adaptations including reductions in blood volume, submaximal and maximal stroke volume, maximal cardiac output, sceletal muscle tone and strength, and aerobic enzyme capacities, as well as increases in venous compliance and submaximal and maximal heart rate. This reduction in physiological capacity can be partially restored by specific countermeasures that provide regular muscular activity or orhtostatic stress or both during the bed rest exposure. The understanding of these physiological and physical responses to exercise following bed rest inactivity has important implications for the solution to safety and health problems that arise in clinical medicine, aerospace medicine, sedentary living, and aging.

  8. From Power to Inaction.

    PubMed

    Durso, Geoffrey R O; Briñol, Pablo; Petty, Richard E

    2016-12-01

    Research has shown that people who feel powerful are more likely to act than those who feel powerless, whereas people who feel ambivalent are less likely to act than those whose reactions are univalent (entirely positive or entirely negative). But what happens when powerful people also are ambivalent? On the basis of the self-validation theory of judgment, we hypothesized that power and ambivalence would interact to predict individuals' action. Because power can validate individuals' reactions, we reasoned that feeling powerful strengthens whatever reactions people have during a decision. It can strengthen univalent reactions and increase action orientation, as shown in past research. Among people who hold an ambivalent judgment, however, those who feel powerful would be less action oriented than those who feel powerless. Two experiments provide evidence for this hypothesized interactive effect of power and ambivalence on individuals' action tendencies during both positive decisions (promoting an employee; Experiment 1) and negative decisions (firing an employee; Experiment 2). In summary, when individuals' reactions are ambivalent, power increases the likelihood of inaction.

  9. Inactive and abandoned noncoal mines

    SciTech Connect

    Not Available

    1991-08-01

    Volume 1 outlines the environmental, health and safety problems at IAMS (Inactive, Abandoned Mine Sites), remediation technologies, remediation costs, the methodology states used in preparing state reports, and state summary tables. It also describes the broad range of policy options for remediation of problems associated with IAMS. Volume 2 gives state reports for inactive and abandoned noncoal mines for the following states: Alaska, Arizona, California, Colorado, Florida, Idaho, Minnesota, Missouri, Montana, Nevada, New Mexico, Oregon, South Carolina, South Dakota, Utah, Washington, Wisconsin and Wyoming. Volume 3 lists the State reports for the inactive and abandoned noncoal mines for the following states: Alabama, Arkansas, Illinois, Indiana, Iowa, Louisiana, Maine, Maryland, Mississippi, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, Texas, and Virginia. A separate abstract is included for each of the 3 volumes of this set.

  10. Health Risks of an Inactive Lifestyle

    MedlinePlus

    ... may develop a hormonal imbalance What are the health risks of an inactive lifestyle? Having an inactive ... the more sedentary you are, the higher your health risks are. How can I get started with ...

  11. Inactive sites and the evolution of cooperation

    NASA Astrophysics Data System (ADS)

    da Silva Júnior, E. J.; Wardil, L. L.; da Silva, J. K. L.

    2016-10-01

    Cooperation is often conditioned on environmental factors. Behaviors may be inactive due to external factors, and yet the trait itself may not change. We study the evolution of cooperation with active and inactive sites. In inactive sites cooperators behave as defectors, receiving but not providing benefits. This unintentional mimicry provides local advantage to cooperation, but also prevents the mutual reinforcement provided by clusters of active cooperators. In general, we found that cooperation is enhanced by inactivity. In particular, if most sites are inactive, cooperation survives even if the temptation to defect is very large. Interestingly, in the square lattice with pairwise comparison rule we found that cooperation is enforced by inactive sites only up to a certain limit.

  12. Obesity and Physical Inactivity in Rural America

    ERIC Educational Resources Information Center

    Patterson, Paul Daniel; Moore, Charity G.; Probst, Janice C.; Shinogle, Judith Ann

    2004-01-01

    Context and Purpose: Obesity and physical inactivity are common in the United States, but few studies examine this issue within rural populations. The present study uses nationally representative data to study obesity and physical inactivity in rural populations. Methods: Data came from the 1998 National Health Interview Survey Sample Adult and…

  13. 21 CFR 312.45 - Inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Inactive status. 312.45 Section 312.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Administrative Actions § 312.45 Inactive status. (a) If...

  14. Regrets of Action and Inaction across Cultures.

    ERIC Educational Resources Information Center

    Gilovich, Thomas; Wang, Ranxiao Frances; Regan, Dennis; Nishina, Sadafumi

    2003-01-01

    Conducted five studies in three cultures considered less individualistic than the United States (China, Japan, and Russia) to investigate regrets related to action and inaction in people's lives. Respondents in all three cultures tended to regret inactions more than actions in the long term. Types of regrets (generally involving the self rather…

  15. 21 CFR 201.117 - Inactive ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Inactive ingredients. 201.117 Section 201.117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... drug that is ordinarily used as an inactive ingredient, such as a coloring, emulsifier, excipient...

  16. Obesity and Physical Inactivity in Rural America

    ERIC Educational Resources Information Center

    Patterson, Paul Daniel; Moore, Charity G.; Probst, Janice C.; Shinogle, Judith Ann

    2004-01-01

    Context and Purpose: Obesity and physical inactivity are common in the United States, but few studies examine this issue within rural populations. The present study uses nationally representative data to study obesity and physical inactivity in rural populations. Methods: Data came from the 1998 National Health Interview Survey Sample Adult and…

  17. 21 CFR 201.117 - Inactive ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Inactive ingredients. 201.117 Section 201.117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.117 Inactive ingredients. A...

  18. 21 CFR 201.117 - Inactive ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Inactive ingredients. 201.117 Section 201.117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.117 Inactive ingredients. A...

  19. Variants of human thymidylate synthase with loop 181–197 stabilized in the inactive conformation

    PubMed Central

    Lovelace, Leslie L; Johnson, Saphronia R; Gibson, Lydia M; Bell, Brittnaie J; Berger, Sondra H; Lebioda, Lukasz

    2009-01-01

    Loop 181–197 of human thymidylate synthase (hTS) populates two major conformations, essentially corresponding to the loop flipped by 180°. In one of the conformations, the catalytic Cys195 residue lies distant from the active site making the enzyme inactive. Ligands stabilizing this inactive conformation may function as allosteric inhibitors. To facilitate the search for such inhibitors, we have expressed and characterized several mutants designed to shift the equilibrium toward the inactive conformer. In most cases, the catalytic efficiency of the mutants was only somewhat impaired with values of kcat/Km reduced by factors in a 2–12 range. One of the mutants, M190K, is however unique in having the value of kcat/Km smaller by a factor of ∼7500 than the wild type. The crystal structure of this mutant is similar to that of the wt hTS with loop 181–197 in the inactive conformation. However, the direct vicinity of the mutation, residues 188–194 of this loop, assumes a different conformation with the positions of Cα shifted up to 7.2 Å. This affects region 116–128, which became ordered in M190K while it is disordered in wt. The conformation of 116–128 is however different than that observed in hTS in the active conformation. The side chain of Lys190 does not form contacts and is in solvent region. The very low activity of M190K as compared to another mutant with a charged residue in this position, M190E, suggests that the protein is trapped in an inactive state that does not equilibrate easily with the active conformer. PMID:19569192

  20. Iron-molybdenum cofactor synthesis in Azotobacter vinelandii Nif- mutants.

    PubMed Central

    Imperial, J; Shah, V K; Ugalde, R A; Ludden, P W; Brill, W J

    1987-01-01

    Nif- mutants of Azotobacter vinelandii defective in dinitrogenase activity synthesized iron-molybdenum cofactor (FeMo-co) and accumulated it in two protein-bound forms: inactive dinitrogenase and a possible intermediate involved in the FeMo-co biosynthetic pathway. FeMo-co from both these proteins could activate apo-dinitrogenase from FeMo-co-deficient mutants. PMID:3470286

  1. Temperature-Compensating Inactive Strain Gauge

    NASA Technical Reports Server (NTRS)

    Moore, Thomas C., Sr.

    1993-01-01

    Thermal contribution to output of active gauge canceled. High-temperature strain gauges include both active gauge wires sensing strains and inactive gauge wires providing compensation for thermal contributions to gauge readings. Inactive-gauge approach to temperature compensation applicable to commercially available resistance-type strain gauges operating at temperatures up to 700 degrees F and to developmental strain gauges operating at temperatures up to 2,000 degrees F.

  2. Inactive Wells: Economic and Policy Issues

    NASA Astrophysics Data System (ADS)

    Krupnick, A.

    2016-12-01

    This paper examines the economic and policy issues associated with various types of inactive oil and gas wells. It covers the costs of decommissioning wells, and compares them to the bonding requirements on these wells, looking at a large number of states. It also reviews the detailed regulations governing treatment of inactive wells by states and the federal government and compares them according to their completeness and stringency.

  3. Physical Inactivity, Sedentary Behavior and Chronic Diseases.

    PubMed

    González, Karimé; Fuentes, Jorge; Márquez, José Luis

    2017-05-01

    New research into physical activity suggests that it is no longer sufficient just to meet minimum levels recommended by health guidelines in order to reduce cardiovascular risk. Both physical inactivity and sedentary behavior have their own health hazards and need to be addressed separately, in order to explore their different deleterious mechanisms. The aim of this review was to define and to characterize both concepts, and their relationship with major non-communicable chronic diseases. A PubMed database search was undertaken, using the following key words: physical activity, physical inactivity, sedentarism, sedentary behavior, and non-communicable chronic disease. This literature review provides an updated view on physical inactivity and sedentary behavior, and reevaluates their prevalence and association with major non-communicable chronic disease.

  4. Elective Mutism Associated with Selective Inactivity.

    ERIC Educational Resources Information Center

    Hill, Linda; Scull, John

    1985-01-01

    Effective treatment procedures for a nine-year-old boy with elective mutism and selective inactivity included increasing the frequency of situations in which he could already speak and decreasing the frequency of those in which he seldom spoke (specifically coercive situations). (CL)

  5. Cloning, preparation and preliminary crystallographic studies of penicillin V acylase autoproteolytic processing mutants

    SciTech Connect

    Chandra, P. Manish; Brannigan, James A.; Prabhune, Asmita; Pundle, Archana; Turkenburg, Johan P.; Dodson, G. Guy; Suresh, C. G.

    2005-01-01

    The production, crystallization and characterization of three inactive mutants of penicillin V acylase from B. sphaericus in their respective precursor and processed forms are reported. The space groups are different for the native enzyme and the mutants. The crystallization of three catalytically inactive mutants of penicillin V acylase (PVA) from Bacillus sphaericus in precursor and processed forms is reported. The mutant proteins crystallize in different primitive monoclinic space groups that are distinct from the crystal forms for the native enzyme. Directed mutants and clone constructs were designed to study the post-translational autoproteolytic processing of PVA. The catalytically inactive mutants will provide three-dimensional structures of precursor PVA forms, plus open a route to the study of enzyme–substrate complexes for this industrially important enzyme.

  6. Physical inactivity and obesity: A vicious circle

    PubMed Central

    Pietiläinen, Kirsi H; Kaprio, Jaakko; Borg, Patrik; Plasqui, Guy; Yki-Järvinen, Hannele; Kujala, Urho M.; Rose, Richard J; Westerterp, Klaas R; Rissanen, Aila

    2007-01-01

    Objective Physical activity (PA) begins to decline in adolescence with concomitant increase in weight. We hypothesized that a vicious circle may arise between decreasing physical activity and weight gain from adolescence to early adulthood. Research Methods and Procedures PA and self-perceived physical fitness assessed in adolescence (16-18 years) were used to predict the development of obesity (BMI≥30 kg/m2) and abdominal obesity (waist≥88 cm in females and ≥102 cm in males) at age 25 in 4240 twin individuals (90% of twins born in Finland 1975-1979). Ten 25-year-old monozygotic (MZ) twin pairs discordant for obesity (16 kg weight difference) were then carefully evaluated for current PA (triaxial accelerometer), total energy expenditure (TEE, doubly labeled water), and basal metabolic rate (BMR, indirect calorimetry). Results Physical inactivity in adolescence strongly predicted the risk of obesity (OR 3.9, 95%CI 1.4-10.9) and abdominal obesity (4.8, 1.9-12.0) at age 25, even after adjusting for baseline and current BMI. Poor physical fitness in adolescence also increased the risk of overall (5.1, 2.0-12.7) and abdominal obesity (3.2, 1.5-6.7) in adulthood. Physical inactivity was both causative and secondary to the development of obesity discordance in the MZ pairs. TEE did not differ between the MZ co-twins. PA levels were lower whereas BMR was higher in the obese co-twins. Discussion Physical inactivity in adolescence strongly and independently predicts total and especially abdominal obesity in young adulthood, favoring the development of a self-perpetuating vicious circle of obesity and physical inactivity. Physical (in)activity should be a major target of obesity prevention in the young. PMID:18239652

  7. Human thymidylate synthase with loop 181-197 stabilized in an inactive conformation: ligand interactions, phosphorylation, and inhibition profiles.

    PubMed

    Luo, BeiBei; Repalli, Jayanthi; Yousef, Al-Motassem; Johnson, Saphronia R; Lebioda, Lukasz; Berger, Sondra H

    2011-01-01

    Thymidylate synthase (TS) is a well-validated cancer target that undergoes conformational switching between active and inactive states. Two mutant human TS (hTS) proteins are predicted from crystal structures to be stabilized in an inactive conformation to differing extents, with M190K populating the inactive conformation to a greater extent than A191K. Studies of intrinsic fluorescence and circular dichroism revealed that the structures of the mutants differ from those of hTS. Inclusion of the substrate dUMP was without effect on M190K but induced structural changes in A191K that are unique, relative to hTS. The effect of strong stabilization in an inactive conformation on protein phosphorylation by casein kinase 2 (CK2) was investigated. M190K was highly phosphorylated by CK2 relative to an active-stabilized mutant, R163K hTS. dUMP had no detectable effect on phosphorylation of M190K; however, dUMP inhibited phosphorylation of hTS and R163K. Studies of temperature dependence of catalysis revealed that the E(act) and temperature optimum are higher for A191K than hTS. The potency of the active-site inhibitor, raltitrexed, was lower for A191K than hTS. The response of A191K to the allosteric inhibitor, propylene diphosphonate (PDPA) was concentration dependent. Mixed inhibition was observed at low concentrations; at higher concentrations, A191K exhibited nonhyperbolic behavior with respect to dUMP and inhibition of catalysis was reversed by substrate saturation. In summary, inactive-stabilized mutants differ from hTS in thermal stability and response to substrates and PDPA. Importantly, phosphorylation of hTS by CK2 is selective for the inactive conformation, providing the first indication of physiological relevance for conformational switching.

  8. Human thymidylate synthase with loop 181–197 stabilized in an inactive conformation: Ligand interactions, phosphorylation, and inhibition profiles

    PubMed Central

    Luo, BeiBei; Repalli, Jayanthi; Yousef, Al-Motassem; Johnson, Saphronia R; Lebioda, Lukasz; Berger, Sondra H

    2011-01-01

    Thymidylate synthase (TS) is a well-validated cancer target that undergoes conformational switching between active and inactive states. Two mutant human TS (hTS) proteins are predicted from crystal structures to be stabilized in an inactive conformation to differing extents, with M190K populating the inactive conformation to a greater extent than A191K. Studies of intrinsic fluorescence and circular dichroism revealed that the structures of the mutants differ from those of hTS. Inclusion of the substrate dUMP was without effect on M190K but induced structural changes in A191K that are unique, relative to hTS. The effect of strong stabilization in an inactive conformation on protein phosphorylation by casein kinase 2 (CK2) was investigated. M190K was highly phosphorylated by CK2 relative to an active-stabilized mutant, R163K hTS. dUMP had no detectable effect on phosphorylation of M190K; however, dUMP inhibited phosphorylation of hTS and R163K. Studies of temperature dependence of catalysis revealed that the Eact and temperature optimum are higher for A191K than hTS. The potency of the active-site inhibitor, raltitrexed, was lower for A191K than hTS. The response of A191K to the allosteric inhibitor, propylene diphosphonate (PDPA) was concentration dependent. Mixed inhibition was observed at low concentrations; at higher concentrations, A191K exhibited nonhyperbolic behavior with respect to dUMP and inhibition of catalysis was reversed by substrate saturation. In summary, inactive-stabilized mutants differ from hTS in thermal stability and response to substrates and PDPA. Importantly, phosphorylation of hTS by CK2 is selective for the inactive conformation, providing the first indication of physiological relevance for conformational switching. PMID:21064161

  9. Fire protection for inactive contaminated structures

    SciTech Connect

    Wyatt, D.M.

    1994-02-01

    In general industry and construction, destruction of an inactive/surplus facility by fire may be considered a blessing. However, in a decommissioned contaminated structure, where radiological and other hazardous materials exist, such a fire could be a major catastrophe. The losses from this type of fire are not only property (i.e., structure and its contents) but also the resulting environmental damage, required cleanup, offsite releases, and public relations and reactions. The purpose of this presentation is to (1) promote an awareness among the waste management community of fire protection engineering aspects that must be considered for inactive/surplus contaminated structures, and (2) present to the fire protection community an opportunity to become involved in the decommissioning process while promoting the DOE objectives to manage the risks associated with these structures.

  10. Exploring human inactivity in computer power consumption

    NASA Astrophysics Data System (ADS)

    Candrawati, Ria; Hashim, Nor Laily Binti

    2016-08-01

    Managing computer power consumption has become an important challenge in computer society and this is consistent with a trend where a computer system is more important to modern life together with a request for increased computing power and functions continuously. Unfortunately, previous approaches are still inadequately designed to handle the power consumption problem due to unpredictable workload of a system caused by unpredictable human behaviors. This is happens due to lack of knowledge in a software system and the software self-adaptation is one approach in dealing with this source of uncertainty. Human inactivity is handled by adapting the behavioral changes of the users. This paper observes human inactivity in the computer usage and finds that computer power usage can be reduced if the idle period can be intelligently sensed from the user activities. This study introduces Control, Learn and Knowledge model that adapts the Monitor, Analyze, Planning, Execute control loop integrates with Q Learning algorithm to learn human inactivity period to minimize the computer power consumption. An experiment to evaluate this model was conducted using three case studies with same activities. The result show that the proposed model obtained those 5 out of 12 activities shows the power decreasing compared to others.

  11. The Global Physical Inactivity Pandemic: An Analysis of Knowledge Production

    ERIC Educational Resources Information Center

    Piggin, Joe; Bairner, Alan

    2016-01-01

    In July 2012, "The Lancet" announced a pandemic of physical inactivity and a global call to action to effect change. The worldwide pandemic is said to be claiming millions of lives every year. Asserting that physical inactivity is pandemic is an important moment. Given the purported scale and significance of physical inactivity around…

  12. The Global Physical Inactivity Pandemic: An Analysis of Knowledge Production

    ERIC Educational Resources Information Center

    Piggin, Joe; Bairner, Alan

    2016-01-01

    In July 2012, "The Lancet" announced a pandemic of physical inactivity and a global call to action to effect change. The worldwide pandemic is said to be claiming millions of lives every year. Asserting that physical inactivity is pandemic is an important moment. Given the purported scale and significance of physical inactivity around…

  13. [Approaching Physically Inactive Elderly for Physical Activity].

    PubMed

    Allmer, H; Allmer, M; Euskirchen, J; Froböse, I; Wallmann, B; Walter, T; Walschek, R

    2015-09-01

    The majority of elderly persons are still not sufficiently physically active. Therefore the aim of this study was to investigate different approaches (physical activity courses, poster, online-survey) for activating elderly to participate in physical activity. The most effective approach was target group physical activity courses with which higher course participation rates in men as well as in people with lower levels of education were achieved. Referring to the transtheoretical model (TTM) it is necessary for future analyses of target group approaches to consider more intensely the initial motivational position of physically inactive elderly.

  14. Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations

    PubMed Central

    Calhan, O. Y.

    2017-01-01

    The lysosomal carboxypeptidase A, Cathepsin A (CathA), is a serine protease with two distinct functions. CathA protects β-galactosidase and sialidase Neu1 against proteolytic degradation by forming a multienzyme complex and activates sialidase Neu1. CathA deficiency causes the lysosomal storage disease, galactosialidosis. These patients present with a broad range of clinical phenotypes, including growth retardation, and neurological deterioration along with the accumulation of the vasoactive peptide, endothelin-1, in the brain. Previous in vitro studies have shown that CathA has specific activity against vasoactive peptides and neuropeptides, including endothelin-1 and oxytocin. A mutant mouse with catalytically inactive CathA enzyme (CathAS190A) shows increased levels of endothelin-1. In the present study, we elucidated the involvement of CathA in learning and long-term memory in 3-, 6-, and 12-month-old mice. Hippocampal endothelin-1 and oxytocin accumulated in CathAS190A mice, which showed learning impairments as well as long-term and spatial memory deficits compared with wild-type littermates, suggesting that CathA plays a significant role in learning and in memory consolidation through its regulatory role in vasoactive peptide processing. PMID:28133419

  15. Electrically inactive poly-silicon grain boundaries

    SciTech Connect

    Chen, S.P.; Kress, J.D.; Voter, A.F.; Albers, R.C.

    1996-05-01

    Structures, energies, and electronic properties of symmetric [001] tilt grain boundaries in Si have been studied using Stillinger-Weber and Tersoff classical potentials, and semi-empirical (tight-binding) electronic structure methods. The calculated lowest energy (310) grain boundary structure and electronic properties are consistent with previous TEM measurement and calculations. For the controversial (710) grain boundaries, the tight-binding calculations do not show any electronic energy levels in the band gap. This indicates that with every atom fully fourfold coordinated, the (710) grain boundary should be electrically inactive. Some high-energy metastable grain boundaries were found to be electrically active by the presence of the levels introduced in the band gap. Also, the vacancy concentration at the (310) GB was found to be enhanced by many orders of magnitude relative to bulk. The dangling bond states of the vacancies should be electrically active.

  16. C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

    PubMed

    Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

    2016-01-01

    We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.

  17. Nurse administrators' intentions and considerations in recruiting inactive nurses.

    PubMed

    Yu, Hsing-Yi; Tang, Fu-In; Chen, I-Ju; Yin, Teresa J C; Chen, Chu-Chieh; Yu, Shu

    2016-07-01

    To understand nurse administrators' intentions and considerations in recruiting inactive nurses and to examine predictors of intent to recruit. Few studies have provided insight into employer intentions and considerations in recruiting inactive nurses. A census survey collected data from 392 nurse administrators via a mailing method. Overall, 89.0% of nurse administrators were willing to recruit inactive nurses. Stepwise regression analysis revealed that the only predictor of nurse administrators' intention to recruit was nurse turnover rate at the hospital. Nurse administrators perceived the most important recruiting considerations were inactive nurses' cooperation with alternating shifts, health status and nursing licence. The most frequent reasons for not recruiting were an inactive nurse's lack of understanding of the medical environment and poor nursing competence. Most hospital nurse administrators were willing to recruit inactive nurses. Inactive nurses who wish to return to work should be qualified, willing to work both day and night shifts, and in good health. Nurse administrators can reduce the nursing shortage by recruiting inactive nurses. Re-entry preparation programmes should be implemented that will provide inactive nurses with knowledge of the current medical environment and the skills required to improve their nursing competence. © 2016 John Wiley & Sons Ltd.

  18. Substitution of Glu-59 by Val in amidase from Pseudomonas aeruginosa results in a catalytically inactive enzyme.

    PubMed

    Karmali, A; Tata, R; Brown, P R

    2000-09-01

    A mutant strain, KLAM59, of Pseudomonas aeruginosa has been isolated that synthesizes a catalytically inactive amidase. The mutation in the amidase gene has been identified (Glu59Val) by direct sequencing of PCR-amplified mutant gene and confirmed by sequencing the cloned PCR-amplified gene. The wild-type and altered amidase genes were cloned into an expression vector and both enzymes were purified by affinity chromatography on epoxy-activated Sepharose 6B-acetamide followed by gel filtration chromatography. The mutant enzyme was catalytically inactive, and it was detected in column fractions by monoclonal antibodies previously raised against the wild-type enzyme using an ELISA sandwich method. The recombinant wild-type and mutant enzymes were purified with a final recovery of enzyme in the range of 70-80%. The wild-type and mutant enzymes behaved differently on the affinity column as shown by their elution profiles. The molecular weights of the purified wild-type and mutant amidases were found to be 210,000 and 78,000 Dalton, respectively, by gel filtration chromatography. On the other hand, the mutant enzyme ran as a single protein band on SDS-PAGE and native PAGE with a M(r) of 38,000 and 78,000 Dalton, respectively. These data suggest that the substitution Glu59Val was responsible for the dimeric structure of the mutant enzyme as opposed to the hexameric form of the wild-type enzyme. Therefore, the Glu59 seems to be a critical residue in the maintenance of the native quaternary structure of amidase.

  19. Characterizing inactive ribosomes in translational profiling

    PubMed Central

    Liu, Botao; Qian, Shu-Bing

    2016-01-01

    ABSTRACT The broad impact of translational regulation has emerged explosively in the last few years in part due to the technological advance in genome-wide interrogation of gene expression. During mRNA translation, the majority of actively translating ribosomes exist as polysomes in cells with multiple ribosomes loaded on a single transcript. The importance of the monosome, however, has been less appreciated in translational profiling analysis. Here we report that the monosome fraction isolated by sucrose sedimentation contains a large quantity of inactive ribosomes that do not engage on mRNAs to direct translation. We found that the elongation factor eEF2, but not eEF1A, stably resides in these non-translating ribosomes. This unique feature permits direct evaluation of ribosome status under various stress conditions and in the presence of translation inhibitors. Ribosome profiling reveals that the monosome has a similar but not identical pattern of ribosome footprints compared to the polysome. We show that the association of free ribosomal subunits minimally contributes to ribosome occupancy outside of the coding region. Our results not only offer a quantitative method to monitor ribosome availability, but also uncover additional layers of ribosome status needed to be considered in translational profiling analysis. PMID:27335722

  20. Physical inactivity and arterial stiffness in COPD

    PubMed Central

    Sievi, Noriane A; Franzen, Daniel; Kohler, Malcolm; Clarenbach, Christian F

    2015-01-01

    Background Arterial stiffness is an important predictor of cardiovascular risk besides classic cardiovascular risk factors. Previous studies showed that arterial stiffness is increased in patients with COPD compared to healthy controls and exercise training may reduce arterial stiffness. Since physical inactivity is frequently observed in patients with COPD and exercise training may improve arterial stiffness, we hypothesized that low daily physical activity may be associated with increased arterial stiffness. Methods In 123 patients with COPD (72% men; mean [standard deviation] age: 62 [7.5] years; median [quartile] forced expiratory volume in 1 second 35 [27/65] %predicted), arterial stiffness was assessed by augmentation index (AI). Daily physical activity level (PAL) was measured by an activity monitor (SenseWear Pro™) >1 week. The association between AI and PAL was investigated by univariate and multivariate regression analysis, taking into account disease-specific characteristics and comorbidities. Results Patients suffered from moderate (35%), severe (32%), and very severe (33%) COPD, and 22% were active smokers. Median (quartile) PAL was 1.4 (1.3/1.5) and mean (standard deviation) AI 26% (9.2%). PAL showed a negative association with AI (B=−9.32, P=0.017) independent of age, sex, blood pressure, and airflow limitation. Conclusion In COPD patients, a higher PAL seems to favorably influence arterial stiffness and therefore may reduce cardiovascular risk. Clinical Trial Registration http://www.ClinicalTrials.gov, NCT01527773 PMID:26392763

  1. Inactive and active states and supramolecular organization of GPCRs: insights from computational modeling

    NASA Astrophysics Data System (ADS)

    Fanelli, Francesca; De Benedetti, Pier G.

    2006-08-01

    Herein we make an overview of the results of our computational experiments aimed at gaining insight into the molecular mechanisms of GPCR functioning either in their normal conditions or when hit by gain-of-function or loss-of-function mutations. Molecular simulations of a number of GPCRs in their wild type and mutated as well as free and ligand-bound forms were instrumental in inferring the structural features, which differentiate the mutation- and ligand-induced active from the inactive states. These features essentially reside in the interaction pattern of the E/DRY arginine and in the degree of solvent exposure of selected cytosolic domains. Indeed, the active states differ from the inactive ones in the weakening of the interactions made by the highly conserved arginine and in the increase in solvent accessibility of the cytosolic interface between helices 3 and 6. Where possible, the structural hallmarks of the active and inactive receptor states are translated into molecular descriptors useful for in silico functional screening of novel receptor mutants or ligands. Computational modeling of the supramolecular organization of GPCRs and their intracellular partners is the current challenge toward a deep understanding of their functioning mechanisms.

  2. Thermostabilization of the β1-adrenergic receptor Correlates with Increased Entropy of the Inactive State

    PubMed Central

    Niesen, Michiel JM; Bhattacharya, Supriyo; Grisshammer, Reinhard; Tate, Christopher G; Vaidehi, Nagarajan

    2013-01-01

    The dynamic nature of GPCRs is a major hurdle in their purification and crystallization, but thermostabilization can facilitate structure determination, as has been shown by the structure of the thermostabilized β1-adrenergic receptor (β1AR) mutant, m23-β1AR, which has been thermostabilized in the inactive state. However, it is unclear from the structure how the six thermostabilizing mutations in m23-β1AR affect receptor dynamics. We have used molecular dynamics simulations in explicit solvent to compare the conformational ensembles for both wild type β1AR (wt-β1AR) and m23-β1AR. Thermostabilization results in an increase in the number of accessible microscopic conformational states within the inactive state ensemble, effectively increasing the side chain entropy of the inactive state at room temperature, while suppressing large-scale main chain conformational changes that lead to activation. We identified several diverse mechanisms of thermostabilization upon mutation. These include, decrease of long range correlated movement between residues in the G-protein coupling site to the extracellular region (Y227A5.58, F338M7.48), formation of new hydrogen bonds (R68S), and reduction of local stress (Y2275.58, F3277.37 and F3387.48). This study provides insights into microscopic mechanisms underlying thermostability that leads to an understanding of the effect of these mutations on the structure of the receptor. PMID:23697892

  3. Mobile App to Reduce Inactivity in Sedentary Overweight Women.

    PubMed

    Finkelstein, Joseph; Bedra, McKenzie; Li, Xuan; Wood, Jeffrey; Ouyang, Pamela

    2015-01-01

    Recent studies demonstrated that the duration of inactivity (sedentary state) is independently associated with increased risk of cardiovascular disease. Our goal was to develop the technology that can measure the amount of inactivity in real time, remind a person that a preprogrammed period of inactivity has occurred and encourage a period of activity, and provide web-based feedback with tailored information to the participant and investigators. Once it was developed, we carried out a pilot study in a group of sedentary overweight women. The objective of the study was to assess potential of the mobile app to reduce inactivity in our target population. A randomized crossover design was employed with study subjects randomly assigned to a 4-week each "message-on" and "message-off" periods. Out of 30 enrolled subjects, 27 completed the study. The average age of particpants was 52±12; BMI: 37±6; 47% were white and 47% were African American. Overall, inactivity was significantly lower (p<0.02) during "message-on" periods (24.6%) as compared to the "message-off" periods (30.4%). We conluded that mobile app monitoring inactivity and providing a real-time notification when inactivity period exceeds healthy limits was able to significantly reduce inactivity periods in overweight sedentary women.

  4. 25 CFR 117.17 - Inactive surplus funds accounts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Inactive surplus funds accounts. 117.17 Section 117.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES DEPOSIT AND EXPENDITURE... COMPETENCY § 117.17 Inactive surplus funds accounts. When the balance of surplus funds to the credit of an...

  5. 25 CFR 117.17 - Inactive surplus funds accounts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Inactive surplus funds accounts. 117.17 Section 117.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES DEPOSIT AND EXPENDITURE... COMPETENCY § 117.17 Inactive surplus funds accounts. When the balance of surplus funds to the credit of an...

  6. 25 CFR 117.17 - Inactive surplus funds accounts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Inactive surplus funds accounts. 117.17 Section 117.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES DEPOSIT AND EXPENDITURE... COMPETENCY § 117.17 Inactive surplus funds accounts. When the balance of surplus funds to the credit of an...

  7. 25 CFR 117.17 - Inactive surplus funds accounts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Inactive surplus funds accounts. 117.17 Section 117.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES DEPOSIT AND EXPENDITURE... COMPETENCY § 117.17 Inactive surplus funds accounts. When the balance of surplus funds to the credit of an...

  8. 25 CFR 117.17 - Inactive surplus funds accounts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Inactive surplus funds accounts. 117.17 Section 117.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES DEPOSIT AND EXPENDITURE... COMPETENCY § 117.17 Inactive surplus funds accounts. When the balance of surplus funds to the credit of an...

  9. 1. AERIAL VIEW, NAVAL INACTIVE SHIPS MAINTENANCE FACILITY, SINCLAIR ISLET, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. AERIAL VIEW, NAVAL INACTIVE SHIPS MAINTENANCE FACILITY, SINCLAIR ISLET, BREMERTON, KITSAP COUNTY, WASHINGTON WITH EX-USS HORNET CVS-12, THREE MINECRAFT ALONGSIDE TO PORT. OTHER INACTIVE SHIPS IN BACKGROUND. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  10. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  11. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  12. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  13. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  14. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  15. Engineered Mononuclear Variants in Bacillus cereus Metallo-beta-lactamase BcII Are Inactive

    SciTech Connect

    Abriata,L.; Gonzalez, L.; Llarrull, L.; Tomatis, P.; Myers, W.; Costello, A.; Tierney, D.; Vila, A.

    2008-01-01

    Metallo-{beta}-lactamases (M{beta}Ls) are zinc enzymes able to hydrolyze almost all {beta}-lactam antibiotics, rendering them inactive, at the same time endowing bacteria high levels of resistance. The design of inhibitors active against all classes of M{beta}Ls has been hampered by their structural diversity and by the heterogeneity in metal content in enzymes from different sources. BcII is the metallo-{beta}-lactamase from Bacillus cereus, which is found in both the mononuclear and dinuclear forms. Despite extensive studies, there is still controversy about the nature of the active BcII species. Here we have designed two mutant enzymes in which each one of the metal binding sites was selectively removed. Both mutants were almost inactive, despite preserving most of the structural features of each metal site. These results reveal that neither site isolated in the M{beta}L scaffold is sufficient to render a fully active enzyme. This suggests that only the dinuclear species is active or that the mononuclear variants can be active only if aided by other residues that would be metal ligands in the dinuclear species.

  16. Decreasing Physical Inactivity in the Veterans Health Administration Employee Population.

    PubMed

    Schult, Tamara M; Schmunk, Sandra K; Awosika, Ebi R

    2016-12-01

    The aim of this study was to describe a comprehensive approach to decrease physical inactivity in the Veterans Health Administration (VHA) employee population. The approach included (1) initiatives to decrease physical inactivity in the workplace; (2) two operational surveys to assess system-wide service provision; and (3) two national employee surveys. From 2010 to 2012, 86 employee fitness centers were completed in VA medical centers. A grants program (2010 to 2015) funded smaller projects designed to decrease physical inactivity in the workplace. Projects involved the provision of equipment to decrease sedentary behaviors, including stability balls, treadmill and sit-to-stand desks, stairwell projects, and funding for on-site fitness classes, bicycle racks, and outdoor par courses and walking paths among others. A comprehensive approach to decrease physical inactivity in VHA employees was successful. Overall, self-reported, age-adjusted physical inactivity in VHA employees decreased from 25.3% in 2010 to 16.1% in 2015.

  17. TFIIH with inactive XPD helicase functions in transcription initiation but is defective in DNA repair.

    PubMed

    Winkler, G S; Araújo, S J; Fiedler, U; Vermeulen, W; Coin, F; Egly, J M; Hoeijmakers, J H; Wood, R D; Timmers, H T; Weeda, G

    2000-02-11

    TFIIH is a multisubunit protein complex involved in RNA polymerase II transcription and nucleotide excision repair, which removes a wide variety of DNA lesions including UV-induced photoproducts. Mutations in the DNA-dependent ATPase/helicase subunits of TFIIH, XPB and XPD, are associated with three inherited syndromes as follows: xeroderma pigmentosum with or without Cockayne syndrome and trichothiodystrophy. By using epitope-tagged XPD we purified mammalian TFIIH carrying a wild type or an active-site mutant XPD subunit. Contrary to XPB, XPD helicase activity was dispensable for in vitro transcription, catalytic formation of trinucleotide transcripts, and promoter opening. Moreover, in contrast to XPB, microinjection of mutant XPD cDNA did not interfere with in vivo transcription. These data show directly that XPD activity is not required for transcription. However, during DNA repair, neither 5' nor 3' incisions in defined positions around a DNA adduct were detected in the presence of TFIIH containing inactive XPD, although substantial damage-dependent DNA synthesis was induced by the presence of mutant XPD both in cells and cell extracts. The aberrant damage-dependent DNA synthesis caused by the mutant XPD does not lead to effective repair, consistent with the discrepancy between repair synthesis and survival in cells from a number of XP-D patients.

  18. An Exploratory Study of Inactive Health Information Seekers

    PubMed Central

    2014-01-01

    Purpose This study aims to identify people who do not actively seek out health information and the demographic characteristics of Inactive Seekers. The possible determinants of inactive seeking behaviors is also explored. Design and Measurements A total of 14,420 survey respondents were drawn from the 2009 Annenberg National Health Communication Survey (ANHCS) data. K-means clustering was used to discriminate Inactive Seekers from Active Seekers. The inactive information seeker group was formed based on their experience with health information seeking. The potential determinants that were tested to predict inactive seeking included the following: health condition, health service use, health media exposure, and computer/Internet activities. Results Within this national survey data, the respondents were more likely to be included in the Inactive Seekers (N=8,312, 58.5%) compared to Active Seekers (N=5,908, 41.5%). The demographic characteristics indicated that the Inactive Seekers were identified as younger, male, highly educated, White, and high household income people. The binary logistic regression results from the study model indicated that healthier people were less likely to seek out health information than their counterparts. In addition, those who were exposed to various media were almost 1.6 times more likely to seek out health information than those who were not exposed to such media. Within this study data, the statistically significant determinants identified were health condition and health media exposure while computer/Internet activities did not show strong indications in predicting inactive seeking behavior. Conclusion The development of more generalizable measures for health literacy or behavioral patterns will bolster advanced study on inactive seeking relating to knowledge of technology and health context. Further study should be directed at estimating the negative aspects of information seeking such as information ignorance or information

  19. Characterization of the basal core promoter and precore regions in anti-HBe-positive inactive carriers of hepatitis B virus.

    PubMed

    Ledesma, María Mora González López; Galdame, Omar; Bouzas, Belén; Tadey, Luciana; Livellara, Beatriz; Giuliano, Silvina; Viaut, Marcela; Paz, Silvia; Fainboim, Hugo; Gadano, Adrian; Campos, Rodolfo; Flichman, Diego

    2011-05-01

    The study of hepatitis B virus (HBV) genomic heterogeneity has become a major issue in investigations aimed at understanding the relationship between HBV mutants and the wide spectrum of clinical and pathological conditions associated with HBV infection. Although most chronically infected HBV patients are inactive carriers, several virological aspects of this state remain unclear. In order to determine the prevalence and clinical significance of mutations in the basal core promoter (BCP) and precore (pC) regions among inactive carriers, the nucleotide sequences from 41 inactive carriers were analyzed and compared with those from 29 individuals with chronic active hepatitis. Genotypes A (24.3%), D (37.1%), F1b (12.9%), and F4 (18.6%) were the most prevalent. Mutations in the BCP/pC regions were observed in most of the inactive carriers (92.7%) and in most of the patients with chronic active hepatitis (93.1%). The prevalence of mutation 1764(A) was significantly higher in patients with chronic active hepatitis (65.5%) than in inactive carriers (36.6%) (p=0.038), whereas the prevalences of mutations at the other positions analyzed were not significantly different. Older patients (>50 years) showed BCP/pC patterns with a higher number of substitutions. Mutations were found to be biased by genotype: the 1896(A) mutation was highly prevalent in genotypes D and F4, while alternative substitutions in the pC region were more prevalent in genotypes A and F1b. Mutations in the BCP/pC regions are the hallmark of chronic anti-HBe-positive individuals; nevertheless, the even distribution of mutations in active and inactive carriers suggests that BCP/pC mutations may occur during HBV infection not strictly related to the HBV infection activity. Copyright © 2011. Published by Elsevier Ltd.

  20. Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity.

    PubMed

    Friend, Danielle M; Devarakonda, Kavya; O'Neal, Timothy J; Skirzewski, Miguel; Papazoglou, Ioannis; Kaplan, Alanna R; Liow, Jeih-San; Guo, Juen; Rane, Sushil G; Rubinstein, Marcelo; Alvarez, Veronica A; Hall, Kevin D; Kravitz, Alexxai V

    2017-02-07

    Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.

  1. Dynamics differentiate between active and inactive inteins

    PubMed Central

    Cronin, Melissa; Coolbaugh, Michael J; Nellis, David; Zhu, Jianwei; Wood, David W.; Nussinov, Ruth; Ma, Buyong

    2014-01-01

    The balance between stability and dynamics for active enzymes can be somewhat quantified by studies of intein splicing and cleaving reactions. Inteins catalyze the ligation of flanking host exteins while excising themselves. The potential for applications led to engineering of a mini-intein splicing domain, where the homing endonuclease domain of the Mycobacterium tuberculosis RecA (Mtu recA) intein was removed. The remaining domains were linked by several short peptides, but splicing activity in all was substantially lower than the full-length intein. Native splicing activity was restored in some cases by a V67L mutation. Using computations and experiments, we examine the impact of this mutation on the stability and conformational dynamics of the mini-intein splicing domain. Molecular dynamics simulations were used to delineate the factors that determine the active state, including the V67L mini-intein mutant, and peptide linker. We found that (1) the V67L mutation lowers the global fluctuations in all modeled mini-inteins, stabilizing the mini-intein constructs; (2) the connecting linker length affects intein dynamics; and (3) the flexibilities of the linker and intein core are higher in the active structure. We have observed that the interaction of the linker region and a turn region around residues 35-41 provides the pathway for the allostery interaction. Our experiments reveal that intein catalysis is characterized by non-linear Arrhenius plot, confirming the significant contribution of protein conformational dynamics to intein function. We conclude that while the V67L mutation stabilizes the global structure, cooperative dynamics of all intein regions appear more important for intein function than high stability. Our studies suggest that effectively quenching the conformational dynamics of an intein through engineered allosteric interactions could deactivate intein splicing or cleaving. PMID:25087201

  2. Can neighborhoods explain racial/ethnic differences in adolescent inactivity?

    PubMed

    Richmond, Tracy K; Field, Alison E; Rich, Michael

    2007-01-01

    To determine if neighborhoods and their attributes contribute to racial/ethnic disparities in adolescent inactivity. We undertook a cross-sectional analysis of the National Longitudinal Study of Adolescent Health (n = 17,007), a nationally representative school-based study in the United States. Stratifying by gender, we used multivariate linear regression and multi-level modeling to determine whether neighborhood of residence may partially explain racial/ethnic disparities in adolescent physical inactivity, defined as hours viewing television or videos/DVDs and/or playing computer/video games each week. Participants lived in largely segregated communities. Black and Hispanic adolescent girls reported higher levels of inactivity than White adolescent girls (21 vs. 15 vs. 13 hours/week, respectively, p <0.001). Similar patterns were seen in adolescent boys, with Black adolescent males reporting a mean of 26 hours/week; Hispanic boys a mean of 20 hours/week; and White boys a mean of 17 hours/week of inactivity (p <0.001). After accounting for between-neighborhood variation, there were no residual within-neighborhood differences in inactivity between Hispanic and White adolescent girls (gamma = -0.06, p =0.93); when living in the same neighborhood Hispanic and White girls had similar levels of inactivity. Black adolescent girls and boys were found to have higher levels of inactivity no matter where they lived (gamma =7.00, p <0.001 for girls; gamma = 6.96, p <0.001 for boys). Hispanic boys had similar patterns of inactivity to White boys (gamma =-1.57, p = 0.12). In both males and females, the reported rate of violent crime in the neighborhood was associated with inactivity, despite the individual's perception of his/her neighborhood as safe not being predictive. Although inactivity varies by race/ethnicity and gender, only in Hispanic adolescent girls does neighborhood fully explain the differential use. Our findings suggest that approaches other than changing

  3. Experiential versus genetic accounts of inactivity: implications for inactive individuals' self-efficacy beliefs and intentions to exercise.

    PubMed

    Beauchamp, Mark R; Rhodes, Ryan E; Kreutzer, Christiane; Rupert, James L

    2011-01-01

    The overall purpose of this study was to examine the effect of deterministic media reports, linking genetics to inactivity, in relation to inactive people's social cognitions concerning physical activity involvement. Sixty three inactive university students were randomly allocated to one of three experimental conditions (control, genetically-primed, experientially-primed) and completed measures of instrumental and affective attitudes, subjective norms, self-efficacy, and exercise intentions. One week later participants in the two experimental conditions were provided with a bogus newspaper report that either reflected a genetic explanation for physical inactivity or an experiential basis for inactivity. Shortly afterwards, participants in all three conditions completed the same measures as at pre-test. The results revealed that after controlling for baseline measures participants in the experientially-primed condition reported significantly higher levels of self-efficacy and intentions to exercise than those in the genetically-primed condition. These findings raise a cautionary flag concerning the presentation of genetic research in the media, especially with regard to inactive populations.

  4. Prevalence and factors associated with physical inactivity among Malaysian adults.

    PubMed

    Ying, Chanying; Kuay, Lim Kuang; Huey, Teh Chien; Hock, Lim Kuang; Hamid, Hamizatul Akmal Abd; Omar, Mohd Azahadi; Ahmad, Noor Ani; Cheong, Kee Chee

    2014-03-01

    Using data from the Third National Health and Morbidity Survey (NHMS III) in 2006, this study examined the association between socio-demographic factors and physical inactivity in a sample of 33,949 adults aged 18 years and above by gender. Physical activity levels were measured using the Global Physical Activity Questionnaire (GPAQ vers 1). Physical inactivity was defined as having a total physical activity level of less than 600 metabolic equivalents-minutes per week (METs-minutes/week) contributed by all three different life domains.Logistic regression analyses were conducted.The prevalence of overall physical inactivity was 43.7% (95% CI: 42.9-44.5). The mean total physical activity level was 894.2 METs-minutes/ week. The means METs-minutes/week for the domain of work, travelling, and leisure time were 518.4, 288.1, and 134.8, respectively. Multivariable logistic regression analyses indicated that females were more likely to be physically inactive than males were (aOR=1.62; 95% CI: 1.53-1.72). Among women, being a housewife (aOR = 1.78; 95% CI: 1.56-2.03), widow/divorcee (aOR = 1.23; 95% CI: 1.05-1.43), and those with no formal education (aOR = 1.20; 95% CI: 1.01-1.43) were found to be significantly associated with physical inactivity.Urban residents, older adults aged 65 years and above, private employees, nonworking group, and those with a monthly household income level of MYR5,000 and above appeared to be consistently associated with physical inactivity across men, women, and combined group (both). Specific health intervention strategies to promote physical activity should be targeted on population subgroups who are inactive.

  5. Purification and in vitro complementation of mutant histidinol dehydrogenases. [Salmonella typhimurium

    SciTech Connect

    Lee, S.Y.; Grubmeyer, C.T.

    1987-09-01

    The biochemistry of interallelic complementation within the Salmonella typhimurium hisD gene was investigated by in vitro protein complementation of mutant histidinol dehydrogenases (EC 1.1.1.23). Double-mutant strains were constructed containing the his01242 (constitutive overproducer) attenuator mutations and selected hisDa or hisDb mutations. Extracts from such hisDa986 and hisDb1799 mutant cells failed to show histidinol dehydrogenase activity but complemented to produce active enzyme. Inactive mutant histidinol dehydrogenases were purified from each of the two mutants by ion-exchange chromatography. Complementation by the purified mutant proteins required the presence of 2-mercaptoethanol and MnCl/sub 2/, and protein-protein titrations indicated that heterodimers were strongly preferred in mixtures of the complementary mutant enzymes. Both purified mutant proteins failed to catalyze NAD-NADH exchange reactions reflective of the first catalytic step of the two-step reaction. The inactive enzymes bound /sup 54/Mn/sup 2 +/ weakly or not at all in the presence of 2-mercaptoethanol, in contrast to wild-type enzyme which bound /sup 54/Mn/sup 2 +/ to 0.6 sites per monomer under the same conditions. The mutant proteins, like wild-type histidinol dehydrogenase, behaved as dimers on analytical gel filtration chromatography, but dissociated to form monomers in the presence of 2-mercaptoethanol. This effect of 20-mercaptoethanol was prevented by low levels of MnCl/sub 2/.

  6. Palmitoylation is required for membrane association of activated but not inactive invertebrate visual Gqalpha.

    PubMed

    Go, Lynle; Mitchell, Jane

    2003-08-01

    The invertebrate visual G protein, iGqalpha plays a central role in invertebrate phototransduction by relaying signals from rhodopsin to phospholipase C leading to membrane depolarization. Previous studies have shown reversible association of iGqalpha with rhabdomeric membranes regulated by light. To address the mechanism of membrane association we cloned iGqalpha from a Loligo pealei photoreceptor cDNA library and expressed it in HEK293T cells. Mutations were introduced to eliminate putative sites for palmitoylation at cysteines in positions 3 and 4. Membrane and soluble fractions were prepared from cells where iGqalpha was either activated or maintained in the GDP-bound form, followed by identification of iGqalpha through immunoblot analysis. The wild-type iGqalpha was entirely membrane-bound and shown to be post-translationally modified by palmitoylation. The mutant iGqalpha (C3,4A) was not palmitoylated yet it was found to be membrane-associated in the inactive state, however, approximately half of the protein became soluble when activated. These results suggest that palmitoylation is not required for membrane association of iGqalpha in the inactive state but is important in maintaining the stable membrane association of activated iGqalpha-GTP. The mechanism by which iGqalpha moves away from the membrane into the cytosol in response to prolonged light-stimulation in the native squid eye appears, therefore, to involve both activation and depalmitoylation processes.

  7. Saccharomyces cerevisiae aldolase mutants.

    PubMed Central

    Lobo, Z

    1984-01-01

    Six mutants lacking the glycolytic enzyme fructose 1,6-bisphosphate aldolase have been isolated in the yeast Saccharomyces cerevisiae by inositol starvation. The mutants grown on gluconeogenic substrates, such as glycerol or alcohol, and show growth inhibition by glucose and related sugars. The mutations are recessive, segregate as one gene in crosses, and fall in a single complementation group. All of the mutants synthesize an antigen cross-reacting to the antibody raised against yeast aldolase. The aldolase activity in various mutant alleles measured as fructose 1,6-bisphosphate cleavage is between 1 to 2% and as condensation of triose phosphates to fructose 1,6-bisphosphate is 2 to 5% that of the wild-type. The mutants accumulate fructose 1,6-bisphosphate from glucose during glycolysis and dihydroxyacetone phosphate during gluconeogenesis. This suggests that the aldolase activity is absent in vivo. PMID:6384192

  8. The Costs of Inaction with Respect to Climate Change

    SciTech Connect

    Cline, William R.

    2005-04-14

    This paper first considers the principal trade-offs in the timing of policy response to climate change. It then turns to a synoptic review of the economic literature on costs and benefits of climate change abatement. The discussion closes with an estimate of the potential economic cost that might be associated with delay in abatement, based on the analysis in the author, published elsewhere. In the specific calculations of the paper, the costs of inaction are specified in two alternative ways. In the first and likely more relevant formulation, it is assumed that inaction persists for only two decades. The costs of inaction are then calculated as the damage arising from the additional climate change above that identified in the optimal abatement path as a consequence of failing to carry out any abatement in the first two decades, net of the savings in abatement costs thereby avoided. In the second and more extreme formulation, inaction is assumed to be permanent (i.e. there is never any reduction in emissions from their baseline path). In this case the costs of inaction are again the net costs of future climate damage after deducting the savings from absence of abatement, but this time over the full time horizon of three centuries.

  9. Parental Predictors of Physical Inactivity in Spanish Adolescents

    PubMed Central

    Sanz-Arazuri, Eva; Ponce-de-León-Elizondo, Ana; Valdemoros-San-Emeterio, María Ángeles

    2012-01-01

    The purpose of this study was to determine some parental predictors of physical inactivity in Spanish adolescents. The sample comprised 1,978 children, aged between 12 and 16 years. A quantitative and qualitative technical triangulation was employed. The study analyzed data of the parents' educational level, the importance they grant to physical-sport activities, and their physical-sport practice. Quantitative technique: a questionnaire (MACOFYD) was used to collect the data. Descriptive, bivariate, and multinomial regression analyses were employed. Statistical significance was set at p < 0.05. Qualitative technique: four discussion groups were conducted, consisting of parents, physical education teachers, teachers of other subjects, and children aged between 12 and 16 years. The results indicated that adolescents are four times more likely to be physically inactive if their parents have never exercised (odds ratio [OR] = 4.065, and = 3.487, for the fathers and mothers, respectively, p < 0.05). When parents grant “some” or “much” importance to physical-sport practice, adolescents are less likely to be physically inactive (OR = 0.185 and 0.118 respectively, p < 0.01). No significant correlation was found between adolescents' physical-sport activity and parents' educational level. However, young people reproach their parents because they emphasize academic goals more than physical-sport practice-an observation that teachers also confirm. Young people perceive their parents as being the education agents with the greatest influence over their inactive lifestyles. Many parents are unaware of their influence and, therefore, do not take responsibility, declaring that the teachers' influence is greater. Key points Parental factors significantly affect adolescent physical inactivity. Parents' physical inactivity is among the most important factors. Statistically significant results were found for gender. Being female tripled the likelihood of being sedentary. The

  10. The economic benefits of reducing physical inactivity: an Australian example

    PubMed Central

    2011-01-01

    Background Physical inactivity has major impacts on health and productivity. Our aim was to estimate the health and economic benefits of reducing the prevalence of physical inactivity in the 2008 Australian adult population. The economic benefits were estimated as 'opportunity cost savings', which represent resources utilized in the treatment of preventable disease that are potentially available for re-direction to another purpose from fewer incident cases of disease occurring in communities. Methods Simulation models were developed to show the effect of a 10% feasible, reduction target for physical inactivity from current Australian levels (70%). Lifetime cohort health benefits were estimated as fewer incident cases of inactivity-related diseases; deaths; and Disability Adjusted Life Years (DALYs) by age and sex. Opportunity costs were estimated as health sector cost impacts, as well as paid and unpaid production gains and leisure impacts from fewer disease events associated with reduced physical inactivity. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of physically active and inactive adults, and valued using the friction cost approach. The impact of an improvement in health status on unpaid household production and leisure time were modeled from time use survey data, as applied to the exposed and non-exposed population subgroups and valued by suitable proxy. Potential costs associated with interventions to increase physical activity were not included. Multivariable uncertainty analyses and univariate sensitivity analyses were undertaken to provide information on the strength of the conclusions. Results A 10% reduction in physical inactivity would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000 fewer DALYs and provide gains in working days (114,000), days of home-based production (180,000) while conferring a AUD96 million reduction in health sector costs. Lifetime potential

  11. Bacteriophage SPO1 development: defects in a gene 31 mutant.

    PubMed Central

    Sarachu, A N; Añón, M C; Grau, O

    1978-01-01

    SPO1 temperature-sensitive mutant ts14-1, located in cistron 31, has a DD (DNA synthesis-delayed) phenotype at 37 degrees C and produces progeny in a stretched program. At 44 degrees C it behaves as a DO (DNA synthesis-defective) mutant and shuts off the viral RNA synthesis about 10 min after infection. The thermal sensitivity of this mutant is due to the inactivity of gp-31 (the product of gene 31) at 44 degrees C. However, gp-31 is synthesized at that temperature and partly recovers its activity at 37 degrees C. Only 5 min at the permissive temperature is enough to trigger the continuation of the phage program and to produce progeny. The partial defect at 37 degrees C and the expansion of the middle program together with the pleiotropic defects at the nonpermissive temperature could be suitable for the study of the controls involved in bacteriophage development. PMID:100606

  12. Watch and Wait Management of Inactive Cystic Echinococcosis - Does the Path to Inactivity Matter - Analysis of a Prospective Patient Cohort.

    PubMed

    Stojkovic, Marija; Rosenberger, Kerstin Daniela; Steudle, Franziska; Junghanss, Thomas

    2016-12-01

    Overdiagnosis and overtreatment are rarely discussed in the context of NTDs despite their relevance for patients under the care of health services with limited resources where the risks of therapy induced complications are often disproportionate to the benefit. The advantages of cyst staging-based management of patients with cystic echinococcosis (CE) are not yet fully explored. Questions are: Do inactive cysts (CE 4 and CE 5) need treatment and is there a difference between cysts which reach CE4 and CE5 naturally or by benzimidazole therapy? Analysis of long-term follow-up data from a prospective CE patient cohort of 223 patients of a national clinical center for echinococcosis. The event of interest "relapse" was defined as the reversal of a cyst from an inactive stage (CE4, CE5) back to an active stage. The watch &wait (ww) group included 30 patients with 46 inactive cysts who never received medical treatment. The benzimidazole-treated (med) group included 15 patients with 17 cysts. There was no relapse in the ww-group whereas 8/17 cysts showed relapse within 18 months after treatment in the med-group. Loss to follow-up was 15.5%. Data from the watch & wait group impressively show how stable naturally inactivated cysts are in contrast to cysts which reach inactivity through treatment with benzimidazoles. A substantial proportion of patients can be spared from treatment through cyst staging. Cysts which inactivated through a natural course do not relapse with very high likelihood. We recommend follow up of 5 years to confirm the stability of the inactive stage. Cysts driven into inactivity through benzimidazole therapy instead need careful monitoring to identify those which reactivate (around 50% within 18 months). 5 years follow-up appears safe to make a final decision on the need for further monitoring.

  13. Identification of inactive medications in narrative medical text.

    PubMed

    Breydo, Eugene M; Chu, Julia T; Turchin, Alexander

    2008-11-06

    Discontinued medications are frequently not removed from EMR medication lists - a patient safety risk. We developed an algorithm to identify inactive medications using in the text of narrative notes in the EMR. The algorithm was evaluated against manual review of 297 randomly selected notes. One in five notes documented inactive medications. Sensitivity and precision of 87.7% and 80.7%, respectively, on per-note basis and 66.3% and 80.0%, respectively, on per-medication basis. When medication names missing from the dictionary were excluded, the algorithm achieved sensitivity of 91.4%. Using real clinical data, the algorithm identified inactive medications documented in the note but still listed as active on the patients medication list in more than one in ten notes. Documentation of inactive medications is common in narrative provider notes and can be computationally extracted. This technology could be employed in real-time patient care as well as for research and quality of care monitoring.

  14. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  15. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  16. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  17. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  18. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  19. Active and inactive faults in southern California viewed from Skylab

    NASA Technical Reports Server (NTRS)

    Merifield, P. M.; Lamar, D. L.

    1975-01-01

    The application is discussed of Skylab imagery along with larger scale photography and field investigations in preparing fault maps of California for use in land use planning. The images were used to assist in distinguishing active from inactive faults (by recognizing indications of recent displacement), determining the length of potentially active faults, identifying previously unmapped faults, and gaining additional information on regional tectonic history.

  20. A New Direction for Wisconsin Inactive Health Personnel.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Univ. Extension.

    Supported by a contract with the United States Public Health Service, the University of Wisconsin Department of Nursing, University Extension, has provided refresher courses for inactive nurses, on a state-wide basis. This is a report of a survey of enrollees in the 18 courses offered between September 1967 and December 1968. The majority of the…

  1. Inactive Health Personnel Project in New Hampshire. Final Report.

    ERIC Educational Resources Information Center

    New Hampshire Health Careers Council, Concord.

    With the goal of more efficient utilization of existing health manpowers in New Hampshire, data were gathered on inactive medical personnel, and the feasibility of various methods of refresher training was explored. Because of New Hampshire's intrinsic characteristics of climate and scattered population and the scarcity of qualified instructors,…

  2. Home Delivery Medicament Program: access, inactivity and cardiovascular risk 1

    PubMed Central

    Araújo, Roque da Silva; Arcuri, Edna Apparecida Moura; Lopes, Victor Cauê

    2016-01-01

    ABSTRACT Objective: to verify causes of inactivity in the Home Delivery Medicament Program, as referred by users from a Primary Health Care Service in São Paulo, comparing them to the causes registered in the program and analyzing them in the theoretical model Concept of Access to Health. Methods: cross-sectional study, interviewing 111 inactive users; and documentary study in the program records. Results: half of the users did not know the condition of inactivity. Discrepancies were found between the user's and the program's information, observing different levels of agreement: Absence of physician and administrative staff member 0%; Transfer to other service 25%; Death 50%; Option to quit 50%; Address change 57% and Change in therapeutic schedule 80%. The users' feeling of accepting the program was observed. In the health access concept, inactivity can be explained in the information dimension, in the degree of asymmetry between the patient's and the health professional's knowledge, identified through the indicators: education, knowledge and information sources. Conclusions: due to the low education level, the user does not assimilate the information on the steps of the program flowchart, does not return for the assessment that guarantees its continuity. Consequently, (s)he stops receiving the medication and spends a long time without treatment, increasing the cardiovascular risk of hypertensive (92% of the sample), diabetic (44%) and dyslipidemic patients (31%). PMID:27737378

  3. Do Dopaminergic Impairments Underlie Physical Inactivity in People with Obesity?

    PubMed Central

    Kravitz, Alexxai V.; O'Neal, Timothy J.; Friend, Danielle M.

    2016-01-01

    Obesity is associated with physical inactivity, which exacerbates the negative health consequences of obesity. Despite a wide consensus that people with obesity should exercise more, there are few effective methods for increasing physical activity in people with obesity. This lack is reflected in our limited understanding of the cellular and molecular causes of physical inactivity in obesity. We hypothesize that impairments in dopamine signaling contribute to physical inactivity in people with obesity, as in classic movement disorders such as Parkinson's disease. Here, we review two lines of evidence supporting this hypothesis: (1) chronic exposure to obesogenic diets has been linked to impairments in dopamine synthesis, release, and receptor function, particularly in the striatum, and (2) striatal dopamine is necessary for the proper control of movement. Identifying the biological determinants of physical inactivity may lead to more effective strategies for increasing physical activity in people with obesity, as well as improve our understanding of why it is difficult for people with obesity to alter their levels of physical activity. PMID:27790107

  4. 30 CFR 57.5045 - Posting of inactive workings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Posting of inactive workings. 57.5045 Section 57.5045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND..., shall be posted against unauthorized entry and designated by signs indicating them as areas in...

  5. 30 CFR 57.5045 - Posting of inactive workings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Posting of inactive workings. 57.5045 Section 57.5045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND..., shall be posted against unauthorized entry and designated by signs indicating them as areas in...

  6. Distinct Recycling of Active and Inactive β1 Integrins

    PubMed Central

    Arjonen, Antti; Alanko, Jonna; Veltel, Stefan; Ivaska, Johanna

    2012-01-01

    Integrin trafficking plays an important role in cellular motility and cytokinesis. Integrins undergo constant endo/exocytic shuttling to facilitate the dynamic regulation of cell adhesion. Integrin activity toward the components of the extracellular matrix is regulated by the ability of these receptors to switch between active and inactive conformations. Several cellular signalling pathways have been described in the regulation of integrin traffic under different conditions. However, the interrelationship between integrin activity conformations and their endocytic fate have remained incompletely understood. Here, we have investigated the endocytic trafficking of active and inactive β1 integrins in cancer cells. Both conformers are endocytosed in a clathrin- and dynamin-dependent manner. The net endocytosis rate of the active β1 integrins is higher, whereas endocytosis of the inactive β1 integrin is counteracted by rapid recycling back to the plasma membrane via an ARF 6- and early endosome antigen 1-positive compartment in an Rab 4a- and actin-dependent manner. Owing to these distinct trafficking routes, the two receptor pools display divergent subcellular localization. At steady state, the inactive β1 integrin is mainly on the plasma membrane, whereas the active receptor is predominantly intracellular. These data provide new insights into the endocytic traffic of integrins and imply the possibility of a previously unappreciated crosstalk between pathways regulating integrin activity and traffic. PMID:22222055

  7. Physical Inactivity, Obesity, and Type 2 Diabetes: An Evolutionary Perspective

    ERIC Educational Resources Information Center

    Eaton, S. Boyd; Eaton, Stanley B.

    2017-01-01

    Physical inactivity (and unhealthy nutrition) has distorted body composition and, in turn, reordered the proportions of myocyte and adipocyte insulin receptors. Insulin acting on adipocyte receptors produces less glucose uptake than does comparable interaction with myocyte receptors. Accordingly, in individuals with disproportionate muscle/fat…

  8. Muscle activity and inactivity periods during normal daily life.

    PubMed

    Tikkanen, Olli; Haakana, Piia; Pesola, Arto J; Häkkinen, Keijo; Rantalainen, Timo; Havu, Marko; Pullinen, Teemu; Finni, Taija

    2013-01-01

    Recent findings suggest that not only the lack of physical activity, but also prolonged times of sedentary behaviour where major locomotor muscles are inactive, significantly increase the risk of chronic diseases. The purpose of this study was to provide details of quadriceps and hamstring muscle inactivity and activity during normal daily life of ordinary people. Eighty-four volunteers (44 females, 40 males, 44.1±17.3 years, 172.3±6.1 cm, 70.1±10.2 kg) were measured during normal daily life using shorts measuring muscle electromyographic (EMG) activity (recording time 11.3±2.0 hours). EMG was normalized to isometric MVC (EMG(MVC)) during knee flexion and extension, and inactivity threshold of each muscle group was defined as 90% of EMG activity during standing (2.5±1.7% of EMG(MVC)). During normal daily life the average EMG amplitude was 4.0±2.6% and average activity burst amplitude was 5.8±3.4% of EMG(MVC) (mean duration of 1.4±1.4 s) which is below the EMG level required for walking (5 km/h corresponding to EMG level of about 10% of EMG(MVC)). Using the proposed individual inactivity threshold, thigh muscles were inactive 67.5±11.9% of the total recording time and the longest inactivity periods lasted for 13.9±7.3 min (2.5-38.3 min). Women had more activity bursts and spent more time at intensities above 40% EMG(MVC) than men (p<0.05). In conclusion, during normal daily life the locomotor muscles are inactive about 7.5 hours, and only a small fraction of muscle's maximal voluntary activation capacity is used averaging only 4% of the maximal recruitment of the thigh muscles. Some daily non-exercise activities such as stair climbing produce much higher muscle activity levels than brisk walking, and replacing sitting by standing can considerably increase cumulative daily muscle activity.

  9. PDGFRA-mutant syndrome.

    PubMed

    Ricci, Riccardo; Martini, Maurizio; Cenci, Tonia; Carbone, Arnaldo; Lanza, Paola; Biondi, Alberto; Rindi, Guido; Cassano, Alessandra; Larghi, Alberto; Persiani, Roberto; Larocca, Luigi M

    2015-07-01

    Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ 'fibrous tumors' of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. 'INF/NF3b' and 'familial GIST' are misleading terms which we propose changing to 'PDGFRA-mutant syndrome'. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs

  10. Reduced Aerobic Capacity and Quality of Life in Physically Inactive Patients With Systemic Lupus Erythematosus With Mild or Inactive Disease.

    PubMed

    Pinto, Ana J; Miyake, Cintia N H; Benatti, Fabiana B; Silva, Clovis A; Sallum, Adriana M E; Borba, Eduardo; de Sá-Pinto, Ana L; Bonfá, Eloisa; Gualano, Bruno

    2016-12-01

    To compare aerobic capacity and health-related quality of life (HRQOL) in physically inactive adult systemic lupus erythematosus (A-SLE) and childhood-onset systemic lupus erythematosus (C-SLE) patients with mild/inactive disease versus healthy controls. In a cross-sectional study, 39 patients (C-SLE: n = 18, ages 9-18 years; and A-SLE: n = 21, ages 23-45 years) with inactive disease activity (Systemic Lupus Erythematosus Disease Activity Index ≤4) and low cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index ≤2) and 30 healthy controls (15 children and adolescents [C-CTRL], 15 adults [A-CTRL]) matched by physical inactivity, age, sex, and body mass index (BMI) were assessed for aerobic capacity and HRQOL. All participants were considered physically inactive according to physical activity guidelines. C-SLE and A-SLE patients showed lower VO2peak (95% CI confidence interval [95% CI] -10.5, -1.2 and -11.1, -3.8, respectively) and higher time-to-exhaustion when compared with C-CTRL and A-CTRL (95% CI -2.8, 0.1 and -3.9, -1.7, respectively). C-SLE patients showed significantly lower scores in scholar functioning from the Pediatric Quality of Life Inventory questionnaire (P < 0.05) whereas A-SLE patients showed lower scores in most domains of the Short Form 36 health survey questionnaire (physical function, role-physical, bodily pain, general health, vitality, social function, and mental health) when compared with healthy controls (P < 0.05 for all). Our study provides novel data suggesting that A-SLE and C-SLE patients with mild/inactive disease have impaired aerobic capacity and HRQOL when compared with controls matched by physical inactivity, age, sex, and BMI. These findings reinforce the recommendation of physical activity in SLE treatment. © 2016, American College of Rheumatology.

  11. Brassinosteroid Mutants of Crops.

    PubMed

    Bishop, Gerard J.

    2003-12-01

    Plant steroid hormones, brassinosteroids (BRs), were originally isolated from extracts of pollen because of their growth-promoting properties and their potential use for enhancing crop production. Mutants in the biosynthesis, metabolism, and signaling of brassinolide (BL), the most bioactive BR, are important resources in helping to establish BRs' essential role in plant growth and development. The dark green and distinctive dwarf phenotype of BR-related mutants identified in pea, tomato, and rice highlights the importance of BRs in crops. These mutants are helping to elucidate both the conserved and the unique features of BR biosynthesis and signaling. Such insights are providing the key knowledge and understanding that will enable the development of strategies towards the production of crops with enhanced qualities.

  12. 200-Area plateau inactive miscellaneous underground storage tanks locations

    SciTech Connect

    Brevick, C.H.

    1997-12-01

    Fluor Daniel Northwest (FDNW) has been tasked by Lockheed Martin Hanford Corporation (LMHC) to incorporate current location data for 64 of the 200-Area plateau inactive miscellaneous underground storage tanks (IMUST) into the centralized mapping computer database for the Hanford facilities. The IMUST coordinate locations and tank names for the tanks currently assigned to the Hanford Site contractors are listed in Appendix A. The IMUST are inactive tanks installed in underground vaults or buried directly in the ground within the 200-East and 200-West Areas of the Hanford Site. The tanks are categorized as tanks with a capacity of less than 190,000 liters (50,000 gal). Some of the IMUST have been stabilized, pumped dry, filled with grout, or may contain an inventory or radioactive and/or hazardous materials. The IMUST have been out of service for at least 12 years.

  13. Bipartite structure of the inactive mouse X chromosome.

    PubMed

    Deng, Xinxian; Ma, Wenxiu; Ramani, Vijay; Hill, Andrew; Yang, Fan; Ay, Ferhat; Berletch, Joel B; Blau, Carl Anthony; Shendure, Jay; Duan, Zhijun; Noble, William S; Disteche, Christine M

    2015-08-07

    In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. We find radically different conformations for the two female mouse X chromosomes. The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. In mouse, the boundary region also contains a minisatellite, Ds-TR, and both Dxz4 and Ds-TR appear to be anchored to the nucleolus. Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase. Fewer short-range intrachromosomal contacts are detected for the inactive alleles of genes subject to X inactivation compared with the active alleles and with genes that escape X inactivation. This pattern is also evident for imprinted genes, in which more chromatin contacts are detected for the expressed allele. By applying a novel Hi-C method to map allelic chromatin contacts, we discover a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing.

  14. Investigation of the organic matter in inactive nuclear tank liquids

    SciTech Connect

    Schenley, R.L.; Griest, W.H.

    1990-08-01

    Environmental Protection Agency (EPA) methodology for regulatory organics fails to account for the organic matter that is suggested by total organic carbon (TOC) analysis in the Oak Ridge National Laboratory (ORNL) inactive nuclear waste-tank liquids and sludges. Identification and measurement of the total organics are needed to select appropriate waste treatment technologies. An initial investigation was made of the nature of the organics in several waste-tank liquids. This report details the analysis of ORNL wastes.

  15. Physical inactivity: the "Cinderella" risk factor for noncommunicable disease prevention.

    PubMed

    Bull, Fiona C; Bauman, Adrian E

    2011-08-01

    There is strong evidence demonstrating the direct and indirect pathways by which physical activity prevents many of the major noncommunicable diseases (NCD) responsible for premature death and disability. Physical inactivity was identified as the 4th leading risk factor for the prevention of NCD, preceded only by tobacco use, hypertension, and high blood glucose levels, and accounting for more than 3 million preventable deaths globally in 2010. Physical inactivity is a global public health priority but, in most countries, this has not yet resulted in widespread recognition nor specific physical activity-related policy action at the necessary scale. Instead, physical inactivity could be described as the Cinderella of NCD risk factors, defined as "poverty of policy attention and resourcing proportionate to its importance." The pressing question is "Why is this so?" The authors identify and discuss 8 possible explanations and the need for more effective communication on the importance of physical activity in the NCD prevention context. Although not all of the issues identified will be relevant for any 1 country, it is likely that at different times and in different combinations these 8 problems continue to delay national-level progress on addressing physical inactivity in many countries. The authors confirm that there is sufficient evidence to act, and that much better use of well-planned, coherent communication strategies are needed in most countries and at the international level. Significant opportunities exist. The Toronto Charter on Physical Activity and the Seven Investments that Work are 2 useful tools to support increased advocacy on physical activity within and beyond the context of the crucial 2011 UN High-Level Meeting on NCDs.

  16. Multimotor transport in a system of active and inactive kinesin-1 motors.

    PubMed

    Scharrel, Lara; Ma, Rui; Schneider, René; Jülicher, Frank; Diez, Stefan

    2014-07-15

    Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Multimotor Transport in a System of Active and Inactive Kinesin-1 Motors

    PubMed Central

    Scharrel, Lara; Ma, Rui; Schneider, René; Jülicher, Frank; Diez, Stefan

    2014-01-01

    Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer’s and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action. PMID:25028878

  18. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  19. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  20. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  1. A Rhizobium meliloti mutant that forms ineffective pseudonodules in alfalfa produces exopolysaccharide but fails to form beta-(1----2) glucan.

    PubMed Central

    Geremia, R A; Cavaignac, S; Zorreguieta, A; Toro, N; Olivares, J; Ugalde, R A

    1987-01-01

    A mutant of Rhizobium meliloti that elicited the formation of inactive nodules in alfalfa was found not to form beta-(1----2) glucan in vivo or in vitro. It was nonmotile because it lacks flagella. The 235-kilodalton protein which acts as an intermediate in beta-(1----2) glucan synthesis was undetectable in the mutant. These properties of the mutant are common to those of chvB mutants of Agrobacterium tumefaciens. Exopolysaccharide formation by the R. meliloti mutant was about double that by the wild type. Images PMID:3804979

  2. ERICA: leisure-time physical inactivity in Brazilian adolescents

    PubMed Central

    Cureau, Felipe Vogt; da Silva, Thiago Luiz Nogueira; Bloch, Katia Vergetti; Fujimori, Elizabeth; Belfort, Dilson Rodrigues; de Carvalho, Kênia Mara Baiocchi; de Leon, Elisa Brosina; de Vasconcellos, Mauricio Teixeira Leite; Ekelund, Ulf; Schaan, Beatriz D

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate the prevalence of leisure-time physical inactivity in Brazilian adolescents and their association with geographical and sociodemographic variables. METHODS The sample was composed by 74,589 adolescents participating in the Study of Cardiovascular Risks in Adolescents (ERICA). This cross-sectional study of school basis with national scope involved adolescents aged from 12 to 17 years in Brazilian cities with more than 100 thousand inhabitants. The prevalence of leisure-time physical inactivity was categorized according to the volume of weekly practice (< 300; 0 min). The prevalences were estimated for the total sample and by sex. Poisson regression models were used to assess associated factors. RESULTS The prevalence of leisure-time physical inactivity was 54.3% (95%CI 53.4-55.2), and higher for the female sex (70.7%, 95%CI 69.5-71.9) compared to the male (38.0%, 95%CI 36.7-39.4). More than a quarter of adolescents (26.5%, 95%CI 25.8-27.3) reported not practicing physical activity in the leisure time, a condition more prevalent for girls (39.8%, 95%CI 38.8-40.9) than boys (13.4%, 95%CI 12.4-14.4). For girls, the variables that were associated with physical inactivity were: reside in the Northeast (RP = 1.13, 95%CI 1.08-1.19), Southeast (RP = 1.16, 95%CI 1.11-1.22) and South (RP = 1.12, 95%CI 1.06-1.18); have 16-17 years (RP = 1.06, 95%CI 1.12-1.15); and belong to the lower economic class (RP = 1.33, 95%CI 1.20-1.48). The same factors, except reside in the Southeast and South, were also associated with not practicing physical activity in the leisure time for the same group. In males, as well as the region, being older (p < 0.001) and declaring to be indigenous (RP = 0.37, 95%CI 0.19-0.73) were also associated with not practicing physical activities in the leisure time. CONCLUSIONS The prevalence of leisure-time physical inactivity in Brazilian adolescents is high. It presents regional variations and is associated with age and low

  3. Who needs 'lazy' workers? Inactive workers act as a 'reserve' labor force replacing active workers, but inactive workers are not replaced when they are removed.

    PubMed

    Charbonneau, Daniel; Sasaki, Takao; Dornhaus, Anna

    2017-01-01

    Social insect colonies are highly successful, self-organized complex systems. Surprisingly however, most social insect colonies contain large numbers of highly inactive workers. Although this may seem inefficient, it may be that inactive workers actually contribute to colony function. Indeed, the most commonly proposed explanation for inactive workers is that they form a 'reserve' labor force that becomes active when needed, thus helping mitigate the effects of colony workload fluctuations or worker loss. Thus, it may be that inactive workers facilitate colony flexibility and resilience. However, this idea has not been empirically confirmed. Here we test whether colonies of Temnothorax rugatulus ants replace highly active (spending large proportions of time on specific tasks) or highly inactive (spending large proportions of time completely immobile) workers when they are experimentally removed. We show that colonies maintained pre-removal activity levels even after active workers were removed, and that previously inactive workers became active subsequent to the removal of active workers. Conversely, when inactive workers were removed, inactivity levels decreased and remained lower post-removal. Thus, colonies seem to have mechanisms for maintaining a certain number of active workers, but not a set number of inactive workers. The rapid replacement (within 1 week) of active workers suggests that the tasks they perform, mainly foraging and brood care, are necessary for colony function on short timescales. Conversely, the lack of replacement of inactive workers even 2 weeks after their removal suggests that any potential functions they have, including being a 'reserve', are less important, or auxiliary, and do not need immediate recovery. Thus, inactive workers act as a reserve labor force and may still play a role as food stores for the colony, but a role in facilitating colony-wide communication is unlikely. Our results are consistent with the often cited, but never

  4. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types... practitioner take and pass a professional responsibility examination. (c) Transfer to disability inactive...

  5. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now inactive...

  6. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now inactive...

  7. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now inactive...

  8. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now inactive...

  9. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now inactive...

  10. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types... circumstances. (c) Transfer to disability inactive status. The USPTO Director, after notice and opportunity...

  11. Selective Inactivity of Pyrazinamide against Tuberculosis in C3HeB/FeJ Mice Is Best Explained by Neutral pH of Caseum.

    PubMed

    Lanoix, Jean-Philippe; Ioerger, Thomas; Ormond, Aimee; Kaya, Firat; Sacchettini, James; Dartois, Véronique; Nuermberger, Eric

    2016-02-01

    Pyrazinamide (PZA) is one of only two sterilizing drugs in the first-line antituberculosis regimen. Its activity is strongly pH dependent; the MIC changes by several orders of magnitude over a range of pH values that may be encountered in various in vivo compartments. We recently reported selective inactivity of PZA in a subset of C3HeB/FeJ mice with large caseous lung lesions. In the present study, we evaluated whether such inactivity was explained by poor penetration of PZA into such lesions or selection of drug-resistant mutants. Despite demonstrating similar dose-proportional PZA exposures in plasma, epithelial lining fluid, and lung lesions, no dose response was observed in a subset of C3HeB/FeJ mice with the highest CFU burden. Although PZA-resistant mutants eventually replaced the susceptible bacilli in BALB/c mice and in C3HeB/FeJ mice with low total CFU burdens, they never exceeded 1% of the total population in nonresponding C3HeB/FeJ mice. The selective inactivity of PZA in large caseous lesions of C3HeB/FeJ mice is best explained by the neutral pH of liquefying caseum.

  12. Permanent recording of light helicity on optically inactive metal surfaces.

    PubMed

    Wang, Jincheng; Guo, Chunlei

    2006-12-15

    We report on an unusual permanent recording of light helicity on optically achiral metals. Following a number of circularly polarized (CP) or elliptically polarized (EP) femtosecond laser pulses, well-defined periodic surface structures are found on metal surfaces. These surface structures show different orientation when formed by left CP/EP compared with right CP/EP light. The formation of these structures is attributed to the interference between the incident light and the excited surface plasmons. To our knowledge, this is the only phenomenon that can permanently record light helicity with an optically inactive material.

  13. Molecular basis for the catalytic inactivity of a naturally occurring near-null variant of human ALOX15.

    PubMed

    Horn, Thomas; Ivanov, Igor; Di Venere, Almerinda; Kakularam, Kumar Reddy; Reddanna, Pallu; Conrad, Melanie L; Richter, Constanze; Scheerer, Patrick; Kuhn, Hartmut

    2013-12-01

    Mammalian lipoxygenases belong to a family of lipid-peroxidizing enzymes, which have been implicated in cardiovascular, hyperproliferative and neurodegenerative diseases. Here we report that a naturally occurring mutation in the hALOX15 gene leads to expression of a catalytically near-null enzyme variant (hGly422Glu). The inactivity may be related to severe misfolding of the enzyme protein, which was concluded from CD-spectra as well as from thermal and chemical stability assays. In silico mutagenesis experiments suggest that most mutations at hGly422 have the potential to induce sterical clash, which might be considered a reason for protein misfolding. hGly422 is conserved among ALOX5, ALOX12 and ALOX15 isoforms and corresponding hALOX12 and hALOX5 mutants also exhibited a reduced catalytic activity. Interestingly, in the hALOX5 Gly429Glu mutants the reaction specificity of arachidonic acid oxygenation was shifted from 5S- to 8S- and 12R-H(p)ETE formation. Taken together, our data indicate that the conserved glycine is of functional importance for these enzyme variants and most mutants at this position lose catalytic activity.

  14. Physical inactivity and obesity underlie the insulin resistance of aging.

    PubMed

    Amati, Francesca; Dubé, John J; Coen, Paul M; Stefanovic-Racic, Maja; Toledo, Frederico G S; Goodpaster, Bret H

    2009-08-01

    OBJECTIVE Age-associated insulin resistance may underlie the higher prevalence of type 2 diabetes in older adults. We examined a corollary hypothesis that obesity and level of chronic physical inactivity are the true causes for this ostensible effect of aging on insulin resistance. RESEARCH DESIGN AND METHODS We compared insulin sensitivity in 7 younger endurance-trained athletes, 12 older athletes, 11 younger normal-weight subjects, 10 older normal-weight subjects, 15 younger obese subjects, and 15 older obese subjects using a glucose clamp. The nonathletes were sedentary. RESULTS Insulin sensitivity was not different in younger endurance-trained athletes versus older athletes, in younger normal-weight subjects versus older normal-weight subjects, or in younger obese subjects versus older obese subjects. Regardless of age, athletes were more insulin sensitive than normal-weight sedentary subjects, who in turn were more insulin sensitive than obese subjects. CONCLUSIONS Insulin resistance may not be characteristic of aging but rather associated with obesity and physical inactivity.

  15. Alterations in protein metabolism during space flight and inactivity

    NASA Technical Reports Server (NTRS)

    Ferrando, Arny A.; Paddon-Jones, Doug; Wolfe, Robert R.

    2002-01-01

    Space flight and the accompanying diminished muscular activity lead to a loss of body nitrogen and muscle function. These losses may affect crew capabilities and health in long-duration missions. Space flight alters protein metabolism such that the body is unable to maintain protein synthetic rates. A concomitant hypocaloric intake and altered anabolic/catabolic hormonal profiles may contribute to or exacerbate this problem. The inactivity associated with bedrest also reduces muscle and whole-body protein synthesis. For this reason, bedrest provides a good model for the investigation of potential exercise and nutritional countermeasures to restore muscle protein synthesis. We have demonstrated that minimal resistance exercise preserves muscle protein synthesis throughout bedrest. In addition, ongoing work indicates that an essential amino acid and carbohydrate supplement may ameliorate the loss of lean body mass and muscle strength associated with 28 d of bedrest. The investigation of inactivity-induced alterations in protein metabolism, during space flight or prolonged bedrest, is applicable to clinical populations and, in a more general sense, to the problems associated with the decreased activity that occur with aging.

  16. Alterations in protein metabolism during space flight and inactivity

    NASA Technical Reports Server (NTRS)

    Ferrando, Arny A.; Paddon-Jones, Doug; Wolfe, Robert R.

    2002-01-01

    Space flight and the accompanying diminished muscular activity lead to a loss of body nitrogen and muscle function. These losses may affect crew capabilities and health in long-duration missions. Space flight alters protein metabolism such that the body is unable to maintain protein synthetic rates. A concomitant hypocaloric intake and altered anabolic/catabolic hormonal profiles may contribute to or exacerbate this problem. The inactivity associated with bedrest also reduces muscle and whole-body protein synthesis. For this reason, bedrest provides a good model for the investigation of potential exercise and nutritional countermeasures to restore muscle protein synthesis. We have demonstrated that minimal resistance exercise preserves muscle protein synthesis throughout bedrest. In addition, ongoing work indicates that an essential amino acid and carbohydrate supplement may ameliorate the loss of lean body mass and muscle strength associated with 28 d of bedrest. The investigation of inactivity-induced alterations in protein metabolism, during space flight or prolonged bedrest, is applicable to clinical populations and, in a more general sense, to the problems associated with the decreased activity that occur with aging.

  17. The zebrafish early arrest mutants.

    PubMed

    Kane, D A; Maischein, H M; Brand, M; van Eeden, F J; Furutani-Seiki, M; Granato, M; Haffter, P; Hammerschmidt, M; Heisenberg, C P; Jiang, Y J; Kelsh, R N; Mullins, M C; Odenthal, J; Warga, R M; Nüsslein-Volhard, C

    1996-12-01

    This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes.

  18. A novel bradykinin potentiating peptide isolated from Bothrops jararacussu venom using catallytically inactive oligopeptidase EP24.15.

    PubMed

    Rioli, Vanessa; Prezoto, Benedito C; Konno, Katsuhiro; Melo, Robson L; Klitzke, Clécio F; Ferro, Emer S; Ferreira-Lopes, Mônica; Camargo, Antonio C M; Portaro, Fernanda C V

    2008-05-01

    Characterization of the peptide content of venoms has a number of potential benefits for basic research, clinical diagnosis, development of new therapeutic agents, and production of antiserum. Here, we use a substrate-capture assay that employs a catalytically inactive mutant of thimet oligopeptidase (EC 3.4.24.15; EP24.15) to identify novel bioactive peptides in Bothrops jararacussu venom. Of the peptides captured with inactive EP24.15 and identified by mass spectrometry, three were previously identified bradykinin-potentiating peptides (BPP), inactive oligopeptidase EP24.15 is a useful tool for the isolation of bioactive peptides from crude biological samples.

  19. High-resolution RNA allelotyping along the inactive X chromosome: evidence of RNA polymerase III in regulating chromatin configuration

    PubMed Central

    Hong, Ru; Lin, Bingqing; Lu, Xinyi; Lai, Lan-Tian; Chen, Xin; Sanyal, Amartya; Ng, Huck-Hui; Zhang, Kun; Zhang, Li-Feng

    2017-01-01

    We carried out padlock capture, a high-resolution RNA allelotyping method, to study X chromosome inactivation (XCI). We examined the gene reactivation pattern along the inactive X (Xi), after Xist (X-inactive specific transcript), a prototype long non-coding RNA essential for establishing X chromosome inactivation (XCI) in early embryos, is conditionally deleted from Xi in somatic cells (Xi∆Xist). We also monitored the behaviors of X-linked non-coding transcripts before and after XCI. In each mutant cell line, gene reactivation occurs to ~6% genes along Xi∆Xist in a recognizable pattern. Genes with upstream regions enriched for SINEs are prone to be reactivated. SINE is a class of retrotransposon transcribed by RNA polymerase III (Pol III). Intriguingly, a significant fraction of Pol III transcription from non-coding regions is not subjected to Xist-mediated transcriptional silencing. Pol III inhibition affects gene reactivation status along Xi∆Xist, alters chromatin configuration and interferes with the establishment XCI during in vitro differentiation of ES cells. These results suggest that Pol III transcription is involved in chromatin structure re-organization during the onset of XCI and functions as a general mechanism regulating chromatin configuration in mammalian cells. PMID:28368037

  20. High-resolution RNA allelotyping along the inactive X chromosome: evidence of RNA polymerase III in regulating chromatin configuration.

    PubMed

    Hong, Ru; Lin, Bingqing; Lu, Xinyi; Lai, Lan-Tian; Chen, Xin; Sanyal, Amartya; Ng, Huck-Hui; Zhang, Kun; Zhang, Li-Feng

    2017-04-03

    We carried out padlock capture, a high-resolution RNA allelotyping method, to study X chromosome inactivation (XCI). We examined the gene reactivation pattern along the inactive X (Xi), after Xist (X-inactive specific transcript), a prototype long non-coding RNA essential for establishing X chromosome inactivation (XCI) in early embryos, is conditionally deleted from Xi in somatic cells (Xi(∆Xist)). We also monitored the behaviors of X-linked non-coding transcripts before and after XCI. In each mutant cell line, gene reactivation occurs to ~6% genes along Xi(∆Xist) in a recognizable pattern. Genes with upstream regions enriched for SINEs are prone to be reactivated. SINE is a class of retrotransposon transcribed by RNA polymerase III (Pol III). Intriguingly, a significant fraction of Pol III transcription from non-coding regions is not subjected to Xist-mediated transcriptional silencing. Pol III inhibition affects gene reactivation status along Xi(∆Xist), alters chromatin configuration and interferes with the establishment XCI during in vitro differentiation of ES cells. These results suggest that Pol III transcription is involved in chromatin structure re-organization during the onset of XCI and functions as a general mechanism regulating chromatin configuration in mammalian cells.

  1. Site-directed mutagenesis in bacteriorhodopsin mutants and their characterization for bioelectrical and biotechnological equipment.

    PubMed

    Saeedi, Pardis; Moosaabadi, Jafar Mohammadian; Sebtahmadi, Seyed Sina; Behmanesh, Mehrdad; Mehrabadi, Jalil Fallah

    2012-03-01

    Bacteriorhodopsin (BR) mutagenesis plays an important role in the development of BR-based materials and tools with enhanced optical and electrical properties. Previously reported protocols for generating BR mutations are inefficient for the preparation and purification of mutant proteins. Therefore, a series of BR mutations were generated by using improved methods, which are described in further detail. The functional activity of the recombinant proteins was confirmed by spectroscopic and electrochemical assays. Modified proteins with different wavelengths and activities form a foundation for color-sensitive sensors and can be utilized to produce unique bioelectrical and biotechnological tools and materials. The proton-pumping activity of the generated mutant D85E was normal, indicating that the mutant could be used in light batteries. However, mutants D85Q and D85N were almost inactive; and D85N had a prolonged M state, suggesting that it could be utilized in light memories.

  2. Social background, bullying, and physical inactivity: National study of 11- to 15-year-olds.

    PubMed

    Henriksen, P W; Rayce, S B; Melkevik, O; Due, P; Holstein, B E

    2016-10-01

    More children from lower social backgrounds are physically inactive than those from higher ones. We studied whether bullying was a mediating factor between lower social background and physical inactivity. We also examined the combined effect of low social class and exposure to bullying on physical inactivity. The Danish sample of the Health Behaviour in School-aged Children (HBSC) study 2006 included 6269 schoolchildren in three age groups: 11-, 13-, and 15-year-olds from a random sample of 80 schools. The students answered the internationally standardized HBSC questionnaire. The applied definition leaves 4.0% in the category physically inactive. The sex and age-adjusted OR (95% CI) for physical inactivity was 2.10 (1.39-3.18) among students with low social class and unclassifiable 3.53 (2.26-5.53). Exposure to bullying was associated with physical inactivity, sex and age-adjusted OR = 2.39 (1.67-3.41). Exposure to bullying did not explain the association between social class and physical inactivity. The association between social class and physical inactivity was more pronounced among participants also exposed to bullying. In conclusion, there was a significantly increased odds ratio for physical inactivity among students from lower social classes and for students exposed to bullying. There was a combined effect of low social class and bullying on physical inactivity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Mechanical properties and fiber type composition of chronically inactive muscles

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Zhong, H.; Monti, R. J.; Vallance, K. A.; Kim, J. A.; Edgerton, V. R.

    2000-01-01

    A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties.

  4. Mechanical properties and fiber type composition of chronically inactive muscles

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Zhong, H.; Monti, R. J.; Vallance, K. A.; Kim, J. A.; Edgerton, V. R.

    2000-01-01

    A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties.

  5. Physical inactivity at leisure and work: a 12-month study of cardiac patients.

    PubMed

    Rogerson, Michelle C; Murphy, Barbara M; Le Grande, Michael R; Worcester, Marian U C

    2013-01-01

    Physical inactivity has been identified as a distinct health risk. However, little is known about how this can vary at leisure and work in cardiac patients. The aim of this study was to examine the prevalence and predictors of inactivity during leisure and work in the 12 months following a cardiac event in Australian cardiac patients. A total of 346 patients consecutively admitted to hospital with acute coronary syndrome or to undergo coronary artery bypass graft surgery were interviewed in hospital, and 4 and 12 months later. Leisure and occupational physical activity was measured using the Stanford Brief Activity Survey. Sociodemographic, psychosocial, and clinical data were also collected. The prevalence of leisure-time physical inactivity declined over time, with 52% inactive preevent and 29% inactive at 12 months. Approximately 50% of participants were physically inactive in their work, regardless of whether this was measured before or after the cardiac event. Logistic regression revealed that the significant predictors of leisure-time physical inactivity at 12 months were non-home ownership (OR = 2.19; P = .007) and physical inactivity in leisure-time prior to the event (OR = 2.44; P = .001). The significant predictors of occupational physical inactivity at 12 months were white-collar occupation (OR = 3.10; P < .001) and physical inactivity at work prior to the event (OR = 12.99; P < .001). Preevent physical inactivity, socioeconomic, and clinical factors predicted both leisure and work inactivity after an acute cardiac event. Effective interventions could be designed and implemented to target those most at risk of being physically inactive at work or leisure.

  6. Nutritional status and physical inactivity in moderated asthmatics

    PubMed Central

    Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

    2016-01-01

    Abstract Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity. Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants. FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12). This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening. PMID:27495092

  7. Inactivity, age, and exercise: single-muscle fiber power generation.

    PubMed

    Kim, Jong-Hee; Thompson, Ladora V

    2013-01-01

    We examined the effects of mild therapeutic exercise during a period of inactivity on size and contractile functions of myosin heavy chain (MHC) type I (n = 204) and type II (n = 419) single fibers from the medial gastrocnemius in three age groups. Young adult (5-12 mo), middle-aged (24-31 mo), and old (32-37 mo) F344BNF1 rats were assigned to one of three groups: weight-bearing control, non-weight bearing (NWB), and NWB plus exercise (NWBX). Fourteen days of hindlimb suspension were applied in NWB rats. The NWBX rats exercised on the treadmill for 15 min, four times a day, during the period of NWB. The NWBX did not improve peak power, but increased normalized power of MHC type I fibers in young adult rats. In MHC type II fibers, NWBX did not change peak power, isometric maximal force, V(max), and fiber size from young adult and middle-aged rats. NWBX did not improve peak power and isometric maximal force and showed a dramatic decline in V(max) and normalized power in the old rats. Collectively, mild treadmill exercise during a period of inactivity does not improve peak power of MHC type I or type II fiber from the gastrocnemius in young, middle-aged, and old rats. However, NWBX is beneficial in enhancing normalized power of MHC type I fibers in young adult rats, most likely due to the stimulus intensity and the ability of the individual fibers to adapt to the stimulus. In contrast, several factors, such as impaired adaptation potential, inappropriate exercise intensity, or increased susceptibility to muscle damage, may contribute to the lack of improvement in the older rats.

  8. KEPLER FLARES. I. ACTIVE AND INACTIVE M DWARFS

    SciTech Connect

    Hawley, Suzanne L.; Davenport, James R. A.; Kowalski, Adam F.; Wisniewski, John P.; Deitrick, Russell; Hilton, Eric J.; Hebb, Leslie

    2014-12-20

    We analyzed Kepler short-cadence M dwarf observations. Spectra from the Astrophysical Research Consortium 3.5 m telescope identify magnetically active (Hα in emission) stars. The active stars are of mid-M spectral type, have numerous flares, and have well-defined rotational modulation due to starspots. The inactive stars are of early M type, exhibit less starspot signature, and have fewer flares. A Kepler to U-band energy scaling allows comparison of the Kepler flare frequency distributions with previous ground-based data. M dwarfs span a large range of flare frequency and energy, blurring the distinction between active and inactive stars designated solely by the presence of Hα. We analyzed classical and complex (multiple peak) flares on GJ 1243, finding strong correlations between flare energy, amplitude, duration, and decay time, with only a weak dependence on rise time. Complex flares last longer and have higher energy at the same amplitude, and higher energy flares are more likely to be complex. A power law fits the energy distribution for flares with log E{sub K{sub p}}> 31 erg, but the predicted number of low-energy flares far exceeds the number observed, at energies where flares are still easily detectable, indicating that the power-law distribution may flatten at low energy. There is no correlation of flare occurrence or energy with starspot phase, the flare waiting time distribution is consistent with flares occurring randomly in time, and the energies of consecutive flares are uncorrelated. These observations support a scenario where many independent active regions on the stellar surface are contributing to the observed flare rate.

  9. Differential membrane fluidization by active and inactive cannabinoid analogues.

    PubMed

    Mavromoustakos, T; Papahatjis, D; Laggner, P

    2001-06-06

    The effects of the two cannabinomimetic drugs (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl-2-(hexyl)-1,3-dithiolane (AMG-3) and its pharmacologically less active 1-methoxy analogue (AMG-18) on the thermotropic and structural properties of dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) liposomes have been studied by X-ray diffraction and differential scanning calorimetry (DSC). DSC data revealed that the incorporation of the drugs affect differently the thermotropic properties of DPPC. The presence of the more active drug distinctly broadened and attenuated both the pretransition and main phase transition of DPPC bilayers, while the inactive analogue had only minor effects. Small and wide angle X-ray diffraction data showed that the two cannabinoids have different effects on the lipid phase structures and on the hydrocarbon chain packing. The pharmacologically active analogue, AMG-3, was found to efficiently fluidize domains of the lipids in the L(beta)' gel phase, and to perturb the regular multibilayer lattice. In the liquid crystalline L(alpha) phase, AMG-3 was also found to cause irregularities in packing, suggesting that the drug induces local curvature. At the same concentration, the inactive AMG-18 had only minor structural effects on the lipids. At about 10-fold or higher concentrations, AMG-18 was found to produce similar but still less pronounced effects in comparison to those observed by AMG-3. The dose-dependent, different thermotropic and structural effects by the two cannabinoid analogues suggest that these may be related to their biological activity.

  10. Enforced physical inactivity increases endothelial microparticle levels in healthy volunteers.

    PubMed

    Navasiolava, Nastassia M; Dignat-George, Françoise; Sabatier, Florence; Larina, Irina M; Demiot, Claire; Fortrat, Jacques-Olivier; Gauquelin-Koch, Guillemette; Kozlovskaya, Inesa B; Custaud, Marc-Antoine

    2010-08-01

    A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endothelium-dependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 + or - 4 vs. 15 + or - 2 arbitrary units and 29 + or - 6% vs. 12 + or - 6%, respectively, P < 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 + or - 8 vs. 65 + or - 10 EMPs/microl, P < 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity.

  11. Acid mine drainage from inactive eastern coal operations.

    PubMed

    Erickson, P M; Ladwig, K J; Kleinmann, R L

    1985-03-01

    The most widely used technique for abatement of acid drainage from inactive surface mines and refuse disposal areas is revegetation of a soil cover applied to the waste material. Nonetheless, acid production often persists and in some cases, limits establishment of vegetation. This paper reports on several field studies intended to determine the location of pyrite oxidation zones and migration pathways of oxidation products at inactive spoil and refuse sites.Oxygen required for pyrite oxidation is believed to he provided in the gaseous state from the atmosphere. Therefore, the oxygen concentration in unsaturated mine waste should provide an estimate of the weathering tendency in the local environment. We are currently monitoring gas composition in refuse and spoil at six sites. Barren refuse appeared to be oxygenated (>2% 02) in a shallow zone extending less than 1 metre below the surface during most of the year. Preliminary data from coal spoil showed that oxygen can be available throughout the unsaturated thickness, even at a revegetated site. Gas composition varied vertically and laterally at a single site and also appeared to show seasonal dependence.Hydrologic factors are also important in acid production and transport. Discharge monitoring alone does not adequately describe the mass transport of acid products through the spoil. For example, at one reclaimed mine the mean sulfate content in six monitoring wells ranged from 24% to 240% of the mean concentration at the discharge point. Sources of recharge and relative flow rates determine the contribution of a particular zone to overall discharge quality.These basic studies of acid production and transport indicate some shortcomings of standard reclamation practices at certain sites. This information will he used to develop alternative abatement technology designed to mitigate acid production at the source.

  12. Physical inactivity post-stroke: a 3-year longitudinal study.

    PubMed

    Kunkel, Dorit; Fitton, Carolyn; Burnett, Malcolm; Ashburn, Ann

    2015-01-01

    To explore change in activity levels post-stroke. We measured activity levels using the activPAL™ in hospital and at 1, 2 and 3 years' post-stroke onset. Of the 74 participants (mean age 76 (SD 11), 39 men), 61 were assessed in hospital: 94% of time was spent in sitting/lying, 4% standing and 2% walking. Activity levels improved over time (complete cases n = 15); time spent sitting/lying decreased (p = 0.001); time spent standing, walking and number of steps increased (p = 0.001, p = 0.028 and p = 0.03, respectively). At year 3, 18% of time was spent in standing and 9% walking. Time spent upright correlated significantly with Barthel (r = 0.69 on admission, r = 0.68 on discharge, both p < 0.01) and functional ambulation category scores (r = 0.55 on admission, 0.63 on discharge, both p < 0.05); correlations remained significant at all assessment points. Depression (in hospital), left hemisphere infarction (Years 1-2), visual neglect (Year 2), poor mobility and balance (Years 1-3) correlated with poorer activity levels. People with stroke were inactive for the majority of time. Time spent upright improved significantly by 1 year post-stroke; improvements slowed down thereafter. Poor activity levels correlated with physical and psychological measures. Larger studies are indicated to identify predictors of activity levels. Implications for Rehabilitation Activity levels (measured using activPAL™ activity monitor), increased significantly by 1 year post-stroke but improvements slowed down at 2 and 3 years. People with stroke were inactive for the majority of their day in hospital and in the community. Poor activity levels correlated with physical and psychological measures. Larger studies are indicated to identify the most important predictors of activity levels.

  13. ECB deacylase mutants

    DOEpatents

    Arnold, Frances H.; Shao, Zhixin; Zhao, Huimin; Giver, Lorraine J.

    2002-01-01

    A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

  14. [Physical inactivity in Galicia (Spain): trends and the impact of changes in the definition].

    PubMed

    Pérez-Ríos, Mónica; Santiago-Pérez, María I; Rodríguez-Camacho, Elena; Malvar, Alberto; Suanzes, Jorge; Hervada, Xurxo

    2015-01-01

    To estimate the prevalence of physical inactivity during leisure time in Galicia (Spain) between 2007 and 2011 and to assess the impact of including non-leisure time activities in the definition of physical inactivity. A cross-sectional study was conducted in the population aged 16 years and older (n=19,235). Physical activity was assessed by the Minnesota Questionnaire. In 2011, inactivity was estimated by including daily activities. Between 2007 and 2011, the prevalence of inactivity in Galicia remained stable (p=0.249) and close to 50%. This prevalence was higher among women and those who worked or were in education. Inactivity decreased from 47% to 16% when non-leisure time activities were included in the definition. Between 2007 and 2011 in Galicia, the prevalence of inactivity remained high and stable. This prevalence was significantly decreased when non-leisure time activities were included in the definition. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  15. Naïve Definitions of Action and Inaction: The Continuum, Spread, and Valence of Behaviors.

    PubMed

    McCulloch, Kathleen C; Li, Hong; Hong, Sungjin; Albarracin, Dolores

    2012-03-01

    The cohesiveness of a society depends, in part, on how its individual members manage their daily activities with respect to the goals of that society. Hence, there should be a degree of social agreement on what constitutes action and what constitutes inaction. The present research investigated the structure of action and inaction definitions, the evaluation of action versus inaction, and individual differences in these evaluations. Action-inaction ratings of behaviors and states showed more social agreement at the ends of the inaction-action continuum than at the middle, suggesting a socially shared construal of this definition. Action-inaction ratings were also shown to correlate with the valence of the rated behaviors, such that the more active the behavior the more positive its valence. Lastly, individual differences in locomotion, need for closure, and Christian religious beliefs correlated positively with a preference for action.

  16. Naïve Definitions of Action and Inaction: The Continuum, Spread, and Valence of Behaviors

    PubMed Central

    McCulloch, Kathleen C.; Li, Hong; Hong, Sungjin; Albarracin, Dolores

    2011-01-01

    The cohesiveness of a society depends, in part, on how its individual members manage their daily activities with respect to the goals of that society. Hence, there should be a degree of social agreement on what constitutes action and what constitutes inaction. The present research investigated the structure of action and inaction definitions, the evaluation of action versus inaction, and individual differences in these evaluations. Action-inaction ratings of behaviors and states showed more social agreement at the ends of the inaction-action continuum than at the middle, suggesting a socially shared construal of this definition. Action-inaction ratings were also shown to correlate with the valence of the rated behaviors, such that the more active the behavior the more positive its valence. Lastly, individual differences in locomotion, need for closure, and Christian religious beliefs correlated positively with a preference for action. PMID:23487013

  17. Calculating a checksum with inactive networking components in a computing system

    DOEpatents

    Aho, Michael E; Chen, Dong; Eisley, Noel A; Gooding, Thomas M; Heidelberger, Philip; Tauferner, Andrew T

    2015-01-27

    Calculating a checksum utilizing inactive networking components in a computing system, including: identifying, by a checksum distribution manager, an inactive networking component, wherein the inactive networking component includes a checksum calculation engine for computing a checksum; sending, to the inactive networking component by the checksum distribution manager, metadata describing a block of data to be transmitted by an active networking component; calculating, by the inactive networking component, a checksum for the block of data; transmitting, to the checksum distribution manager from the inactive networking component, the checksum for the block of data; and sending, by the active networking component, a data communications message that includes the block of data and the checksum for the block of data.

  18. Calculating a checksum with inactive networking components in a computing system

    DOEpatents

    Aho, Michael E; Chen, Dong; Eisley, Noel A; Gooding, Thomas M; Heidelberger, Philip; Tauferner, Andrew T

    2014-12-16

    Calculating a checksum utilizing inactive networking components in a computing system, including: identifying, by a checksum distribution manager, an inactive networking component, wherein the inactive networking component includes a checksum calculation engine for computing a checksum; sending, to the inactive networking component by the checksum distribution manager, metadata describing a block of data to be transmitted by an active networking component; calculating, by the inactive networking component, a checksum for the block of data; transmitting, to the checksum distribution manager from the inactive networking component, the checksum for the block of data; and sending, by the active networking component, a data communications message that includes the block of data and the checksum for the block of data.

  19. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.89 Ratings for inactive nonpulmonary...

  20. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.89 Ratings for inactive nonpulmonary...

  1. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.89 Ratings for inactive nonpulmonary...

  2. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.89 Ratings for inactive nonpulmonary...

  3. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.89 Ratings for inactive nonpulmonary...

  4. Structural organization of the inactive X chromosome in the mouse.

    PubMed

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  5. Characterization of inactive renin ("prorenin") from renin-secreting tumors of nonrenal origin. Similarity to inactive renin from kidney and normal plasma.

    PubMed Central

    Atlas, S A; Hesson, T E; Sealey, J E; Dharmgrongartama, B; Laragh, J H; Ruddy, M C; Aurell, M

    1984-01-01

    Inactive renin comprises well over half the total renin in normal human plasma. There is a direct relationship between active and inactive renin levels in normal and hypertensive populations, but the proportion of inactive renin varies inversely with the active renin level; as much as 98% of plasma renin is inactive in patients with low renin, whereas the proportion is consistently lower (usually 20-60%) in high-renin states. Two hypertensive patients with proven renin-secreting carcinomas of non-renal origin (pancreas and ovary) had high plasma active renin (119 and 138 ng/h per ml) and the highest inactive renin levels we have ever observed (5,200 and 14,300 ng/h per ml; normal range 3-50). The proportion of inactive renin (98-99%) far exceeded that found in other patients with high active renin levels. A third hypertensive patient with a probable renin-secreting ovarian carcinoma exhibited a similar pattern. Inactive renins isolated from plasma and tumors of these patients were biochemically similar to semipurified inactive renins from normal plasma or cadaver kidney. All were bound by Cibacron Blue-agarose, were not retained by pepstatin-Sepharose, and had greater apparent molecular weights (Mr) than the corresponding active forms. Plasma and tumor inactive renins from the three patients were similar in size (Mr 52,000-54,000), whereas normal plasma inactive renin had a slightly larger Mr than that from kidney (56,000 vs. 50,000). Inactive renin from each source was activated irreversibly by trypsin and reversibly by dialysis to pH 3.3 at 4 degrees C; the reversal process followed the kinetics of a first-order reaction in each instance. The trypsin-activated inactive renins were all identical to semipurified active renal renin in terms of pH optimum (pH 5.5-6.0) and kinetics with homologous angiotensinogen (Michaelis constants, 0.8-1.3 microM) and inhibition by pepstatin or by serial dilutions of renin-specific antibody. These results indicate that a markedly

  6. [Ribosome engineering of streptomyces sp. FJ3 from Three Gorges reservoir area and metabolic product of the selected mutant strain].

    PubMed

    Hai, Le; Huang, Yuqi; Liao, Guojian; Hu, Changhua

    2011-07-01

    To explore new resource from inactive actinomycete strains, we screened resistant mutant strains by ribosome engineering, and analyzed the products derived from the selected mutant strains. Three Gorges reservoir area-derived actinomycete strains including BD20, FJ3, WZ20 and FJ5 were used as initial strains, which showed no-antibacterial activities. The streptomycin-resistant (str(R)) mutants and rifampicin-resistant (rif(R)) mutants were screened by single colony isolation on streptomycin-containing plates and rifampicin-containing plates according to the method for obtaining drug-resistant mutants in ribosome engineering. The four initial strains and their str(R)-mutants and rif(R)-mutants were fermented in a liquid medium with the same composition. Mutants with anti-Staphylococcus aureus activity were obtained by paper chromatography. The components of fermentation broth were analyzed by high performance liquid chromatography (HPLC) and high performance liquid chromatography-mass spectrometry (LC-MS). Furthermore, FJ3 strain was identified by 16S rDNA and morphology. The minimal inhibitory concentration (MIC) of streptomycin and rifampicin for FJ3 was: 0.5 microg/mL and 110 microg/mL, respectively. Twenty-four strR-mutant strains and 20 rif(R)-mutant strains of FJ3 mutant strains were selected for bioassay. The result of the antibacterial activity screening demonstrated that six strains inhibited bacteria. Two strains (FJ3-2 and FJ3-6) were screened from the streptomycin-resistance mutants of inactive strain FJ3. The result of bioassay showed that the fermentation broth of FJ3-2 and FJ3-6 exhibited obvious anti-Staphylococcus aureus activity. The assay of paper chromatography showed that the active substance may be nucleic acid class antibiotic via using solvent system Doskochilova. Moreover, the results of HPLC and LC-MS exhibited that this substance may be thiolutin. Ribosome engineering for changing the secondary metabolic function of the inactive wild

  7. Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling

    PubMed Central

    Dhawan, Neil S.; scopton, Alex P.; Dar, Arvin C.

    2016-01-01

    Deregulation of the Ras–mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies1. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes2. Kinase suppressor of Ras (KSR) is a MAPK scaffold3–5 that is subject to allosteric regulation through dimerization with RAF6,7. Direct targeting of KSR could have important therapeutic implications for cancer; however, testing this hypothesis has been difficult owing to a lack of small-molecule antagonists of KSR function. Guided by KSR mutations that selectively suppress oncogenic, but not wild-type, Ras signalling, we developed a class of compounds that stabilize a previously unrecognized inactive state of KSR. These compounds, exemplified by APS-2-79, modulate KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK (mitogen-activated protein kinase kinase). Furthermore, APS-2-79 increased the potency of several MEK inhibitors specifically within Ras-mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. These results reveal conformational switching in KSR as a druggable regulator of oncogenic Ras, and further suggest co-targeting of enzymatic and scaffolding activities within Ras–MAPK signalling complexes as a therapeutic strategy for overcoming Ras-driven cancers. PMID:27556948

  8. Catalytic inactive heme oxygenase-1 protein regulates its own expression in oxidative stress.

    PubMed

    Lin, Qing S; Weis, Sebastian; Yang, Guang; Zhuang, Tiangang; Abate, Aida; Dennery, Phyllis A

    2008-03-01

    Heme oxygenase-1 (HO-1) catalyzes the degradation of heme and forms antioxidant bile pigments as well as the signaling molecule carbon monoxide. HO-1 is inducible in response to a variety of chemical and physical stress conditions to function as a cytoprotective molecule. Therefore, it is important to maintain the basal level of HO-1 expression even when substrate availability is limited. We hypothesized that the HO-1 protein itself could regulate its own expression in a positive feedback manner, and that this positive feedback was important in the HO-1 gene induction in response to oxidative stress. In cultured NIH 3T3 cells, transfection of HO-1 cDNA or intracellular delivery of pure HO-1 protein resulted in activation of a 15-kb HO-1 promoter upstream of luciferase as visualized by bioluminescent technology and increased HO-1 mRNA and protein levels. These effects were independent of HO activity because an enzymatically inactive mutant form of HO-1 similarly activated the HO-1 promoter and incubation with HO inhibitor metalloporphyrin SnPP did not affect the promoter activation. In addition, HO-1-specific siRNA significantly reduced hemin and cadmium chloride-mediated HO-1 induction. Furthermore, deletion analyses demonstrated that the E1 and E2 distal enhancers of the HO-1 promoter are required for this HO-1 autoregulation. These experiments document feed-forward autoregulation of HO-1 in oxidative stress and suggest that HO-1 protein has a role in the induction process. We speculate that this mechanism may be useful for maintaining HO-1 expression when substrate is limited and may also serve to up-regulate other genes to promote cytoprotection and to modulate cell proliferation.

  9. Isolation and Characterization of Pediocin AcH Chimeric Protein Mutants with Altered Bactericidal Activity

    PubMed Central

    Miller, Kurt W.; Schamber, Robin; Osmanagaoglu, Ozlem; Ray, Bibek

    1998-01-01

    A collection of pediocin AcH amino acid substitution mutants was generated by PCR random mutagenesis of DNA encoding the bacteriocin. Mutants were isolated by cloning mutagenized DNA into an Escherichia coli malE plasmid that directs the secretion of maltose binding protein-pediocin AcH chimeric proteins and by screening transformant colonies for bactericidal activity against Lactobacillus plantarum NCDO955 (K. W. Miller, R. Schamber, Y. Chen, and B. Ray, 1998. Appl. Environ. Microbiol. 64:14–20, 1998). In all, 17 substitution mutants were isolated at 14 of the 44 amino acids of pediocin AcH. Seven mutants (N5K, C9R, C14S, C14Y, G37E, G37R, and C44W) were completely inactive against the pediocin AcH-sensitive strains L. plantarum NCDO955, Listeria innocua Lin11, Enterococcus faecalis M1, Pediococcus acidilactici LB42, and Leuconostoc mesenteroides Ly. A C24S substitution mutant constructed by other means also was inactive against these bacteria. Nine other mutants (K1N, W18R, I26T, M31T, A34D, N41K, H42L, K43N, and K43E) retained from <1% to ∼60% of wild-type activity when assayed against L. innocua Lin11. One mutant, K11E, displayed ∼2.8-fold-higher activity against this indicator. About one half of the mutations mapped to amino acids that are conserved in the pediocin-like family of bacteriocins. All four cysteines were found to be required for activity, although only C9 and C14 are conserved among pediocin-like bacteriocins. Several basic amino acids as well as nonpolar amino acids located within the hydrophobic C-terminal region also were found to be important. The mutations are discussed in the context of structural models that have been proposed for the bacteriocin. PMID:9603806

  10. Effects of Physical (In)activity on Platelet Function.

    PubMed

    Heber, Stefan; Volf, Ivo

    2015-01-01

    As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality.

  11. EPA Facility Registry Service (FRS): RCRA_INACTIVE

    EPA Pesticide Factsheets

    This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of hazardous waste facilities that link to the Resource Conservation and Recovery Act Information System (RCRAInfo). EPA's comprehensive information system in support of the Resource Conservation and Recovery Act (RCRA) of 1976 and the Hazardous and Solid Waste Amendments (HSWA) of 1984, RCRAInfo tracks many types of information about generators, transporters, treaters, storers, and disposers of hazardous waste. FRS identifies and geospatially locates facilities, sites or places subject to environmental regulations or of environmental interest. Using vigorous verification and data management procedures, FRS integrates facility data from EPA's national program systems, other federal agencies, and State and tribal master facility records and provides EPA with a centrally managed, single source of comprehensive and authoritative information on facilities. This data set contains the subset of FRS integrated facilities that link to inactive RCRAInfo hazardous waste facilities once the RCRAInfo data has been integrated into the FRS database. Additional information on FRS is available at the EPA website https://www.epa.gov/enviro/facility-registry-service-frs.

  12. Effects of Physical (In)activity on Platelet Function

    PubMed Central

    Heber, Stefan; Volf, Ivo

    2015-01-01

    As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality. PMID:26557653

  13. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis.

    PubMed

    Motl, R W; Goldman, M

    2011-02-01

    We examined the associations among physical activity, neurological disability, and cardiorespiratory fitness in two studies of individuals with multiple sclerosis (MS). Study 1 included 25 women with relapsing-remitting MS (RRMS) who undertook an incremental exercise test for measuring peak oxygen (VO₂(peak) ) consumption, wore an accelerometer during a 7-day period, and completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Study 2 was a follow-up of Study 1 and included 24 women with RRMS who completed the self-reported Expanded Disability Status Scale (EDSS), undertook an incremental exercise test, wore an accelerometer during a 7-day period, and completed the GLTEQ. Study 1 indicated that VO₂(peak) was significantly correlated with accelerometer counts (pr = 0.69) and GLTEQ scores (pr = 0.63) even after controlling for age and MS duration. Study 2 indicated that VO₂(peak) was significantly correlated with accelerometer counts (pr = 0.50), GLTEQ scores (pr = 0.59), and EDSS scores (pr = -0.43) even after controlling for age and MS duration; there was a moderate partial correlation between accelerometer counts and EDSS scores (pr = -0.43). Multiple linear regression analysis indicated that both accelerometer counts (β = 0.32) and EDSS scores (β = -0.40) had statistically significant associations with VO₂(peak). The findings indicate that physical inactivity and neurological disability might represent independent risk factors for reduced levels of cardiorespiratory fitness in this population. © 2010 John Wiley & Sons A/S.

  14. The development of low temperature inactive (Lti) baker's yeast.

    PubMed

    Gysler, C; Niederberger, P

    2002-02-01

    The construction of a novel baker's yeast variety via traditional genetic techniques is described. The phenotype was designated "Lti" ("Low temperature inactive"). Lti mutations with the desired characteristics within a genetically well-defined haploid laboratory strain of Saccharomyces cerevisiae were isolated, and two different approaches were taken to obtain baker's yeast strains, which exhibit reduced fermenting activity at refrigeration temperatures. In a first approach, a chosen Lti strain carrying mutation lti9 was combined with other laboratory strains carrying defined MAL alleles. In a second approach, the same lti mutation was introduced in the genetic background of polyploid commercial baker's yeast strains that harbor important "industrial" properties. Lti strains arising from both approaches were characterized with specifically developed screening procedures. Strains of the "academic" Lti strain family displayed between 85% and 92% of the biomass yield of a commercial reference strain, whereas strains of the "industrial" Lti strain family showed a variation between 60% and 115%. Lti strains from both families varied strongly among each other in their activity in model doughs: at 8 degrees C they displayed activities between 5% and 30%, and at 30 degrees C between 40% and 113% of a commercial reference baker's yeast strain.

  15. Neighborhood safety and physical inactivity in adults from Curitiba, Brazil.

    PubMed

    Rech, Cassiano Ricardo; Reis, Rodrigo Siqueira; Hino, Adriano Akira Ferreira; Rodriguez-Añez, Ciro Romélio; Fermino, Rogério Cesar; Gonçalves, Priscila Bezerra; Hallal, Pedro Curi

    2012-06-12

    Neighborhood safety is one of the environmental aspects that can influence physical activity. We analyzed the association between perceived neighborhood safety and physical inactivity (PI) in adults and examined effect modification according to sociodemographic variables. A cross-sectional study was conducted with 1,261 adults (62% women), age 18-69 years from Curitiba, Brazil. The perception of unsafe neighborhood was higher among women, older participants, those classified in the high socioeconomic (SES) group, overweighed and also among those reporting to have PA equipments and children. The association between perception safety of walking during the day and walking for leisure (women PR=1.12 CI95%=1.02-1.22; men PR=0.82 CI95%=0.64-1.05; interaction term PR=1.38 CI95%=1.03-1.83) and safe perception was associated with PI, just in the highest SES group (PR=1.09; CI95%=1.00-1.19; p trend=0.032) when compared with their counterparts (low SES PR=0.99; CI95%=0.90-1.04; p trend=0.785; interaction term PR=1.09; CI95%=1.03-1.15; p trend=0.007). The perception of safety in the neighborhood was associated with PI in transport, but this association varies across of sociodemographic variables.

  16. Adolescent reproductive health in Indonesia: contested values and policy inaction.

    PubMed

    Utomo, Iwu Dwisetyani; McDonald, Peter

    2009-06-01

    This study examines the changing social and political context of adolescent sexual and reproductive health policy in Indonesia. We describe how, in 2001, Indonesia was on the brink of implementing an adolescent reproductive health policy that was consistent with international agreements to which the Indonesian government was a party. Although the health of young Indonesians was known to be at risk, the opportunity for reform passed quickly with the emergence of a new competing force, Middle Eastern fundamentalist Islam. Faced with the risk of regional separatism and competing politico-religious influences, the Indonesian government retreated to the safety of inaction in this area of policy. In the absence of a supportive and committed political environment that reinforces policy specifically targeted to young people's reproductive health, extremist approaches that involve considerable health risk prevailed. The sexual and reproductive values and behaviors that are emerging among single young people in contemporary Indonesia are conditioned by a political context that allows the conflicting forces of traditional Indonesian values, Westernization, and the strong emerging force of fundamentalist Islam to compete for the allegiance of young people.

  17. [Burden of mortality associated to physical inactivity in Bogota, Colombia].

    PubMed

    Lobelo, Felipe; Pate, Rusell; Parra, Diana; Duperly, John; Pratt, Michael

    2006-12-01

    Estimates of the burden of mortality associated to physical inactivity (PI) have not been quantified for large urban centers located in developing countries. To estimate the burden of mortality due to six chronic diseases (CDZ) associated to PI and the number of potentially preventable deaths associated to reductions in the prevalence of PI. PI exposure prevalence obtained via population surveys was linked to mortality data registered during 2002 among adult (> 45 y) Bogotá residents. The strength of association between PI and disease-specific mortality was obtained from the literature. Population attributable risk (PAR) was used to calculate the CDZ mortality attributable to PI and to estimate the number of potentially preventable deaths associated to a 30 % reduction in the prevalence of PI. A 53,2 % PI exposure prevalence was associated to a PAR of 19,3 % for coronary artery disease, 24,2 % for stroke, 13,8 % for arterial hypertension, 21 % for Diabetes Mellitus, 17,9 % for colon cancer and 14,2 % for breast cancer. An estimated 7,6 % of all-cause mortality and 20,1 % of CDZ mortality could be attributed to PI. An estimated 5% of the CDZ mortality could be prevented if PI prevalence is reduced by 30 %. Conservative estimates indicate that a considerable proportion of deaths due to highly prevalent CDZ could be attributed to PI. Strategies to reduce the prevalence of PI in Bogotá could lead to progressive reductions in the burden of CDZ mortality.

  18. Hedgehog signaling pathway is inactive in colorectal cancer cell lines.

    PubMed

    Chatel, Guillaume; Ganeff, Corine; Boussif, Naima; Delacroix, Laurence; Briquet, Alexandra; Nolens, Gregory; Winkler, Rosita

    2007-12-15

    The Hedgehog (Hh) signaling pathway plays an important role in human development. Abnormal activation of this pathway has been observed in several types of human cancers, such as the upper gastro-intestinal tract cancers. However, activation of the Hh pathway in colorectal cancers is controversial. We analyzed the expression of the main key members of the Hh pathway in 7 colon cancer cell lines in order to discover whether the pathway is constitutively active in these cells. We estimated the expression of SHH, IHH, PTCH, SMO, GLI1, GLI2, GLI3, SUFU and HHIP genes by RT-PCR. Moreover, Hh ligand, Gli3 and Sufu protein levels were quantified by western blotting. None of the cell lines expressed the complete set of Hh pathway members. The ligands were absent from Colo320 and HCT116 cells, Smo from Colo205, HT29 and WiDr. GLI1 gene was not expressed in SW480 cells nor were GLI2/GLI3 in Colo205 or Caco-2 cells. Furthermore the repressive form of Gli3, characteristic of an inactive pathway, was detected in SW480 and Colo320 cells. Finally treatment of colon cancer cells with cyclopamine, a specific inhibitor of the Hh pathway, did not downregulate PTCH and GLI1 genes expression in the colorectal cells, whereas it did so in PANC1 control cells. Taken together, these results indicate that the aberrant activation of the Hh signaling pathway is not common in colorectal cancer cell lines.

  19. [Juvenile obesity and the role of physical activity and inactivity].

    PubMed

    Graf, C

    2010-07-01

    Physical activity has important health benefits. Despite of the use of different measurement instruments, a decrease in physical activity and an increase in sedentary habits has been described in children and adolescents. As a consequence, a reduction in physical performance and motor abilities and an increase in overweight and fat mass is found associated with comorbidities, e.g., ranging from insulin resistance up to the metabolic syndrome. Therefore, beside the therapeutic use of exercise in obesity programs, adequate preventive strategies are warranted. However, within this discussion, it must be taken into consideration that special subgroups are more affected by insufficient physical activity/sedentary habits, e.g., females, adolescents, ethnicity, lower socioeconomic status. In many other groups, recommendations for physical activity (1 h/day) are achieved. Hence, interventions must focus on these at-risk groups and intensified. In addition, recommendations related to physical activity and inactivity, in terms of TV consumption, must be critically analyzed as to whether the recommendations are sufficient and how they can be implemented to achieve lasting results.

  20. Resurrecting inactive antimicrobial peptides from the lipopolysaccharide trap.

    PubMed

    Mohanram, Harini; Bhattacharjya, Surajit

    2014-01-01

    Host defense antimicrobial peptides (AMPs) are a promising source of antibiotics for the treatment of multiple-drug-resistant pathogens. Lipopolysaccharide (LPS), the major component of the outer leaflet of the outer membrane of Gram-negative bacteria, functions as a permeability barrier against a variety of molecules, including AMPs. Further, LPS or endotoxin is the causative agent of sepsis killing 100,000 people per year in the United States alone. LPS can restrict the activity of AMPs inducing aggregations at the outer membrane, as observed for frog AMPs, temporins, and also in model AMPs. Aggregated AMPs, "trapped" by the outer membrane, are unable to traverse the cell wall, causing their inactivation. In this work, we show that these inactive AMPs can overcome LPS-induced aggregations while conjugated with a short LPS binding β-boomerang peptide motif and become highly bactericidal. The generated hybrid peptides exhibit activity against Gram-negative and Gram-positive bacteria in high-salt conditions and detoxify endotoxin. Structural and biophysical studies establish the mechanism of action of these peptides in LPS outer membrane. Most importantly, this study provides a new concept for the development of a potent broad-spectrum antibiotic with efficient outer membrane disruption as the mode of action.

  1. Histone acetylation controls the inactive X chromosome replication dynamics

    PubMed Central

    Casas-Delucchi, Corella S.; Brero, Alessandro; Rahn, Hans-Peter; Solovei, Irina; Wutz, Anton; Cremer, Thomas; Leonhardt, Heinrich; Cardoso, M. Cristina

    2011-01-01

    In mammals, dosage compensation between male and female cells is achieved by inactivating one female X chromosome (Xi). Late replication of Xi was proposed to be involved in the maintenance of its silenced state. Here, we show a highly synchronous replication of the Xi within 1 to 2 h during early-mid S-phase by following DNA replication in living mammalian cells with green fluorescent protein-tagged replication proteins. The Xi was replicated before or concomitant with perinuclear or perinucleolar facultative heterochromatin and before constitutive heterochromatin. Ectopic expression of the X-inactive-specific transcript (Xist) gene from an autosome imposed the same synchronous replication pattern. We used mutations and chemical inhibition affecting different epigenetic marks as well as inducible Xist expression and we demonstrate that histone hypoacetylation has a key role in controlling Xi replication. The epigenetically controlled, highly coordinated replication of the Xi is reminiscent of embryonic genome replication in flies and frogs before genome activation and might be a common feature of transcriptionally silent chromatin. PMID:21364561

  2. Home Delivery Medicament Program: access, inactivity and cardiovascular risk.

    PubMed

    Araújo, Roque da Silva; Arcuri, Edna Apparecida Moura; Lopes, Victor Cauê

    2016-10-10

    to verify causes of inactivity in the Home Delivery Medicament Program, as referred by users from a Primary Health Care Service in São Paulo, comparing them to the causes registered in the program and analyzing them in the theoretical model Concept of Access to Health. cross-sectional study, interviewing 111 inactive users; and documentary study in the program records. half of the users did not know the condition of inactivity. Discrepancies were found between the user's and the program's information, observing different levels of agreement: Absence of physician and administrative staff member 0%; Transfer to other service 25%; Death 50%; Option to quit 50%; Address change 57% and Change in therapeutic schedule 80%. The users' feeling of accepting the program was observed. In the health access concept, inactivity can be explained in the information dimension, in the degree of asymmetry between the patient's and the health professional's knowledge, identified through the indicators: education, knowledge and information sources. due to the low education level, the user does not assimilate the information on the steps of the program flowchart, does not return for the assessment that guarantees its continuity. Consequently, (s)he stops receiving the medication and spends a long time without treatment, increasing the cardiovascular risk of hypertensive (92% of the sample), diabetic (44%) and dyslipidemic patients (31%). verificar causas de inatividade no Programa Remédio em Casa, referidas por usuários de Unidade Básica de Saúde de São Paulo, comparando-as às registradas pelo programa e analisando-as no modelo teórico Conceito de Acesso à Saúde. estudo transversal entrevistando 111 usuários inativos; e documental, nos registros do programa. metade dos usuários desconhecia a condição de inatividade. Constatadas discrepâncias nas informações usuário versus programa, observando-se diferentes níveis de concordância: Falta de médico e funcion

  3. A nuclear export signal in the N-terminal regulatory domain of IκBα controls cytoplasmic localization of inactive NF-κB/IκBα complexes

    PubMed Central

    Huang, Tony T.; Kudo, Nobuaki; Yoshida, Minoru; Miyamoto, Shigeki

    2000-01-01

    Appropriate subcellular localization is crucial for regulation of NF-κB function. Herein, we show that latent NF-κB complexes can enter and exit the nucleus in preinduction states. The nuclear export inhibitor leptomycin B (LMB) sequestered NF-κB/IκBα complexes in the nucleus. Using deletion and site-directed mutagenesis, we identified a previously uncharacterized nuclear export sequence in residues 45–54 of IκBα that was required for cytoplasmic localization of inactive complexes. This nuclear export sequence also caused nuclear exclusion of heterologous proteins in a LMB-sensitive manner. Importantly, a LMB-insensitive CRM1 mutant (Crm1-K1) abolished LMB-induced nuclear accumulation of the inactive complexes. Moreover, a cell-permeable p50 NF-κB nuclear localization signal peptide also blocked these LMB effects. These results suggest that NF-κB/IκBα complexes shuttle between the cytoplasm and nucleus by a nuclear localization signal-dependent nuclear import and a CRM1-dependent nuclear export. The LMB-induced nuclear complexes could not bind DNA and were inaccessible to signaling events, because LMB inhibited NF-κB activation without affecting the subcellular localization of upstream kinases IKKβ and NIK. Our findings indicate that the dominant nuclear export over nuclear import contributes to the largely cytoplasmic localization of the inactive complexes to achieve efficient NF-κB activation by extracellular signals. PMID:10655476

  4. Burden of physical inactivity and hospitalization costs due to chronic diseases

    PubMed Central

    Bielemann, Renata Moraes; da Silva, Bruna Gonçalves Cordeiro; Coll, Carolina de Vargas Nunes; Xavier, Mariana Otero; da Silva, Shana Ginar

    2015-01-01

    OBJECTIVE To evaluate the physical inactivity-related inpatient costs of chronic non-communicable diseases. METHODS This study used data from 2013, from Brazilian Unified Health System, regarding inpatient numbers and costs due to malignant colon and breast neoplasms, cerebrovascular diseases, ischemic heart diseases, hypertension, diabetes, and osteoporosis. In order to calculate the share physical inactivity represents in that, the physical inactivity-related risks, which apply to each disease, were considered, and physical inactivity prevalence during leisure activities was obtained from Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey). The analysis was stratified by genders and residing country regions of subjects who were 40 years or older. The physical inactivity-related hospitalization cost regarding each cause was multiplied by the respective share it regarded to. RESULTS In 2013, 974,641 patients were admitted due to seven different causes in Brazil, which represented a high cost. South region was found to have the highest patient admission rate in most studied causes. The highest prevalences for physical inactivity were observed in North and Northeast regions. The highest inactivity-related share in men was found for osteoporosis in all regions (≈ 35.0%), whereas diabetes was found to have a higher share regarding inactivity in women (33.0% to 37.0% variation in the regions). Ischemic heart diseases accounted for the highest total costs that could be linked to physical inactivity in all regions and for both genders, being followed by cerebrovascular diseases. Approximately 15.0% of inpatient costs from Brazilian Unified Health System were connected to physical inactivity. CONCLUSIONS Physical inactivity significantly impacts the number of patient admissions due to the evaluated causes and through their resulting costs, with different genders and country regions representing different shares. PMID:26487291

  5. Network social capital, social participation, and physical inactivity in an urban adult population.

    PubMed

    Legh-Jones, Hannah; Moore, Spencer

    2012-05-01

    Research on individual social capital and physical activity has tended to focus on the association among physical activity, generalized trust, and social participation. Less is known about the association between network social capital, i.e., the resources accessed through one's social connections, and physical inactivity. Using formal network measures of social capital, this study examined which specific dimension of network capital (i.e. diversity, reach and range) was associated with physical inactivity, and whether network social capital mediated the association between physical inactivity and social participation. Data came from the 2008 Montreal (Canada) Neighbourhood Networks and Healthy Aging survey, in which 2707 adults 25 years and older in 300 Montreal neighbourhoods were surveyed. Physical activity was self-reported using the International Physical Activity Questionnaire (IPAQ). IPAQ guidelines provided the basis for the physical inactivity cutoff. Network social capital was measured with a position generator instrument. Multilevel logistic methods were used to examine the association between physical inactivity and individual social capital dimensions, while adjusting for socio-demographic and -economic factors. Higher network diversity was associated with a decreased likelihood of physical inactivity. Consistent with previous findings, individuals who did not participate in any formal associations were more likely to be physically inactive compared to those with high levels of participation. Network diversity mediated the association between physical inactivity and participation. Generalized trust and the network components of reach and range were not shown associated with physical inactivity. Findings highlight the importance of social participation and network social capital and the added value of network measures in the study of social capital and physical inactivity. Population-based programs targeting physical inactivity among adults might

  6. Computed structures of point deletion mutants and their enzymatic activities

    PubMed Central

    Berrondo, Monica; Gray, Jeffrey J.

    2011-01-01

    Point deletions in enzymes can vary in effect from negligible to complete loss of activity, however, these effects are not generally predictable. Deletions are widely observed in nature and often result in diseases such as cancer, cystic fibrosis, or osteogenesis imperfecta. Here, we have developed an algorithm to model the perturbed structures of deletion mutants with the ultimate goal of predicting their activities. The algorithm works by deleting the specified residue from the wild-type structure, creating a gap that is closed using a combination of local and global moves that change the backbone torsion angles of the protein structure. On a set of five proteins for which both wild-type and deletion mutant x-ray crystal structures are available, the algorithm produces deep, narrow energy funnels within 1.5 Å of the crystal structure for the deletion mutants. To assess the ability of our algorithm to predict activity from the predicted structures, we tested the correlation of experimental activity with several measures of the predicted structure ensemble using a set of 45 point deletions from ricin. Estimates incorporating likely prevalence of active and inactive deletion sites suggest that activity can be predicted correctly over 60% of the time from the active site rmsd of the lowest energy predicted structures. The predictions are stronger than simple sequence organization measures, but more fundamental work is required in structure prediction and enzyme activity determination to allow consistent prediction of activity. PMID:21905110

  7. Social determinants of physical inactivity in the Northern Manhattan Study (NOMAS)

    PubMed Central

    Willey, Joshua Z.; Paik, Myunghee C; Sacco, Ralph; Elkind, Mitchell S.V.; Boden-Albala, Bernadette

    2010-01-01

    Background Physical inactivity is an important and modifiable cardiovascular disease risk factor. Little is known about the social determinants of physical inactivity in older, urban-dwelling populations. Methods We collected socio-demographic and medical risk factor information and physical activity questionnaires in the Northern Manhattan Study. Logistic regression models were constructed to examine whether measures of social isolation, race-ethnicity, and sex were associated with physical inactivity. Results Physical inactivity was present in 40.5% of the cohort. In multivariable models adjusted for medical comorbidities, Hispanic race-ethnicity (compared to non-Hispanic white) was associated with higher odds of physical inactivity (OR 2.18, 95% CI 1.78, 2.67), while women were more likely to be inactive than men (OR 1.33, 95% CI 1.15, 1.54). Having Medicaid/being uninsured (OR 1.20, 95% CI 1.02, 1.42), and having fewer than 3 friends (1.41, 95% CI 1.15, 1.72) were also associated with physical inactivity. Conclusions Physical inactivity is common, particularly in Hispanics, women, and those who are socially isolated. Public health interventions aimed at increasing physical activity in these more sedentary groups are required. PMID:20574777

  8. Excess Medical Care Costs Associated with Physical Inactivity among Korean Adults: Retrospective Cohort Study.

    PubMed

    Min, Jin-Young; Min, Kyoung-Bok

    2016-01-18

    Physical inactivity is a major risk factor for chronic diseases and premature death. The increased health risks associated with physical inactivity may also generate a heavier economic burden to society. We estimated the direct medical costs attributable to physical inactivity among adults using data from the 2002-2010 Korean National Health Insurance Service-National Sample Cohort. A total of 68,556 adults whose reported physical activity status did not change during the study period was included for this study. Propensity scores for inactive adults were used to match 23,645 inactive groups with 23,645 active groups who had similar propensity scores. We compared medical expenditures between the two groups using generalized linear models with a gamma distribution and a log link. Direct medical costs were based on the reimbursement records of all medical facilities from 2005 to 2010. The average total medical costs for inactive individuals were $1110.5, which was estimated to be 11.7% higher than the costs for physically active individuals. With respect to specific diseases, the medical costs of inactive people were significantly higher than those of active people, accounting for approximately 8.7% to 25.3% of the excess burden. Physical inactivity is associated with considerable medical care expenditures per capita among Korean adults.

  9. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types... practitioner take and pass a professional responsibility examination. (c) Transfer to disability...

  10. Relationship between Physical Inactivity and Health Characteristics among Participants in an Employee Wellness Program

    PubMed Central

    Birdee, Gurjeet S.; Byrne, Daniel W.; McGown, Paula W.; Rothman, Russell L.; Rolando, Lori A.; Holmes, Marilyn C.; Yarbrough, Mary I.

    2013-01-01

    Objective To characterize factors associated with physical inactivity among employees with access to workplace wellness program. Methods We examined data on physical inactivity, defined as exercise less than once a week, from the 2010 health risk assessment (HRA) completed by employees at a major academic institution (n=16,976). Results Among employees, 18% individuals reported physical activity less than once a week. Individuals who were physically inactive as compared with physically active reported higher prevalence of cardiovascular diseases (AOR 1.36 [1.23–1.51], fair or poor health status (AOR 3.52 [2.97–4.17]) and absenteeism from work (AOR 1.59 [1.41–1.79]). Overall, physically inactive employees as compared to physically active employees reported more interest in health education programs. Conclusions Future research is needed to address barriers to physical inactivity to improve employee wellness and potentially lower health utility costs. PMID:23618884

  11. Motor-Driven (Passive) Cycling: A Potential Physical Inactivity Countermeasure?

    PubMed

    Peterman, James E; Wright, Kenneth P; Melanson, Edward L; Kram, Rodger; Byrnes, William C

    2016-09-01

    We have previously shown that motor-driven (passive) stationary cycling elevates energy expenditure (EE). This study aimed to quantify how acute passive cycling affects glucose and insulin responses to an oral glucose tolerance test (OGTT) and basic cognition compared with sitting and moderate-intensity active cycling. Twenty-four physically inactive healthy males completed three trials in randomized order involving 30-min conditions of sitting, passive cycling, and moderate-intensity cycling. During each condition, EE was measured, and participants performed cognitive tests. After each condition, a 2-h OGTT was performed. EE was significantly higher during the cycling conditions compared with sitting (1.36 ± 0.58 and 6.50 ± 1.73 kcal·min greater than sitting for passive and moderate-intensity, respectively). A significant correlation was found between body fat percentage and postsitting OGTT 2-h postplasma glucose (r = 0.30, P < 0.05); thus, participants were divided into lean (n = 11) and nonlean (n = 13) groups. In the nonlean group, compared with sitting, passive cycling lowered 2-h postplasma glucose (7.7 ± 1.3 vs 6.9 ± 1.6 mmol·L, respectively, P < 0.05), and the Matsuda whole-body insulin sensitivity index (WBISI) was higher (2.74 ± 0.86 vs 3.36 ± 1.08, P < 0.05). In addition, passive and moderate-intensity cycling had similar beneficial effects on 2-h postplasma glucose and WBISI. Cognitive performance did not significantly differ between the sitting and passive cycling conditions. Two-hour postplasma glucose was lower and WBISI after acute passive cycling was higher in nonlean participants. Given that and the increase in EE without changes in cognitive performance, we propose passive cycling as a promising intervention to counteract some of the deleterious effects of prolonged sitting in the workplace.

  12. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis

    PubMed Central

    Motl, R. W.; Goldman, M.

    2011-01-01

    Objective We examined the associations among physical activity, neurological disability, and cardiorespiratory fitness in two studies of individuals with multiple sclerosis (MS). Method Study 1 included 25 women with relapsing-remitting MS (RRMS) who undertook an incremental exercise test for measuring peak oxygen (V̇O2peak) consumption, wore an accelerometer during a 7-day period, and completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Study 2 was a follow-up of Study 1 and included 24 women with RRMS who completed the self-reported Expanded Disability Status Scale (EDSS), undertook an incremental exercise test, wore an accelerometer during a 7-day period, and completed the GLTEQ. Results Study 1 indicated that V̇O2peak was significantly correlated with accelerometer counts (pr = 0.69) and GLTEQ scores (pr = 0.63) even after controlling for age and MS duration. Study 2 indicated that V̇O2peak was significantly correlated with accelerometer counts (pr = 0.50), GLTEQ scores (pr = 0.59), and EDSS scores (pr = −0.43) even after controlling for age and MS duration; there was a moderate partial correlation between accelerometer counts and EDSS scores (pr = −0.43). Multiple linear regression analysis indicated that both accelerometer counts (β = 0.32) and EDSS scores (β = −0.40) had statistically significant associations with V̇O2peak. Conclusion The findings indicate that physical inactivity and neurological disability might represent independent risk factors for reduced levels of cardiorespiratory fitness in this population. PMID:21108624

  13. Effects of Physical Activity and Inactivity on Muscle Fatigue

    PubMed Central

    Bogdanis, Gregory C.

    2012-01-01

    The aim of this review was to examine the mechanisms by which physical activity and inactivity modify muscle fatigue. It is well known that acute or chronic increases in physical activity result in structural, metabolic, hormonal, neural, and molecular adaptations that increase the level of force or power that can be sustained by a muscle. These adaptations depend on the type, intensity, and volume of the exercise stimulus, but recent studies have highlighted the role of high intensity, short-duration exercise as a time-efficient method to achieve both anaerobic and aerobic/endurance type adaptations. The factors that determine the fatigue profile of a muscle during intense exercise include muscle fiber composition, neuromuscular characteristics, high energy metabolite stores, buffering capacity, ionic regulation, capillarization, and mitochondrial density. Muscle fiber-type transformation during exercise training is usually toward the intermediate type IIA at the expense of both type I and IIx myosin heavy-chain isoforms. High-intensity training results in increases of both glycolytic and oxidative enzymes, muscle capillarization, improved phosphocreatine resynthesis and regulation of K+, H+, and lactate ions. Decreases of the habitual activity level due to injury or sedentary lifestyle result in partial or even compete reversal of the adaptations due to previous training, manifested by reductions in fiber cross-sectional area, decreased oxidative capacity, and capillarization. Complete immobilization due to injury results in markedly decreased force output and fatigue resistance. Muscle unloading reduces electromyographic activity and causes muscle atrophy and significant decreases in capillarization and oxidative enzymes activity. The last part of the review discusses the beneficial effects of intermittent high-intensity exercise training in patients with different health conditions to demonstrate the powerful effect of exercise on health and well being. PMID

  14. Superstructures of wet inactive chromatin and the chromosome surface.

    PubMed

    Basu, S

    1979-01-01

    Superpacking of chromatin and the surface features of metaphase chromosomes have been studied by SiO replication of wet, unstained, and unfixed specimens in an exceedingly thin (less than or equal to nm) aqueous layer, keeping them wet. Hydrophilic Formvar substrates allow controlled thinning of the aqueous layer covering the wet specimens. Whole mounts of chromatin and chromosomes were prepared by applying a microsurface spreading method to swollen nuclei and mitotic cells at metaphase. The highest level of nucleosome folding of the inactive chromatin in chicken erythrocytes and rat liver nuclei is basically a second-order superhelical organization (width 150--200 nm, pitch distance 50--150 nm) of the elementary nucleosome filament. In unfavorable environments (as determined by ionic agents, fixative, and dehydrating agetns) this superstructure collapses into chains of superbeads and beads. Formalin (10%) apparently attacks at discrete sites of chromatin, which are then separated into superbeads. The latter consist of 4--6 nucleosomes and seemingly correspond to successive turns of an original solenoidal coil (width 30--35 nm), which forms the superhilical organization. When this organization is unfolded, eg, in 1--2 mM EDTA, DNAse-sensitive filaments (diameter 1.7 nm) are seen to be wrapped around the nucleosomes. The wet chromosomes in each metaphase spread are held to each other by smooth microtubular fibers, 20--20 nm in diameter. Before they enter into a chromsome, these fibers branch into 9--13 protofilaments, each 5 nm wide. The chromosome surface contains a dense distribution of subunits about 10--25 nm in diameter. This size distribution corresponds to that of nucleosomes and their superbeads. Distinct from this beaded chromosome surface are several smooth, 23--30-nm-diameter fibers, which are longitudinal at the centromere and seem to continue into the chromatid structure. The surface replicas of dried chromosomes do not show these features, which are

  15. Neighborhood safety and physical inactivity in adults from Curitiba, Brazil

    PubMed Central

    2012-01-01

    Background Neighborhood safety is one of the environmental aspects that can influence physical activity. We analyzed the association between perceived neighborhood safety and physical inactivity (PI) in adults and examined effect modification according to sociodemographic variables. Methods A cross-sectional study was conducted with 1,261 adults (62% women), age 18–69 years from Curitiba, Brazil. Results The perception of unsafe neighborhood was higher among women, older participants, those classified in the high socioeconomic (SES) group, overweighed and also among those reporting to have PA equipments and children. The association between perception safety of walking during the day and walking for leisure (women PR = 1.12 CI95% = 1.02–1.22; men PR = 0.82 CI95% = 0.64–1.05; interaction term PR = 1.38 CI95% = 1.03–1.83) and safe perception was associated with PI, just in the highest SES group (PR = 1.09; CI95% = 1.00–1.19; p trend = 0.032) when compared with their counterparts (low SES PR = 0.99; CI95% = 0.90–1.04; p trend = 0.785; interaction term PR = 1.09; CI95% = 1.03–1.15; p trend = 0.007). Conclusion The perception of safety in the neighborhood was associated with PI in transport, but this association varies across of sociodemographic variables. PMID:22691163

  16. Career redevelopment programmes for inactive nurses in Japan.

    PubMed

    Tanaka, Sachiko; Serizawa, Takako; Sakaguchi, Chizuru

    2008-12-01

    The purpose of this paper is to examine the challenges and problems in using career redevelopment programmes and individual hospital programmes to prepare inactive nurses to re-enter into the workforce in Japan. It is critical to supply sufficient skilled health human resources for medical care. Although, Japan has a mandatory retraining programme for supporting nurses to return to the workplace after a career break, it is unclear to what extent there are benefits to nurses from these programmes. The research of career redevelopment programme was undertaken in three administrative divisions' nurse centres in local prefecture A, B and C. A survey of nurses participating in the programme running in T Hospital was also conducted. The issues examined were the background and motivations of participants, the length of career break, the percentages returning to work and the effectiveness of each programme. The average age of participants was 40 years, ranging widely from the 20-60 years. Local prefecture A tended to have narrower age range than others, namely from the 30-50 years. The average period of career break was around eight years at two of three. Length of experience was quite varied from entry level to 20 or 30 years in nursing. Feedback from nurses in the case study T Hospital suggests that the most effective ways of providing support through the programme was to meet the need for continuing support, including working styles after return to work and using the resources programme in their own area of domicile. In the potential return of the nurse, the following are important: (i) job support system by using social resources effectively in the community level; and (ii) introduction of diverse working styles that take account of varying work-life balance, as well as childcare support, by using existing facilities or human resources.

  17. A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD).

    PubMed

    Wrobe, D; Henseler, M; Huettler, S; Pascual Pascual, S I; Chabas, A; Sandhoff, K

    2000-02-01

    The lysosomal degradation of sphingolipids with short oligosaccharide chains depends on small glycosylated non-enzymatic sphingolipid activator proteins (SAPs, saposins). Four of the five known SAPs, SAP-A, -B, -C and -D, are derived by proteolytic processing from a common precursor protein (SAP-precursor) that is encoded by a gene on chromosome 10 consisting of 15 exons and 14 introns. SAP-B is a non-specific glycolipid binding protein that stimulates in vitro the hydrolysis of about 20 glycolipids by different enzymes. In vivo SAP-B stimulates in particular the degradation of sulphatides by arylsulphatase A. So far, four different point mutations have been identified on the SAP-B domain of the SAP-precursor gene. The mutations result in a loss of mature SAP-B, causing the lysosomal accumulation of sulphatides and other sphingolipids, resulting in variant forms of metachromatic leukodystrophy (MLD). Here we report on a patient with SAP-B deficiency that is caused by a new homoallelic point mutation that has been identified by mRNA and DNA analysis. A 643A > C transversion results in the exchange of asparagine 215 to histidine and eliminates the single glycosylation site of SAP-B. Metabolic labelling experiments showed that the mutation had no effect on the intracellular transport of the encoded precursor to the acidic compartments and its maturation in the patient's cells. All four SAPs (SAP-A to SAP-D) were detectable by immunochemical methods. SAP-B in the patient's cells was found to be slightly less stable than the protein in normal cells and corresponded in size to the deglycosylated form of the wild-type SAP-B. Feeding studies with non-glycosylated SAP-precursor, generating non-glycosylated SAP-B, showed that the loss of the carbohydrate chain reduced the intracellular activity of the protein significantly. The additional structural change of the patient's SAP-B, caused by the change of amino acid 215 from asparagine to histidine, presumably resulted in an

  18. Mapping the Prevalence of Physical Inactivity in U.S. States, 1984-2015.

    PubMed

    An, Ruopeng; Xiang, Xiaoling; Yang, Yan; Yan, Hai

    2016-01-01

    Physical inactivity is a leading cause of morbidity, disability and premature mortality in the U.S. and worldwide. This study aimed to map the prevalence of physical inactivity across U.S. states over the past three decades, and estimate the over-time adjusted changes in the prevalence of physical inactivity in each state. Individual-level data (N = 6,701,954) were taken from the 1984-2015 Behavioral Risk Factor Surveillance System (BRFSS), an annually repeated cross-sectional survey of state-representative adult population. Prevalence of self-reported leisure-time physical inactivity was estimated by state and survey year, accounting for the BRFSS sampling design. Logistic regressions were performed to estimate the changes in the prevalence of physical inactivity over the study period for each state, adjusting for individual characteristics including sex, age, race/ethnicity, education, marital status, and employment status. The prevalence of leisure-time physical inactivity varied substantially across states and survey years. In general, the adjusted prevalence of physical inactivity gradually declined over the past three decades in a majority of states. However, a substantial proportion of American adults remain physically inactive. Among the 50 states and District of Columbia, 45 had over a fifth of their adult population without any leisure-time physical activity, and 8 had over 30% without physical activity in 2015. Moreover, the adjusted prevalence of physical inactivity in several states (Arizona, North Carolina, North Dakota, Utah, West Virginia, and Wyoming) remained largely unchanged or even increased (Minnesota and Ohio) over the study period. Although the prevalence of physical inactivity declined over the past three decades in a majority of states, the rates remain substantially high and vary considerably across states. Closely monitoring and tracking physical activity level using the state physical activity maps can help guide policy and program

  19. Mapping the Prevalence of Physical Inactivity in U.S. States, 1984-2015

    PubMed Central

    Xiang, Xiaoling; Yang, Yan; Yan, Hai

    2016-01-01

    Background Physical inactivity is a leading cause of morbidity, disability and premature mortality in the U.S. and worldwide. This study aimed to map the prevalence of physical inactivity across U.S. states over the past three decades, and estimate the over-time adjusted changes in the prevalence of physical inactivity in each state. Methods Individual-level data (N = 6,701,954) were taken from the 1984–2015 Behavioral Risk Factor Surveillance System (BRFSS), an annually repeated cross-sectional survey of state-representative adult population. Prevalence of self-reported leisure-time physical inactivity was estimated by state and survey year, accounting for the BRFSS sampling design. Logistic regressions were performed to estimate the changes in the prevalence of physical inactivity over the study period for each state, adjusting for individual characteristics including sex, age, race/ethnicity, education, marital status, and employment status. Results The prevalence of leisure-time physical inactivity varied substantially across states and survey years. In general, the adjusted prevalence of physical inactivity gradually declined over the past three decades in a majority of states. However, a substantial proportion of American adults remain physically inactive. Among the 50 states and District of Columbia, 45 had over a fifth of their adult population without any leisure-time physical activity, and 8 had over 30% without physical activity in 2015. Moreover, the adjusted prevalence of physical inactivity in several states (Arizona, North Carolina, North Dakota, Utah, West Virginia, and Wyoming) remained largely unchanged or even increased (Minnesota and Ohio) over the study period. Conclusions Although the prevalence of physical inactivity declined over the past three decades in a majority of states, the rates remain substantially high and vary considerably across states. Closely monitoring and tracking physical activity level using the state physical activity

  20. Reexamination of alcohol dehydrogenase structural mutants in Drosophila using protein blotting

    SciTech Connect

    Hollocher, H.; Place, A.R.

    1987-06-01

    Using protein blotting and an immuno-overlay procedure, the authors have reexamined the cross-reacting material produced by ADH null-activity mutants generated with ethyl methanesulfonate (EMS). Of the 13 mutants, 11 have an immunodetectable polypeptide of wild-type size. The native and urea denatured isoelectric points (pI) establish that 7 of 13 of the mutations have no effect on protein charge. The electrophoretic mobilities of each variant on increasing percent acrylamide gels (Ferguson analysis), reveal that 9 of the 11 immunodetectable mutations have retained the ability form dimers under native conditions. None of the inactive mutant proteins has the ability to form the adduct-bound isozyme. The authors have found no correlation between protein pI and i vivo stability. The observed frequencies of specific charge class alterations do not dispute the propensity of G:A transitions previously found for EMS mutagenesis.

  1. An episomal expression vector for screening mutant gene libraries in Pichia pastoris.

    PubMed

    Lee, Charles C; Williams, Tina G; Wong, Dominic W S; Robertson, George H

    2005-07-01

    Screening mutant gene libraries for isolating improved enzyme variants is a powerful technique that benefits from effective and reliable biological expression systems. Pichia pastoris is a very useful organism to express proteins that are inactive in other hosts such as Escherichia coli and Saccharomyces cerevisiae. However, most P. pastoris expression plasmids are designed to integrate into the host chromosome and hence are not as amenable to high-throughput screening projects. We have designed a P. pastoris expression vector, pBGP1, incorporating an autonomous replication sequence that allows the plasmid to exist as an episomal element. This vector contains the alpha-factor signal sequence to direct secretion of the mutant enzymes. Expression of the genes is driven by the constitutive GAP promoter, thus eliminating the need for timed or cell density-specific inductions. The pBGP1 plasmid was used to screen a xylanase gene library to isolate higher activity mutants.

  2. Positive mood + action = negative mood + inaction: effects of general action and inaction concepts on decisions and performance as a function of affect.

    PubMed

    Albarracin, Dolores; Hart, William

    2011-08-01

    General action and inaction concepts have been shown to produce broad, goal-mediated effects on cognitive and motor activity irrespective of the type of activity. The current research tested a model in which action and inaction goals interact with the valence of incidental moods to guide behavior. Over four experiments, participants' moods were manipulated to be positive (happy), neutral, or negative (angry or sad), and then general action, inaction, and neutral concepts were primed. In Experiment 1, action primes increased intellectual performance when participants experienced a positive (happy) or neutral mood, whereas inaction primes increased performance when participants experienced a negative (angry) mood. Including a control-prime condition, Experiments 2 and 3 replicated these results measuring the number of general interest articles participants were willing to read and participants' memory for pictures of celebrities. Experiment 4 replicated the results comparing happiness with sadness and suggested that the effect of the prime's adoption was automatic. Overall, the findings supported an interactive model by which action concepts and positive affect produce the same increases in active behavior as inaction concepts and negative affect.

  3. Positive Mood + Action = Negative Mood + Inaction: Effects of General Action and Inaction Concepts on Decisions and Performance as a Function of Affect

    PubMed Central

    Albarracin, Dolores; Hart, William

    2013-01-01

    General action and inaction concepts have been shown to produce broad, goal-mediated effects on cognitive and motor activity irrespective of the type of activity. The current research tested a model in which action and inaction goals interact with the valence of incidental moods to guide behavior. Over four experiments, participants’ moods were manipulated to be positive (happy), neutral, or negative (angry or sad), and then general action, inaction, and neutral concepts were primed. In Experiment 1, action primes increased intellectual performance when participants experienced a positive (happy) or neutral mood, whereas inaction primes increased performance when participants experienced a negative (angry) mood. Including a control-prime condition, Experiments 2 and 3 replicated these results measuring the number of general interest articles participants were willing to read and participants’ memory for pictures of celebrities. Experiment 4 replicated the results comparing happiness with sadness and suggested that the effect of the prime’s adoption was automatic. Overall, the findings supported an interactive model by which action concepts and positive affect produce the same increases in active behavior as inaction concepts and negative affect. PMID:21859209

  4. Tetrahymena mutants with short telomeres.

    PubMed Central

    Ahmed, S; Sheng, H; Niu, L; Henderson, E

    1998-01-01

    Telomere length is dynamic in many organisms. Genetic screens that identify mutants with altered telomere lengths are essential if we are to understand how telomere length is regulated in vivo. In Tetrahymena thermophila, telomeres become long at 30 degrees, and growth rate slows. A slow-growing culture with long telomeres is often overgrown by a variant cell type with short telomeres and a rapid-doubling rate. Here we show that this variant cell type with short telomeres is in fact a mutant with a genetic defect in telomere length regulation. One of these telomere growth inhibited forever (tgi) mutants was heterozygous for a telomerase RNA mutation, and this mutant telomerase RNA caused telomere shortening when overexpressed in wild-type cells. Several other tgi mutants were also likely to be heterozygous at their mutant loci, since they reverted to wild type when selective pressure for short telomeres was removed. These results illustrate that telomere length can regulate growth rate in Tetrahymena and that this phenomenon can be exploited to identify genes involved in telomere length regulation. PMID:9755196

  5. Motor-Driven (Passive) Cycling: A Potential Physical Inactivity Countermeasure?

    PubMed Central

    Peterman, James E.; Wright, Kenneth P.; Melanson, Edward L.; Kram, Rodger; Byrnes, William C.

    2016-01-01

    We have previously shown that motor-driven (passive) stationary cycling elevates energy expenditure (EE). Purpose To quantify how acute passive cycling affects glucose and insulin responses to an oral glucose tolerance test (OGTT) and basic cognition compared to sitting and moderate-intensity active cycling. Methods Twenty-four physically inactive healthy males completed three trials in randomized order involving 30-minute conditions of sitting, passive cycling and moderate-intensity cycling. During each condition, EE was measured and participants performed cognitive tests. Following each condition, a 2-hour OGTT was performed. Results EE was significantly higher during the cycling conditions compared to sitting (1.36±0.58 and 6.50±1.73 kcal·min−1 greater than sitting for passive and moderate-intensity, respectively). A significant correlation was found between body fat percentage and post-sitting OGTT 2-h post plasma glucose (r2=0.30, p<0.05) so participants were divided into lean (n=11) and non-lean (n=13) groups. In the non-lean group, compared to sitting, passive cycling lowered 2-h post plasma glucose (7.7±1.3 vs. 6.9±1.6mmol·L−1, respectively, p<0.05) and Matsuda whole body insulin sensitivity index (WBISI) was higher (2.74±0.86 vs. 3.36±1.08, p<0.05). Additionally, passive and moderate-intensity cycling had similar beneficial effects on 2-h post plasma glucose and WBISI. Cognitive performance did not significantly differ between the sitting and passive cycling conditions. Conclusion 2-h post plasma glucose was lower and WBISI following acute passive cycling was higher in non-lean participants. Given that and the increase in EE without changes in cognitive performance, we propose passive cycling as a promising intervention to counteract some of the deleterious effects of prolonged sitting in the workplace. PMID:27054677

  6. Physical Inactivity Differentially Alters Dietary Oleate and Palmitate Trafficking

    PubMed Central

    Bergouignan, Audrey; Trudel, Guy; Simon, Chantal; Chopard, Angèle; Schoeller, Dale A.; Momken, Iman; Votruba, Susanne B.; Desage, Michel; Burdge, Graham C.; Gauquelin-Koch, Guillemette; Normand, Sylvie; Blanc, Stéphane

    2009-01-01

    OBJECTIVE— Obesity and diabetes are characterized by the incapacity to use fat as fuel. We hypothesized that this reduced fat oxidation is secondary to a sedentary lifestyle. RESEARCH DESIGN AND METHODS— We investigated the effect of a 2-month bed rest on the dietary oleate and palmitate trafficking in lean women (control group, n = 8) and the effect of concomitant resistance/aerobic exercise training as a countermeasure (exercise group, n = 8). Trafficking of stable isotope–labeled dietary fats was combined with muscle gene expression and magnetic resonance imaging–derived muscle fat content analyses. RESULTS— In the control group, bed rest increased the cumulative [1-13C]oleate and [d31]palmitate appearance in triglycerides (37%, P = 0.009, and 34%, P = 0.016, respectively) and nonesterified fatty acids (NEFAs) (37%, P = 0.038, and 38%, P = 0.002) and decreased muscle lipoprotein lipase (P = 0.043) and fatty acid translocase CD36 (P = 0.043) mRNA expressions. Plasma NEFA-to-triglyceride ratios for [1-13C]oleate and [d31]palmitate remained unchanged, suggesting that the same proportion of tracers enters the peripheral tissues after bed rest. Bed rest did not affect [1-13C]oleate oxidation but decreased [d31]palmitate oxidation by −8.2 ± 4.9% (P < 0.0001). Despite a decreased spontaneous energy intake and a reduction of 1.9 ± 0.3 kg (P = 0.001) in fat mass, exercise training did not mitigate these alterations but partially maintained fat-free mass, insulin sensitivity, and total lipid oxidation in fasting and fed states. In both groups, muscle fat content increased by 2.7% after bed rest and negatively correlated with the reduction in [d31]palmitate oxidation (r2 = 0.48, P = 0.003). CONCLUSIONS— While saturated and monounsaturated fats have similar plasma trafficking and clearance, physical inactivity affects the partitioning of saturated fats toward storage, likely leading to an accumulation of palmitate in muscle fat. PMID:19017764

  7. Maternal inactivity: 45-year trends in mothers' use of time.

    PubMed

    Archer, Edward; Lavie, Carl J; McDonald, Samantha M; Thomas, Diana M; Hébert, James R; Taverno Ross, Sharon E; McIver, Kerry L; Malina, Robert M; Blair, Steven N

    2013-12-01

    To examine 45-year trends in time use and physical activity energy expenditure (PAEE) in a nationally representative sample of US mothers. We quantified time allocation to physical activity (PA), sedentary behaviors (SED), and PAEE from 1965 to 2010 in mothers with older children (MOC) (>5 to ≤18 years) and mothers with younger children (MYC) (≤5 years). Physical activity was the sum of time allocated to housework, child care, laundry, food preparation, postmeal cleanup, and exercise. Sedentary behavior was the sum of time spent in a vehicle and using screen-based media. Physical activity energy expenditure was calculated using body weights from national surveys and metabolic equivalents. From 1965 to 2010, the time allocated to PA decreased by 11.1 h/wk (from 32.0 to 20.9 h/wk) in MOC and by 13.9 h/wk (from 43.6 to 29.7 h/wk) in MYC. The time spent in SED increased by 7.0 h/wk in MOC (from 17.7 to 24.7 h/wk) and increased by 5.7 h/wk in MYC (from 17.0 to 22.7 h/wk). Physical activity energy expenditure decreased by 1237.6 kcal/wk (176.8 kcal/d) in MOC (from 5835.3 to 4597.7 kcal/wk), and in MYC, PAEE decreased by 1572.5 kcal/wk (224.6 kcal/d), from 7690.5 to 6118.0 kcal/wk. There was a significant reallocation of time by mothers from PA (eg, housework) to SED (eg, watching television) between 1965 and 2010. Given the essential role of PA for health and the potential for the intergenerational transmission of obesity and obesogenic behaviors, these results suggest that maternal inactivity may be an important target for the primary prevention of chronic noncommunicable diseases and obesity. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  8. Physical inactivity among older adults across Europe based on the SHARE database.

    PubMed

    Gomes, Marcos; Figueiredo, Daniela; Teixeira, Laetitia; Poveda, Verónica; Paúl, Constança; Santos-Silva, Alice; Costa, Elísio

    2017-01-20

    Regular physical activity is one of the key components of a healthy lifestyle. It is associated with better physical and cognitive functioning in later life and with increased life expectancy. The purpose of this study was to evaluate the prevalence of, and factors related to, physical inactivity among older adults across Europe. In this cross-sectional analysis, we used data from participants aged 55 or older in Wave 4 of the Survey of Health, Ageing, and Retirement in Europe (SHARE) database, a multidisciplinary and cross-national panel database covering health, socioeconomic status, and social and family networks. Individuals included in this study were classified as physically active or physically inactive. Clinical, psychosocial and sociodemographic variables were evaluated for their association with physical inactivity. From the total of 58,489 individuals in SHARE, we selected 19,298 people age 55 or older (mean age 67.8 ± 8.9 years; 11,430 (59.2%) female). The overall prevalence of inactivity among individuals age 55 or older in the 16 included countries was 12.5%. The prevalence of physical inactivity varied between countries, ranging from 4.9% (Sweden) to 29% (Portugal). Increasing age, depression, physical limitations, poor sense of meaning in life, social support and memory loss were significant variables associated with physical inactivity. Physical inactivity can be explained by physical, cognitive and psychological conditions. Interventions aimed at promoting physical activity among older people are needed to address this diversity of factors.

  9. Influence of physical inactivity in psychophysiological state of breast cancer survivors.

    PubMed

    Ariza-García, A; Galiano-Castillo, N; Cantarero-Villanueva, I; Fernández-Lao, C; Díaz-Rodríguez, L; Arroyo-Morales, M

    2013-11-01

    Physical inactivity has been postulated as mediator of the relationship between cancer-related symptoms and psychoneurobiological alterations. The aim of the study was to evaluate the influence of physical inactivity level on mood state, fitness level as well as on salivary markers of the hypothalamic-pituitary-adrenal axis (cortisol) and the SNS (α-amylase) in breast cancer survivors. One hundred and eight breast cancer survivors (stages I-IIIa) participated in this cross-sectional study. Data were gathered on the following: Minnesota Leisure Time Physical Activity Questionnaire, profile of mood state, 6-min walk test, force handgrip, blood pressure, salivary cortisol concentration and salivary α-amylase activity. For our analysis, two groups were formed based on physical activity level measured as energy expenditure during diary leisure activities of the participants at the moment of the study, a physical inactivity level group (<3 METs × h/week) and an adequate physical activity level group (>3 METs × h/week). Fitness level was significantly higher in the active than the inactive group, while anger, fatigue, depression, confusion, mood disturbance, diastolic blood pressure and salivary α-amylase activity were significantly greater in the inactive than the active group. These results suggest that physical inactivity induces a worse psychoneurobiological state in inactive than in active breast cancer survivors. © 2013 John Wiley & Sons Ltd.

  10. Inactive nurses in Taiwan: human capital, intention to return to hospital nursing, and incentives for returning.

    PubMed

    Yu, Hsing-Yi; Tang, Fu-In; Chen, I-Ju; Yin, Teresa J C; Chen, Chu-Chieh; Yu, Shu

    2016-04-01

    To investigate inactive nurses' human capital, intention to return to hospital nursing and incentives for returning. Few studies have discussed the loss of human capital with regard to inactive nurses and how to attract them to return to clinical work. Systematic random sampling was used, with 328 subjects completing the mailed questionnaires, resulting in a response rate of 25.4%. Inactive nurses not only had moderate to high human capital (average years of nursing experience was 10.29, with moderate to high levels of nursing professional commitment and nursing competence) and were young. Forty-three percent of subjects reported intending to return to hospital nursing. Sufficient nurse staffing, greater safety in the working environment, and re-entry preparation programmes were incentives for returning. Recruiting inactive nurses back to hospital work is vital and feasible as inactive nurses had a moderate to high degree of human capital. The most feasible way is offering reasonable working conditions, in particular, providing sufficient staffing, a safe working environment and re-entry preparation programmes. The findings confirm the human capital of inactive nurses and provide concrete directions for nursing managers to follow when recruiting inactive nurses to hospital nursing. © 2015 John Wiley & Sons Ltd.

  11. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium

    PubMed Central

    Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A.; Hong, Chi-Chen; Sucheston-Campbell, Lara E.; Eng, Kevin H.; Szender, J. Brian; Chang-Claude, Jenny; Schmalfeldt, Barbara; Klapdor, Ruediger; Gower, Emily; Minlikeeva, Albina N.; Zirpoli, Gary; Bandera, Elisa V.; Berchuck, Andrew; Cramer, Daniel; Doherty, Jennifer A.; Edwards, Robert P.; Fridley, Brooke L.; Goode, Ellen L.; Goodman, Marc T.; Hogdall, Estrid; Hosono, Satoyo; Jensen, Allan; Jordan, Susan; Kjaer, Susanne K.; Matsuo, Keitaro; Ness, Roberta B.; Olsen, Catherine M.; Olson, Sara H.; Pearce, Celeste Leigh; Pike, Malcolm C.; Rossing, Mary Anne; Szamreta, Elizabeth A.; Thompson, Pamela J.; Tseng, Chiu-Chen; Vierkant, Robert A.; Webb, Penelope M.; Wentzensen, Nicolas; Wicklund, Kristine G.; Winham, Stacey J.; Wu, Anna H.; Modugno, Francesmary; Schildkraut, Joellen M.; Terry, Kathryn L.; Kelemen, Linda E.; Moysich, Kirsten B.

    2016-01-01

    Background Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium (OCAC) to investigate the association between chronic recreational physical inactivity and EOC risk. Methods In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race and body mass index (BMI). Results The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR=1.34, 95% CI: 1.14-1.57) and similar associations were observed for each histotype. Conclusions In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. Impact These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. PMID:27197285

  12. Prevalence of Irritable Bowel Syndrome–like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease

    PubMed Central

    Tomita, Toshihiko; Kato, Yu; Takimoto, Mayu; Yamasaki, Takahisa; Kondo, Takashi; Kono, Tomoaki; Tozawa, Katsuyuki; Yokoyama, Yoko; Ikehara, Hisatomo; Ohda, Yoshio; Oshima, Tadayuki; Fukui, Hirokazu; Tanaka, Shigemi; Shima, Masayuki; Watari, Jiro; Miwa, Hiroto

    2016-01-01

    Background/Aims Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. Methods IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. Results IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. Conclusions The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients. PMID:27193973

  13. Watch and Wait Management of Inactive Cystic Echinococcosis – Does the Path to Inactivity Matter – Analysis of a Prospective Patient Cohort

    PubMed Central

    Stojkovic, Marija; Rosenberger, Kerstin Daniela; Steudle, Franziska; Junghanss, Thomas

    2016-01-01

    Background Overdiagnosis and overtreatment are rarely discussed in the context of NTDs despite their relevance for patients under the care of health services with limited resources where the risks of therapy induced complications are often disproportionate to the benefit. The advantages of cyst staging-based management of patients with cystic echinococcosis (CE) are not yet fully explored. Questions are: Do inactive cysts (CE 4 and CE 5) need treatment and is there a difference between cysts which reach CE4 and CE5 naturally or by benzimidazole therapy? Methodology/Principal findings Analysis of long-term follow-up data from a prospective CE patient cohort of 223 patients of a national clinical center for echinococcosis. The event of interest “relapse” was defined as the reversal of a cyst from an inactive stage (CE4, CE5) back to an active stage. The watch &wait (ww) group included 30 patients with 46 inactive cysts who never received medical treatment. The benzimidazole-treated (med) group included 15 patients with 17 cysts. There was no relapse in the ww-group whereas 8/17 cysts showed relapse within 18 months after treatment in the med-group. Loss to follow-up was 15.5%. Conclusions Data from the watch & wait group impressively show how stable naturally inactivated cysts are in contrast to cysts which reach inactivity through treatment with benzimidazoles. A substantial proportion of patients can be spared from treatment through cyst staging. Cysts which inactivated through a natural course do not relapse with very high likelihood. We recommend follow up of 5 years to confirm the stability of the inactive stage. Cysts driven into inactivity through benzimidazole therapy instead need careful monitoring to identify those which reactivate (around 50% within 18 months). 5 years follow-up appears safe to make a final decision on the need for further monitoring. PMID:27992434

  14. Paradoxical gain-of-function mutant of the G-protein-coupled receptor PROKR2 promotes early puberty.

    PubMed

    Fukami, Maki; Suzuki, Erina; Izumi, Yoko; Torii, Tomohiro; Narumi, Satoshi; Igarashi, Maki; Miyado, Mami; Katsumi, Momori; Fujisawa, Yasuko; Nakabayashi, Kazuhiko; Hata, Kenichiro; Umezawa, Akihiro; Matsubara, Yoichi; Yamauchi, Junji; Ogata, Tsutomu

    2017-03-24

    The human genome encodes ~750 G-protein-coupled receptors (GPCRs), including prokineticin receptor 2 (PROKR2) involved in the regulation of sexual maturation. Previously reported pathogenic gain-of-function mutations of GPCR genes invariably encoded aberrant receptors with excessive signal transduction activity. Although in vitro assays demonstrated that an artificially created inactive mutant of PROKR2 exerted paradoxical gain-of-function effects when co-transfected with wild-type proteins, such a phenomenon has not been observed in vivo. Here, we report a heterozygous frameshift mutation of PROKR2 identified in a 3.5-year-old girl with central precocious puberty. The mutant mRNA escaped nonsense-mediated decay and generated a GPCR lacking two transmembrane domains and the carboxyl-terminal tail. The mutant protein had no in vitro signal transduction activity; however, cells co-expressing the mutant and wild-type PROKR2 exhibited markedly exaggerated ligand-induced Ca(2+) responses. The results indicate that certain inactive PROKR2 mutants can cause early puberty by enhancing the functional property of coexisting wild-type proteins. Considering the structural similarity among GPCRs, this paradoxical gain-of-function mechanism may underlie various human disorders.

  15. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036

    PubMed Central

    Chan, Wayne W.; Wise, Scott C.; Kaufman, Michael D.; Ahn, Yu Mi; Ensinger, Carol L.; Haack, Torsten; Hood, Molly M.; Jones, Jennifer; Lord, John W.; Lu, Wei Ping; Miller, David; Patt, William C.; Smith, Bryan D.; Petillo, Peter A.; Rutkoski, Thomas J.; Telikepalli, Hanumaiah; Vogeti, Lakshminarayana; Yao, Tony; Chun, Lawrence; Clark, Robin; Evangelista, Peter; Gavrilescu, L. Cristina; Lazarides, Katherine; Zaleskas, Virginia M.; Stewart, Lance J.; Van Etten, Richard A.; Flynn, Daniel L.

    2011-01-01

    Summary Acquired resistance to ABL1 tyrosine kinase inhibitors (TKIs) through ABL1 kinase domain mutations, particularly the gatekeeper mutant T315I, is a significant problem for chronic myeloid leukemia (CML) patients. Using structure-based drug design, we developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. The lead “switch-control” inhibitor, DCC-2036, potently inhibits both unphosphorylated and phosphorylated ABL1 by inducing a type II inactive conformation, and retains efficacy against the majority of clinically relevant CML resistance mutants, including T315I. DCC-2036 inhibits BCR-ABL1T315I-expressing cell lines, prolongs survival in mouse models of T315I-mutant CML and B-lymphoblastic leukemia, and inhibits primary patient leukemia cells expressing T315I in vitro and in vivo, supporting its clinical development in TKI-resistant Ph+ leukemia. PMID:21481795

  16. Costameric proteins in human skeletal muscle during muscular inactivity

    PubMed Central

    Anastasi, Giuseppe; Cutroneo, Giuseppina; Santoro, Giuseppe; Arco, Alba; Rizzo, Giuseppina; Bramanti, Placido; Rinaldi, Carmen; Sidoti, Antonina; Amato, Aldo; Favaloro, Angelo

    2008-01-01

    normal, or slightly increased, compared with that in normal skeletal muscle fibres. We also observed a lower level of α7B- and β1D-integrin mRNA and a normal, or slightly higher than normal, level of α7A-integrin mRNA in the skeletal muscle fibres of the patients with sensitive-motor polyneuropathy, compared with those in the skeletal muscle of normal patients. Additionally, transmission electron microscopy of transverse sections of skeletal muscle fibres indicated that the normal muscle fibre architecture was disrupted, with no myosin present inside the actin hexagons. Based on our results, we hypothesize that skeletal muscle inactivity, such as that found after denervation, could result in a reorganization of the costameres, with α7B-integrin being replaced by α7A-integrin. In this way, the viability of the skeletal muscle fibre is maintained. It will be interesting to clarify, by future experimentation, the mechanisms that lead to the down-regulation of integrins and agrin in muscular dystrophies. PMID:18537849

  17. Using a novel environmental quality measure to understand population-level physical inactivity

    EPA Science Inventory

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Understanding the role of the overall ambient environment in population inactivi...

  18. Patterns of association between environmental quality and physical inactivity vary across the rural-urban continuum

    EPA Science Inventory

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Many studies have shown associations between specific environmental features (la...

  19. A new light on DNA replication from the inactive X chromosome.

    PubMed

    Aladjem, Mirit I; Fu, Haiqing

    2014-06-01

    While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, "silent" chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular.

  20. Increasing and decreasing motor and cognitive output: a model of general action and inaction goals.

    PubMed

    Albarracín, Dolores; Handley, Ian M; Noguchi, Kenji; McCulloch, Kathleen C; Li, Hong; Leeper, Joshua; Brown, Rick D; Earl, Allison; Hart, William P

    2008-09-01

    General action and inaction goals can influence the amount of motor or cognitive output irrespective of the type of behavior in question, with the same stimuli producing trivial and important motor and cognitive manifestations normally viewed as parts of different systems. A series of experiments examined the effects of instilling general action and inaction goals using word primes, such as "action" and "rest." The first 5 experiments showed that the same stimuli influenced motor output, such as doodling on a piece of paper and eating, as well as cognitive output, such as recall and problem solving. The last 2 experiments supported the prediction that these diverse effects can result from the instigation of general action and inaction goals. Specifically, these last 2 studies confirmed that participants were motivated to achieve active or inactive states and that attaining them decreased the effects of the primes on behavior.

  1. General Action and Inaction Goals: Their Behavioral, Cognitive, and Affective Origins and Influences.

    PubMed

    Albarracin, Dolores; Hepler, Justin; Tannenbaum, Melanie

    2011-04-01

    Since the 1970s, researchers on motivation and behavior have taken the stance that important human behaviors are determined by specific attitudes, intentions, and goals. In the present article, we review evidence suggesting that, in addition to specific motivational constructs, general goals of action and inaction are also vital determinants of many important human behaviors. This research examines the effects of these goals on motor behavior, cognitive performance, and political participation. Furthermore, we connect these general action and inaction goals with other important areas in psychology, including affect, approach/avoidance, energization, material resources, mindsets, and power. Finally, we conclude with a discussion of individual and regional/cultural differences in action and inaction. Overall, general goals for action and inaction are shown to influence a vast array of important behaviors, suggesting that in addition to considering specific attitudes, intentions, and goals, researchers may gain important insight into human behavior by considering general motivations.

  2. General Action and Inaction Goals: Their Behavioral, Cognitive, and Affective Origins and Influences

    PubMed Central

    Albarracin, Dolores; Hepler, Justin; Tannenbaum, Melanie

    2013-01-01

    Since the 1970s, researchers on motivation and behavior have taken the stance that important human behaviors are determined by specific attitudes, intentions, and goals. In the present article, we review evidence suggesting that, in addition to specific motivational constructs, general goals of action and inaction are also vital determinants of many important human behaviors. This research examines the effects of these goals on motor behavior, cognitive performance, and political participation. Furthermore, we connect these general action and inaction goals with other important areas in psychology, including affect, approach/avoidance, energization, material resources, mindsets, and power. Finally, we conclude with a discussion of individual and regional/cultural differences in action and inaction. Overall, general goals for action and inaction are shown to influence a vast array of important behaviors, suggesting that in addition to considering specific attitudes, intentions, and goals, researchers may gain important insight into human behavior by considering general motivations. PMID:23766569

  3. Being Active and Impulsive: The Role of Goals for Action and Inaction in Self-Control

    PubMed Central

    Hepler, Justin; Albarracin, Dolores; McCulloch, Kathleen C.; Noguchi, Kenji

    2013-01-01

    Although self-control often requires behavioral inaction (i.e., not eating a piece of cake), the process of inhibiting impulsive behavior is commonly characterized as cognitively active (i.e., actively exerting self-control). Two experiments examined whether motivation for action or inaction facilitates self-control behavior in the presence of tempting stimuli. Experiment 1 used a delay discounting task to assess the ability to delay gratification with respect to money. Experiment 2 used a Go/No-Go task to assess the ability to inhibit a dominant but incorrect motor response to the words “condom” and “sex”. The results demonstrate that goals for inaction promote self-control, whereas goals for action promote impulsive behavior. These findings are discussed in light of recent evidence suggesting that goals for action and inaction modulate physiological resources that promote behavioral execution. PMID:23766548

  4. Being Active and Impulsive: The Role of Goals for Action and Inaction in Self-Control.

    PubMed

    Hepler, Justin; Albarracin, Dolores; McCulloch, Kathleen C; Noguchi, Kenji

    2012-12-01

    Although self-control often requires behavioral inaction (i.e., not eating a piece of cake), the process of inhibiting impulsive behavior is commonly characterized as cognitively active (i.e., actively exerting self-control). Two experiments examined whether motivation for action or inaction facilitates self-control behavior in the presence of tempting stimuli. Experiment 1 used a delay discounting task to assess the ability to delay gratification with respect to money. Experiment 2 used a Go/No-Go task to assess the ability to inhibit a dominant but incorrect motor response to the words "condom" and "sex". The results demonstrate that goals for inaction promote self-control, whereas goals for action promote impulsive behavior. These findings are discussed in light of recent evidence suggesting that goals for action and inaction modulate physiological resources that promote behavioral execution.

  5. 37 CFR 11.19 - Disciplinary jurisdiction; Jurisdiction to transfer to disability inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactive status. (1) Grounds for discipline include: (i) Conviction of a serious crime; (ii) Discipline on... appearing before any Federal program or agency; (iii) Failure to comply with any order of a Court...

  6. Increasing and Decreasing Motor and Cognitive Output: A Model of General Action and Inaction Goals

    PubMed Central

    Albarracín, Dolores; Handley, Ian M.; Noguchi, Kenji; McCulloch, Kathleen C.; Li, Hong; Leeper, Joshua; Brown, Rick D.; Earl, Allison; Hart, William P.

    2013-01-01

    General action and inaction goals can influence the amount of motor or cognitive output irrespective of the type of behavior in question, with the same stimuli producing trivial and important motor and cognitive manifestations normally viewed as parts of different systems. A series of experiments examined the effects of instilling general action and inaction goals using word primes, such as “action” and “rest.” The first 5 experiments showed that the same stimuli influenced motor output, such as doodling on a piece of paper and eating, as well as cognitive output, such as recall and problem solving. The last 2 experiments supported the prediction that these diverse effects can result from the instigation of general action and inaction goals. Specifically, these last 2 studies confirmed that participants were motivated to achieve active or inactive states and that attaining them decreased the effects of the primes on behavior. PMID:18729691

  7. Evidence for a chemoautotrophically based food web at inactive hydrothermal vents (Manus Basin)

    NASA Astrophysics Data System (ADS)

    Erickson, K. L.; Macko, S. A.; Van Dover, C. L.

    2009-09-01

    Hydrothermal vents are ephemeral systems. When venting shuts down, sulfide-dependent taxa die off, and non-vent taxa can colonize the hard substrata. In Manus Basin (Papua New Guinea), where hydrothermally active and inactive sites are interspersed, hydroids, cladorhizid sponges, barnacles, bamboo corals, and other invertebrate types may occupy inactive sites. Carbon and nitrogen isotopic compositions of animals occupying inactive sites are consistent with nutritional dependence on either chemoautotrophically or photosynthetically produced organic material, but sulfur isotopic compositions of these animals point to a chemoautotrophic source of sulfur from dissolved sulfide in vent fluids rather than sulfur derived from seawater sulfate through photosynthesis. Given that suspension-feeding and micro-carnivorous invertebrates are the biomass dominants at inactive sites, the primary source of chemoautotrophic nutrition is likely suspended particulates and organisms delivered from nearby active vents.

  8. Evidence for a Chemoautotrophically Based Food Web at Inactive Hydrothermal Vents (Manus Basin)

    NASA Astrophysics Data System (ADS)

    van Dover, C. L.; Erickson, K.; Macko, S.

    2008-12-01

    Hydrothermal vents are ephemeral systems. When venting shuts down, sulfide-dependent taxa die off, and non-vent taxa can colonize the hard substrata. In Manus Basin (Papua New Guinea), where active and inactive sulfide mounds are interspersed, hydroids, cladorhizid sponges, barnacles, and bamboo sponges, and other invertebrate types may occupy inactive sulfide mounds. Carbon and nitrogen isotopic compositions of animals occupying inactive sulfide mounds are consistent with nutritional dependence on either chemoautotrophically or photosynthetically produced organic material, but sulfur isotopic compositions of these animals point to a chemoautotrophic source of sulfur from dissolved sulfide in vent fluids rather than sulfur derived from seawater sulfate through photosynthesis. Given that suspension-feeding and micro- carnivorous invertebrates are the biomass dominants at inactive sulfide mounds, the primary source of chemoautotrophic nutrition is likely suspended particulates and organisms delivered from nearby active vents.

  9. Patterns of association between environmental quality and physical inactivity vary across the rural-urban continuum

    EPA Science Inventory

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Many studies have shown associations between specific environmental features (la...

  10. Using a novel environmental quality measure to understand population-level physical inactivity

    EPA Science Inventory

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Understanding the role of the overall ambient environment in population inactivi...

  11. Are U.S. Teens Now as Inactive as 60-Year-Olds?

    MedlinePlus

    ... news/fullstory_166666.html Are U.S. Teens Now as Inactive as 60-Year-Olds? The lack of exercise more ... Here's some compelling evidence that Americans have become a sedentary bunch: Research suggests that the average teen ...

  12. SEMINAR PUBLICATION: MANAGING ENVIRONMENTAL PROBLEMS AT INACTIVE AND ABANDONED METALS MINE SITES

    EPA Science Inventory

    Environmental problems associated with abandoned and inactive mines are addressed along with some approaches to resolving those problems, including case studies demonstrating technologies that have worked. New technologies being investigated are addressed also.

  13. Labeling of human clots in vitro with an active-site mutant of t-PA

    SciTech Connect

    Fry, E.T.; Mack, D.L.; Monge, J.C.; Billadello, J.J.; Sobel, B.E. )

    1990-02-01

    Prompt detection of acute thrombosis and its response to treatment with thrombolytic agents generally require angiography. Scintigraphic approaches with labeled antibodies to or components of the coagulation and fibrinolytic systems have been disappointing because of prolonged circulating half-lives of tracers and relatively slow or limited binding to thrombi. Accordingly, we developed and characterized a thrombolytically inactive, active-site mutant (Ser-478----Thr) of tissue-type plasminogen activator (t-PA) designed to detect thrombi in vivo. Binding of iodine-125-({sup 125}I) labeled Ser----Thr t-PA to thrombi in vitro was time- and concentration-dependent, and specific judging from inhibition by pre-incubation with anti-t-PA IgG. Clearance of 125I-labeled mutant t-PA in rabbits was rapid and biexponential (alpha t1/2 = 1.9 +/- 0.4 min, beta t1/2 = 39.8 +/- 11.2 min). Thus, the amidolytically inactive mutant of t-PA designed binds rapidly and specifically to human thrombi in vitro and is cleared rapidly from the circulation in vivo--properties rendering it attractive as a potentially useful clot imaging agent.

  14. The economic burden of physical inactivity: a global analysis of major non-communicable diseases.

    PubMed

    Ding, Ding; Lawson, Kenny D; Kolbe-Alexander, Tracy L; Finkelstein, Eric A; Katzmarzyk, Peter T; van Mechelen, Willem; Pratt, Michael

    2016-09-24

    The pandemic of physical inactivity is associated with a range of chronic diseases and early deaths. Despite the well documented disease burden, the economic burden of physical inactivity remains unquantified at the global level. A better understanding of the economic burden could help to inform resource prioritisation and motivate efforts to increase levels of physical activity worldwide. Direct health-care costs, productivity losses, and disability-adjusted life-years (DALYs) attributable to physical inactivity were estimated with standardised methods and the best data available for 142 countries, representing 93·2% of the world's population. Direct health-care costs and DALYs were estimated for coronary heart disease, stroke, type 2 diabetes, breast cancer, and colon cancer attributable to physical inactivity. Productivity losses were estimated with a friction cost approach for physical inactivity related mortality. Analyses were based on national physical inactivity prevalence from available countries, and adjusted population attributable fractions (PAFs) associated with physical inactivity for each disease outcome and all-cause mortality. Conservatively estimated, physical inactivity cost health-care systems international $ (INT$) 53·8 billion worldwide in 2013, of which $31·2 billion was paid by the public sector, $12·9 billion by the private sector, and $9·7 billion by households. In addition, physical inactivity related deaths contribute to $13·7 billion in productivity losses, and physical inactivity was responsible for 13·4 million DALYs worldwide. High-income countries bear a larger proportion of economic burden (80·8% of health-care costs and 60·4% of indirect costs), whereas low-income and middle-income countries have a larger proportion of the disease burden (75·0% of DALYs). Sensitivity analyses based on less conservative assumptions led to much higher estimates. In addition to morbidity and premature mortality, physical inactivity is

  15. Oxidative Weathering and Microbial Diversity of an Inactive Seafloor Hydrothermal Sulfide Chimney.

    PubMed

    Li, Jiangtao; Cui, Jiamei; Yang, Qunhui; Cui, Guojie; Wei, Bingbing; Wu, Zijun; Wang, Yong; Zhou, Huaiyang

    2017-01-01

    When its hydrothermal supply ceases, hydrothermal sulfide chimneys become inactive and commonly experience oxidative weathering on the seafloor. However, little is known about the oxidative weathering of inactive sulfide chimneys, nor about associated microbial community structures and their succession during this weathering process. In this work, an inactive sulfide chimney and a young chimney in the early sulfate stage of formation were collected from the Main Endeavor Field of the Juan de Fuca Ridge. To assess oxidative weathering, the ultrastructures of secondary alteration products accumulating on the chimney surface were examined and the presence of possible Fe-oxidizing bacteria (FeOB) was investigated. The results of ultrastructure observation revealed that FeOB-associated ultrastructures with indicative morphologies were abundantly present. Iron oxidizers primarily consisted of members closely related to Gallionella spp. and Mariprofundus spp., indicating Fe-oxidizing species likely promote the oxidative weathering of inactive sulfide chimneys. Abiotic accumulation of Fe-rich substances further indicates that oxidative weathering is a complex, dynamic process, alternately controlled by FeOB and by abiotic oxidization. Although hydrothermal fluid flow had ceased, inactive chimneys still accommodate an abundant and diverse microbiome whose microbial composition and metabolic potential dramatically differ from their counterparts at active vents. Bacterial lineages within current inactive chimney are dominated by members of α-, δ-, and γ-Proteobacteria and they are deduced to be closely involved in a diverse set of geochemical processes including iron oxidation, nitrogen fixation, ammonia oxidation and denitrification. At last, by examining microbial communities within hydrothermal chimneys at different formation stages, a general microbial community succession can be deduced from early formation stages of a sulfate chimney to actively mature sulfide

  16. Oxidative Weathering and Microbial Diversity of an Inactive Seafloor Hydrothermal Sulfide Chimney

    PubMed Central

    Li, Jiangtao; Cui, Jiamei; Yang, Qunhui; Cui, Guojie; Wei, Bingbing; Wu, Zijun; Wang, Yong; Zhou, Huaiyang

    2017-01-01

    When its hydrothermal supply ceases, hydrothermal sulfide chimneys become inactive and commonly experience oxidative weathering on the seafloor. However, little is known about the oxidative weathering of inactive sulfide chimneys, nor about associated microbial community structures and their succession during this weathering process. In this work, an inactive sulfide chimney and a young chimney in the early sulfate stage of formation were collected from the Main Endeavor Field of the Juan de Fuca Ridge. To assess oxidative weathering, the ultrastructures of secondary alteration products accumulating on the chimney surface were examined and the presence of possible Fe-oxidizing bacteria (FeOB) was investigated. The results of ultrastructure observation revealed that FeOB-associated ultrastructures with indicative morphologies were abundantly present. Iron oxidizers primarily consisted of members closely related to Gallionella spp. and Mariprofundus spp., indicating Fe-oxidizing species likely promote the oxidative weathering of inactive sulfide chimneys. Abiotic accumulation of Fe-rich substances further indicates that oxidative weathering is a complex, dynamic process, alternately controlled by FeOB and by abiotic oxidization. Although hydrothermal fluid flow had ceased, inactive chimneys still accommodate an abundant and diverse microbiome whose microbial composition and metabolic potential dramatically differ from their counterparts at active vents. Bacterial lineages within current inactive chimney are dominated by members of α-, δ-, and γ-Proteobacteria and they are deduced to be closely involved in a diverse set of geochemical processes including iron oxidation, nitrogen fixation, ammonia oxidation and denitrification. At last, by examining microbial communities within hydrothermal chimneys at different formation stages, a general microbial community succession can be deduced from early formation stages of a sulfate chimney to actively mature sulfide

  17. Light saturation response of inactive photosystem II reaction centers in spinach.

    PubMed

    Chylla, R A; Whitmarsh, J

    1990-07-01

    The effective absorption cross section of inactive photosystem II (PS II) centers, which is the product of the effective antenna size and the quantum yield for photochemistry, was investigated by comparing the light saturation curves of inactive PS II and active reaction centers in intact chloroplasts and thylakoid membranes of spinach (Spinacia oleracea). Inactive PS II centers are defined as the impaired PS II reaction centers that require greater than 50 ms for the reoxidation of QA (-) subsequent to a single turnover flash. Active reaction centers are defined as the rapidly turning over PS II centers (recovery time less than 50 ms) and all of the PS I centers. The electrochromic shift, measured by the flash-induced absorbance increase at 518 nm, was used to probe the activity of the reaction centers. Light saturation curves were generated for inactive PS II centers and active reaction centers by measuring the extent of the absorbance increase at 518 nm induced by red actinic flashes of variable energy. The light saturation curves show that inactive PS II centers required over twice as many photons as active reaction centers to achieve the same yield. The ratio of the flash energy required for 50% saturation for active reaction centers (PS II active + PS I) compared to inactive PS II centers was 0.45±0.04 in intact chloroplasts, and 0.54±0.11 in thylakoid membranes. Analysis of the light saturation curves using a Poisson statistical model in which the ratio of the antenna size of active PS II centers to that of PS I is considered to range from 1 to 1.5, indicates that the effective absorption cross section of inactive PS II centers was 0.54-0.37 times that of active PS II centers. If the quantum yield for photochemistry is assumed to be one, we estimate that the antenna system serving the inactive PS II centers contains approx. 110 chlorophyll molecules.

  18. Prevalence and Correlates of Physical Inactivity among Older Adults in Rio Grande do Sul, Brazil

    PubMed Central

    Souza, Adelle M. R.; Fillenbaum, Gerda G.; Blay, Sergio L.

    2015-01-01

    Background Current information on the epidemiology of physical inactivity among older adults is lacking, making it difficult to target the inactive and to plan for interventions to ameliorate adverse effects. Objectives To present statewide representative findings on the prevalence of physical inactivity among older community residents, its correlates and associated health service use. Methods A representative non-institutionalized random sample of 6963 individuals in Rio Grande do Sul, Brazil, aged ≥60 years, was interviewed face-to-face. Information was obtained on demographic characteristics, social resources, health conditions and behaviors, health service use, and physical inactivity. Controlled logistic regression was used to determine the association of physical inactivity with these characteristics. Results Overall, 62% reported no regular physical activity. Physical inactivity was significantly more prevalent among women, older persons, those with lower education and income, Afro-Brazilians (73%; White: 61%; “other”: 64%), those no longer married, and was associated with multiple individual health conditions and impaired activities of daily living (ADL). In adjusted analyses, associations remained for sociodemographic characteristics, social participation, impaired self-rated health, ADL, vision, and depression (odds ratios (OR) 1.2–1.7). Physically inactive respondents were less likely to report outpatient visits (OR 0.81), but more likely to be hospitalized (OR 1.41). Conclusions Physical inactivity is highly prevalent, particularly among Afro -Brazilians. It is associated with adverse sociodemographic characteristics; lack of social interaction; and poor self-rated health, ADL, vision, and depression; although not with other health conditions. Self-care may be neglected, resulting in hospitalization. PMID:25700161

  19. Reduced chlorophyll biosynthesis in heterozygous barley magnesium chelatase mutants.

    PubMed

    Braumann, Ilka; Stein, Nils; Hansson, Mats

    2014-05-01

    Chlorophyll biosynthesis is initiated by magnesium chelatase, an enzyme composed of three proteins, which catalyzes the insertion of Mg2+ into protoporphyrin IX to produce Mg-protoporphyrin IX. In barley (Hordeum vulgare L.) the three proteins are encoded by Xantha-f, Xantha-g and Xantha-h. Two of the gene products, XanH and XanG, belong to the structurally conserved family of AAA+ proteins (ATPases associated with various cellular activities) and form a complex involving six subunits of each protein. The complex functions as an ATP-fueled motor of the magnesium chelatase that uses XanF as substrate, which is the catalytic subunit responsible for the insertion of Mg2+ into protoporphyrin IX. Previous studies have shown that semi-dominant Xantha-h mutations result in non-functional XanH subunits that participate in the formation of inactive AAA complexes. In the present study, we identify severe mutations in the barley mutants xantha-h.38, -h.56 and -h.57. A truncated form of the protein is seen in xantha-h.38, whereas no XanH is detected in xantha-h.56 and -h.57. Heterozygous mutants show a reduction in chlorophyll content by 14-18% suggesting a slight semi-dominance of xantha-h.38, -h.56 and -h.57, which otherwise have been regarded as recessive mutations.

  20. A mutant O-GlcNAcase enriches Drosophila developmental regulators.

    PubMed

    Selvan, Nithya; Williamson, Ritchie; Mariappa, Daniel; Campbell, David G; Gourlay, Robert; Ferenbach, Andrew T; Aristotelous, Tonia; Hopkins-Navratilova, Iva; Trost, Matthias; van Aalten, Daan M F

    2017-08-01

    Protein O-GlcNAcylation is a reversible post-translational modification of serines and threonines on nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is essential for early embryogenesis. The Drosophila melanogaster gene supersex combs (sxc), which encodes OGT, is a polycomb gene, whose null mutants display homeotic transformations and die at the pharate adult stage. However, the identities of the O-GlcNAcylated proteins involved and the underlying mechanisms linking these phenotypes to embryonic development are poorly understood. Identification of O-GlcNAcylated proteins from biological samples is hampered by the low stoichiometry of this modification and by limited enrichment tools. Using a catalytically inactive bacterial O-GlcNAcase mutant as a substrate trap, we have enriched the O-GlcNAc proteome of the developing Drosophila embryo, identifying, among others, known regulators of Hox genes as candidate conveyors of OGT function during embryonic development.

  1. Effect of CCS on the Accumulation of FALS SOD1 Mutant-containing Aggregates and on Mitochondrial Translocation of SOD1 Mutants: Implication of a Free Radical Hypothesis

    PubMed Central

    Kim, Ha Kun; Chung, Youn Wook; Chock, P. Boon; Yim, Moon B.

    2011-01-01

    Missense mutations of SOD1 are linked to familial amyotrophic lateral sclerosis (FALS) through a yet-to-be identified toxic-gain-of-function. One of the proposed mechanisms involves enhanced aggregate formation. However, a recent study showed that dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated FALS symptoms with enhanced mitochondrial pathology compared to G93A mice. Using a dicistronic mRNA to simultaneously generate hSOD1 mutants, G93A, A4V and G85R, and hCCS in AAV293 cells, we revealed: (i) CCS is degraded primarily via a macroautophagy pathway. It forms a stable heterodimer with inactive G85R, and via its novel copper chaperone-independent molecular chaperone activity facilitates G85R degradation via a macroautophagy-mediated pathway. For active G93A and A4V, CCS catalyzes their maturation to form active and soluble homodimers. (ii) CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H2O2, mitochondrial translocation of inactive SOD1 mutants. These results, together with previous reports showing FALS SOD1 mutants enhanced free radical-generating activity, provide a mechanistic explanation for the observations with G93A/CCS dual transgenic mice and suggest that free radical generation by FALS SOD1, enhanced by CCS, may, in part, be responsible for the FALS SOD1 mutant-linked aggregation, mitochondrial translocation, and degradation. PMID:21354101

  2. Effect of CCS on the accumulation of FALS SOD1 mutant-containing aggregates and on mitochondrial translocation of SOD1 mutants: implication of a free radical hypothesis.

    PubMed

    Kim, Ha Kun; Chung, Youn Wook; Chock, P Boon; Yim, Moon B

    2011-05-15

    Missense mutations of SOD1 are linked to familial amyotrophic lateral sclerosis (FALS) through a yet-to-be identified toxic-gain-of-function. One of the proposed mechanisms involves enhanced aggregate formation. However, a recent study showed that dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated FALS symptoms with enhanced mitochondrial pathology compared to G93A mice. Using a dicistronic mRNA to simultaneously generate hSOD1 mutants, G93A, A4V and G85R, and hCCS in AAV293 cells, we revealed: (i) CCS is degraded primarily via a macroautophagy pathway. It forms a stable heterodimer with inactive G85R, and via its novel copper chaperone-independent molecular chaperone activity facilitates G85R degradation via a macroautophagy-mediated pathway. For active G93A and A4V, CCS catalyzes their maturation to form active and soluble homodimers. (ii) CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H(2)O(2), mitochondrial translocation of inactive SOD1 mutants. These results, together with previous reports showing FALS SOD1 mutants enhanced free radical-generating activity, provide a mechanistic explanation for the observations with G93A/CCS dual transgenic mice and suggest that free radical generation by FALS SOD1, enhanced by CCS, may, in part, be responsible for the FALS SOD1 mutant-linked aggregation, mitochondrial translocation, and degradation. Published by Elsevier Inc.

  3. [Physical inactivity and associated factors in adults, São Paulo, Brazil].

    PubMed

    Zanchetta, Luane Margarete; Barros, Marilisa Berti de Azevedo; César, Chester Luiz Galvão; Carandina, Luana; Goldbaum, Moisés; Alves, Maria Cecília Goi Porto

    2010-09-01

    To analyze the prevalence of overall and leisure time physical inactivity and associated factors and types of exercises or sports modalities according to schooling in 2,050 adults from 18 to 59 years of age - state of São Paulo, Brazil. Population-based cross-sectional study with a stratified sample of clusters performed in multiple stages. Physical inactivity was determined using the short version of the International Physical Activity Questionnaire - IPAQ and by a question on the regular practice of leisure time physical activity. Data analysis took the sample design into account. Prevalence of physical inactivity during leisure was higher among women. Poisson multiple regression model in man indicated that overall sedentarism was lower among single and separated men, students and without car in the household. Leisure physical inactivity was greater among men over forty years, among those with less schooling and full-time students. Overall physical inactivity was more prevalent among woman with more schooling, with less qualified occupations and widows. Leisure physical inactivity decreased with age and schooling. Among modalities practiced for leisure, walking was more prevalent among women and football was more prevalent among men. Most modalities were directly associated with schooling; approximately 25% of the individuals with more than 12 years of schooling practiced walking. These results suggest that interventions and public policies to promote physical activity should consider differences in gender and socioeconomic status as well as the preferences for different modalities and the context in which the physical activity is practiced.

  4. Ocular surface characteristics and impression cytology in patients with active versus inactive Thyroid Eye Disease.

    PubMed

    Xu, Nuo; Huang, Danping; Yang, Huasheng; Lai, Zhaoguang; Luo, Quan

    2012-06-01

    To compare the clinical findings, tear film function and impression cytology between patients with active and inactive Thyroid Eye Disease (TED). A total of 56 patients with TED and 30 controls were recruited in this prospective observational cohort study. TED patients were divided into active TED and inactive TED types according to a seven-point modified formulation of the Clinical Activity Score (CAS). All participants underwent full eye examinations including Ocular Surface Disease Index (OSDI) score, tear film break-up time (TBUT), fluorescein staining and Schirmer I test. Thirty nine patients with thyroid-associated orbitopathy (TAO) received Nelson's grade with conjunctival impression cytology. Proptosis, palpebral fissure width and lagophthalmos were assessed. Ocular surface parameters including proptosis, palpebral fissure width and lagophthalmos did not differ between active and inactive TED patients (P>0.05). Both active and inactive TED patients obtained higher fluorescein staining scores, lower TBUT scores and significantly lower Schirmer test scores than those of controls (P<0.001 for all). Additionally, the TBUT score was significantly lower and the OSDI score significantly higher in the active TED group compared with those in the inactive TED group (P<0.001 for both). Impression cytology revealed a higher proportion of grade 2-3 changes in the active TED group compared with the inactive TED group (P<0.001). Orbital inflammation in TED patients may lead to decreased tear film stability and ocular surface squamous metaplasia.

  5. The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer

    PubMed Central

    Chaligné, Ronan; Popova, Tatiana; Mendoza-Parra, Marco-Antonio; Saleem, Mohamed-Ashick M.; Gentien, David; Ban, Kristen; Piolot, Tristan; Leroy, Olivier; Mariani, Odette

    2015-01-01

    Disappearance of the Barr body is considered a hallmark of cancer, although whether this corresponds to genetic loss or to epigenetic instability and transcriptional reactivation is unclear. Here we show that breast tumors and cell lines frequently display major epigenetic instability of the inactive X chromosome, with highly abnormal 3D nuclear organization and global perturbations of heterochromatin, including gain of euchromatic marks and aberrant distributions of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells and a significant degree of aberrant gene activity from the inactive X chromosome, including several genes involved in cancer promotion. We demonstrate that many of these genes are aberrantly reactivated in primary breast tumors, and we further demonstrate that epigenetic instability of the inactive X can lead to perturbed dosage of X-linked factors. Taken together, our study provides the first integrated analysis of the inactive X chromosome in the context of breast cancer and establishes that epigenetic erosion of the inactive X can lead to the disappearance of the Barr body in breast cancer cells. This work offers new insights and opens up the possibility of exploiting the inactive X chromosome as an epigenetic biomarker at the molecular and cytological levels in cancer. PMID:25653311

  6. Childhood adversities and socioeconomic position as predictors of leisure-time physical inactivity in early adulthood.

    PubMed

    Kestilä, Laura; Mäki-Opas, Tomi; Kunst, Anton E; Borodulin, Katja; Rahkonen, Ossi; Prättälä, Ritva

    2015-02-01

    Limited knowledge exists on how childhood social, health-related and economic circumstances predict adult physical inactivity. Our aim was a) to examine how various childhood adversities and living conditions predict leisure-time physical inactivity in early adulthood and b) to find out whether these associations are mediated through the respondent's own education. Young adults aged 18-29 were used from the Health 2000 Study of the Finnish. The cross-sectional data were based on interviews and questionnaires including retrospective information on childhood circumstances. The analyses were carried out on 68% of the original sample (N = 1894). The outcome measure was leisure-time physical inactivity. Only a few of the 11 childhood adversities were related with physical activity in early adulthood. Having been bullied at school was associated with physical inactivity independently of the other childhood circumstances and the respondent's own education. Low parental education predicted leisure-time physical inactivity in men and the association was mediated by the respondent's own education. Respondents with only primary or vocational education were more likely to be physically inactive during leisure-time compared with those with secondary or higher education. There is some evidence that few specific childhood adversities, especially bullying at school, have long-lasting effects on physical activity levels.

  7. Motives for Physical Activity among Active and Inactive Persons in Their Mid-Thirties

    PubMed Central

    Aaltonen, Sari; Rottensteiner, Mirva; Kaprio, Jaakko; Kujala, Urho M

    2013-01-01

    The purpose of this study was to examine the motives for leisure time physical activity among active and inactive men and women in their mid-thirties. We used both cross-sectional and longitudinal designs. Altogether, 2308 participants (mean age 33.9 years, 53.4 % women) were identified from the population-based FinnTwin16 Cohort. Physically active and inactive individuals were identified on the basis of their leisure time MET hours/day. We evaluated participants’ physical activity motivation with a modified version of the Recreational Exercise Motivation Measure. Comparisons between active and inactive individuals were analysed using the Wald test for equality of means, and effect sizes were calculated as Cohen’s d. Motives related to mastery, physical fitness, social aspect of physical activity, psychological state, enjoyment, willingness to be fitter/look better than others and appearance were significantly more important for the active than inactive participants. Conforming to others’ expectations was the only item on which the inactive persons scored higher than active persons. The longitudinal results for physical activity were parallel to the cross-sectional results. This study supports to the view that motivation factors differ between active and inactive persons, and that intrinsic motives are associated with consistent leisure time physical activity. PMID:23331765

  8. Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli

    PubMed Central

    Senkevich, Tatiana G.; Koonin, Eugene V.; Moss, Bernard

    2011-01-01

    The F16L gene of vaccinia virus (VACV) is conserved in all chordopoxviruses except avipoxviruses. The crocodile poxvirus F16 protein ortholog has highly significant similarity to prokaryotic serine recombinases and contains all amino acids that comprise the catalytic site. In contrast, F16 orthologs encoded by other poxviruses show only marginally significant similarity to serine recombinases, lack essential amino acids of the active site and are most likely inactive derivatives of serine recombinases. Nevertheless, the conservation of F16L in non-avian poxviruses suggested an important function. However, a VACV mutant with the F16L gene knocked out replicated normally in dividing and quiescent cells. The F16 protein was synthesized early after infection and detected in virus cores. When expressed in infected or uninfected cells, F16 accumulated in nucleoli depending on the level of expression and confluency of cells. Evidence was obtained that F16 forms multimers, which might regulate concentration-dependent intracellular localization. PMID:21752417

  9. Reconstitution of the quinoprotein methanol dehydrogenase from inactive Ca(2+)-free enzyme with Ca2+, Sr2+ or Ba2+.

    PubMed Central

    Goodwin, M G; Avezoux, A; Dales, S L; Anthony, C

    1996-01-01

    The reconstitution of active holoenzyme containing calcium from inactive calcium-free methanol dehydrogenase, isolated from a moxA mutant of Methylobacterium extorquens, has a pH optimum of about pH 10, with a well defined pK for the process at pH 9.3. Two Ca2+ ions were irreversibly incorporated per alpha 2 beta 2 tetramer. Calcium could be replaced in the incorporation process by strontium or barium, the affinities for these ions being similar to that for Ca2+. Arrhenius plots for measurement of the activation energy of reconstitution were biphasic; the lower activation energy was typical of most biological processes, while the higher activation energy was at least three times greater, implying the involvement of a large conformational change during incorporation of the cations. The activation energy for incorporation of Ba2+ was considerably higher than that for incorporation of Ca2+. The novel disulphide bridge that is at the active site of the enzyme was not involved in the incorporation process. Studies of the time courses for incorporation of 45Ca2+, production of active enzyme and changes in absorption spectra failed to show any intermediates in the incorporation process. PMID:8920988

  10. 9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: design, synthesis, and biological evaluation.

    PubMed

    Huang, Wei-Sheng; Zhu, Xiaotian; Wang, Yihan; Azam, Mohammad; Wen, David; Sundaramoorthi, Raji; Thomas, R Mathew; Liu, Shuangying; Banda, Geetha; Lentini, Scott P; Das, Sasmita; Xu, Qihong; Keats, Jeff; Wang, Frank; Wardwell, Scott; Ning, Yaoyu; Snodgrass, Joseph T; Broudy, Marc I; Russian, Karin; Daley, George Q; Iuliucci, John; Dalgarno, David C; Clackson, Tim; Sawyer, Tomi K; Shakespeare, William C

    2009-08-13

    A novel series of potent dual Src/Abl kinase inhibitors based on a 9-(arenethenyl)purine core has been identified. Unlike traditional dual Src/Abl inhibitors targeting the active enzyme conformation, these inhibitors bind to the inactive, DFG-out conformation of both kinases. Extensive SAR studies led to the discovery of potent and orally bioavailable inhibitors, some of which demonstrated in vivo efficacy. Once-daily oral administration of inhibitor 9i (AP24226) significantly prolonged the survival of mice injected intravenously with wild type Bcr-Abl expressing Ba/F3 cells at a dose of 10 mg/kg. In a separate model, oral administration of 9i to mice bearing subcutaneous xenografts of Src Y527F expressing NIH 3T3 cells elicited dose-dependent tumor shrinkage with complete tumor regression observed at the highest dose. Notably, several inhibitors (e.g., 14a, AP24163) exhibited modest cellular potency (IC50 = 300-400 nM) against the Bcr-Abl mutant T315I, a variant resistant to all currently marketed therapies for chronic myeloid leukemia.

  11. The prognosis of hepatitis B inactive carriers in Japan: a multicenter prospective study.

    PubMed

    Taida, Takashi; Arai, Makoto; Kanda, Tatsuo; Hige, Shuhei; Ueno, Yoshiyuki; Imazeki, Fumio; Izumi, Namiki; Tanaka, Eiji; Shinkai, Noboru; Yoshioka, Kentaro; Nakamoto, Yasunari; Nishiguchi, Shuhei; Tsuge, Masataka; Abe, Masanori; Sata, Michio; Yatsuhashi, Hiroshi; Ido, Akio; Kita, Kazuhiko; Azemoto, Ryousaku; Kitsukawa, Yoshio; Goto, Nobuaki; Yokosuka, Osamu

    2017-01-01

    Hepatitis B e antigen (HBeAg)-negative inactive carriers, the majority of hepatitis B virus (HBV) carriers, are considered to have a good prognosis. The definition of the inactive HBV carrier state has been based on HBV DNA and alanine aminotransferase (ALT) levels. Here we conducted a prospective study involving 18 hospitals to clarify the prognosis of HBeAg-negative inactive carriers. Three hundred eighty-eight HBeAg-negative inactive carriers at the baseline were observed prospectively from January 2011 to November 2015. We evaluated the primary end point, defined as the development of cirrhosis, hepatocellular carcinoma (HCC), or liver-related death. Also, we analyzed the factors associated with inactive carrier dropout and markedly increased levels of ALT or HBV DNA or both during the follow-up period. At the baseline, the mean age was 57.5 ± 13.1 years and 42 % of patients were male. No individual developed cirrhosis, HCC, or liver-related death during the follow-up period (1035 ± 252 days). Loss of inactive carrier status was seen in 75 patients (19.3 %). Factors associated with failure to meet the inactive carrier criteria in the multivariate analysis were the levels of ALT (hazard ratio 1.13, 95 % confidence interval 1.07-1.19, p < 0.001), HBV DNA (hazard ratio 2.70, 95 % confidence interval 1.63-4.49, p < 0.001), and γ-glutamyl transpeptidase (hazard ratio 1.01, 95 % confidence interval 1.00-1.02, p = 0.003) at the baseline. Most inactive carriers in Japan had a good prognosis. However, despite the short observation period, some patients had loss of IC status. The long-term prognosis of inactive carriers remains unclear; therefore, careful follow-up of inactive carriers is needed.

  12. Mechanisms of mutant PDE6 proteins underlying retinal diseases.

    PubMed

    Gopalakrishna, Kota N; Boyd, Kimberly; Artemyev, Nikolai O

    2017-09-01

    Mutations in PDE6 genes encoding the effector enzymes in rods and cones underlie severe retinal diseases including retinitis pigmentosa (RP), autosomal dominant congenital stationary night blindness (adCSNB), and achromatopsia (ACHM). Here we examined a spectrum of pathogenic missense mutations in PDE6 using the system based on co-expression of cone PDE6C with its specialized chaperone AIPL1 and the regulatory Pγ subunit as a potent co-chaperone. We uncovered two mechanisms of PDE6C mutations underlying ACHM: (a) folding defects leading to expression of catalytically inactive proteins and (b) markedly diminished ability of Pγ to co-chaperone mutant PDE6C proteins thereby dramatically reducing the levels of functional enzyme. The mechanism of the Rambusch adCSNB associated with the H258N substitution in PDE6B was probed through the analysis of the model mutant PDE6C-H262N. We identified two interrelated deficits of PDE6C-H262N: disruption of the inhibitory interaction of Pγ with mutant PDE6C that markedly reduced the ability of Pγ to augment the enzyme folding. Thus, we conclude that the Rambusch adCSNB is triggered by low levels of the constitutively active PDE6. Finally, we examined PDE6C-L858V, which models PDE6B-L854V, an RP-linked mutation that alters the protein isoprenyl modification. This analysis suggests that the type of prenyl modifications does not impact the folding of PDE6, but it modulates the enzyme affinity for its trafficking partner PDE6D. Hence, the pathogenicity of PDE6B-L854V likely arises from its trafficking deficiency. Taken together, our results demonstrate the effectiveness of the PDE6C expression system to evaluate pathogenicity and elucidate the mechanisms of PDE6 mutations in retinal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. In vivo expression of mammalian BiP ATPase mutants causes disruption of the endoplasmic reticulum.

    PubMed Central

    Hendershot, L M; Wei, J Y; Gaut, J R; Lawson, B; Freiden, P J; Murti, K G

    1995-01-01

    BiP possesses ATP binding/hydrolysis activities that are thought to be essential for its ability to chaperone protein folding and assembly in the endoplasmic reticulum (ER). We have produced a series of point mutations in a hamster BiP clone that inhibit ATPase activity and have generated a species-specific anti-BiP antibody to monitor the effects of mutant hamster BiP expression in COS monkey cells. The enzymatic inactivation of BiP did not interfere with its ability to bind to Ig heavy chains in vivo but did inhibit ATP-mediated release of heavy chains in vitro. Immunofluorescence staining and electron microscopy revealed vesiculation of the ER membranes in COS cells expressing BiP ATPase mutants. ER disruption was not observed when a "44K" fragment of BiP that did not include the protein binding domain was similarly mutated but was observed when the protein binding region of BiP was expressed without an ATP binding domain. This suggests that BiP binding to target proteins as an inactive chaperone is responsible for the ER disruption. This is the first report on the in vivo expression of mammalian BiP mutants and is demonstration that in vitro-identified ATPase mutants behave as dominant negative mutants when expressed in vivo. Images PMID:7612964

  14. Bacteriorhodopsin mutants of Halobacterium sp. GRB. II. Characterization of mutants.

    PubMed

    Soppa, J; Otomo, J; Straub, J; Tittor, J; Meessen, S; Oesterhelt, D

    1989-08-05

    The bacterioopsin genes of Halobacterium sp. GRB (Ebert, K., Goebel, W., and Pfeifer, F. (1984) Mol. & Gen. Genet. 194, 91-97) wild type and 10 independent mutants of different phenotypes have been cloned and sequenced. The wild type gene has two conservative changes compared to the gene of Halobacterium halobium, so that the proteins of the two species are identical. Six different mutations at five different codons have been found, leading to the following amino acid changes compared to the wild type: Trp10----Cys (three cases), Tyr57----Asn, Asp85----Glu, Asp06----Asn (three cases), Asp96----Gly, Trp138----Arg. A first characterization of the mutant proteins is given, and their implications for models of bacteriorhodopsin structure and function are discussed.

  15. Exploring the Linkage between Activity-Friendly Zoning, Inactivity, and Cancer Incidence in the United States.

    PubMed

    Nicholson, Lisa M; Leider, Julien; Chriqui, Jamie F

    2017-03-07

    Background: Physical activity (PA) protects against cancer and enhances cancer survivorship. Given high inactivity rates nationwide, population-level physical activity facilitators are needed. Several authoritative bodies have recognized that zoning and planning helps create activity-friendly environments. This study examined the association between activity-friendly zoning, inactivity, and cancer in 478 of the most populous U.S. counties.Methods: County geocodes linked county-level data: cancer incidence and smoking (State Cancer Profiles), inactivity (Behavioral Risk Factor Surveillance System), 11 zoning measures (compiled by the study team), and covariates (from the American Community Survey and NAVTEQ). For each zoning measure, single mediation regression models and Sobel tests examined whether activity-friendly zoning was associated with reduced cancer incidence, and whether inactivity mediated those associations. All models were clustered on state with robust SEs and significance at the P < 0.05 level.Results: Zoning for crosswalks, bike-pedestrian connectivity, and bike-pedestrian trails/paths were associated with reduced cancer incidence (β between -0.71 and -1.27, P < 0.05), about 1 case per 100,000 for each 10 percentage-point increase in county population exposure to zoning. Except for crosswalks, each association was mediated by inactivity. However, county smoking attenuated these results, with only crosswalks remaining significant. Results were similar for males (with zoning for bike-pedestrian connectivity, street connectivity, and bike-pedestrian trails/paths), but not females, alone.Conclusions: Zoning can help to create activity-friendly environments that support decreased inactivity, and possibly reduced cancer incidence.Impact: Given low physical activity levels nationwide, cross-sectoral collaborations with urban planning can inform cancer prevention and public health efforts to decrease inactivity and cancer. Cancer Epidemiol Biomarkers Prev

  16. Adult physical inactivity prevalence in the Muslim world: Analysis of 38 countries

    PubMed Central

    Kahan, David

    2015-01-01

    Objective Physical inactivity surveillance informs policy and treatment options toward meeting the World Health Organization's (WHO) goal of a 10% reduction in its prevalence by 2025. We currently do not know the aggregate prevalence for Muslim-majority countries, many of which have extremely high rates of comorbidities associated with physical inactivity. Method Based on data for 163, 556 persons in 38 Muslim countries that were collected by the Global Physical Activity Questionnaire and the International Physical Activity Questionnaire, unweighted and weighted physical inactivity prevalence estimates were calculated. I used two-proportion Z tests to determine gender and ethnic differences within the sample and between the sample and 94 non-Muslim countries and odds ratios to determine the magnitude of significant differences. Results Total physical inactivity prevalence was 32.3% (95% CI: 31.9, 32.7). Prevalence among males and females was 28.8% and 35.5%, respectively. Prevalence among non-Arabs and Arabs was 28.6% and 43.7%, respectively. Females and Arabs were more likely physically inactive than their respective counterparts [OR = 1.36 (1.33, 1.39) and OR = 1.94 (1.90, 1.98)]. Muslim countries were more likely physically inactive [OR = 1.23 (1.22, 1.25)] than non-Muslim ones, which was primarily due to the influence of Arabs [OR = 2.01 (1.97, 2.04)], and in particular female Arabs [OR = 2.22 (2.17, 2.27)]. Conclusion Physical inactivity prevalence in the Muslim world is higher than non-Muslim countries and the difference is primarily due to higher rates among Arabs. PMID:26844051

  17. Motivating patients to exercise: translating high blood pressure into equivalent risk of inactivity.

    PubMed

    Li, Chu-Shiu; Liu, Chwen-Chi; Tsai, Min-Kuang; Tai, Ya-Ping; Wai, Jackson Pui Man; Tsao, Chwen-Keng; Wen, Chi-Pang

    2015-02-01

    Even with the 2008 physical activity guidelines for Americans and the strong epidemiological evidence, physicians are not routinely emphasizing the importance of exercise. We try to explore an innovative way to communicate the benefits of physical activity in a term familiar to patients. A cohort of 470, 163 adults from a medical screening program in Taiwan were recruited between 1994 and 2008. Their vital status was followed up by matching with the National Death File. Individuals were classified as 'inactive', 'low active', or 'fully active', with 'fully active' meeting the current exercise recommendation of 150  min per week or more. Cox proportional model was used to calculate the hazard ratio. More than one-half of the cohort was inactive (54%), with one-quarter fully active (24%). One in seven was hypertensive (14%), defined as SBP at least 140  mmHg. Among the hypertensive individuals, mortality risks were increased by 37% for the inactive. Inactive individuals had higher all-cause mortality than active ones across all blood pressure (BP) levels. At 110-119  mmHg, the inactive had a risk as high as the risk at 155  mmHg, an increased mortality risk equivalent to a risk of BP increase of 41.2 mmHg. The mortality risk of being inactive was equivalent to an increase of around 40  mmHg in SBP or 20  mmHg in DBP, a number relevant to hypertensive patients. Appreciating this relationship may convince the inactive to start exercising, a behavior as important as controlling BP.

  18. Variation in Its C-Terminal Amino Acids Determines Whether Endo-β-Mannanase Is Active or Inactive in Ripening Tomato Fruits of Different Cultivars1

    PubMed Central

    Bourgault, Richard; Bewley, J. Derek

    2002-01-01

    Endo-β-mannanase cDNAs were cloned and characterized from ripening tomato (Lycopersicon esculentum Mill. cv Trust) fruit, which produces an active enzyme, and from the tomato cv Walter, which produces an inactive enzyme. There is a two-nucleotide deletion in the gene from tomato cv Walter, which results in a frame shift and the deletion of four amino acids at the C terminus of the full-length protein. Other cultivars that produce either active or inactive enzyme show the same absence or presence of the two-nucleotide deletion. The endo-β-mannanase enzyme protein was purified and characterized from ripe fruit to ensure that cDNA codes for the enzyme from fruit. Immunoblot analysis demonstrated that non-ripening mutants, which also fail to exhibit endo-β-mannanase activity, do so because they fail to express the protein. In a two-way genetic cross between tomato cvs Walter and Trust, all F1 progeny from both crosses produced fruit with active enzyme, suggesting that this form is dominant and homozygous in tomato cv Trust. Self-pollination of a plant from the heterozygous F1 generation yielded F2 plants that bear fruit with and without active enzyme at a ratio appropriate to Mendelian genetic segregation of alleles. Heterologous expression of the two endo-β-mannanase genes in Escherichia coli resulted in active enzyme being produced from cultures containing the tomato cv Trust gene and inactive enzyme being produced from those containing the tomato cv Walter gene. Site-directed mutagenesis was used to establish key elements in the C terminus of the endo-β-mannanase protein that are essential for full enzyme activity. PMID:12427992

  19. Mutant power: using mutant allele collections for yeast functional genomics

    PubMed Central

    Norman, Kaitlyn L.

    2016-01-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. PMID:26453908

  20. Mutant power: using mutant allele collections for yeast functional genomics.

    PubMed

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.

    PubMed

    Washburn, Michael C; Kakaradov, Boyko; Sundararaman, Balaji; Wheeler, Emily; Hoon, Shawn; Yeo, Gene W; Hundley, Heather A

    2014-02-27

    Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need to study deaminase-independent control of editing. C. elegans have two ADAR proteins, ADR-2 and the theoretically catalytically inactive ADR-1. Using high-throughput RNA sequencing of wild-type and adr mutant worms, we expand the repertoire of C. elegans edited transcripts over 5-fold and confirm that ADR-2 is the only active deaminase in vivo. Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3' UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2, and mutations within its double-stranded RNA (dsRNA) binding domains abolish both binding and editing regulation. We conclude that ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.

  2. The solution configurations of inactive and activated DntR have implications for the sliding dimer mechanism of LysR transcription factors.

    PubMed

    Lerche, Michael; Dian, Cyril; Round, Adam; Lönneborg, Rosa; Brzezinski, Peter; Leonard, Gordon A

    2016-01-28

    LysR Type Transcriptional Regulators (LTTRs) regulate basic metabolic pathways or virulence gene expression in prokaryotes. Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo- configuration that represses transcription to an active, expanded holo- form that promotes it. However, no LTTR has yet been observed to adopt both configurations. Here, we report the results of structural studies of various forms of the LTTR DntR. Crystal structures of apo-DntR and of a partially autoinducing mutant H169T-DntR suggest that active and inactive DntR maintain a compact homotetrameric configuration. However, Small Angle X-ray Scattering (SAXS) studies on solutions of apo-, H169T- and inducer-bound holo-DntR indicate a different behaviour, suggesting that while apo-DntR maintains a compact configuration in solution both H169T- and holo-DntR adopt an expanded conformation. Models of the SAXS-obtained solution conformations of apo- and holo-DntR homotetramers in complex with promoter-operator region DNA are consistent with previous observations of a shifting of LTTR DNA binding sites upon activation and a consequent relaxation in the bend of the promoter-operator region DNA. Our results thus provide clear evidence at the molecular level which strongly supports the 'sliding dimer' hypothesis concerning LTTR activation mechanisms.

  3. The proportion of youths’ physical inactivity attributable to neighbourhood built environment features

    PubMed Central

    2013-01-01

    Objective We investigated the independent association between several neighbourhood built environment features and physical inactivity within a national sample of Canadian youth, and estimated the proportion of inactivity within the population that was attributable to these built environment features. Methods This was a cross-sectional study of 6626 youth aged 11–15 years from 272 schools across Canada. Participants resided within 1 km of their school. Walkability, outdoor play areas (parks, wooded areas, yards at home, cul-de-sacs on roads), recreation facilities, and aesthetics were measured objectively within each school neighbourhood using geographic information systems. Physical inactivity (<5 days/week of 60 minutes of moderate-to-vigorous physical activity) was assessed by questionnaire. Multilevel logistic regression analyses, which controlled for several covariates, examined relationships between built environment features and physical inactivity. Results The final regression model indicated that, by comparison to youth living in the least walkable neighbourhoods, the risks for physical inactivity were 28-44% higher for youth living in neighbourhoods in the remaining three walkability quartiles. By comparison to youth living in neighbourhoods with the highest density of cul-de-sacs, risks for physical inactivity were 28-32% higher for youth living in neighbourhoods in the lowest two quartiles. By comparison to youth living in neighbourhoods with the least amount of park space, risks for physical inactivity were 28-37% higher for youth living in the neighbourhoods with a moderate to high (quartiles 2 and 3) park space. Population attributable risk estimates suggested that 23% of physical inactivity within the population was attributable to living in walkable neighbourhoods, 16% was attributable to living in neighbourhoods with a low density of cul-de-sacs, and 15% was attributable to living in neighbourhoods with a moderate to high amount of park

  4. Prevalence and variables associated with physical inactivity in individuals with high and low socioeconomic status.

    PubMed

    Reis, Helena França Correia dos; Ladeia, Ana Marice Teixeira; Passos, Everton Carvalho; Santos, Flávio Guilherme de Oliveira; Wasconcellos, Larissa Tapioca de; Correia, Luís Cláudio Lemos; Menezes, Marta Silva; Santos, Renata Dáttoli Gouvêa; Bomfim, Victor Guerrero do; Rocha, Mário de Seixas

    2009-03-01

    Studies that considered only the leisure physical activity found that the physical inactivity is higher among lower-income individuals. There is a possibility that this association shows modifications, when considering transportation, work and domestic activities. To determine whether there is a difference between the prevalence of physical inactivity between individuals of high and low socioeconomic levels. The sample consisted of individuals of both sexes, aged 18 or older, from two groups of different socioeconomic levels. The low socioeconomic level (LSEL) group consisted of the parents of students from a public school. The high socioeconomic level (HSEL) group consisted of the parents of students from a private College. The International Physical Activity Questionnaire (IPAQ) was used to determine the level of physical activity. A total of 91 individuals were evaluated in the LSEL group and 59 in the HSEL group. In the LSEL group, 42.9% (39) of the individuals were classified as insufficiently active, compared to 57.6% (34) of individuals in the HSEL group. Taking as a parameter of physical inactivity the time of weekly physical activity < 150 minutes, there was a decrease in the classification of inactivity in both groups, although with the maintenance of higher inactivity among individuals of HSEL (49.2% vs 28.6%; p= 0.01). The individuals of HSEL are more sedentary than the individuals of LSEL.

  5. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States

    PubMed Central

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-01-01

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA’s influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence—influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being. PMID:27548195

  6. The Effect of Whole-body Vibration on Muscle Activity in Active and Inactive Subjects.

    PubMed

    Lienhard, K; Vienneau, J; Friesenbichler, B; Nigg, S; Meste, O; Nigg, B M; Colson, S S

    2015-06-01

    The purpose of this study was to compare lower limb muscle activity between physically active and inactive individuals during whole-body vibration exercises. Additionally, transmissibility of the vertical acceleration to the head was quantified. 30 active and 28 inactive participants volunteered to stand in a relaxed (20°) and a squat (60°) position on a side-alternating WBV platform that induced vibrations at 16 Hz and 4 mm amplitude. Surface electromyography (sEMG) was measured in selected lower limb muscles and was normalized to the corresponding sEMG recorded during a maximal voluntary contraction. The vertical acceleration on the head was evaluated and divided by the vertical platform acceleration to obtain transmissibility values. Control trials without vibration were also assessed. The outcomes of this study showed that (1) WBV significantly increased muscle activity in the active (absolute increase: +7%, P <0.05) and inactive participants (+8%, P <0.05), (2) with no differences in sEMG increases between the groups (P>0.05). However, (3), transmissibility to the head was greater in the active (0.080) than the inactive participants (0.065, P <0.05). In conclusion, inactive individuals show similar responses in sEMG due to WBV as their active counterparts, but are at lower risk for potential side-effects of vibration exposure. © Georg Thieme Verlag KG Stuttgart · New York.

  7. A theory for fluidelastic instability of tube-support-plate inactive modes

    SciTech Connect

    Cai, Y.; Chen, S.S. ); Chandra, S. )

    1990-01-01

    Fluidelastic instability of loosely supported tubes, vibrating in a tube support plate (TSP)-inactive mode, is suspected to be one of the main causes of tube failures in some operating steam generators and heat exchangers. A mathematical model, which incorporates all motion-dependent fluid-forces based on the unsteady flow theory, is presented here for fluidelastic instability of loosely supported tubes exposed to nonuniform crossflow. In the unstable region associated with a TSP-inactive mode, the tube motion can be described by two linear models: TSP-inactive mode when tubes do not contact with the TSP and TSP-active mode when tubes contact the TSP. A bilinear model, consisting of these linear models, is presented in this paper to simulate the characteristics of fluidelastic instability of loosely supported tubes in the stable and unstable region associated with TSP-inactive modes. The analytical results are compared with published experimental data; they agree reasonably well. The prediction procedure presented for fluidelastic instability response of loosely supported tubes is applicable in the stable regions of TSP-inactive mode. 25 refs., 10 figs., 2 tabs.

  8. Monthly estimates of leisure-time physical inactivity--United States, 1994.

    PubMed

    1997-05-09

    Physical inactivity increases the risk for heart disease, diabetes, colon cancer, high blood pressure, obesity, osteoporosis, muscle and joint disorders, and symptoms of anxiety and depression. However, approximately one third of adults in the United States report no leisure-time physical activity, and rates of inactivity have been higher in January than in June. Among adults, the prevalence of leisure-time physical inactivity is highest among those who are older, Hispanic, and residing in southern states. A national health objective for the year 2000 is to reduce to < or = 15% the proportion of persons reporting no leisure-time physical activity (objecive 1.5). To assist in monitoring efforts to achieve this objective, CDC analyzed data from the 1994 Behavioral Risk Factor Surveillance system (BRFSS) and estimated for each month the proportion of adults from selected demographic groups who reported no leisure-time physical activity. The findings indicate seasonal patterns in the prevalence of reported leisure-time physical inactivity; however, monthly rates of inactivity were higher and more stable among older persons, Hispanics, and residents of southern states.

  9. Daily energy expenditure in active and inactive persons with spinal cord injury.

    PubMed

    Yamasaki, M; Irizawa, M; Komura, T; Kikuchi, K; Sasaki, H; Kai, K; Ohdoko, K

    1992-12-01

    Daily energy expenditure (DEE) was evaluated seventeen male subjects with spinal cord injury (SSCI), who had active (N = 9) and inactive (N = 8) lifestyles, and in seven normal males. DEE was estimated from the mean 24-hr heart rate and heart rate-energy expenditure relationship determined in an arm cranking exercise. The DEE of SSCI on active days did not differ from those of normal subjects. On inactive days, SSCI had significantly lower DEE than on active days and than normal subjects. In contrast, the mean 24-hr heart rates of SSCI on active days and inactive SSCI were significantly greater than those of normal subjects, suggesting that SSCI, particularly inactive SSCI, exhibited a slight degree of tachycardia when compared to normal subjects. On inactive days, the DEE was fairly independent of the level of spinal cord injury. However, on active days, there was a clear tendency for SSCI with a low lesion level to have a higher DEE. Even if a SSCI with a high lesion level engaged in active sports, his DEE was relatively small. This lower DEE was largely attributable to the smaller functional muscle mass due to the limitation of physical activity.

  10. Physical inactivity and anthropometric measures in schoolchildren from Paranavaí, Paraná, Brazil

    PubMed Central

    Guilherme, Flávio Ricardo; Molena-Fernandes, Carlos Alexandre; Guilherme, Vânia Renata; Fávero, Maria Teresa Martins; dos Reis, Eliane Josefa Barbosa; Rinaldi, Wilson

    2015-01-01

    OBJECTIVE: To investigate the association between physical inactivity and anthropometric measures in schoolchildren from Paranavaí-Parana, Brazil. METHODS: Cross-sectional survey, carried out in July and August 2013. Sample of 566 students (287 boys and 279 girls) from 6th to 9th grade, aged 10 to 14 years, from public and private schools of Paranavaí - PR, Southern Brazil. The variables analyzed were: time of weekly physical activity through a questionnaire (physical inactivity <300 minutes/week), body mass index (BMI) and waist circumference (WC). In the statistical analysis, the U Mann-Whitney and Student's t tests were used for comparison between genders. To identify factors associated with insufficient levels of physical activity, univariate and multivariate logistic regression analysis was applied and expressed in Odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: There was an association between physical inactivity and anthropometric measurements for BMI (p<0.001) and WC (p<0.001), with a prevalence rate of 56.1% and 52.7% of inactive adolescents, respectively. In the multivariate analysis, there was significant association of physical inactivity and overweight (OR 1.8, 95%CI: 1.1-3.0) and with increased waist circumference (OR 2.8, 95%CI: 1.4-3.8). CONCLUSIONS: Inadequate levels of physical activity is a determining factor for overweight and abdominal adiposity. Accordingly, preventive measures should be taken, especially in schools, emphasizing the importance of exercise for body composition control and weight reduction. PMID:25623726

  11. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States.

    PubMed

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-08-17

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA's influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence-influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being.

  12. The influence of the inactives subset generation on the performance of machine learning methods

    PubMed Central

    2013-01-01

    Background A growing popularity of machine learning methods application in virtual screening, in both classification and regression tasks, can be observed in the past few years. However, their effectiveness is strongly dependent on many different factors. Results In this study, the influence of the way of forming the set of inactives on the classification process was examined: random and diverse selection from the ZINC database, MDDR database and libraries generated according to the DUD methodology. All learning methods were tested in two modes: using one test set, the same for each method of inactive molecules generation and using test sets with inactives prepared in an analogous way as for training. The experiments were carried out for 5 different protein targets, 3 fingerprints for molecules representation and 7 classification algorithms with varying parameters. It appeared that the process of inactive set formation had a substantial impact on the machine learning methods performance. Conclusions The level of chemical space limitation determined the ability of tested classifiers to select potentially active molecules in virtual screening tasks, as for example DUDs (widely applied in docking experiments) did not provide proper selection of active molecules from databases with diverse structures. The study clearly showed that inactive compounds forming training set should be representative to the highest possible extent for libraries that undergo screening. PMID:23561266

  13. An Activator of Mutant and Wildtype Aldehyde Dehydrogenase Reduces Ischemic Damage to the Heart

    PubMed Central

    Chen, Che-Hong; Budas, Grant R.; Churchill, Eric N.; Disatnik, Marie-Helene; Hurley, Thomas D.; Mochly-Rosen, Daria

    2009-01-01

    There is substantial interest in the development of drugs that limit the extent of ischemia-induced cardiac damage caused by myocardial infarction or by certain surgical procedures. Here an unbiased proteomic search identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models. A high-throughput screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats prior to an ischemic event, reduced infarct size by 60%, most likely through its inhibitory effect on the formation of cytotoxic aldehydes. In vitro, Alda-1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is found in 40% of East Asian populations. Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wildtype or mutant ALDH2 subjected to cardiac ischemia, such as during coronary bypass surgery. (140/140 words) PMID:18787169

  14. Synthesis of nitrogenase in mutants of the cyanobacterium Anabaena sp. strain PCC 7120 affected in heterocyst development or metabolism.

    PubMed Central

    Ernst, A; Black, T; Cai, Y; Panoff, J M; Tiwari, D N; Wolk, C P

    1992-01-01

    Mutants of Anabaena sp. strain PCC 7120 that are incapable of sustained growth with air as the sole source of nitrogen were generated by using Tn5-derived transposons. Nitrogenase was expressed only in mutants that showed obvious morphological signs of heterocyst differentiation. Even under rigorously anaerobic conditions, nitrogenase was not synthesized in filaments that were unable to develop heterocysts. These results suggest that competence to synthesize nitrogenase requires a process that leads to an early stage of visible heterocyst development and are consistent with the idea that synthesis of nitrogenase is under developmental control (J. Elhai and C. P. Wolk, EMBO J. 9:3379-3388, 1990). We isolated mutants in which differentiation was arrested at an intermediate stage of heterocyst formation, suggesting that differentiation proceeds in stages; those mutants, as well as mutants with aberrant heterocyst envelopes and a mutant with defective respiration, expressed active nitrogenase under anaerobic conditions only. These results support the idea that the heterocyst envelope and heterocyst respiration are required for protection of nitrogenase from inactivation by oxygen. In the presence of air, such mutants contained less nitrogenase than under anaerobic conditions, and the Fe-protein was present in a posttranslationally modified inactive form. We conclude that internal partial oxygen pressure sufficient to inactivate nitrogenase is insufficient to repress synthesis of the enzyme completely. Among mutants with an apparently intact heterocyst envelope and normal respiration, three had virtually undetectable levels of dinitrogenase reductase under all conditions employed. However, three others expressed oxygen-sensitive nitrogenase activity, suggesting that respiration and barrier to diffusion of gases may not suffice for oxygen protection of nitrogenase in these mutants; two of these mutants reduced acetylene to ethylene and ethane. Images PMID:1328150

  15. Site energies of active and inactive pheophytins in the reaction center of Photosystem II from Chlamydomonas reinhardtii.

    PubMed

    Acharya, K; Neupane, B; Zazubovich, V; Sayre, R T; Picorel, R; Seibert, M; Jankowiak, R

    2012-03-29

    It is widely accepted that the primary electron acceptor in various Photosystem II (PSII) reaction center (RC) preparations is pheophytin a (Pheo a) within the D1 protein (Pheo(D1)), while Pheo(D2) (within the D2 protein) is photochemically inactive. The Pheo site energies, however, have remained elusive, due to inherent spectral congestion. While most researchers over the past two decades placed the Q(y)-states of Pheo(D1) and Pheo(D2) bands near 678-684 and 668-672 nm, respectively, recent modeling [Raszewski et al. Biophys. J. 2005, 88, 986 - 998; Cox et al. J. Phys. Chem. B 2009, 113, 12364 - 12374] of the electronic structure of the PSII RC reversed the assignment of the active and inactive Pheos, suggesting that the mean site energy of Pheo(D1) is near 672 nm, whereas Pheo(D2) (~677.5 nm) and Chl(D1) (~680 nm) have the lowest energies (i.e., the Pheo(D2)-dominated exciton is the lowest excited state). In contrast, chemical pigment exchange experiments on isolated RCs suggested that both pheophytins have their Q(y) absorption maxima at 676-680 nm [Germano et al. Biochemistry 2001, 40, 11472 - 11482; Germano et al. Biophys. J. 2004, 86, 1664 - 1672]. To provide more insight into the site energies of both Pheo(D1) and Pheo(D2) (including the corresponding Q(x) transitions, which are often claimed to be degenerate at 543 nm) and to attest that the above two assignments are most likely incorrect, we studied a large number of isolated RC preparations from spinach and wild-type Chlamydomonas reinhardtii (at different levels of intactness) as well as the Chlamydomonas reinhardtii mutant (D2-L209H), in which the active branch Pheo(D1) is genetically replaced with chlorophyll a (Chl a). We show that the Q(x)-/Q(y)-region site energies of Pheo(D1) and Pheo(D2) are ~545/680 nm and ~541.5/670 nm, respectively, in good agreement with our previous assignment [Jankowiak et al. J. Phys. Chem. B 2002, 106, 8803 - 8814]. The latter values should be used to model excitonic

  16. Site Energies of Active and Inactive Pheophytins in the Reaction Center of Photosystem II from Chlamydomonas Reinhardtii

    SciTech Connect

    Acharya, K.; Neupane, B.; Zazubovich, V.; Sayre, R. T.; Picorel, R.; Seibert, M.; Jankowiak, R.

    2012-03-29

    It is widely accepted that the primary electron acceptor in various Photosystem II (PSII) reaction center (RC) preparations is pheophytin {alpha} (Pheo {alpha}) within the D1 protein (Pheo{sub D1}), while Pheo{sub D2} (within the D2 protein) is photochemically inactive. The Pheo site energies, however, have remained elusive, due to inherent spectral congestion. While most researchers over the past two decades placed the Q{sub y}-states of Pheo{sub D1} and Pheo{sub D2} bands near 678-684 and 668-672 nm, respectively, recent modeling [Raszewski et al. Biophys. J. 2005, 88, 986-998; Cox et al. J. Phys. Chem. B 2009, 113, 12364-12374] of the electronic structure of the PSII RC reversed the assignment of the active and inactive Pheos, suggesting that the mean site energy of Pheo{sub D1} is near 672 nm, whereas Pheo{sub D2} ({approx}677.5 nm) and Chl{sub D1} ({approx}680 nm) have the lowest energies (i.e., the Pheo{sub D2}-dominated exciton is the lowest excited state). In contrast, chemical pigment exchange experiments on isolated RCs suggested that both pheophytins have their Q{sub y} absorption maxima at 676-680 nm [Germano et al. Biochemistry 2001, 40, 11472-11482; Germano et al. Biophys. J. 2004, 86, 1664-1672]. To provide more insight into the site energies of both Pheo{sub D1} and Pheo{sub D2} (including the corresponding Q{sub x} transitions, which are often claimed to be degenerate at 543 nm) and to attest that the above two assignments are most likely incorrect, we studied a large number of isolated RC preparations from spinach and wild-type Chlamydomonas reinhardtii (at different levels of intactness) as well as the Chlamydomonas reinhardtii mutant (D2-L209H), in which the active branch Pheo{sub D1} is genetically replaced with chlorophyll {alpha} (Chl {alpha}). We show that the Q{sub x}-/Q{sub y}-region site energies of Pheo{sub D1} and Pheo{sub D2} are {approx}545/680 nm and {approx}541.5/670 nm, respectively, in good agreement with our previous assignment

  17. Destroying God's Temple? Physical Inactivity, Poor Diet, Obesity, and Other "Sin" Behaviors.

    PubMed

    Faries, Mark D; McClendon, Megan; Jones, Eric J

    2017-02-17

    On average, our participants (N = 112), who self-proclaimed to be Christians, believed that physically inactive lifestyles, unhealthy eating, overeating, and being obese destroy the body, God's temple. However, these beliefs were less definitive, than those of other common "sin" behaviors, such as drug use, smoking, and excessive drinking of alcohol. In addition, destroying the body with physical inactivity or poor diet was not necessarily viewed as sinful. Subsequently, these beliefs did not relate to self-reported physical activity, dietary behavior, or body mass index. It is possible that inactivity, poor dietary habits, and obesity are not internalized into the spiritual perspective as destroying the body, God's temple, in the same way as other "sin" behaviors.

  18. Discrimination of active and inactive sand from remote sensing - Kelso dunes, Mojave Desert, California

    NASA Technical Reports Server (NTRS)

    Paisley, Elizabeth C. I.; Lancaster, Nicholas; Gaddis, Lisa R.; Greeley, Ronald

    1991-01-01

    Landsat TM images, field data, and laboratoray reflectance spectra were examined for the Kelso dunes, Mojave Desert, California to assess the use of visible and near-infrared (VNIR) remote sensing data to discriminate aeolian sand populations on the basis of spectral brightness. Results show that areas of inactive sand have a larger percentage of dark, fine-grained materials compared to those composed of active sand, which contain less dark fines and a higher percentage of quartz sand-size grains. Both areas are spectrally distinct in the VNIR, suggesting that VNIR spectral data can be used to discriminate active and inactive sand populations in the Mojave Desert. Analysis of laboratory spectra was complicated by the presence of magnetite in the active sands, which decreases their laboratory reflectance values to those of inactive sands. For this application, comparison of TM and laboratory spectra suggests that less than 35 percent vegetation cover does not influence the TM spectra.

  19. Discrimination of active and inactive sand from remote sensing - Kelso dunes, Mojave Desert, California

    NASA Technical Reports Server (NTRS)

    Paisley, Elizabeth C. I.; Lancaster, Nicholas; Gaddis, Lisa R.; Greeley, Ronald

    1991-01-01

    Landsat TM images, field data, and laboratoray reflectance spectra were examined for the Kelso dunes, Mojave Desert, California to assess the use of visible and near-infrared (VNIR) remote sensing data to discriminate aeolian sand populations on the basis of spectral brightness. Results show that areas of inactive sand have a larger percentage of dark, fine-grained materials compared to those composed of active sand, which contain less dark fines and a higher percentage of quartz sand-size grains. Both areas are spectrally distinct in the VNIR, suggesting that VNIR spectral data can be used to discriminate active and inactive sand populations in the Mojave Desert. Analysis of laboratory spectra was complicated by the presence of magnetite in the active sands, which decreases their laboratory reflectance values to those of inactive sands. For this application, comparison of TM and laboratory spectra suggests that less than 35 percent vegetation cover does not influence the TM spectra.

  20. Mental health, places and people: a multilevel analysis of economic inactivity and social deprivation.

    PubMed

    Fone, David L; Dunstan, Frank

    2006-09-01

    Using data on 24,975 respondents to the Welsh Health Survey 1998 aged 17-74 years, we investigated associations between individual mental health status measured using the SF-36 instrument, social class, economic inactivity and the electoral division Townsend deprivation score. In a multilevel modelling analysis, we found mental health was significantly associated with the Townsend score after adjusting for composition, and this effect was strongest in respondents who were economically inactive. Further contextual effects were shown by significant random variability in the slopes of the relation between mental health and economic inactivity at the electoral division level. Our results suggest that the places in which people live affect their mental health, supporting NHS policy that multi-agency planning to reduce inequalities in mental health status should address the wider determinants of health, as well as services for individual patients.

  1. [Inequalities in physical inactivity according educational level in Spain, 1987 and 2007].

    PubMed

    Maestre-Miquel, Clara; Martínez, David; Polonio, Begoña; Astasio, Paloma; Santos, Juana; Regidor, Enrique

    2014-12-01

    To compare the magnitude of inequalities in the frequency of physical inactivity in Spain in 1987 and 2007, and assess whether the magnitude of inequality varies depending on the wealth of the area of residence. Descriptive cross-sectional study, national scope. Data from the National Health Survey, 1987 and 2007, adult population between 25-64 years: 30,000 individuals (1987) and 29,478 (2006/7). Main outcomes variable, leisure-time physical inactivity; exposure factor, educational level. An analysis was made of the prevalence and association using odds ratio (OR). Adjustment for socioeconomic variables: age, marital status, employment status, social class of head of household, and household income. Physical inactivity prevalence decreased in the two decades. There were more than three times more inactive males among those with primary education or less, compared to those with university studies. The magnitude of inequalities has increased in time: in a 45-64 years old man with primary school education: OR 2.43 (1.91-3.09) in 1987, to OR 2.77 (2.17-3.54) in 2007, adjusted for all socioeconomic variables. The prevalence of physical inactivity decreased between 1987 and 2007, and the largest decreases were in individuals with university studies. The gap in the differences in prevalence and OR of leisure-time physical inactivity has increased over time. It's necessary to contribute, with health education strategies and equity promotion are needed to help reduce the inequalities in risk behaviors. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  2. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012.

    PubMed

    Geiss, Linda S; Kirtland, Karen; Lin, Ji; Shrestha, Sundar; Thompson, Ted; Albright, Ann; Gregg, Edward W

    2017-01-01

    Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC). Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC) from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004-2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008-2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48). APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity.

  3. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012

    PubMed Central

    Kirtland, Karen; Lin, Ji; Shrestha, Sundar; Thompson, Ted; Albright, Ann; Gregg, Edward W.

    2017-01-01

    Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC). Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC) from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004–2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008–2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48). APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity. PMID

  4. Linking geology and microbiology: inactive pockmarks affect sediment microbial community structure.

    PubMed

    Haverkamp, Thomas H A; Hammer, Øyvind; Jakobsen, Kjetill S

    2014-01-01

    Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined what the microbial composition of inactive pockmarks is and if it shows a similar pattern as the macrofauna. The Norwegian Oslofjord contains many inactive pockmarks and they are well suited to study the influence of these geological features on the microbial community in the sediment. Here we present a detailed analysis of the microbial communities found in three inactive pockmarks and two control samples at two core depth intervals. The communities were analyzed using high-throughput amplicon sequencing of the 16S rRNA V3 region. Microbial communities of surface pockmark sediments were indistinguishable from communities found in the surrounding seabed. In contrast, pockmark communities at 40 cm sediment depth had a significantly different community structure from normal sediments at the same depth. Statistical analysis of chemical variables indicated significant differences in the concentrations of total carbon and non-particulate organic carbon between 40 cm pockmarks and reference sample sediments. We discuss these results in comparison with the taxonomic classification of the OTUs identified in our samples. Our results indicate that microbial communities at the sediment surface are affected by the water column, while the deeper (40 cm) sediment communities are affected by local conditions within the sediment.

  5. The Association of Ambient Air Pollution and Physical Inactivity in the United States

    PubMed Central

    Roberts, Jennifer D.; Voss, Jameson D.; Knight, Brandon

    2014-01-01

    Background Physical inactivity, ambient air pollution and obesity are modifiable risk factors for non-communicable diseases, with the first accounting for 10% of premature deaths worldwide. Although community level interventions may target each simultaneously, research on the relationship between these risk factors is lacking. Objectives After comparing spatial interpolation methods to determine the best predictor for particulate matter (PM2.5; PM10) and ozone (O3) exposures throughout the U.S., we evaluated the cross-sectional association of ambient air pollution with leisure-time physical inactivity among adults. Methods In this cross-sectional study, we assessed leisure-time physical inactivity using individual self-reported survey data from the Centers for Disease Control and Prevention's 2011 Behavioral Risk Factor Surveillance System. These data were combined with county-level U.S. Environmental Protection Agency air pollution exposure estimates using two interpolation methods (Inverse Distance Weighting and Empirical Bayesian Kriging). Finally, we evaluated whether those exposed to higher levels of air pollution were less active by performing logistic regression, adjusting for demographic and behavioral risk factors, and after stratifying by body weight category. Results With Empirical Bayesian Kriging air pollution values, we estimated a statistically significant 16–35% relative increase in the odds of leisure-time physical inactivity per exposure class increase of PM2.5 in the fully adjusted model across the normal weight respondents (p-value<0.0001). Evidence suggested a relationship between the increasing dose of PM2.5 exposure and the increasing odds of physical inactivity. Conclusions In a nationally representative, cross-sectional sample, increased community level air pollution is associated with reduced leisure-time physical activity particularly among the normal weight. Although our design precludes a causal inference, these results provide

  6. Insulin-induced reactivation of an inactive herpes simplex thymidine kinase gene.

    PubMed Central

    Clough, D W; Morse, B S; Kucherlapati, R S; Davidson, R L

    1984-01-01

    A line of mouse cells transformed with ultraviolet-irradiated herpes simplex virus type 1 and containing a methylated and inactive viral thymidine kinase (TK) gene was treated with insulin in an attempt to induce expression of the inactive gene. Insulin was found to be capable of inducing the inactive TK gene in these cells. The induction of the TK+ phenotype was dose dependent (from 1-100 micrograms of insulin per ml), and the TK activity induced was shown to be of viral origin. Analysis of the methylation pattern of the viral TK gene by using the methylation-sensitive restriction endonucleases Sma I, Hpa II, and Hha I revealed that the active viral TK gene in the parental transformed cells was hypomethylated, whereas the inactive TK gene in the uninduced TK- cells was methylated. The active TK gene in three insulin-induced TK+ lines also was methylated, but the methylation patterns in the insulin-induced lines all were different from the uninduced TK- line. These data suggest that extensive hypomethylation of the inactive TK gene is not required for insulin induction. Four other transformed lines containing an inactive viral TK gene were tested for insulin inducibility, but insulin was unable to induce expression of the TK gene in any of the other lines. Thus, insulin inducibility does not seem to be a function of the viral TK gene itself. These results suggest that insulin inducibility of the viral TK gene may be a reflection of the region of the host genome into which the TK gene was integrated. Images PMID:6322172

  7. Light saturation curves show competence of the water splitting complex in inactive Photosystem II reaction centers.

    PubMed

    Nedbal, L; Gibas, C; Whitmarsh, J

    1991-12-01

    Photosystem II complexes of higher plants are structurally and functionally heterogeneous. While the only clearly defined structural difference is that Photosystem II reaction centers are served by two distinct antenna sizes, several types of functional heterogeneity have been demonstrated. Among these is the observation that in dark-adapted leaves of spinach and pea, over 30% of the Photosystem II reaction centers are unable to reduce plastoquinone to plastoquinol at physiologically meaningful rates. Several lines of evidence show that the impaired reaction centers are effectively inactive, because the rate of oxidation of the primary quinone acceptor, QA, is 1000 times slower than in normally active reaction centers. However, there are conflicting opinions and data over whether inactive Photosystem II complexes are capable of oxidizing water in the presence of certain artificial electron acceptors. In the present study we investigated whether inactive Photosystem II complexes have a functional water oxidizing system in spinach thylakoid membranes by measuring the flash yield of water oxidation products as a function of flash intensity. At low flash energies (less that 10% saturation), selected to minimize double turnovers of reaction centers, we found that in the presence of the artificial quinone acceptor, dichlorobenzoquinone (DCBQ), the yield of proton release was enhanced 20±2% over that observed in the presence of dimethylbenzoquinone (DMBQ). We argue that the extra proton release is from the normally inactive Photosystem II reaction centers that have been activated in the presence of DCBQ, demonstrating their capacity to oxidize water in repetitive flashes, as concluded by Graan and Ort (Biochim Biophys Acta (1986) 852: 320-330). The light saturation curves indicate that the effective antenna size of inactive reaction centers is 55±12% the size of active Photosystem II centers. Comparison of the light saturation dependence of steady state oxygen evolution

  8. Proposed Nomenclature for Mutants of Adenoviruses

    PubMed Central

    Ginsberg, Harold S.; Williams, James F.; Doerfler, Walter H.; Shimojo, Hiroto

    1973-01-01

    In accord with the nomenclature proposed for mutants of simian virus 40 the same rules, with minor modifications, are recommended for naming mutants of adenoviruses. It is further suggested that these rules, which pertain to a system of classification based primarily upon complementation analysis, also be applied to mutants of other DNA-containing animal viruses. PMID:4355864

  9. Problem-Solving Test: Tryptophan Operon Mutants

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  10. Problem-Solving Test: Tryptophan Operon Mutants

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  11. Systemic endothelial function is preserved in men with both active and inactive variant angina pectoris.

    PubMed

    Ito, K; Akita, H; Kanazawa, K; Yamada, S; Shiga, N; Terashima, M; Matsuda, Y; Takai, E; Iwai, C; Takaoka, H; Yokoyama, M

    1999-12-01

    To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.

  12. Associations between physical inactivity and sedentary behaviors among adolescents in 10 cities in China

    PubMed Central

    2014-01-01

    Background Studies in western countries have revealed that excessive sedentary behavior is a major risk factor for physical inactivity in adolescents. This study was performed to investigate the association between sedentary behavior and physical inactivity in Chinese adolescents using a large-scale cross-sectional survey design. Methods This study was part of the 2011 Chinese Youth Risk Behavior Survey. Between March and September 2011, 10,214 11–18-year-olds were recruited for survey participation in 18 schools in 10 cities in China. Demographic and socioeconomic characteristics, and the prevalences of physical inactivity and sedentary behaviors, were examined. Correlations between sedentary behavior and physical inactivity were analyzed using baseline logistic regression. Results Among the final 9,901 students, physical inactivity (~80%) and sedentary behaviors (television viewing, 43%; computer use, 30.2%) were prevalent. More male than female students reported sedentary behaviors (television viewing > 2 h: 5.5% vs. 3.9%; computer use > 2 h: 7.2% vs. 3.5%; both p < 0.05), but more males were physically active than females (25.1% vs.14.6%; p < 0.05). Television viewing was associated with lower odds of no physical activity (No PA) in males [0–2 h: adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68–0.96; >4 h: OR = 0.34, 95% CI = 0.18–0.64], but not in females. A similar pattern between insufficient physical activity and >4 h TV viewing (AOR = 0.42, 95% CI = 0.23–0.76) and >4 h computer use (AOR = 0.49, 95% CI = 0.30–0.78) was observed in males. In females, 0–2 h daily computer use was associated with higher odds of physical inactivity (No PA: AOR = 1.42, 95% CI = 1.10–1.82; Insufficient PA: AOR = 1.58, 95% CI = 1.24–2.01), while TV viewing was not associated with No PA or Insufficient PA. The probability of physical inactivity significantly increased with

  13. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs.

    PubMed

    1997-02-01

    Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded.

  14. Analysis by substituted cysteine scanning mutagenesis of the fourth transmembrane domain of the CXCR4 receptor in its inactive and active state.

    PubMed

    Boulais, Philip E; Escher, Emanuel; Leduc, Richard

    2013-02-15

    The chemokine SDF-1 (CXCL12) selectively binds to CXCR4, a member of the G protein-coupled receptor (GPCR) superfamily. In this study, we used the substituted-cysteine accessibility method (SCAM) to identify specific residues of the fourth transmembrane domain (TM4) that contribute to the formation of the binding pocket of CXCR4 in its inactive and active state. We successively substituted each residue from E179((4.68)) to K154((4.43)) with cysteine and expressed the mutants in COS-7 cells. Mutant receptors were then alkylated with methanethiosulfonate-ethylammonium (MTSEA), and binding inhibition was monitored using the CXCR4 antagonist FC131 [cyclo(-D-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)], which displays anti-HIV activity. MTSEA treatment resulted in a significant reduction of FC131 binding to D171C((4.60)) and P170C((4.59)). To assess TM4 accessibility in an active state of CXCR4, TM4 cysteine mutants were transposed within the constitutively active mutant N119S((3.35)). MTSEA treatment of TM4 mutants N119S-S178C((4.67)), N119S-V177C((4.66)) and N119S-I173C((4.62)) resulted in a significant reduction in FC131 binding. Protection assays using FC131 prior to MTSEA treatment significantly reduced the alkylation of all MTSEA-sensitive mutants. The accessibility of the D171C((4.60)) and P170C((4.59)) residues suggests that they are oriented towards a water-accessible area of the binding pocket of CXCR4. S178C((4.67)), V177C((4.66)) and I173C((4.62)) showed binding inhibition only in an N119S((3.35)) background. Taken together our results suggest that TM4 and ECL2 undergo conformational changes during CXCR4 activation and also demonstrate how TM4 is an important feature for the binding of anti-HIV compounds.

  15. Nif- Hup- mutants of Rhizobium japonicum.

    PubMed Central

    Moshiri, F; Stults, L; Novak, P; Maier, R J

    1983-01-01

    Two H2 uptake-negative (Hup-) Rhizobium japonicum mutants were obtained that also lacked symbiotic N2 fixation (acetylene reduction) activity. One of the mutants formed green nodules and was deficient in heme. Hydrogen oxidation activity in this mutant could be restored by the addition of heme plus ATP to crude extracts. Bacteroid extracts from the other mutant strain lacked hydrogenase activity and activity for both of the nitrogenase component proteins. Hup+ revertants of the mutant strains regained both H2 uptake ability and nitrogenase activity. Images PMID:6874648

  16. Revocation of Office of Generic Drug's interim policy statement on inactive ingredients. Food and Drug Administration, HHS. Notice.

    PubMed

    1999-04-30

    The Food and Drug Administration (FDA) is revoking an interim policy statement on inactive ingredients in parenteral, ophthalmic, otic, and topical generic drug products (Interim Inactive Ingredient Policy). These generic drug products are the subjects of abbreviated new drug applications (ANDA's). The Interim Inactive Ingredient Policy was issued as a memorandum from the Acting Director of the Center for Drug Evaluation and Research's (CDER's) Office of Generic Drugs, FDA, to CDER's Associate Director for Science and Medical Affairs, FDA. FDA is taking this action because the Interim Inactive Ingredient Policy no longer represents current agency policy.

  17. Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation.

    PubMed

    Wang, Aoli; Yan, Xiao-E; Wu, Hong; Wang, Wenchao; Hu, Chen; Chen, Cheng; Zhao, Zheng; Zhao, Peng; Li, Xixiang; Wang, Li; Wang, Beilei; Ye, Zi; Wang, Jinhua; Wang, Chu; Zhang, Wei; Gray, Nathanael S; Weisberg, Ellen L; Chen, Liang; Liu, Jing; Yun, Cai-Hong; Liu, Qingsong

    2016-10-25

    Ibrutinib, a clinically approved irreversible BTK kinase inhibitor for Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL) etc, has been reported to be potent against EGFR mutant kinase and currently being evaluated in clinic for Non Small Cell Lung Cancer (NSCLC). Through EGFR wt/mutant engineered isogenic BaF3 cell lines we confirmed the irreversible binding mode of Ibrutinib with EGFR wt/mutant kinase via Cys797. However, comparing to typical irreversible EGFR inhibitor, such as WZ4002, the washing-out experiments revealed a much less efficient covalent binding for Ibrutinib. The biochemical binding affinity examination in the EGFR L858R/T790M kinase revealed that, comparing to more efficient irreversible inhibitor WZ4002 (Kd: 0.074 μM), Ibrutinib exhibited less efficient binding (Kd: 0.18 μM). An X-ray crystal structure of EGFR (T790M) in complex with Ibrutinib exhibited a unique DFG-in/c-Helix-out inactive binding conformation, which partially explained the less efficiency of covalent binding and provided insight for further development of highly efficient irreversible binding inhibitor for the EGFR mutant kinase. These results also imply that, unlike the canonical irreversible inhibitor, sustained effective concentration might be required for Ibrutinib in order to achieve the maximal efficacy in the clinic application against EGFR driven NSCLC.

  18. Characterization of mutant histidine-containing proteins of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli and Salmonella typhimurium

    SciTech Connect

    Waygood, E.B.; Reiche, B.; Hengstenberg, W.; Lee, J.S.

    1987-06-01

    Histidine-containing phosphocarrier protein (HPr) is common to all of the phosphoenolpyruvate:sugar phosphotransferase systems (PTS) in Escherichia coli and Salmonella typhimurium, except the fructose-specific PTS. Strains which lack HPr activity (ptsH) have been characterized in the past, and it has proved difficult to delineate between tight and leaky mutants. In this study four different parameters of ptsH strains were measured: in vitro sugar phosphorylation activity of the mutant HPr; detection of /sup 32/P-labeled P-HPr; ability of monoclonal antibodies to bind mutant HPr; and sensitivity of ptsH strains to fosfomycin. Tight ptsH strains could be defined; they were fosfomycin resistant and produced no HPr protein or completely inactive mutant HPr. All leaky ptsH strains were fosfomycin sensitive, Usually produced normal amounts of mutant HPr protein, and had low but measurable activity, and HPr was detectable as a phosphoprotein. This indicates that the regulatory functions of the PTS require a very low level of HPr activity (about 1%). The antibodies used to detect mutant HPr in crude extracts were two monoclonal immunoglobulin G antibodies Jel42 and Jel44. Both antibodies, which have different pIs, inhibited PTS sugar phosphorylation assays, but the antibody-JPr complex could still be phosphorylated by enzyme I. Preliminary evidence suggests that the antibodies bind to two different epitopes which are in part located in a ..beta..-sheet structure.

  19. A Classroom Demonstration of Rayleigh Light Scattering in Optically Active and Inactive Systems.

    ERIC Educational Resources Information Center

    Pecina, Monica Avalos; Smith, Charles A.

    1999-01-01

    Argues that the concept of optical activity is vague to students because it is difficult for instructors to demonstrate the phenomenon in the classroom. Presents a demonstration that allows students to observe and manipulate the optical path of polarized light through optically inactive and active solutions. (CCM)

  20. Past-Year Sexual Inactivity among Older Married Persons and Their Partners

    ERIC Educational Resources Information Center

    Karraker, Amelia; DeLamater, John

    2013-01-01

    Family scholars have focused on the onset of sexual activity early in the life course, but little is known about the cessation of sexual activity in relationships in later life. We use event-history analysis techniques and logistic regression to identify the correlates of sexual inactivity among older married men and women. We analyze data for…

  1. Artist-Teachers' In-Action Mental Models While Teaching Visual Arts

    ERIC Educational Resources Information Center

    Russo-Zimet, Gila

    2017-01-01

    Studies have examined the assumption that teachers have previous perceptions, beliefs and knowledge about learning (Cochran-Smith & Villegas, 2015). This study presented the In-Action Mental Model of twenty leading artist-teachers while teaching Visual Arts in three Israeli art institutions of higher Education. Data was collected in two…

  2. Variables associated with active and inactive behavior during the after-school period.

    PubMed

    Wickel, Eric

    2013-05-01

    This study analyzed time-use interviews to report levels of active and inactive behavior during the after-school period (3-6 pm). Interviews were conducted on random days from three separate seasons during third and fourth grade. Youth with at least two interviews during third (356 completed 2 interviews; 506 completed 3 interviews [9 yrs; 50% boys]) and fourth (186 completed 2 interviews; 768 completed 3 interviews [10 yrs; 50% boys]) grade were included to report levels of moderate-to-vigorous physical activity (MVPA), light physical activity, inactive screen time, inactive nonscreen time, and travel by location and who the activity was undertaken with. Reporting time outside the home and with peers (single or group) was related to higher levels of MVPA. While inside the home, screen and nonscreen proportions were comparable (38% and 40%, respectively), despite unique patterns (screen: boys > girls; nonscreen: girls > boys). Reporting time with both parents was associated with more nonscreen time; whereas reporting time with peer groups was associated with lower screen time. Understanding active and inactive patterns of children's behavior outside of school hours can be very important in contributing toward the development of innovative interventions for increasing physical activity.

  3. Past-Year Sexual Inactivity among Older Married Persons and Their Partners

    ERIC Educational Resources Information Center

    Karraker, Amelia; DeLamater, John

    2013-01-01

    Family scholars have focused on the onset of sexual activity early in the life course, but little is known about the cessation of sexual activity in relationships in later life. We use event-history analysis techniques and logistic regression to identify the correlates of sexual inactivity among older married men and women. We analyze data for…

  4. Teacher Educators' In-Action Mental Models in Different Teaching Situations

    ERIC Educational Resources Information Center

    Mevorach, Miriam; Strauss, Sidney

    2012-01-01

    In previous studies on teachers' cognition, we discovered that teachers' teaching can be described via a general in-action mental model (IAMM) concerning the structure of the mind and the roles of teaching in fostering children's learning. The purpose of our study was to examine teacher educators' IAMM regarding student teachers' minds and…

  5. Exploring Socio-Ecological Factors Influencing Active and Inactive Spanish Students in Years 12 and 13

    ERIC Educational Resources Information Center

    Devís-Devís, José; Beltrán-Carrillo, Vicente J.; Peiró-Velert, Carmen

    2015-01-01

    This paper explores socio-ecological factors and their interplay that emerge from a qualitative study and influence adolescents' physical activity and sport participation. A total of 13 boys and 7 girls active and inactive adolescents, from years 12 and 13 and different types of school (state and private), participated in semi-structured…

  6. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  7. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  8. Results of myringoplasty operations in active and inactive ears in adults.

    PubMed

    Mills, Robert; Thiel, Gundula; Mills, Nadtaya

    2013-09-01

    To determine whether the presence of aural discharge at the time of surgery adversely affects the success rate of myringoplasty operations. Case series comparing the success rate of surgery in active and inactive ears. Data pertaining to 268 operations involving repair of the tympanic membrane without ossiculoplasty carried out in Edinburgh, United Kingdom, between 1999 and 2009 by one senior surgeon and trainees working under his supervision were collected prospectively. Other factors that might potentially influence the outcome of the surgery were investigated using logistical regression analysis. The main outcome measure was number of patients with an intact tympanic membrane 6 months after surgery in the two groups (active and inactive). Of the 268 operations carried out, 203 were successful, with an intact tympanic membrane, 6 months postoperatively, 43 had persistent perforations, and 22 patients were lost to follow-up before 6 months. The success rates for closure of the perforation at 6 months after surgery were 83% for inactive and 82% for active ears (P = .9). There is no clinically significant difference in the success rate for myringoplasty in patients whose ears are active or inactive at the time of surgery. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Effects of inactivity on myosin heavy chain composition and size of rat soleus fibers

    NASA Technical Reports Server (NTRS)

    Grossman, E. J.; Roy, R. R.; Talmadge, R. J.; Zhong, H.; Edgerton, V. R.

    1998-01-01

    Myosin heavy chain (MHC) and fiber size properties of the adult rat soleus were determined after 4-60 days of complete inactivity, i.e., lumbar spinal cord isolation. Soleus atrophy was rapid and progressive, i.e., 25% and 64% decrease in weight and 33% and 75% decrease in fiber size after 4 and 60 days of inactivity, respectively. Changes in MHC occurred at a slower rate than the atrophic response. After 15 days there was de novo expression of type IIx MHC (approximately 10%). By 60 days, type IIx MHC accounted for 33% of the total MHC content, and 7% of the fibers contained only type IIx MHC. The relative amount of type I MHC was reduced from 93% in control to 49% after 60 days of inactivity. Therefore, the effects of 60 days of inactivity suggest that during this time period at least 75% of fiber size and approximately 40% of type I MHC composition of the adult rat soleus can be attributed to activation-related events.

  10. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes.

    PubMed

    Wei, M; Gibbons, L W; Kampert, J B; Nichaman, M Z; Blair, S N

    2000-04-18

    Although physical activity is recommended as a basic treatment for patients with diabetes, its long-term association with mortality in these patients is unknown. To evaluate the association of low cardiorespiratory fitness and physical inactivity with mortality in men with type 2 diabetes. Prospective cohort study. Preventive medicine clinic. 1263 men (50+/-10 years of age) with type 2 diabetes who received a thorough medical examination between 1970 and 1993 and were followed for mortality up to 31 December 1994. Cardiorespiratory fitness measured by a maximal exercise test, self-reported physical inactivity at baseline, and subsequent death determined by using the National Death Index. During an average follow-up of 12 years, 180 patients died. After adjustment for age, baseline cardiovascular disease, fasting plasma glucose level, high cholesterol level, overweight, current smoking, high blood pressure, and parental history of cardiovascular disease, men in the low-fitness group had an adjusted risk for all-cause mortality of 2.1 (95% CI, 1.5 to 2.9) compared with fit men. Men who reported being physically inactive had an adjusted risk for mortality that was 1.7-fold (CI, 1.2-fold to 2.3-fold) higher than that in men who reported being physically active. Low cardiorespiratory fitness and physical inactivity are independent predictors of all-cause mortality in men with type 2 diabetes. Physicians should encourage patients with type 2 diabetes to participate in regular physical activity and improve cardiorespiratory fitness.

  11. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  12. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  13. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  14. Short term clinical effect of active and inactive Salvadora persica miswak on dental plaque and gingivitis.

    PubMed

    Sofrata, Abier; Brito, Fernanda; Al-Otaibi, Meshari; Gustafsson, Anders

    2011-10-11

    Salvadora persica shrub has been used traditionally in folk medicine for different medical condition treatments. The habitual use of Salvadora persica roots (chewing sticks) for dental hygiene is still wildly spread throughout parts of Asia, Africa, and Middle. It is one of the most important species with its reported strong antibacterial, antifungal, and antiviral effects. Mechanical removal of dental plaque is regarded as an effective mean of controlling progression of periodontal disease. To evaluate the effect of active and inactive miswak on dental plaque, subgingival microbiota and gingival inflammation in patients with gingivitis. In this double blinded randomized controlled trial 68 gingivitis patients were randomly assigned to either active or inactive miswak group, and were instructed to use only issued miswaks for oral hygiene during 3 weeks experimental period. Registration of plaque, gingival inflammation, and plaque samples were taken at baseline and on completion of the study. Plaque samples were analyzed by DNA-DNA hybridization technique. Active miswak significantly reduced dental plaque (p = 0.007). There were no differences between active and inactive miswak in reduction of approximal plaque and composition of subgingival microbiota. Miswak has an overall effect on dental plaque and gingival inflammation scores. Similar results were achieved by active and inactive miswak in difficult to reach areas, indicating miswak has limited chemical effects on this study population. Therefore, miswak can be used as a dental hygiene method in conjunction with interproximal cleaning aides. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

  16. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

  17. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

  18. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

  19. 17 CFR 210.3-11 - Financial statements of an inactive registrant.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Financial statements of an... COMMISSION FORM AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933, SECURITIES... Financial Statements § 210.3-11 Financial statements of an inactive registrant. If a registrant is an...

  20. [The costs of physical inactivity in the world: a general review].

    PubMed

    Bueno, Denise Rodrigues; Marucci, Maria de Fátima Nunes; Codogno, Jamile Sanches; Roediger, Manuela de Almeida

    2016-04-01

    There is convincing evidence in the scientific literature of the effectiveness of regular physical activity and physical exercise in the conservation of health and the prevention of various ailments. However, studies into the association between costs of medical services and physical inactivity have not been duly addressed. International studies have quantified these costs and revealed the association between physical activity and/or sedentary behavior. Therefore, this review sought to gather information available from several countries and analyze the global costs associated with physical inactivity over the past few decades. The results of twenty-four original and well-researched articles in nine countries, including Brazil, were analyzed. The results showed that physical inactivity, irrespective of the method of classification, is burdensome to the economy of health worldwide, and directly responsible for the high cost of medication, the incidence of hospitalization and the frequency of medical appointments. The costs of the group of the physically inactive population affected by chronic diseases feature among the major components of the total costs involved in public health.

  1. Epidemiology of physical inactivity, sedentary behaviors, and unhealthy eating habits among Brazilian adolescents: a systematic review.

    PubMed

    Barbosa Filho, Valter Cordeiro; de Campos, Wagner; Lopes, Adair da Silva

    2014-01-01

    This systematic review analyzed the prevalence of physical inactivity, sedentary behaviors and unhealthy eating habits among Brazilian adolescents. Searches were conducted in five databases (Lilacs, SciELO, Medline, Web of Science, and Google Scholar) and in the references cited in the articles retrieved. The literature search yielded 5,872 potentially relevant titles and a total of 69 studies met all the inclusion criteria. The risk behavior most often evaluated was physical inactivity (48/69; 69.6%), and its prevalence rate ranged from 2.3% to 93.5%. Twenty-eight studies estimated the prevalence of physical inactivity at over 50%. Most studies observed the prevalence of greater physical inactivity among girls. The prevalence of sedentary behaviors (lengthy screen time or TV use) was also frequently over 50%. Several variables were used to identify unhealthy eating habits, and some criteria/studies have indicated unhealthy eating habit estimates at close to 100% among adolescents. In conclusion, the estimates of these risk behaviors among Brazilians adolescents were very close to or even greater than those found in developed countries in several studies analyzed in this review.

  2. Inactive tanks remediation program strategy and plans for Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-03-01

    This report presents plans and strategies for remediation of the liquid low-level waste (LLLW) tanks that have been removed from service (also known as inactive tanks) at Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee. These plans and strategies will be carried out by the Environmental Restoration Program`s Inactive LLLW Tank Program at ORNL. These tanks are defined as Category D tanks because they are existing tank systems without secondary containment that are removed from service. The approach to remediation of each tank or tank farm must be adapted in response to the specific circumstances of individual tank sites. The approach will be tailored to accommodate feedback on lessons learned from previous tank remediation activities and will not be a rigid step-by-step approach that must be conducted identically for every tank system. However, the approach will follow a multistep decision process. The overall objective of the Inactive Tank Program is to remediate all LLLW tanks that have been removed from service to the extent practicable in accordance with the FFA requirements. The Inactive Tank Program will focus on the remediation of the tank residues (i.e., contents after tank has been emptied) and tank shell. This strategy is discussed in detail in this report.

  3. Inactive tanks remediation program strategy and plans for Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-11-01

    This report presents plans and strategies for remediation of the liquid low-level waste (LLLW) tanks that have been removed from service (also known as inactive tanks) at Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee. These plans and strategies will be carried out by the Environmental Restoration Program`s Inactive LLLW Tank Program at ORNL. The approach to remediation of each tank or tank farm must be adapted in response to the specific circumstances of individual tank sites. The approach will be tailored to accommodate feedback on lessons learned from previous tank remediation activities and will not be a rigid step-by-step approach that must be conducted identically for every tank system. However, the approach will follow a multistep decision process. The overall objective of the Inactive Tank Program is to remediate all LLLW tanks that have been removed from service to the extent practicable in accordance with the FFA requirements. The Inactive Tank Program will focus on the remediation of the tank residues and tank shell. This strategy is discussed in detail in this report.

  4. "Learning-in-Action" and "Learning Inaction": Advancing the Theory and Practice of Critical Action Learning

    ERIC Educational Resources Information Center

    Vince, Russ

    2008-01-01

    This paper seeks to improve our understanding of the emotional and political dynamics that are generated (and too often avoided) in action learning. The idea at the centre of the paper is a distinction between "learning-in-action" and "learning inaction". The phrase "learning-in-action" represents the value of action…

  5. Physical inactivity and obesity: Using a novel environmental quality measure to control confounding

    EPA Science Inventory

    Physical inactivity is well-established as a contributor to obesity prevalence in the US. Many aspects of the ambient environment (e.g., air pollution, food deserts, neighborhood socioeconomics) have also been associated with obesity. Yet, controlling for the overall ambient envi...

  6. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  7. YMDD motif variants in inactive hepatitis B carriers detected by Inno-Lipa HBV DR assay.

    PubMed

    Akarsu, Mesut; Sengonul, Aylin; Tankurt, Ethem; Sayiner, Ayca Arzu; Topalak, Omer; Akpinar, Hale; Abacioglu, Yusuf Hakan

    2006-12-01

    Mutations of hepatitis B virus (HBV) polymerase, especially occurring at the highly conserved YMDD region, are related to resistance to lamivudine. Although these mutations are frequently secondary to lamivudine use, they can also occur naturally. The aim of the present study was to determine the prevalence of YMDD variants that exist naturally in patients who are inactive HBV carriers. Seventy-one adult inactive HBV carriers were studied. All of the patients were confirmed to have maintained normal alanine aminotransferase (ALT) values for one or more years by monitoring serum ALT levels at 3-monthly intervals. None of the patients received interferon or antiviral agents. YMDD variants were analyzed by the HBV Drug Resistance Line Probe assay (Inno-Lipa HBV-DR). YMDD variants were detected in 13 (18.3%) of the 71 anti-HBe positive inactive HBV carriers. Of the 13 patients, 10 (76.9%) also had accompanying L180M mutation. The combination of wild type and YMDD variant HBV was present in 11 of 13 patients. In two patients, only YIDD and/or YVDD variants plus L180M were detected without the presence of wild YMDD motif. Naturally occurring YMDD motif variants were detected at a high rate in a group of lamivudine-untreated inactive HBV carriers.

  8. [Physical inactivity among non-institutionalized elderly individuals: a population-based study].

    PubMed

    Queiroz, Bruno Morbeck de; Coqueiro, Raildo da Silva; Leal Neto, João de Souza; Borgatto, Adriano Ferreti; Barbosa, Aline Rodrigues; Fernandes, Marcos Henrique

    2014-08-01

    The scope of this study is to assess the prevalence of physical inactivity among the elderly in Northeast Brazil and analyze the associated lifestyle and socio-demographic factors and health conditions. The work presented here is a descriptive and association-based study using secondary data derived from a population-based epidemiological study that included 316 elderly participants. The physical activity level of each participant was assessed using the International Physical Activity Questionnaire. The explanatory variables examined in this study were gender, age group, family set-up, ability to read and write, paid or voluntary employment, smoking, symptoms of depression, high blood pressure, fasting hyperglycemia and functional capacity. The prevalence of physical inactivity was 46.5. The results of the multivariate analysis indicated that physical inactivity was positively associated with the age group ≥ 80 years (PR = 2.37), with the lack of an occupation (PR = 4.86) and with dependence on instrumental activities of daily life (PR = 1.47) and basic activities of daily life (PR = 1.60). Physical inactivity was highly prevalent in the surveyed population, making it essential to discuss programs that encourage and enable increased physical activity to combat the risk factors of a sedentary lifestyle.

  9. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

  10. CONTRIBUTION OF AXIAL MOTOR IMPAIRMENT TO PHYSICAL INACTIVITY IN PARKINSON'S DISEASE

    PubMed Central

    Bryant, Mon S; Hou, Jyhgong Gabriel; Collins, Robert L; Protas, Elizabeth J

    2015-01-01

    Objective To investigate the relationships between motor symptoms of Parkinson’s disease (PD) and activity limitations in persons with PD. Design/Methods Cross-sectional study of persons with mild to moderate PD (N=90). Associations among axial motor features, limb motor signs, the Physical Activity Scale for Elders (PASE), the ability to perform Activities of Daily Living (ADL) and level of ADL dependency were studied. A composite score of axial motor features included the following UPDRS items: speech, rigidity of the neck, arising from chair, posture, gait and postural stability. A composite score of limb motor signs included the following UPDRS items: tremor at rest of all extremities, action tremor, rigidity of all extremities, finger taps, hand movement, rapid alternating hand movements and foot tapping. Results Axial motor features of PD were significantly correlated with physical inactivity (p<.001), decreased ADL (p<.001) and increase in ADL dependency (p<.001). Limb motor signs significantly correlated with decreased ADL (p<.001) and level of ADL dependency (p=.035), but was not correlated with physical inactivity. After controlling for age, gender, disease duration and comorbidity, axial motor features contributed significantly to physical inactivity, decreased ADL and increase in ADL dependency, whereas the limb motor signs did not. Conclusions Axial motor impairment contributed to physical inactivity and decreased ability to perform ADLs in persons with PD. PMID:26368837

  11. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  12. Effects of inactivity on myosin heavy chain composition and size of rat soleus fibers

    NASA Technical Reports Server (NTRS)

    Grossman, E. J.; Roy, R. R.; Talmadge, R. J.; Zhong, H.; Edgerton, V. R.

    1998-01-01

    Myosin heavy chain (MHC) and fiber size properties of the adult rat soleus were determined after 4-60 days of complete inactivity, i.e., lumbar spinal cord isolation. Soleus atrophy was rapid and progressive, i.e., 25% and 64% decrease in weight and 33% and 75% decrease in fiber size after 4 and 60 days of inactivity, respectively. Changes in MHC occurred at a slower rate than the atrophic response. After 15 days there was de novo expression of type IIx MHC (approximately 10%). By 60 days, type IIx MHC accounted for 33% of the total MHC content, and 7% of the fibers contained only type IIx MHC. The relative amount of type I MHC was reduced from 93% in control to 49% after 60 days of inactivity. Therefore, the effects of 60 days of inactivity suggest that during this time period at least 75% of fiber size and approximately 40% of type I MHC composition of the adult rat soleus can be attributed to activation-related events.

  13. Physical inactivity and obesity: Using a novel environmental quality measure to control confounding

    EPA Science Inventory

    Physical inactivity is well-established as a contributor to obesity prevalence in the US. Many aspects of the ambient environment (e.g., air pollution, food deserts, neighborhood socioeconomics) have also been associated with obesity. Yet, controlling for the overall ambient envi...

  14. Emotional Outlook on Life Predicts Increases in Physical Activity among Initially Inactive Men

    ERIC Educational Resources Information Center

    Baruth, Meghan; Lee, Duck-Chul; Sui, Xuemei; Church, Timothy S.; Marcus, Bess H.; Wilcox, Sara; Blair, Steven N.

    2011-01-01

    This study examined the relationship between emotional outlook on life and change in physical activity among inactive adults in the Aerobics Center Longitudinal Study. A total of 2,132 sedentary adults completed a baseline medical examination and returned for a follow-up examination at least 6 months later. Participants self-reported physical…

  15. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  16. Overweight and Physical Inactivity Among African American Students at a Historically Black University.

    PubMed

    Sa, Jaesin; Heimdal, James; Sbrocco, Tracy; Seo, Dong-Chul; Nelson, Beatrice

    2016-02-01

    Little is known about correlates of overweight, obesity, and physical inactivity among African American students at historically Black colleges and universities. To assess overweight, obesity, and physical inactivity among African American college students at a historically Black university in Maryland in the USA. Data were collected from 268 African American college students in 2013. Data were analyzed with percentage difference z-tests, chi-square tests, and multiple logistic regression. Cross-sectional survey (student response rate = 49.9%). The overweight/obesity rate of participants was 47.5%, which was higher than that of the U.S. college student population overall (34.1%) and a representative sample of African American college students (38.3%). When age and sex were controlled, a family history of obesity, skipping breakfast, drinking caffeinated drinks, lower family income, and smoking a pipe, cigars, or cigarettes daily were significant correlates of overweight (obesity included). The percentage of physical inactivity was 68.3, and physical inactivity was higher among women and overweight or obese students. Given the high overweight and obesity prevalence among African American college students, historically Black colleges and universities in the USA should increase health promotion efforts targeting weight-related behaviors, particularly physical activity. Copyright © 2016. Published by Elsevier Inc.

  17. Evaluating Equity: A Framework for Understanding Action and Inaction on Social Justice Issues

    ERIC Educational Resources Information Center

    Opfer, V. Darleen

    2006-01-01

    This article relies on a case study of a policy evaluation to illustrate how issues of social justice arise for action or inaction in a political environment. The article uses the case study to show that social justice issue formation is shaped by the personal beliefs of the actors, the prevailing political culture, the evolutionary path of the…

  18. Exploring Socio-Ecological Factors Influencing Active and Inactive Spanish Students in Years 12 and 13

    ERIC Educational Resources Information Center

    Devís-Devís, José; Beltrán-Carrillo, Vicente J.; Peiró-Velert, Carmen

    2015-01-01

    This paper explores socio-ecological factors and their interplay that emerge from a qualitative study and influence adolescents' physical activity and sport participation. A total of 13 boys and 7 girls active and inactive adolescents, from years 12 and 13 and different types of school (state and private), participated in semi-structured…

  19. When Physical Activity Participation Promotes Inactivity: Negative Experiences of Spanish Adolescents in Physical Education and Sport

    ERIC Educational Resources Information Center

    Beltran-Carrillo, Vicente J.; Devis-Devis, Jose; Peiro-Velert, Carmen; Brown, David H. K.

    2012-01-01

    This article analyses negative experiences in physical education and sport reported during qualitative interviews of a group of inactive adolescent Spanish boys and girls. The purpose of this analysis is twofold. First and most important, it seeks to give voice to these young people reporting negative experiences and connect them to contexts of…

  20. Expression, purification and characterization of inactive and active forms of ERK2 from insect expression system.

    PubMed

    Yan, Kelly; Merritt, Hanne; Crawford, Kenneth; Pardee, Gwynn; Cheng, Jan Marie; Widger, Stephania; Hekmat-Nejad, Mohammad; Zaror, Isabel; Sim, Janet

    2015-06-01

    Extracellular signal-regulated kinase 2 (ERK2) is a serine/threonine protein kinase involved in many cellular programs, such as cell proliferation, differentiation, motility and programed cell-death. It is therefore considered an important target in the treatment of cancer. In an effort to support biochemical screening and small molecule drug discovery, we established a robust system to generate both inactive and active forms of ERK2 using insect expression system. We report here, for the first time, that inactive ERK2 can be expressed and purified with 100% homogeneity in the unphosphorylated form using insect system. This resulted in a significant 20-fold yield improvement compared to that previously reported using bacterial expression system. We also report a newly developed system to generate active ERK2 in insect cells through in vivo co-expression with a constitutively active MEK1 (S218D S222D). Isolated active ERK2 was confirmed to be doubly phosphorylated at the correct sites, T185 and Y187, in the activation loop of ERK2. Both ERK2 forms, inactive and active, were well characterized by biochemical activity assay for their kinase function. Inactive and active ERK2 were the two key reagents that enabled successful high through-put biochemical assay screen and structural drug discovery studies.

  1. Emotional Outlook on Life Predicts Increases in Physical Activity among Initially Inactive Men

    ERIC Educational Resources Information Center

    Baruth, Meghan; Lee, Duck-Chul; Sui, Xuemei; Church, Timothy S.; Marcus, Bess H.; Wilcox, Sara; Blair, Steven N.

    2011-01-01

    This study examined the relationship between emotional outlook on life and change in physical activity among inactive adults in the Aerobics Center Longitudinal Study. A total of 2,132 sedentary adults completed a baseline medical examination and returned for a follow-up examination at least 6 months later. Participants self-reported physical…

  2. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  3. 2014 consensus statement from the first Economics of Physical Inactivity Consensus (EPIC) conference (Vancouver).

    PubMed

    Davis, Jennifer C; Verhagen, Evert; Bryan, Stirling; Liu-Ambrose, Teresa; Borland, Jeff; Buchner, David; Hendriks, Marike R C; Weiler, Richard; Morrow, James R; van Mechelen, Willem; Blair, Steven N; Pratt, Mike; Windt, Johann; al-Tunaiji, Hashel; Macri, Erin; Khan, Karim M

    2014-06-01

    This article describes major topics discussed from the 'Economics of Physical Inactivity Consensus Workshop' (EPIC), held in Vancouver, Canada, in April 2011. Specifically, we (1) detail existing evidence on effective physical inactivity prevention strategies; (2) introduce economic evaluation and its role in health policy decisions; (3) discuss key challenges in establishing and building health economic evaluation evidence (including accurate and reliable costs and clinical outcome measurement) and (4) provide insight into interpretation of economic evaluations in this critically important field. We found that most methodological challenges are related to (1) accurately and objectively valuing outcomes; (2) determining meaningful clinically important differences in objective measures of physical inactivity; (3) estimating investment and disinvestment costs and (4) addressing barriers to implementation. We propose that guidelines specific for economic evaluations of physical inactivity intervention studies are developed to ensure that related costs and effects are robustly, consistently and accurately measured. This will also facilitate comparisons among future economic evidence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. The R163K Mutant of Human Thymidylate Synthase Is Stabilized in an Active Conformation: Structural Asymmetry and Reactivity of Cysteine 195

    SciTech Connect

    Gibson, Lydia M.; Lovelace, Leslie L.; Lebioda, Lukasz

    2008-06-16

    Loop 181-197 of human thymidylate synthase (hTS) populates two conformational states. In the first state, Cys195, a residue crucial for catalytic activity, is in the active site (active conformer); in the other conformation, it is about 10 {angstrom} away, outside the active site (inactive conformer). We have designed and expressed an hTS variant, R163K, in which the inactive conformation is destabilized. The activity of this mutant is 33% higher than that of wt hTS, suggesting that at least one-third of hTS populates the inactive conformer. Crystal structures of R163K in two different crystal forms, with six and two subunits per asymmetric part of the unit cells, have been determined. All subunits of this mutant are in the active conformation while wt hTS crystallizes as the inactive conformer in similar mother liquors. The structures show differences in the environment of catalytic Cys195, which correlate with Cys195 thiol reactivity, as judged by its oxidation state. Calculations show that the molecular electrostatic potential at Cys195 differs between the subunits of the dimer. One of the dimers is asymmetric with a phosphate ion bound in only one of the subunits. In the absence of the phosphate ion, that is in the inhibitor-free enzyme, the tip of loop 47-53 is about 11 {angstrom} away from the active site.

  5. Why are Jupiter-family comets active and asteroids in cometary-like orbits inactive?. How hydrostatic compression leads to inactivity

    NASA Astrophysics Data System (ADS)

    Gundlach, B.; Blum, J.

    2016-05-01

    Context. Surveys in the visible and near-infrared spectral range have revealed the presence of low-albedo asteroids in cometary-like orbits (ACOs). In contrast to Jupiter-family comets (JFCs), ACOs are inactive, but possess similar orbital parameters. Aims: In this work, we discuss why ACOs are inactive, whereas JFCs show gas-driven dust activity, although both belong to the same class of primitive solar system bodies. Methods: We hypothesize that ACOs and JFCs have formed under the same physical conditions, namely by the gravitational collapse of ensembles of ice and dust aggregates. We use the memory effect of dust-aggregate layers under gravitational compression to discuss under which conditions the gas-driven dust activity of these bodies is possible. Results: Owing to their smaller sizes, JFCs can sustain gas-driven dust activity much longer than the bigger ACOs, whose sub-surface regions possess an increased tensile strength, due to gravitational compression of the material. The increased tensile strength leads to the passivation against dust activity after a relatively short time of activity. Conclusions: The gravitational-collapse model of the formation of planetesimals, together with the gravitational compression of the sub-surface material simultaneously, explains the inactivity of ACOs and the gas-driven dust activity of JFCs. Their initially larger sizes means that ACOs possess a higher tensile strength of their sub-surface material, which leads to a faster termination of gas-driven dust activity. Most objects with radii larger than 2 km have already lost their activity due to former gravitational compression of their current surface material.

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

    PubMed

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

    2015-01-01

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

  7. Overcoming EGFR T790M and C797S resistance with mutant-selective allosteric inhibitors

    PubMed Central

    Jia, Yong; Yun, Cai-Hong; Park, Eunyoung; Ercan, Dalia; Manuia, Mari; Juarez, Jose; Xu, Chunxiao; Rhee, Kevin; Chen, Ting; Zhang, Haikuo; Palakurthi, Sangeetha; Jang, Jaebong; Lelais, Gerald; DiDonato, Michael; Bursulaya, Badry; Michellys, Pierre-Yves; Epple, Robert; Marsilje, Thomas H.; McNeill, Matthew; Lu, Wenshuo; Harris, Jennifer; Bender, Steven; Wong, Kwok-Kin; Jänne, Pasi A.; Eck, Michael J.

    2016-01-01

    EGFR tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harboring activating mutations in the EGFR kinase1,2, but resistance arises rapidly, most frequently due to the secondary T790M mutation within the ATP-site of the receptor.3,4 Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant5,6, but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond7. All current EGFR TKIs target the ATP-site of the kinase, highlighting the need for therapeutic agents with alternate mechanisms of action. Here we describe rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild type receptor. A crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays, but as a single agent is not effective in blocking EGFR-driven proliferation in cells due to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state8. We observe dramatic synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization9,10, rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by L858R/T790M EGFR and by L858R/T790M/C797S EGFR, a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors. PMID:27251290

  8. The Impact of Smoking on Airflow Limitation in Subjects with History of Asthma and Inactive Tuberculosis

    PubMed Central

    Kim, Hyun Jung; Baek, Seunghee; Kim, Hee Jin; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2015-01-01

    Background Although smoking is the most important and modifiable cause of chronic obstructive pulmonary disease (COPD), other risk factors including asthma and tuberculosis (TB) are also associated. It is common for COPD patients to have more than one of these risk factors. The aims of this study were to determine the prevalence of airflow limitation (FEV1/FVC<0.7) according to the risk factors and to investigate their impact and interaction in airflow limitation. Methods From the Korean National Health and Nutrition Examination Survey between 2008 and 2012, we analyzed participants over 40 years of age by spirometry, chest radiograph and questionnaire about asthma and smoking history. Results Of 12,631 participants, 1,548 (12.3%) had airflow limitation. The prevalence of airflow limitation in smokers (≥10 pack-year), asthmatics, and those with inactive TB was 23.9%, 32.1%, and 33.6%. The prevalence increased with the number of risk factors: 86.1% had airflow limitation if they had all three risk factors. Impacts of inactive TB and asthma on airflow limitation were equivalent to 47 and 69 pack-years of smoking, respectively. Airflow limitation resulted from lower levels of smoking in those with inactive TB and asthma. A potential interaction between smoking and inactive tuberculosis in the development of airflow limitation was identified (p = 0.054). Conclusions Asthma and inactive TB lesions increase susceptibility to smoking in the development of airflow limitation. People with these risk factors should be seen as a major target population for anti-smoking campaigns to prevent COPD. PMID:25915938

  9. Body image emotions, perceptions, and cognitions distinguish physically active and inactive smokers

    PubMed Central

    Contreras, Gisèle A.; Sabiston, Catherine M.; O'Loughlin, Erin K.; Bélanger, Mathieu; O'Loughlin, Jennifer

    2015-01-01

    Objectives To determine if body image emotions (body-related shame and guilt, weight-related stress), perceptions (self-perceived overweight), or cognitions (trying to change weight) differ between adolescents characterized by smoking and physical activity (PA) behavior. Methods Data for this cross-sectional analysis were collected in 2010–11 and were available for 1017 participants (mean (SD) age = 16.8 (0.5) years). Participants were categorized according to smoking and PA status into four groups: inactive smokers, inactive non-smokers, active smokers and active non-smokers. Associations between body image emotions, perceptions and cognitions, and group membership were estimated in multinomial logistic regression. Results Participants who reported body-related shame were less likely (OR (95% CI) = 0.52 (0.29–0.94)) to be in the active smoker group than the inactive smoker group; those who reported body-related guilt and those trying to gain weight were more likely (2.14 (1.32–3.48) and 2.49 (1.22–5.08), respectively) to be in the active smoker group than the inactive smoker group; those who were stressed about weight and those perceiving themselves as overweight were less likely to be in the active non-smoker group than the inactive smoker group (0.79 (0.64–0.97) and 0.41 (0.19–0.89), respectively). Conclusion Body image emotions and cognitions differentiated the active smoker group from the other three groups. PMID:26844062

  10. PRC2 represses transcribed genes on the imprinted inactive X chromosome in mice.

    PubMed

    Maclary, Emily; Hinten, Michael; Harris, Clair; Sethuraman, Shriya; Gayen, Srimonta; Kalantry, Sundeep

    2017-05-03

    Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which marks many transcriptionally silent genes throughout the mammalian genome. Although H3K27me3 is associated with silenced gene expression broadly, it remains unclear why some but not other PRC2 target genes require PRC2 and H3K27me3 for silencing. Here we define the transcriptional and chromatin features that predict which PRC2 target genes require PRC2/H3K27me3 for silencing by interrogating imprinted mouse X-chromosome inactivation. H3K27me3 is enriched at promoters of silenced genes across the inactive X chromosome. To abrogate PRC2 function, we delete the core PRC2 protein EED in F1 hybrid trophoblast stem cells (TSCs), which undergo imprinted inactivation of the paternally inherited X chromosome. Eed (-/-) TSCs lack H3K27me3 and Xist lncRNA enrichment on the inactive X chromosome. Despite the absence of H3K27me3 and Xist RNA, only a subset of the inactivated X-linked genes is derepressed in Eed (-/-) TSCs. Unexpectedly, in wild-type (WT) TSCs these genes are transcribed and are enriched for active chromatin hallmarks on the inactive-X, including RNA PolII, H3K27ac, and H3K36me3, but not the bivalent mark H3K4me2. By contrast, PRC2 targets that remain repressed in Eed (-/-) TSCs are depleted for active chromatin characteristics in WT TSCs. A comparative analysis of transcriptional and chromatin features of inactive X-linked genes in WT and Eed (-/-) TSCs suggests that PRC2 acts as a brake to prevent induction of transcribed genes on the inactive X chromosome, a mode of PRC2 function that may apply broadly.

  11. Addressing physical inactivity in Omani adults: perceptions of public health managers.

    PubMed

    Mabry, Ruth M; Al-Busaidi, Zakiya Q; Reeves, Marina M; Owen, Neville; Eakin, Elizabeth G

    2014-03-01

    To explore barriers and solutions to addressing physical inactivity and prolonged sitting in the adult population of Oman. Qualitative study involving semi-structured interviews that took place from October 2011 to January 2012. Participants were recruited through purposive sampling. Data collection and analysis was an iterative process; later interviews explored emerging themes. Interviews were audio-recorded and transcribed and continued until data saturation; this occurred by the tenth interviewee. Thematic content analysis was carried out, guided by an ecological model of health behaviour. Muscat, Oman. Ten mid-level public health managers. Barriers for physical inactivity were grouped around four themes: (i) intrapersonal (lack of motivation, awareness and time); (ii) social (norms restricting women's participation in outdoor activity, low value of physical activity); (iii) environment (lack of places to be active, weather); and (iv) policy (ineffective health communication, limited resources). Solutions focused on culturally sensitive interventions at the environment (building sidewalks and exercise facilities) and policy levels (strengthening existing interventions and coordinating actions with relevant sectors). Participants' responses regarding sitting time were similar to, but much more limited than those related to physical inactivity, except for community participation and voluntarism, which were given greater emphasis as possible solutions to reduce sitting time. Given the increasing prevalence of chronic disease in Oman and the Arabian Gulf, urgent action is required to implement gender-relevant public health policies and programmes to address physical inactivity, a key modifiable risk factor. Additionally, research on the determinants of physical inactivity and prolonged sitting time is required to guide policy makers.

  12. Lactate and H+ uptake in inactive muscles during intense exercise in man.

    PubMed Central

    Bangsbo, J; Aagaard, T; Olsen, M; Kiens, B; Turcotte, L P; Richter, E A

    1995-01-01

    1. The present study examined how uptake of lactate and H+ in resting muscle is affected by blood flow, arterial lactate concentration and muscle metabolism. 2. Six males subjects performed intermittent arm exercise in two separate 32 min periods (Part I and Part II) and in one subsequent 20 min period in which one leg knee-extensor exercise was also performed (Part III). The exercise was performed at various intensities in order to obtain different steady-state arterial blood lactate concentrations. In the inactive leg, femoral venous blood flow (draining about 7.7 kg of muscles) was measured and femoral arterial and venous blood was collected frequently. Biopsies were taken from m. vastus lateralis of the inactive leg at rest and 10 and 30 min into both Part I and Part II as well as 10 min into recovery from Part II. 3. The arterial plasma lactate concentrations were 7, 9 and 16 mmol l-1 after 10 min of Parts I, II and III, respectively, and the corresponding arterial-venous difference (a-vdiff) for lactate in the resting leg was 1.3, 1.4 and 2.0 mmol l-1. The muscle lactate concentration was 2.8 mmol (kg wet wt)-1 after 10 min of Part I and remained constant throughout the experiment. During Parts I and II, a-vdiff lactate decreased although the arterial lactate concentration and plasma-muscle lactate gradient were unaltered throughout each period. Thus, membrane transport of lactate decreased during each period. 4. Blood flow in the inactive leg was about 2-fold higher during arm exercise compared to the rest periods, resulting in a 2-fold higher lactate uptake. Thus, lactate uptake by inactive muscles was closely related to blood flow. 5. Throughout the experiment a-vdiff for actual base excess and for lactate were of similar magnitude. Thus, in inactive muscles lactate uptake appears to be coupled to the transport of H+. PMID:8568658

  13. [Physical inactivity and anthropometric measures in school children from Paranavaí, Paraná, Brazil].

    PubMed

    Guilherme, Flávio Ricardo; Molena-Fernandes, Carlos Alexandre; Guilherme, Vânia Renata; Fávero, Maria Teresa Martins; dos Reis, Eliane Josefa Barbosa; Rinaldi, Wilson

    2015-01-01

    To investigate the association between physical inactivity and anthropometric measurements in school children from Paranavaí-Paraná, Brazil. Cross-sectional survey, conducted in July and August 2013. Sample of 566 students (287 boys and 278 girls) from 6th to 9th grade aged 10 to 14 years of public and private schools from Paranavaí-PR, Southern Brazil. The variables analyzed were: time of weekly physical activity by a questionnaire (physical inactivity <300 minutes/week), body mass index (BMI) and waist circumference (WC). In the statistical analysis the U Mann-Whitney and Student t test were used for comparison between genders. To identify factors associated with insufficient levels of physical activity, univariate and multivariate logistic regression analysis was applied and expressed in Odds ratio (OR) and 95% confidence interval (CI). There was an association between physical inactivity and anthropometric measurements for BMI (p<0.001) and WC (p<0.001), with a prevalence rate of 56.1% and 52.7% of inactive adolescents, respectively. In the multivariate analysis, there was significant association of physical inactivity and overweight (OR 1.8, 95%CI: 1.1-3.0) and with increased waist circumference (OR 2.8, 95%CI: 1.4-3.8). Inadequate levels of physical activity is a determining factor for overweight and abdominal adiposity. Accordingly, preventive measures should be taken, especially in schools, emphasizing the importance of exercise in the control of body composition and reduction of weight. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  14. Selection of chemotaxis mutants of Dictyostelium discoideum

    PubMed Central

    1987-01-01

    A method has been developed for the efficient selection of chemotaxis mutants of Dictyostelium discoideum. Mutants defective in the chemotactic response to folate could be enriched up to 30-fold in one round of selection using a chamber in which a compartment that contained the chemoattractant was separated by a sandwich of four nitrocellulose filters from a compartment that contained buffer. Mutagenized cells were placed in the center of the filter layer and exposed to the attractant gradient built up between the compartments for a period of 3-4 h. While wild-type cells moved through the filters in a wave towards the compartment that contained attractant, mutant cells remained in the filter to which they were applied. After several repetitions of the selection procedure, mutants defective in chemotaxis made up 10% of the total cell population retained in that filter. Mutants exhibiting three types of alterations were collected: motility mutants with either reduced speed of movement, or altered rates of turning; a single mutant defective in production of the attractant- degrading enzyme, folate deaminase; and mutants with normal motility but reduced chemotactic responsiveness. One mutant showed drastically reduced sensitivity in folate-induced cGMP production. Morphogenetic alterations of mutants defective in folate chemotaxis are described. PMID:3793759

  15. Structural Insights into Conformational Stability of Wild-Type and Mutant β1-Adrenergic Receptor

    PubMed Central

    Balaraman, Gouthaman S.; Bhattacharya, Supriyo; Vaidehi, Nagarajan

    2010-01-01

    Abstract Recent experiments to derive a thermally stable mutant of turkey beta-1-adrenergic receptor (β1AR) have shown that a combination of six single point mutations resulted in a 20°C increase in thermal stability in mutant β1AR. Here we have used the all-atom force-field energy function to calculate a stability score to detect stabilizing point mutations in G-protein coupled receptors. The calculated stability score shows good correlation with the measured thermal stability for 76 single point mutations and 22 multiple mutants in β1AR. We have demonstrated that conformational sampling of the receptor for various mutants improve the prediction of thermal stability by 50%. Point mutations Y227A5.58, V230A5.61, and F338M7.48 in the thermally stable mutant m23-β1AR stabilizes key microdomains of the receptor in the inactive conformation. The Y227A5.58 and V230A5.61 mutations stabilize the ionic lock between R1393.50 on transmembrane helix3 and E2856.30 on transmembrane helix6. The mutation F338M7.48 on TM7 alters the interaction of the conserved motif NPxxY(x)5,6F with helix8 and hence modulates the interaction of TM2-TM7-helix8 microdomain. The D186-R317 salt bridge (in extracellular loops 2 and 3) is stabilized in the cyanopindolol-bound wild-type β1AR, whereas the salt bridge between D184-R317 is preferred in the mutant m23. We propose that this could be the surrogate to a similar salt bridge found between the extracellular loop 2 and TM7 in β2AR reported recently. We show that the binding energy difference between the inactive and active states is less in m23 compared to the wild-type, which explains the activation of m23 at higher norepinephrine concentration compared to the wild-type. Results from this work throw light into the mechanism behind stabilizing mutations. The computational scheme proposed in this work could be used to design stabilizing mutations for other G-protein coupled receptors. PMID:20643076

  16. A profile of inactive information seekers on influenza prevention: a survey of health care workers in Central Kentucky.

    PubMed

    Kim, Sujin; Real, Kevin

    2016-09-01

    This study developed a profile of inactive information seekers by characterising how they are different from active seekers, identifying possible determinants of inactive seekers and understanding characteristics of frequently asked influenza-related questions. A survey and follow-up interviews were conducted between December 2010 and January 2011. A total of 307 health care workers in three hospitals in Central Kentucky (USA) are included. Four study groups were formed based on their information-seeking and vaccination uptake status: (1) Inactive Seekers with Vaccination (N = 141); (2) Inactive Seekers without Vaccination (N = 49); (3) Active Seekers with Vaccination (N = 107); and (4) Active Seekers without Vaccination (N = 10). Inactive Seekers without Vaccination are found to be least responsive to health outcomes. Inactive Seeker groups do not prefer to use sources such as Internet or family/friends. In predicting inactive seekers, Information Needs and Knowledge Perception made significant contributions to prediction. The most frequently asked questions included information about survival duration of influenza virus (N = 25) followed by the incubation period for influenza (N = 24). Profiling inactive seekers can serve as a way to better design customised influenza information sources and services for health care workers, thus giving hospitals through medical libraries additional tools to reduce the spread of influenza. © 2016 Health Libraries Group.

  17. Clustering of Physical Inactivity in Leisure, Work, Commuting, and Household Domains: Data From 47,477 Industrial Workers in Brazil.

    PubMed

    Del Duca, Giovâni F; Garcia, Leandro Martin Totaro; da Silva, Shana Ginar; da Silva, Kelly Samara; Oliveira, Elusa S; Barros, Mauro V; Nahas, Markus V

    2015-09-01

    Physical inactivity in each domain (leisure, work, commuting, and household) is not completely independent. This study aimed to describe the clustering of physical inactivity in different domains and its association with sociodemographic factors among Brazilian industrial workers. This was a cross-sectional, population-based study using data from 23 Brazilian states and the Federal District collected via questionnaires between 2006 and 2008. Physical inactivity in each domain was defined as nonparticipation in specific physical activities. Clustering of physical inactivity was identified using the ratio of the observed (O) and expected (E) percentages of each combination. Multinomial logistic regression was used to identify sociodemographic factors with the outcome. Among the 44,477 interviewees, most combinations exceeded expectations, particularly the clustering of physical inactivity in all domains among men (O/E = 1.37; 95% CI: 1.30; 1.44) and women (O/E = 1.47; 95% CI: 1.36; 1.60). Physical inactivity in 2 or more domains was observed more frequently in women, older age groups, individuals living without a partner, and those with higher education and income levels. Physical inactivity tends to be observed in clusters regardless of gender. Women and workers with higher income levels were the main factors associated with to be physically inactive in 2 or more domains.

  18. Probing kinetic drug binding mechanism in voltage-gated sodium ion channel: open state versus inactive state blockers.

    PubMed

    Pal, Krishnendu; Gangopadhyay, Gautam

    2015-01-01

    The kinetics and nonequilibrium thermodynamics of open state and inactive state drug binding mechanisms have been studied here using different voltage protocols in sodium ion channel. We have found that for constant voltage protocol, open state block is more efficient in blocking ionic current than inactive state block. Kinetic effect comes through peak current for mexiletine as an open state blocker and in the tail part for lidocaine as an inactive state blocker. Although the inactivation of sodium channel is a free energy driven process, however, the two different kinds of drug affect the inactivation process in a different way as seen from thermodynamic analysis. In presence of open state drug block, the process initially for a long time remains entropy driven and then becomes free energy driven. However in presence of inactive state block, the process remains entirely entropy driven until the equilibrium is attained. For oscillating voltage protocol, the inactive state blocking is more efficient in damping the oscillation of ionic current. From the pulse train analysis it is found that inactive state blocking is less effective in restoring normal repolarisation and blocks peak ionic current. Pulse train protocol also shows that all the inactive states behave differently as one inactive state responds instantly to the test pulse in an opposite manner from the other two states.

  19. 42 CFR 407.32 - Prejudice to enrollment rights because of Federal Government misrepresentation, inaction, or error.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... enrollment rights because of Federal Government misrepresentation, inaction, or error. If an individual's..., misrepresentation, on inaction of a Federal employee or any person authorized by the Federal Government to act in... 42 Public Health 2 2014-10-01 2014-10-01 false Prejudice to enrollment rights because of...

  20. 42 CFR 407.32 - Prejudice to enrollment rights because of Federal Government misrepresentation, inaction, or error.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... enrollment rights because of Federal Government misrepresentation, inaction, or error. If an individual's..., misrepresentation, on inaction of a Federal employee or any person authorized by the Federal Government to act in... 42 Public Health 2 2013-10-01 2013-10-01 false Prejudice to enrollment rights because of...

  1. 42 CFR 407.32 - Prejudice to enrollment rights because of Federal Government misrepresentation, inaction, or error.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... enrollment rights because of Federal Government misrepresentation, inaction, or error. If an individual's..., misrepresentation, on inaction of a Federal employee or any person authorized by the Federal Government to act in... 42 Public Health 2 2011-10-01 2011-10-01 false Prejudice to enrollment rights because of...

  2. 42 CFR 407.32 - Prejudice to enrollment rights because of Federal Government misrepresentation, inaction, or error.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... enrollment rights because of Federal Government misrepresentation, inaction, or error. If an individual's..., misrepresentation, on inaction of a Federal employee or any person authorized by the Federal Government to act in... 42 Public Health 2 2010-10-01 2010-10-01 false Prejudice to enrollment rights because of...

  3. 42 CFR 407.32 - Prejudice to enrollment rights because of Federal Government misrepresentation, inaction, or error.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... enrollment rights because of Federal Government misrepresentation, inaction, or error. If an individual's..., misrepresentation, on inaction of a Federal employee or any person authorized by the Federal Government to act in... 42 Public Health 2 2012-10-01 2012-10-01 false Prejudice to enrollment rights because of...

  4. Places where preschoolers are (in)active: An observational study on Latino preschoolers and their parents using objective measures

    USDA-ARS?s Scientific Manuscript database

    To combat the disproportionately higher risk of childhood obesity in Latino preschool-aged children, multilevel interventions targeting physical (in)activity are needed. These require the identification of environmental and psychosocial determinants of physical (in)activity for this ethnic group. Th...

  5. Urban-Rural Differences in Overweight Status and Physical Inactivity among US Children Aged 10-17 Years

    ERIC Educational Resources Information Center

    Liu, Jihong; Bennett, Kevin J.; Harun, Nusrat; Probst, Janice C.

    2008-01-01

    Context: Few studies have examined the prevalence of overweight status and physical inactivity among children and adolescents living in rural America. Purpose: We examined urban and rural differences in the prevalence of overweight status and physical inactivity among US children. Methods: Data were drawn from the 2003 National Survey of…

  6. Urban-Rural Differences in Overweight Status and Physical Inactivity among US Children Aged 10-17 Years

    ERIC Educational Resources Information Center

    Liu, Jihong; Bennett, Kevin J.; Harun, Nusrat; Probst, Janice C.

    2008-01-01

    Context: Few studies have examined the prevalence of overweight status and physical inactivity among children and adolescents living in rural America. Purpose: We examined urban and rural differences in the prevalence of overweight status and physical inactivity among US children. Methods: Data were drawn from the 2003 National Survey of…

  7. Physical Inactivity from Adolescence to Young Adulthood: The Relevance of Various Dimensions of Inequality in a Swedish Longitudinal Sample

    ERIC Educational Resources Information Center

    Wells, Laura; Nermo, Magnus; Östberg, Viveca

    2017-01-01

    As physical inactivity may track from adolescence to adulthood, it is important to identify social determinants of physical inactivity in early life. However, most studies have measured socioeconomic position as one dimension. We examine whether multiple dimensions of socioeconomic position, in addition to other dimensions of inequality (i.e.,…

  8. The x-ray crystal structure of mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome.

    PubMed

    Yongqing, Tang; Wilmann, Pascal G; Reeve, Shane B; Coetzer, Theresa H; Smith, A Ian; Whisstock, James C; Pike, Robert N; Wijeyewickrema, Lakshmi C

    2013-08-02

    The mannose-binding lectin associated-protease-3 (MASP-3) is a member of the lectin pathway of the complement system, a key component of human innate and active immunity. Mutations in MASP-3 have recently been found to be associated with Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome, a severe developmental disorder manifested by cleft palate, intellectual disability, and skeletal abnormalities. However, the molecular basis for MASP-3 function remains to be understood. Here we characterize the substrate specificity of MASP-3 by screening against a combinatorial peptide substrate library. Through this approach, we successfully identified a peptide substrate that was 20-fold more efficiently cleaved than any other identified to date. Furthermore, we demonstrated that mutant forms of the enzyme associated with 3MC syndrome were completely inactive against this substrate. To address the structural basis for this defect, we determined the 2.6-Å structure of the zymogen form of the G666E mutant of MASP-3. These data reveal that the mutation disrupts the active site and perturbs the position of the catalytic serine residue. Together, these insights into the function of MASP-3 reveal how a mutation in this enzyme causes it to be inactive and thus contribute to the 3MC syndrome.

  9. The X-ray Crystal Structure of Mannose-binding Lectin-associated Serine Proteinase-3 Reveals the Structural Basis for Enzyme Inactivity Associated with the Carnevale, Mingarelli, Malpuech, and Michels (3MC) Syndrome*

    PubMed Central

    Yongqing, Tang; Wilmann, Pascal G.; Reeve, Shane B.; Coetzer, Theresa H.; Smith, A. Ian; Whisstock, James C.; Pike, Robert N.; Wijeyewickrema, Lakshmi C.

    2013-01-01

    The mannose-binding lectin associated-protease-3 (MASP-3) is a member of the lectin pathway of the complement system, a key component of human innate and active immunity. Mutations in MASP-3 have recently been found to be associated with Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome, a severe developmental disorder manifested by cleft palate, intellectual disability, and skeletal abnormalities. However, the molecular basis for MASP-3 function remains to be understood. Here we characterize the substrate specificity of MASP-3 by screening against a combinatorial peptide substrate library. Through this approach, we successfully identified a peptide substrate that was 20-fold more efficiently cleaved than any other identified to date. Furthermore, we demonstrated that mutant forms of the enzyme associated with 3MC syndrome were completely inactive against this substrate. To address the structural basis for this defect, we determined the 2.6-Å structure of the zymogen form of the G666E mutant of MASP-3. These data reveal that the mutation disrupts the active site and perturbs the position of the catalytic serine residue. Together, these insights into the function of MASP-3 reveal how a mutation in this enzyme causes it to be inactive and thus contribute to the 3MC syndrome. PMID:23792966

  10. [Synergism between aggregation mutants of Dictyostelium discoideum].

    PubMed

    Barra, J

    1977-02-21

    The cells of an aggregateless mutant of Dictyostelium discoïdeum, agip 235, can cooperate with other aggregateless or wild strains to form differentiated aggregates. A soluble mediator liberated by the coaggregating cells seems responsible for the development of agip 235. In most cases, the development of mutant agip 235 stops at the aggregation stage; however, its coaggregation with the mutant 518 results in cosporulation, with the production of viable spores of each genotype, effecting a phenotypic suppression of both mutations.

  11. Identifying representative drug resistant mutants of HIV

    PubMed Central

    2015-01-01

    Background Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. Results In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. Conclusion This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID:26678327

  12. Electrophysiological study of Drosophila rhodopsin mutants

    PubMed Central

    1986-01-01

    Electrophysiological investigations were carried out on several independently isolated mutants of the ninaE gene, which encodes opsin in R1-6 photoreceptors, and a mutant of the ninaD gene, which is probably important in the formation of the rhodopsin chromophore. In these mutants, the rhodopsin content in R1-6 photoreceptors is reduced by 10(2)-10(6)-fold. Light-induced bumps recorded from even the most severely affected mutants are physiologically normal. Moreover, a detailed noise analysis shows that photoreceptor responses of both a ninaE mutant and a ninaD mutant follow the adapting bump model. Since any extensive rhodopsin-rhodopsin interactions are not likely in these mutants, the above results suggest that such interactions are not needed for the generation and adaptation of light-induced bumps. Mutant bumps are strikingly larger in amplitude than wild-type bumps. This difference is observed both in ninaD and ninaE mutants, which suggests that it is due to severe depletion of rhodopsin content, rather than to any specific alterations in the opsin protein. Lowering or buffering the intracellular calcium concentration by EGTA injection mimics the effects of the mutations on the bump amplitude, but, unlike the mutations, it also affects the latency and kinetics of light responses. PMID:3097245

  13. Expression and characterization of glycogen synthase kinase-3 mutants and their effect on glycogen synthase activity in intact cells.

    PubMed Central

    Eldar-Finkelman, H; Argast, G M; Foord, O; Fischer, E H; Krebs, E G

    1996-01-01

    In these studies we expressed and characterized wild-type (WT) GSK-3 (glycogen synthase kinase-3) and its mutants, and examined their physiological effect on glycogen synthase activity. The GSK-3 mutants included mutation at serine-9 either to alanine (S9A) or glutamic acid (S9E) and an inactive mutant, K85,86MA. Expression of WT and the various mutants in a cell-free system indicated that S9A and S9E exhibit increased kinase activity as compared with WT. Subsequently, 293 cells were transiently transfected with WT GSK-3 and mutants. Cells expressing the S9A mutant exhibited higher kinase activity (2.6-fold of control cells) as compared with cells expressing WT and S9E (1.8- and 2.0-fold, respectively, of control cells). Combined, these results suggest serine-9 as a key regulatory site of GSK-3 inactivation, and indicate that glutamic acid cannot mimic the function of the phosphorylated residue. The GSK-3-expressing cell system enabled us to examine whether GSK-3 can induce changes in the endogenous glycogen synthase activity. A decrease in glycogen synthase activity (50%) was observed in cells expressing the S9A mutant. Similarly, glycogen synthase activity was suppressed in cells expressing WT and the S9E mutant (20-30%, respectively). These studies indicate that activation of GSK-3 is sufficient to inhibit glycogen synthase in intact cells, and provide evidence supporting a physiological role for GSK-3 in regulating glycogen synthase and glycogen metabolism. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8816781

  14. Transcriptome analysis of the epidermis of the purple quail-like (q-lp) mutant of silkworm, Bombyx mori

    PubMed Central

    Xia, Dingguo; Tang, Shunming; Shen, Xingjia

    2017-01-01

    A new purple quail-like (q-lp) mutant found from the plain silkworm strain 932VR has pigment dots on the epidermis similar to the pigment mutant quail (q). In addition, q-lp mutant larvae are inactive, consume little and grow slowly, with a high death rate and other developmental abnormalities. Pigmentation of the silkworm epidermis consists of melanin, ommochrome and pteridine. Silkworm development is regulated by ecdysone and juvenile hormone. In this study, we performed RNA-Seq on the epidermis of the q-lp mutant in the 4th instar during molting, with 932VR serving as the control. The results showed 515 differentially expressed genes, of which 234 were upregulated and 281 downregulated in q-lp. BLASTGO analysis indicated that the downregulated genes mainly encode protein-binding proteins, membrane components, oxidation/reduction enzymes, and proteolytic enzymes, whereas the upregulated genes largely encode cuticle structural constituents, membrane components, transport related proteins, and protein-binding proteins. Quantitative reverse transcription PCR was used to verify the accuracy of the RNA-Seq data, focusing on key genes for biosynthesis of the three pigments and chitin as well as genes encoding cuticular proteins and several related nuclear receptors, which are thought to play key roles in the q-lp mutant. We drew three conclusions based on the results: 1) melanin, ommochrome and pteridine pigments are all increased in the q-lp mutant; 2) more cuticle proteins are expressed in q-lp than in 932VR, and the number of upregulated cuticular genes is significantly greater than downregulated genes; 3) the downstream pathway regulated by ecdysone is blocked in the q-lp mutant. Our research findings lay the foundation for further research on the developmental changes responsible for the q-lp mutant. PMID:28414820

  15. Transcriptome analysis of the epidermis of the purple quail-like (q-lp) mutant of silkworm, Bombyx mori.

    PubMed

    Wang, Pingyang; Qiu, Zhiyong; Xia, Dingguo; Tang, Shunming; Shen, Xingjia; Zhao, Qiaoling

    2017-01-01

    A new purple quail-like (q-lp) mutant found from the plain silkworm strain 932VR has pigment dots on the epidermis similar to the pigment mutant quail (q). In addition, q-lp mutant larvae are inactive, consume little and grow slowly, with a high death rate and other developmental abnormalities. Pigmentation of the silkworm epidermis consists of melanin, ommochrome and pteridine. Silkworm development is regulated by ecdysone and juvenile hormone. In this study, we performed RNA-Seq on the epidermis of the q-lp mutant in the 4th instar during molting, with 932VR serving as the control. The results showed 515 differentially expressed genes, of which 234 were upregulated and 281 downregulated in q-lp. BLASTGO analysis indicated that the downregulated genes mainly encode protein-binding proteins, membrane components, oxidation/reduction enzymes, and proteolytic enzymes, whereas the upregulated genes largely encode cuticle structural constituents, membrane components, transport related proteins, and protein-binding proteins. Quantitative reverse transcription PCR was used to verify the accuracy of the RNA-Seq data, focusing on key genes for biosynthesis of the three pigments and chitin as well as genes encoding cuticular proteins and several related nuclear receptors, which are thought to play key roles in the q-lp mutant. We drew three conclusions based on the results: 1) melanin, ommochrome and pteridine pigments are all increased in the q-lp mutant; 2) more cuticle proteins are expressed in q-lp than in 932VR, and the number of upregulated cuticular genes is significantly greater than downregulated genes; 3) the downstream pathway regulated by ecdysone is blocked in the q-lp mutant. Our research findings lay the foundation for further research on the developmental changes responsible for the q-lp mutant.

  16. Dynamic characteristics of heat exchanger tubes vibrating in a tube support plate inactive mode

    SciTech Connect

    Jendrzejczyk, J.A.

    1984-06-01

    Tubes in shell-and-tube heat exchangers, including nuclear plant steam generators, derive their support from longitudinally positioned tube support plates (TSPs). Typically there is a clearance between the tube and TSP hole. Depending on design and fabrication tolerances, the tube may or may not contract all of the TSPs. Noncontact results in an inactive TSP which can lead to detrimental flow induced tube vibrations under certain conditions dependent on the resulting tube-TSP interaction dynamics and the fluid excitation forces. The purpose of this study is to investigate the tube-TSP interaction dynamics. Results of an experimental study of damping and natural frequency as functions of tube-TSP diametral clearance and TSP thickness are reported. Calculated values of damping ratio and frequency of a tube vibrating within an inactive TSP are also presented together with a comparison of calculated and experimental quantities.

  17. Dynamic characteristics of heat exchanger tubes vibrating in a tube support plate inactive mode

    SciTech Connect

    Jendrzejczyk, J.A.

    1985-01-01

    Tubes in shell-and-tube heat exchangers, including nuclear plant steam generators, derive their support from longitudinally positioned tube support plates (TSPs). Typically there is a clearance between the tube and TSP hole. Depending on design and fabrication tolerances, the tube may or may not contact all of the TSPs. Noncontact results in an inactive TSP which can lead to detrimental flow induced tube vibrations under certain conditions dependent on the resulting tube-TSP interaction dynamics and the fluid excitation forces. The purpose of this study is to investigate the tube-TSP interaction dynamics. Results of an experimental study of damping and natural frequency as functions of tube-TSP diametral clearance and TSP thickness are reported. Calculated values of damping ratio and frequency of a tube vibrating within an inactive TSP are also presented together with a comparison of calculated and experimetnal quantities.

  18. Influence of radiative processes on the ignition of deuterium-tritium plasma containing inactive impurities

    NASA Astrophysics Data System (ADS)

    Gus'kov, S. Yu.; Sherman, V. E.

    2016-08-01

    The degree of influence of radiative processes on the ignition of deuterium-tritium (DT) plasma has been theoretically studied as dependent on the content of inactive impurities in plasma. The analytic criterion of plasma ignition in inertial confinement fusion (ICF) targets is modified taking into account the absorption of intrinsic radiation from plasma in the ignition region. The influence of radiative processes on the DT plasma ignition has been analytically and numerically studied for plasma that contains a significant fraction of inactive impurities either as a result of DT fuel mixing with ICF target ablator material or as a result of using light metal DT-hydrides as solid noncryogenic fuel. It has been shown that the effect of the absorption of intrinsic radiation leads to lower impurity-induced increase in the ignition energy as compared to that calculated in the approximation of optically transparent ignition region.

  19. Estimating the peer effect on youth overweight and inactivity using an intervention study.

    PubMed

    Quinto Romani, Annette

    2014-10-01

    Understanding peer effect is potentially important for finding ways to combat the obesity epidemic. Nevertheless, it is not clear whether a peer effect exists because of the composition of the peer group, because the group members have similar, unobserved individual characteristics, or because of an endogenous effect. This issue is addressed here by using a unique longitudinal data set of 573 schoolchildren attending state schools in the Municipality of Aalborg, Denmark, during 2008-2010. To identify the spillover effect of a targeted intervention on peers, we use a difference-in-differences approach. A targeted health intervention reduced body mass index (BMI) among overweight, inactive individuals and, more interestingly, that BMI among the nontreated peers was reduced by 1.04%. The analysis suggests that individually targeted health intervention has a health benefit beyond the treated individual, which needs to be included when evaluating targeted policies aiming to combat childhood overweight and inactivity. © 2014, American School Health Association.

  20. The importance of dietary protein for muscle health in inactive, hospitalized older adults.

    PubMed

    Thalacker-Mercer, Anna E; Drummond, Micah J

    2014-11-01

    Dietary protein and amino acids are necessary for overall human health. Insufficient protein intake induces a negative protein balance with adverse outcomes such as muscle atrophy and functional decline--outcomes that are worsened in older adults. Furthermore, during inactivity, such as bed rest/hospitalization, skeletal muscle protein synthesis is reduced, protein balance is negative, and older adults lose significant amounts of muscle. Dietary protein and amino acid supplementation (∼ 30 g protein and ∼ 3 g leucine) stimulate skeletal muscle protein anabolism in healthy, community-dwelling older adults and may be considered as possible nutritional interventions to improve the muscle protein balance and potentially support skeletal muscle maintenance in hospitalized older adults. The following is a timely review of metabolic and dietary challenges faced by hospitalized older adults and potential dietary protein and amino acids solutions for maintaining skeletal muscle health during hospitalization-induced inactivity in this population. © 2014 New York Academy of Sciences.

  1. Revegetation and rock cover for stabilization of inactive uranium mill tailings disposal sites. Final report

    SciTech Connect

    Beedlow, P.A.

    1984-05-01

    Guidelines for using vegetation and rock to protect inactive uranium mill tailings from erosion were developed by Pacific Northwest Laboratory as part of the Department of Energy's Uranium Mill Tailings Remedial Action Project (UMTRAP) Technology Development program. Information on soils, climate, and vegetation were collected for 20 inactive tailings sites in the western United States. Sites were grouped according to similarities in climate and vegetation. Soil loss for those sites was characterized using the Universal Soil Loss Equation. Test plots were used to evaluate (1) the interaction between vegetation and sealant barrier systems and (2) the effects of surface rock on soil water and vegetation. Lysimeter and simulation studies were used to direct and support field experiments. 49 references, 17 figures, 16 tables.

  2. Geophysical Characterization of Inactive Mine Tailings: A First Step for Economical Design of Vegetative Covers

    NASA Astrophysics Data System (ADS)

    Berger, P. A.; Heinse, R.; Abdu, H.; Tuller, M.; Jones, S. B.; Schaap, M. G.; Artiola, J. F.

    2008-12-01

    The ability to sustain native vegetation on inactive mine tailings mitigates numerous environmental issues such as mass movement due to wind and water, leaching of hazardous chemicals, as well as aesthetic concerns. Mine tailings commonly exhibit a gradient of narrow particle size distributions similar to river delta sediment patterns, which result in poor plant water availability. To develop strategies for optimizing hydrological conditions in mine tailings in the arid Southwest we conducted an electromagnetic induction (EMI)surface survey and applied electrical resistivity imaging (ERI) along selected transects of an inactive tailings site. EMI and ERI data were applied in conjunction with geostatistical analysis to determine contrasting locations for core sampling and installation of time domain transmission (TDT) sensors for long- term monitoring of profile water status. The obtained subsurface maps will be used in combination with numerical modeling to propose cost-efficient designs for vegetative tailings covers.

  3. Transport dynamics of molecular motors that switch between an active and inactive state.

    PubMed

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  4. Influence of radiative processes on the ignition of deuterium–tritium plasma containing inactive impurities

    SciTech Connect

    Gus’kov, S. Yu.; Sherman, V. E.

    2016-08-15

    The degree of influence of radiative processes on the ignition of deuterium–tritium (DT) plasma has been theoretically studied as dependent on the content of inactive impurities in plasma. The analytic criterion of plasma ignition in inertial confinement fusion (ICF) targets is modified taking into account the absorption of intrinsic radiation from plasma in the ignition region. The influence of radiative processes on the DT plasma ignition has been analytically and numerically studied for plasma that contains a significant fraction of inactive impurities either as a result of DT fuel mixing with ICF target ablator material or as a result of using light metal DT-hydrides as solid noncryogenic fuel. It has been shown that the effect of the absorption of intrinsic radiation leads to lower impurity-induced increase in the ignition energy as compared to that calculated in the approximation of optically transparent ignition region.

  5. Major initiatives related to childhood obesity and physical inactivity in Canada: the year in review.

    PubMed

    Tremblay, Mark S

    2007-01-01

    This commentary briefly reviews 10 significant initiatives related to childhood obesity and physical inactivity in Canada in 2007. These include: the Children's Fitness Tax Credit; CAN-PLAY research findings from the Canadian Fitness and Lifestyle Research Institute; resurrection of ParticipACTION; Healthy Weights for Healthy Kids report from the Standing Committee on Health; launch of the Canadian Health Measures Survey; publication of the Canadian Clinical Practice Guidelines on the Management and Prevention of Obesity in Adults and Children; Canada's food and beverage industry initiatives launch; hosting the International Conference on Physical Activity and Obesity in Children; release of the Active Healthy Kids Canada report card on physical activity for children and youth; and publication of the "advancing the future of Canada's physical activity measurement and guidelines" project. The diversity and intensity of activity addressing the childhood obesity and physical inactivity "epidemic" in Canada is encouraging and must be maintained.

  6. Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity.

    PubMed

    Mitra, Ananya; Mitra, Siddhartha S; Tsien, Richard W

    2011-12-18

    Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic tetrodotoxin treatment greatly reduced the percentage of connected CA3-CA3 neurons, but enhanced the strength of the remaining connections; presynaptic release probability sharply increased, whereas quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas three-dimensional anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while protecting network stability.

  7. The effects of exergaming on physical activity among inactive children in a physical education classroom.

    PubMed

    Fogel, Victoria A; Miltenberger, Raymond G; Graves, Rachel; Koehler, Shannon

    2010-01-01

    Childhood obesity, which is due in part to lack of physical activity, is a serious concern that requires the attention of the behavioral community. Although excessive video game play has been noted in the literature as a contributor to childhood obesity, newer video gaming technology, called exergaming, has been designed to capitalize on the reinforcing effects of video games to increase physical activity in children. This study evaluated the effects of exergaming on physical activity among 4 inactive children in a physical education (PE) classroom. Results showed that exergaming produced substantially more minutes of physical activity and more minutes of opportunity to engage in physical activity than did the standard PE program. In addition, exergaming was socially acceptable to both the students and the PE teacher. Exergaming appears to hold promise as a method for increasing physical activity among inactive children and might be a possible intervention for childhood obesity.

  8. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation

    PubMed Central

    Elf, Shannon; Abdelfattah, Nouran S.; Chen, Edwin; Perales-Patón, Javier; Rosen, Emily A.; Ko, Amy; Peisker, Fabian; Florescu, Natalie; Giannini, Silvia; Wolach, Ofir; Morgan, Elizabeth A.; Tothova, Zuzana; Losman, Julie-Aurore; Schneider, Rebekka K.; Al-Shahrour, Fatima; Mullally, Ann

    2016-01-01

    Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN) but the mechanism by which mutant CALR is oncogenic remains unclear. Here, we demonstrate that expression of mutant CALR alone is sufficient to engender MPN in mice and recapitulates the disease phenotype of CALR-mutant MPN patients. We further show that the thrombopoietin receptor, MPL is required for mutant CALR-driven transformation through JAK-STAT pathway activation, thus rendering mutant CALR-transformed hematopoietic cells sensitive to JAK2 inhibition. Finally, we demonstrate that the oncogenicity of mutant CALR is dependent on the positive electrostatic charge of the C-terminus of the mutant protein, which is necessary for physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel paradigm of cancer pathogenesis and reveal how CALR mutations induce MPN. PMID:26951227

  9. Arctic Ground Squirrels Limit Bone Loss during the Prolonged Physical Inactivity Associated with Hibernation.

    PubMed

    Wojda, Samantha J; Gridley, Richard A; McGee-Lawrence, Meghan E; Drummer, Thomas D; Hess, Ann; Kohl, Franziska; Barnes, Brian M; Donahue, Seth W

    2016-01-01

    Prolonged disuse (e.g., physical inactivity) typically results in increased bone porosity, decreased mineral density, and decreased bone strength, leading to increased fracture risk in many mammals. However, bears, marmots, and two species of ground squirrels have been shown to preserve macrostructural bone properties and bone strength during long seasons of hibernation while they remain mostly inactive. Some small hibernators (e.g., 13-lined ground squirrels) show microstructural bone loss (i.e., osteocytic osteolysis) during hibernation, which is not seen in larger hibernators (e.g., bears and marmots). Arctic ground squirrels (Urocitellus parryii) are intermediate in size between 13-lined ground squirrels and marmots and are perhaps the most extreme rodent hibernator, hibernating for up to 8 mo annually with body temperatures below freezing. The goal of this study was to quantify the effects of hibernation and inactivity on cortical and trabecular bone properties in arctic ground squirrels. Cortical bone geometrical properties (i.e., thickness, cross-sectional area, and moment of inertia) at the midshaft of the femur were not different in animals sampled over the hibernation and active seasons. Femoral ultimate stress tended to be lower in hibernators than in summer animals, but toughness was not affected by hibernation. The area of osteocyte lacunae was not different between active and hibernating animals. There was an increase in osteocytic lacunar porosity in the hibernation group due to increased lacunar density. Trabecular bone volume fraction in the proximal tibia was unexpectedly greater in the hibernation group than in the active group. This study shows that, similar to other hibernators, arctic ground squirrels are able to preserve many bone properties during hibernation despite being physically inactive for up to 8 mo.

  10. Daily pilates exercise or inactivity for patients with low back pain: a clinical prospective observational study.

    PubMed

    Notarnicola, A; Fischetti, F; Maccagnano, G; Comes, R; Tafuri, S; Moretti, B

    2014-02-01

    Studies have shown the effectiveness of a few weekly pilates sessions as helping to reduce lower back pain (LBP). However many patients fear that physical activity can actually make the pain and disability worse. We carried out this observational prospective clinical study to look at the effects that taking part in daily pilates has one on side and on the other the effects of LBP management without physical exercise. The volunteers who participated in this study were recruited from among some local cultural associations. Patients affected by LBP were evaluated. The subjects were 60 volunteers (27 males and 33 females) with a mean age of 51.2 years who had chronic low back pain (CLBP). They were allocated to pilates group (N.=30) or inactivity control group (N.=30). The pilates group performed one-hour lesson of pilates exercise, 5 lessons per week during the following 6 months. The inactivity group continued with their normal daily activities. The Roland-Morris Disability, the Oswestry, the SF-36 and the Spinal Functional Sort Questionaries of all subjects were measured at the baseline (T1) and at 6 months (T2). At T2 improvements were observed in the pilates group with increases in physical and social functioning, general health and vitality (P<0.05) and decreases in disability and pain (P<0.05). The inactivity group showed worsening in the same measures at T2. We found an important improvement of pain, disability and physical and psychological perception of health in individuals who did the daily sessions of pilates. Some authors underlined the possible risk of a lack of adherence to an exercise program at home. This study suggests that a daily pilates program is effective for the management of CLBP. On the other hand, the inactivity contributes to further worsening, inducing a vicious cycle in which pain and physical activity intolerance follow each other.

  11. School Social Fragmentation, Economic Deprivation and Social Cohesion and Adolescent Physical Inactivity: A Longitudinal Study

    PubMed Central

    Pabayo, Roman; Janosz, Michel; Bisset, Sherri; Kawachi, Ichiro

    2014-01-01

    Objectives To examine the independent influence of school economic deprivation, social fragmentation, and social cohesion on the likelihood of participating in no physical activity among students. Methods Data are from a large-scale longitudinal study of schools based in disadvantaged communities in Quebec, Canada. Questionnaires were administered every year between 2002 and 2008 among n = 14,924 students aged 12 to 18 from a sample of 70 schools. Cross-sectional and longitudinal analyses were conducted. Multilevel modeling was utilized to account for the clustering of students within schools. Schools were categorized as being low, moderate or high economic deprivation, social fragmentation and social cohesion. Those who indicated that they do no participate in any physical activity during the week were identified as being physically inactive. Results In baseline multilevel cross-sectional analyses, adolescents attending schools in the highest (compared to the lowest) levels of socioeconomic deprivation and social fragmentation were more likely to be physically inactive (OR = 1.33, 95% CI = 1.03, 1.72; and OR = 1.24, 95% CI = 0.98, 1.56, respectively). Conversely, students attending schools with the highest cohesion were less likely to be physically inactive (OR = 0.78, 95% CI = 0.61, 0.99). In longitudinal analysis, physically active students who attended schools with the highest social fragmentation were more likely to become physically inactive over two years (OR = 1.65, 95% CI = 1.09, 2.51). Conclusion The school socioeconomic environment appears to be an important contextual influence on participation in no physical activity among adolescents. Following adolescents beyond two years is necessary to determine if these environments have a lasting effect on physical activity behavior. PMID:24932679

  12. Exercise for fitness does not decrease the muscular inactivity time during normal daily life.

    PubMed

    Finni, T; Haakana, P; Pesola, A J; Pullinen, T

    2014-02-01

    The time spent in sedentary behaviors has been shown to be independent of exercise in epidemiological studies. We examined within an individual whether exercise alters the time of muscular inactivity within his/her normal daily life. Quadriceps and hamstring muscle electromyographic activities and heart rate were measured during 1 to 6 days of normal daily living of ordinary people. Of 84 volunteers measured, 27 (15 men, 12 women, 40.7 years ± 16.5 years) fulfilled the criteria of having at least 1 day with and 1 day without exercise for fitness (total of 87 days analyzed, 13.0 h ± 2.5 h/day). Reported exercises varied from Nordic walking to strength training and ball games lasting 30 min-150 min (mean 83 min ± 30 min). Exercise increased the time spent at moderate-to-vigorous muscle activity (6% ± 4% to 9% ± 6%, P < 0.01) and energy expenditure (13% ± 22%, P < 0.05). Muscular inactivity, defined individually below that measured during standing, comprised 72% ± 12% of day without and 68% ± 13% of day with exercise (not significant). Duration of exercise correlated positively to the increase in moderate-to-vigorous muscle activity time (r = 0.312, P < 0.05) but not with inactivity time. In conclusion, exercise for fitness, regardless of its duration, does not decrease the inactivity time during normal daily life. This is possible by slight modifications in daily nonexercise activities. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. School social fragmentation, economic deprivation and social cohesion and adolescent physical inactivity: a longitudinal study.

    PubMed

    Pabayo, Roman; Janosz, Michel; Bisset, Sherri; Kawachi, Ichiro

    2014-01-01

    To examine the independent influence of school economic deprivation, social fragmentation, and social cohesion on the likelihood of participating in no physical activity among students. Data are from a large-scale longitudinal study of schools based in disadvantaged communities in Quebec, Canada. Questionnaires were administered every year between 2002 and 2008 among n = 14,924 students aged 12 to 18 from a sample of 70 schools. Cross-sectional and longitudinal analyses were conducted. Multilevel modeling was utilized to account for the clustering of students within schools. Schools were categorized as being low, moderate or high economic deprivation, social fragmentation and social cohesion. Those who indicated that they do no participate in any physical activity during the week were identified as being physically inactive. In baseline multilevel cross-sectional analyses, adolescents attending schools in the highest (compared to the lowest) levels of socioeconomic deprivation and social fragmentation were more likely to be physically inactive (OR = 1.33, 95% CI = 1.03, 1.72; and OR = 1.24, 95% CI = 0.98, 1.56, respectively). Conversely, students attending schools with the highest cohesion were less likely to be physically inactive (OR = 0.78, 95% CI = 0.61, 0.99). In longitudinal analysis, physically active students who attended schools with the highest social fragmentation were more likely to become physically inactive over two years (OR = 1.65, 95% CI = 1.09, 2.51). The school socioeconomic environment appears to be an important contextual influence on participation in no physical activity among adolescents. Following adolescents beyond two years is necessary to determine if these environments have a lasting effect on physical activity behavior.

  14. Comparison of Vitamin D Levels in Naive, Treated, and Inactive Carriers with Chronic Hepatitis B Virus

    PubMed Central

    Sali, Shahnaz; Tavakolpour, Soheil; Farkhondemehr, Baharan

    2016-01-01

    Abstract Background and Aims: During recent years, the relationship between vitamin D levels and chronic hepatitis B (CHB) infection has attracted many researchers’ attention. However, the results relating to the association of vitamin D levels and HBV infection have been conflicting and there remains a lack of knowledge about the effects of antiviral treatments on vitamin D level. Methods: Eighty-four patients with CHB were assessed and divided into three groups: inactive carriers (n = 28), treated (n = 34), and new (treatment-naïve) cases (n = 22). Thirty-two healthy controls (HCs) were included to enable comparison with the CHB groups. The levels of vitamin D3 were measured and statistically compared among the various groups. Results: Male subjects had higher levels of vitamin D3 (41.25 vs 28.85, p < 0.01). No association was found among any of the groups when compared with the HC group. Despite the significant association, the HCs demonstrated a higher level of vitamin D3, which was lower in the treated group, the inactive carrier group, and the new cases group (new case [29.82] < inactive carrier [32.91] < treated [39.56] < control [44.88]). The HBV DNA levels were not associated with vitamin D3 levels in the inactive carriers (p = 0.171), the treated groups (p = 0.192), and the new cases (p = 0.369). Moreover, the alanine transaminase and aspartate transaminase levels were not associated with vitamin D3 levels for any of the HBV-infected groups. Conclusions: Vitamin D3 contributes to the clinical statues of CHB patients. There is also a possible correlation between clinically healthy CHB patients and vitamin D3 level. PMID:28097099

  15. Pyridinediimine Iron Complexes with Pendant Redox-Inactive Metals Located in the Secondary Coordination Sphere.

    PubMed

    Delgado, Mayra; Ziegler, Joshua M; Seda, Takele; Zakharov, Lev N; Gilbertson, John D

    2016-01-19

    A series of pyridinediimine (PDI) iron complexes that contain a pendant 15-crown-5 located in the secondary coordination sphere were synthesized and characterized. The complex Fe((15c5)PDI)(CO)2 (2) was shown in both the solid state and solution to encapsulate redox-inactive metal ions. Modest shifts in the reduction potential of the metal-ligand scaffold were observed upon encapsulation of either Na(+) or Li(+).

  16. Screen time by different devices in adolescents: association with physical inactivity domains and eating habits.

    PubMed

    Delfino, Leandro D; Dos Santos Silva, Diego A; Tebar, William R; Zanuto, Edner F; Codogno, Jamile S; Fernandes, Rômulo A; Christofaro, Diego G

    2017-04-28

    Sedentary behaviors in adolescents are associated with using screen devices, analyzed as the total daily time in television viewing, using the computer and video game. However, an independent and clustered analysis of devices allows greater understanding of associations with physical inactivity domains and eating habits in adolescents. Sample of adolescents aged 10-17 years (n=1011) from public and private schools, randomly selected. The use of screen devices was measured by hours per week spent in each device: TV, computer, videogames and mobile phone/tablet. Physical inactivity domains (school, leisure and sports), eating habits (weekly food consumption frequency) and socioeconomic status were assessed by questionnaire. The prevalence of high use of mobile phone/tablet was 70% among adolescents, 63% showed high use of TV or computer and 24% related high use of videogames. High use of videogames was greater among boys and high use of mobile phone/tablet was higher among girls. Significant associations of high use of TV [OR= 1.43 (95% CI=1.04-1.99)], computer [OR= 1.44 (95% CI=1.03-2.02)], videogames [OR= 1.65 (95% CI=1.13-2.69)] and consumption of snacks were observed. High use of computer was associated with fried foods consumption [OR= 1.32 (95% CI=1.01-1.75)] and physical inactivity [OR= 1.41 (95% CI=1.03-1.95)]. Mobile phone was associated with consumption of sweets [OR= 1.33 (95% CI=1.00-1.80)]. Cluster using screen devices showed associations with high consumption of snacks, fried foods and sweets, even after controlling for confounding variables. The high use of screen devices was associated with high consumption of snacks, fried foods, sweets and physical inactivity in adolescents.

  17. Inactive end cell assembly for fuel cells for improved electrolyte management and electrical contact

    DOEpatents

    Yuh, Chao-Yi; Farooque, Mohammad; Johnsen, Richard

    2007-04-10

    An assembly for storing electrolyte in a carbonate fuel cell is provided. The combination of a soft, compliant and resilient cathode current collector and an inactive anode part including a foam anode in each assembly mitigates electrical contact loss during operation of the fuel cell stack. In addition, an electrode reservoir in the positive end assembly and an electrode sink in the negative end assembly are provided, by which ribbed and flat cathode members inhibit electrolyte migration in the fuel cell stack.

  18. Food reward in active compared to inactive men: Roles for gastric emptying and body fat.

    PubMed

    Horner, Katy M; Finlayson, Graham; Byrne, Nuala M; King, Neil A

    2016-06-01

    Habitual exercise could contribute to weight management by altering processes of food reward via the gut-brain axis. We investigated hedonic processes of food reward in active and inactive men and characterised relationships with gastric emptying and body fat. Forty-four men (active: n=22; inactive: n=22, BMI range 21-36kg/m(2); percent fat mass range 9-42%) were studied. Participants were provided with a standardised fixed breakfast and an ad libitum lunch meal 5h later. Explicit liking, implicit wanting and preference among high-fat, low-fat, sweet and savoury food items were assessed immediately post-breakfast (fed state) and again pre-lunch (hungry state) using the Leeds Food Preference Questionnaire. Gastric emptying was assessed by (13)C-octanoic acid breath test. Active individuals exhibited a lower liking for foods overall and a greater implicit wanting for low-fat savoury foods in the fed state, compared to inactive men. Differences in the fed state remained significant after adjusting for percent fat mass. Active men also had a greater increase in liking for savoury foods in the interval between breakfast and lunch. Faster gastric emptying was associated with liking for savoury foods and with an increase in liking for savoury foods in the postprandial interval. In contrast, greater implicit wanting for high-fat foods was associated with slower gastric emptying. These associations were independent of each other, activity status and body fat. In conclusion, active and inactive men differ in processes of food reward. The rate of gastric emptying may play a role in the association between physical activity status and food reward, via the gut-brain axis. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Ambient fine particulate matter air pollution and leisure-time physical inactivity among US adults.

    PubMed

    An, R; Xiang, X

    2015-12-01

    There is mounting evidence documenting the adverse health effects of short- and long-term exposure to ambient fine particulate matter (PM2.5) air pollution, but population-based evidence linking PM2.5 and health behaviour remains lacking. This study examined the relationship between ambient PM2.5 air pollution and leisure-time physical inactivity among US adults 18 years of age and above. Retrospective data analysis. Participant-level data (n = 2,381,292) from the Behavioral Risk Factor Surveillance System 2003-2011 surveys were linked with Wide-ranging Online Data for Epidemiologic Research air quality data by participants' residential county and interview month/year. Multilevel logistic regressions were performed to examine the effect of ambient PM2.5 air pollution on participants' leisure-time physical inactivity, accounting for various individual and county-level characteristics. Regressions were estimated on the overall sample and subsamples stratified by sex, age cohort, race/ethnicity and body weight status. One unit (μg/m(3)) increase in county monthly average PM2.5 concentration was found to be associated with an increase in the odds of physical inactivity by 0.46% (95% confidence interval = 0.34%-0.59%). The effect was similar between the sexes but to some extent (although not always statistically significant) larger for younger adults, Hispanics, and overweight/obese individuals compared with older adults, non-Hispanic whites or African Americans, and normal weight individuals, respectively. Ambient PM2.5 air pollution is found to be associated with a modest but measurable increase in individuals' leisure-time physical inactivity, and the relationship tends to differ across population subgroups. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  20. At Least I Tried: The Relationship between Regulatory Focus and Regret Following Action vs. Inaction

    PubMed Central

    Itzkin, Adi; Van Dijk, Dina; Azar, Ofer H.

    2016-01-01

    Regret is an unpleasant feeling that may arise following decisions that ended poorly, and may affect the decision-maker's well-being and future decision making. Some studies show that a decision to act leads to greater regret than a decision not to act when both resulted in failure, because the latter is usually the norm. In some cases, when the norm is to act, this pattern is reversed. We suggest that the decision maker's regulatory focus, affects regret after action or inaction. Specifically, promotion-focused individuals, who tend to be more proactive, view action as more normal than prevention-focused individuals, and therefore experience regulatory fit when an action decision is made. Hence, we hypothesized that promotion-focused individuals will feel less regret than prevention-focused individuals when a decision to act ended poorly. In addition, we hypothesized that a trigger for change implied in the situation, decreases the level of regret following action. We tested our hypotheses on a sample of 330 participants enrolled in an online survey. The participants received six decision scenarios, in which they were asked to evaluate the level of regret following action and inaction. Individual regulatory focus was measured by two different scales. Promotion-focused individuals attributed less regret than prevention-focused individuals to action decisions. Regret following inaction was not affected by regulatory focus. In addition, a trigger for change decreases regret following action. Orthodox people tend to attribute more regret than non-orthodox to a person who made an action decision. The results contribute to the literature by showing that not only the situation but also the decision maker's orientation affects the regret after action vs. inaction. PMID:27833581

  1. Investigation of the organic matter in inactive nuclear tank liquids. Environmental Restoration Program

    SciTech Connect

    Schenley, R.L.; Griest, W.H.

    1990-08-01

    Environmental Protection Agency (EPA) methodology for regulatory organics fails to account for the organic matter that is suggested by total organic carbon (TOC) analysis in the Oak Ridge National Laboratory (ORNL) inactive nuclear waste-tank liquids and sludges. Identification and measurement of the total organics are needed to select appropriate waste treatment technologies. An initial investigation was made of the nature of the organics in several waste-tank liquids. This report details the analysis of ORNL wastes.

  2. The effect of intradermal administration of inactive platelet-rich plasma on flap viability in rats.

    PubMed

    Orhan, Erkan; Uysal, Ahmet Çağrı; Başer, Engin; Keskin, Dürdane; Demiroğlu-Yakut, Çiğdem

    2017-04-01

    To evaluate the effect of inactive form of platelet rich plasma (PRP) on the flap viability. Thirty six rats were used. Rats were divided into six groups then 9x3 cm random pattern skin flaps were elevated from dorsum of all rats. For precluding vascularization from the base, a silicone layer was placed under the flap in groups 2(only flap+silicone), 4(saline+silicone) and 6(PRP+silicone). In groups 1(only flap), 2(only flap+silicone) nothing was done except flap surgery. In groups 3(saline) and 4(saline+silicone), saline was applied intradermally , in groups 5(PRP) and 6(PRP+silicone), inactive form of PRP which obtained from different 16 rats was applied intradermally, into certain points of flaps immediately after surgery. After 7 days flap necrosis ratio was measured in all groups. Mean necrosis rate in group 5(PRP) (16.05%) was statistically significantly lower than group 1(only flap) (31,93%) and group 3(saline) (30,43%) (p<0.001). Mean necrosis rate in group 6(PRP+silicone) (36.37%) was statistically significantly lower than group 2(only flap+silicone) (47.93%) and group 4(saline+silicone) (45.65%) (p<0.001). Intradermal inactive platelet rich plasma administration decreases flap necrosis so for skin application.

  3. A Mononuclear Non-Heme Manganese(IV)-Oxo Complex Binding Redox-Inactive Metal Ions

    SciTech Connect

    Chen, Junying; Lee, Yong-Min; Davis, Katherine M.; Wu, Xiujuan; Seo, Mi Sook; Cho, Kyung-Bin; Yoon, Heejung; Park, Young Jun; Fukuzumi, Shunichi; Pushkar, Yulia N.; Nam, Wonwoo

    2013-05-29

    Redox-inactive metal ions play pivotal roles in regulating the reactivities of high-valent metal–oxo species in a variety of enzymatic and chemical reactions. A mononuclear non-heme Mn(IV)–oxo complex bearing a pentadentate N5 ligand has been synthesized and used in the synthesis of a Mn(IV)–oxo complex binding scandium ions. The Mn(IV)–oxo complexes were characterized with various spectroscopic methods. The reactivities of the Mn(IV)–oxo complex are markedly influenced by binding of Sc3+ ions in oxidation reactions, such as a ~2200-fold increase in the rate of oxidation of thioanisole (i.e., oxygen atom transfer) but a ~180-fold decrease in the rate of C–H bond activation of 1,4-cyclohexadiene (i.e., hydrogen atom transfer). The present results provide the first example of a non-heme Mn(IV)–oxo complex binding redox-inactive metal ions that shows a contrasting effect of the redox-inactive metal ions on the reactivities of metal–oxo species in the oxygen atom transfer and hydrogen atom transfer reactions.

  4. Redox-Inactive Metals Modulate the Reduction Potential in Heterometallic Manganese-Oxido Clusters

    PubMed Central

    Tsui, Emily Y.; Tran, Rosalie; Yano, Junko; Agapie, Theodor

    2013-01-01

    Redox-inactive metals are found in biological and heterogeneous water oxidation catalysts, but their roles in catalysis are currently not well understood. A series of high oxidation state tetranuclear-dioxido clusters comprised of three manganese centers and a redox-inactive metal (M) of various charge is reported. Crystallographic studies show an unprecedented Mn3M(μ4-O)(μ2-O) core that remains intact upon changing M or the manganese oxidation state. Electrochemical studies reveal that the reduction potentials span a window of 700 mV, dependent upon the Lewis acidity of the second metal. With the pKa of the redox-inactive metal-aqua complex as a measure of Lewis acidity, these compounds display a linear dependence between reduction potential and acidity with a slope of ca. 100 mV per pKa unit. The Sr2+ and Ca2+ compounds show similar potentials, an observation that correlates with the behavior of the OEC, which is active only in the presence of one of these two metals. PMID:23511417

  5. Using gender-based analyses to understand physical inactivity among women in Yellowstone County, Montana.

    PubMed

    Duin, Diane K; Golbeck, Amanda L; Keippel, April Ennis; Ciemins, Elizabeth; Hanson, Hillary; Neary, Tracy; Fink, Heather

    2015-08-01

    Physical inactivity contributes to many health problems. Gender, the socially constructed roles and activities deemed appropriate for men and women, is an important factor in women's physical inactivity. To better understand how gender influences participation in leisure-time physical activity, a gender analysis was conducted using sex-disaggregated data from a county-wide health assessment phone survey and a qualitative analysis of focus group transcripts. From this gender analysis, several gender-based constraints emerged, including women's roles as caregivers, which left little time or energy for physical activity, women's leisure time activities and hobbies, which were less active than men's hobbies, and expectations for women's appearance that made them uncomfortable sweating in front of strangers. Gender-based opportunities included women's enjoyment of activity as a social connection, less rigid gender roles for younger women, and a sense of responsibility to set a good example for their families. The gender analysis was used to gain a deeper understanding of gender-based constraints and opportunities related to physical activity. This understanding is being used in the next step of our research to develop a gender-specific intervention to promote physical activity in women that addresses the underlying causes of physical inactivity through accommodation or transformation of those gender norms.

  6. The Relationship Between Neighborhood Socioeconomic Characteristics and Physical Inactivity Among Adolescents Living in Boston, Massachusetts

    PubMed Central

    Molnar, Beth E.; Cradock, Angie; Kawachi, Ichiro

    2014-01-01

    Objectives. We sought to determine whether the socioeconomic environment was associated with no participation in physical activity among adolescents in Boston, Massachusetts. Methods. We used cross-sectional data from 1878 urban adolescents living in 38 neighborhoods who participated in the 2008 Boston Youth Survey, a biennial survey of high school students (aged 14–19 years). We used multilevel multiple regression models to determine the association between neighborhood-level exposures of economic deprivation, social fragmentation, social cohesion, danger and disorder, and students’ reports of no participation in physical activity in the previous week. Results. High social fragmentation within the residential neighborhood was associated with an increased likelihood of being inactive (odds ratio = 1.53; 95% confidence interval = 1.14, 2.05). No other neighborhood exposures were associated with physical inactivity. Conclusions. Social fragmentation might be an important correlate of physical inactivity among youths living in urban settings. Interventions might be needed to assist youths living in unstable neighborhoods to be physically active. PMID:25211727

  7. Inactive DNMT3B splice variants modulate de novo DNA methylation.

    PubMed

    Gordon, Catherine A; Hartono, Stella R; Chédin, Frédéric

    2013-01-01

    Inactive DNA methyltransferase (DNMT) 3B splice isoforms are associated with changes in DNA methylation, yet the mechanisms by which they act remain largely unknown. Using biochemical and cell culture assays, we show here that the inactive DNMT3B3 and DNMT3B4 isoforms bind to and regulate the activity of catalytically competent DNMT3A or DNMT3B molecules. DNMT3B3 modestly stimulated the de novo methylation activity of DNMT3A and also counteracted the stimulatory effects of DNMT3L, therefore leading to subtle and contrasting effects on activity. DNMT3B4, by contrast, significantly inhibited de novo DNA methylation by active DNMT3 molecules, most likely due to its ability to reduce the DNA binding affinity of co-complexes, thereby sequestering them away from their substrate. Immunocytochemistry experiments revealed that in addition to their effects on the intrinsic catalytic function of active DNMT3 enzymes, DNMT3B3 and DNMT34 drive distinct types of chromatin compaction and patterns of histone 3 lysine 9 tri-methylation (H3K9me3) deposition. Our findings suggest that regulation of active DNMT3 members through the formation of co-complexes with inactive DNMT3 variants is a general mechanism by which DNMT3 variants function. This may account for some of the changes in DNA methylation patterns observed during development and disease.

  8. Effects of exercise and inactivity on intravascular volume and cardiovascular control mechanisms

    NASA Astrophysics Data System (ADS)

    Convertino, Victor A.

    Exercise, inactivity and confinement have been used as effective tools to assess the contributions of vascular volume and baroreflexes to orthostatic hypotension associated with exposure to microgravity. Prolonged exposure to bedrest, physical inactivity, or wheelchair confinement removes baroreceptor unloading caused by regular upright standing and induces attenuation of cardiovascular baroreflex responses. The magnitude of reduced baroreflex sensitivity following bedrest or wheelchair confinement is related to the degree of orthostatic hypotension. Reduction in vascular volume caused by bedrest or progressive hypovolemia does not affect carotid-cardiac baroreflex function. In contrast, intense exercise that increases arterial baroreceptor loading causes an acute increase in carotid baroreceptor sensitivity and has been associated with enhanced orthostatic stability following exposure to simulated microgravity. Endurance exercise training designed to enhance orthostatic stability was associated with increased blood volume and vasoconstrictive reserve, but no change in the carotid baroreflex response. Therefore, using models of exercise, inactivity and confinement, integrated and redundant roles for vascular volume and cardiovascular baroreflexes have been demonstrated as probable underlying mechanisms that contribute independently to the development of orthostatic hypotension following spaceflight. These data suggest that loading of arterial baroreceptors may be necessary to maintain baroreflex function.

  9. Estimation of cancer incidence and mortality attributable to overweight, obesity, and physical inactivity in China.

    PubMed

    Wang, Ding; Zheng, Wei; Wang, Shao-Ming; Wang, Jian-Bing; Wei, Wen-Qiang; Liang, Hao; Qiao, You-Lin; Boffetta, Paolo

    2012-01-01

    The objective was to provide an evidence-based, systematic assessment of the burden of cancer due to overweight/obesity and physical inactivity in China. This study evaluated the proportion of cancers of colon, rectum, pancreas, breast (postmenopausal), endometrium, and kidney attributable to overweight [30 kg/m(2) > body mass index (BMI) ≥ 25 kg/m(2))/obesity (BMI ≥ 30 kg/m(2)) and physical inactivity in China in 2005. Data of prevalence of overweight/obesity and lack of physical activity were derived from cross-sectional surveys among representative samples of Chinese population, and data of relative risks on cancers were derived from meta-analyses or large-scale studies from China and East Asian populations. The attributable fractions were calculated by combining both data of prevalence and relative risks. In China in 2005, 0.32% of cancer deaths and 0.65% of cancer cases were attributable to overweight and obesity combined. Lack of physical activity was responsible for 0.27% of cancer deaths and 0.39% of cancer cases. Future projections indicate that the contribution of overweight and obesity to the overall cancer burden will increase in the next decades. The largest increased attributable fractions will be for endometrial cancer. The increase in attributable fractions would be greater in men and in rural populations. Although the current burden of cancer associated with overweight/obesity and physical inactivity is still relatively small in China, it is expected to increase in the future.

  10. Estimation of Cancer Incidence and Mortality Attributable to Overweight, Obesity, and Physical Inactivity in China

    PubMed Central

    Wang, Ding; Zheng, Wei; Wang, Shao-Ming; Wang, Jian-Bing; Wei, Wen-Qiang; Liang, Hao; Qiao, You-Lin; Boffetta, Paolo

    2015-01-01

    The Objectives was to provide an evidence-based, systematic assessment of the burden of cancer due to overweight/obesity and physical inactivity in China. This study evaluated the proportion of cancers of colon, rectum, pancreas, breast (postmenopausal), endometrium and kidney attributable to overweight (30 kg/m2>BMI≥25 kg/m2)/obesity (BMI≥30 kg/m2) and physical inactivity in China in 2005. Data of prevalence of overweight/obesity, and lack of physical activity were derived from cross-sectional surveys among representative samples of Chinese population, and data of relative risks on cancers were derived from meta-analyses or large-scale studies from China and East Asian populations. The attributable fractions were calculated by combining both data of prevalence and relative risks. In China in 2005, 0.32% of cancer deaths and 0.65% of cancer cases were attributable to overweight and obesity combined. Lack of physical activity was responsible for 0.27% of cancer deaths and 0.39% of cancer cases. Future projections indicate that the contribution of overweight and obesity to the overall cancer burden will increase in the next decades. The largest increased attributable fractions will be for endometrial cancer. The increase in attributable fractions would be greater in men and in rural populations. Although the current burden of cancer associated with overweight/obesity and physical inactivity is still relatively small in China, it is expected to increase in the future. PMID:22136606

  11. A mononuclear non-heme manganese(IV)-oxo complex binding redox-inactive metal ions.

    PubMed

    Chen, Junying; Lee, Yong-Min; Davis, Katherine M; Wu, Xiujuan; Seo, Mi Sook; Cho, Kyung-Bin; Yoon, Heejung; Park, Young Jun; Fukuzumi, Shunichi; Pushkar, Yulia N; Nam, Wonwoo

    2013-05-01

    Redox-inactive metal ions play pivotal roles in regulating the reactivities of high-valent metal-oxo species in a variety of enzymatic and chemical reactions. A mononuclear non-heme Mn(IV)-oxo complex bearing a pentadentate N5 ligand has been synthesized and used in the synthesis of a Mn(IV)-oxo complex binding scandium ions. The Mn(IV)-oxo complexes were characterized with various spectroscopic methods. The reactivities of the Mn(IV)-oxo complex are markedly influenced by binding of Sc(3+) ions in oxidation reactions, such as a ~2200-fold increase in the rate of oxidation of thioanisole (i.e., oxygen atom transfer) but a ~180-fold decrease in the rate of C-H bond activation of 1,4-cyclohexadiene (i.e., hydrogen atom transfer). The present results provide the first example of a non-heme Mn(IV)-oxo complex binding redox-inactive metal ions that shows a contrasting effect of the redox-inactive metal ions on the reactivities of metal-oxo species in the oxygen atom transfer and hydrogen atom transfer reactions.

  12. Health culture and the clinical encounter: Vietnamese refugees' responses to preventive drug treatment of inactive tuberculosis.

    PubMed

    Ito, K L

    1999-09-01

    A majority of Vietnamese refugees entering the United States test positive for inactive tuberculosis (TB). In asymptomatic conditions like inactive TB, it is often difficult to obtain compliance with medical treatment. The clinical encounter has been analyzed as a form of symbolic action between doctor and patient critical to patient trust and compliance. However, it is equally, if not more, important to understand the health culture of patients, that is, the broader sociocultural context of the patient within which his or her illness is interpreted and understood. In this article I look at health culture elements that influence compliance and noncompliance by Vietnamese American clients with courses of preventive drug therapy for inactive TB. Key factors in compliance are: (1) cultural interpretations of the therapy's side effects as "hot"; (2) the role of family members and peers; and (3) community perceptions of the drug treatment. Culturally incongruent elements of the clinical encounter and the funding of community-based organizations for health education also are examined.

  13. Mating-Type Mutations in SCHIZOSACCHAROMYCES POMBE: Isolation of Mutants and Analysis of Strains with an h- or h+ Phenotype

    PubMed Central

    Meade, James H.; Gutz, Herbert

    1976-01-01

    Mutants defective in various steps of the sexual cycle have been isolated from homothallic strains of Schizosaccharomyces pombe by Bresch, Müller and Egel (1968). These mutants include heterothallic h+ and h- strains. We have isolated additional h+ and h- mutants from homothallic strains. Those mutants which are due to mutations in the mating-type region were analyzed in detail. Our results show that the mating-type gene mat2 not only has a function in copulation and meiosis, but that it also regulates the formation of the map1 gene product (map1 is a mating-type auxiliary gene). Some of the h - mutants have lost only one of the three functions while others are defective in at least two, and perhaps all three, functions. Further, we show that the mat1- allele of h90 strains can mutate to mat1+ but that mutations in mat2 appear to affect the mutational behavior of mat1. Finally, we describe a new inactive mating-type allele, mat2*, which is different from mat20 in that it can mutate to mat2+. PMID:17248713

  14. Mating-Type Mutations in SCHIZOSACCHAROMYCES POMBE: Isolation of Mutants and Analysis of Strains with an h or h Phenotype.

    PubMed

    Meade, J H; Gutz, H

    1976-06-01

    Mutants defective in various steps of the sexual cycle have been isolated from homothallic strains of Schizosaccharomyces pombe by Bresch, Müller and Egel (1968). These mutants include heterothallic h(+) and h(-) strains. We have isolated additional h(+) and h(- ) mutants from homothallic strains. Those mutants which are due to mutations in the mating-type region were analyzed in detail. Our results show that the mating-type gene mat2 not only has a function in copulation and meiosis, but that it also regulates the formation of the map1 gene product (map1 is a mating-type auxiliary gene). Some of the h( -) mutants have lost only one of the three functions while others are defective in at least two, and perhaps all three, functions. Further, we show that the mat1(-) allele of h(90) strains can mutate to mat1(+) but that mutations in mat2 appear to affect the mutational behavior of mat1. Finally, we describe a new inactive mating-type allele, mat2*, which is different from mat2(0) in that it can mutate to mat2(+).

  15. Expression and In Vivo Rescue of Human ABCC6 Disease-Causing Mutants in Mouse Liver

    PubMed Central

    Le Saux, Olivier; Fülöp, Krisztina; Yamaguchi, Yukiko; Iliás, Attila; Szabó, Zalán; Brampton, Christopher N.; Pomozi, Viola; Huszár, Krisztina; Arányi, Tamás; Váradi, András

    2011-01-01

    Loss-of-function mutations in ABCC6 can cause chronic or acute forms of dystrophic mineralization described in disease models such as pseudoxanthoma elasticum (OMIM 26480) in human and dystrophic cardiac calcification in mice. The ABCC6 protein is a large membrane-embedded organic anion transporter primarily found in the plasma membrane of hepatocytes. We have established a complex experimental strategy to determine the structural and functional consequences of disease-causing mutations in the human ABCC6. The major aim of our study was to identify mutants with preserved transport activity but failure in intracellular targeting. Five missense mutations were investigated: R1138Q, V1298F, R1314W, G1321S and R1339C. Using in vitro assays, we have identified two variants; R1138Q and R1314W that retained significant transport activity. All mutants were transiently expressed in vivo, in mouse liver via hydrodynamic tail vein injections. The inactive V1298F was the only mutant that showed normal cellular localization in liver hepatocytes while the other mutants showed mostly intracellular accumulation indicating abnormal trafficking. As both R1138Q and R1314W displayed endoplasmic reticulum localization, we tested whether 4-phenylbutyrate (4-PBA), a drug approved for clinical use, could restore their intracellular trafficking to the plasma membrane in MDCKII and mouse liver. The cellular localization of R1314W was significantly improved by 4-PBA treatment, thus potentially rescuing its physiological function. Our work demonstrates the feasibility of the in vivo rescue of cellular maturation of some ABCC6 mutants in physiological conditions very similar to the biology of the fully differentiated human liver and could have future human therapeutic application. PMID:21935449

  16. Rational design of an enzyme mutant for anti-cocaine therapeutics

    NASA Astrophysics Data System (ADS)

    Zheng, Fang; Zhan, Chang-Guo

    2008-09-01

    (-)-Cocaine is a widely abused drug and there is no available anti-cocaine therapeutic. The disastrous medical and social consequences of cocaine addiction have made the development of an effective pharmacological treatment a high priority. An ideal anti-cocaine medication would be to accelerate (-)-cocaine metabolism producing biologically inactive metabolites. The main metabolic pathway of cocaine in body is the hydrolysis at its benzoyl ester group. Reviewed in this article is the state-of-the-art computational design of high-activity mutants of human butyrylcholinesterase (BChE) against (-)-cocaine. The computational design of BChE mutants have been based on not only the structure of the enzyme, but also the detailed catalytic mechanisms for BChE-catalyzed hydrolysis of (-)-cocaine and (+)-cocaine. Computational studies of the detailed catalytic mechanisms and the structure-and-mechanism-based computational design have been carried out through the combined use of a variety of state-of-the-art techniques of molecular modeling. By using the computational insights into the catalytic mechanisms, a recently developed unique computational design strategy based on the simulation of the rate-determining transition state has been employed to design high-activity mutants of human BChE for hydrolysis of (-)-cocaine, leading to the exciting discovery of BChE mutants with a considerably improved catalytic efficiency against (-)-cocaine. One of the discovered BChE mutants (i.e., A199S/S287G/A328W/Y332G) has a ˜456-fold improved catalytic efficiency against (-)-cocaine. The encouraging outcome of the computational design and discovery effort demonstrates that the unique computational design approach based on the transition-state simulation is promising for rational enzyme redesign and drug discovery.

  17. Anti-oncogenic activity of signalling-defective epidermal growth factor receptor mutants.

    PubMed Central

    Redemann, N; Holzmann, B; von Rüden, T; Wagner, E F; Schlessinger, J; Ullrich, A

    1992-01-01

    Overexpression and autocrine activation of the epidermal growth factor receptor (EGF-R) cause transformation of cultured cells and correlate with tumor progression in cancer patients. Dimerization and transphosphorylation are crucial events in the process by which receptors with tyrosine kinase activity generate normal and transforming cellular signals. Interruption of this process by inactive receptor mutants offers the potential to inhibit ligand-induced cellular responses. Using recombinant retroviruses, we have examined the effects of signalling-incompetent EGF-R mutants on the growth-promoting and transforming potential of ligand-activated, overexpressed wild-type EGF-R and the v-erbB oncogene product. Expression of a soluble extracellular EGF-R domain had little if any effect on the growth and transformation of NIH 3T3 cells by either tyrosine kinase. However, both a kinase-negative EGF-R point mutant (HERK721A) and an EGF-R lacking 533 C-terminal amino acids efficiently inhibited wild-type EGF-R-mediated, de novo DNA synthesis and cell transformation in a dose-dependent manner. Furthermore, coexpression with the v-erbBES4 oncogene product in NIH 3T3 cells resulted in transphosphorylation of the HERK721A mutant receptor and reduced soft-agar colony growth but had no effect in a focus formation assay. These results demonstrate that signalling-defective receptor tyrosine kinase mutants differentially interfere with oncogenic signals generated by either overexpressed EGF-R or the retroviral v-erbBES4 oncogene product. Images PMID:1346334

  18. A cytochrome c mutant with high electron transfer and antioxidant activities but devoid of apoptogenic effect.

    PubMed Central

    Abdullaev, Ziedulla Kh; Bodrova, Marina E; Chernyak, Boris V; Dolgikh, Dmitry A; Kluck, Ruth M; Pereverzev, Mikhail O; Arseniev, Alexander S; Efremov, Roman G; Kirpichnikov, Mikhail P; Mokhova, Elena N; Newmeyer, Donald D; Roder, Heinrich; Skulachev, Vladimir P

    2002-01-01

    A cytochrome c mutant lacking apoptogenic function but competent in electron transfer and antioxidant activities has been constructed. To this end, mutant species of horse and yeast cytochromes c with substitutions in the N-terminal alpha-helix or position 72 were obtained. It was found that yeast cytochrome c was much less effective than the horse protein in activating respiration of rat liver mitoplasts deficient in endogenous cytochrome c as well as in inhibition of H(2)O(2) production by the initial segment of the respiratory chain of intact rat heart mitochondria. The major role in the difference between the horse and yeast proteins was shown to be played by the amino acid residue in position 4 (glutamate in horse, and lysine in yeast; horse protein numbering). A mutant of the yeast cytochrome c containing K4E and some other "horse" modifications in the N-terminal alpha-helix, proved to be (i) much more active in electron transfer and antioxidant activity than the wild-type yeast cytochrome c and (ii), like the yeast cytochrome c, inactive in caspase stimulation, even if added in 400-fold excess compared with the horse protein. Thus this mutant seems to be a good candidate for knock-in studies of the role of cytochrome c-mediated apoptosis, in contrast with the horse K72R, K72G, K72L and K72A mutant cytochromes that at low concentrations were less active in apoptosis than the wild-type, but were quite active when the concentrations were increased by a factor of 2-12. PMID:11879204

  19. Who needs ‘lazy’ workers? Inactive workers act as a ‘reserve’ labor force replacing active workers, but inactive workers are not replaced when they are removed

    PubMed Central

    Sasaki, Takao; Dornhaus, Anna

    2017-01-01

    Social insect colonies are highly successful, self-organized complex systems. Surprisingly however, most social insect colonies contain large numbers of highly inactive workers. Although this may seem inefficient, it may be that inactive workers actually contribute to colony function. Indeed, the most commonly proposed explanation for inactive workers is that they form a ‘reserve’ labor force that becomes active when needed, thus helping mitigate the effects of colony workload fluctuations or worker loss. Thus, it may be that inactive workers facilitate colony flexibility and resilience. However, this idea has not been empirically confirmed. Here we test whether colonies of Temnothorax rugatulus ants replace highly active (spending large proportions of time on specific tasks) or highly inactive (spending large proportions of time completely immobile) workers when they are experimentally removed. We show that colonies maintained pre-removal activity levels even after active workers were removed, and that previously inactive workers became active subsequent to the removal of active workers. Conversely, when inactive workers were removed, inactivity levels decreased and remained lower post-removal. Thus, colonies seem to have mechanisms for maintaining a certain number of active workers, but not a set number of inactive workers. The rapid replacement (within 1 week) of active workers suggests that the tasks they perform, mainly foraging and brood care, are necessary for colony function on short timescales. Conversely, the lack of replacement of inactive workers even 2 weeks after their removal suggests that any potential functions they have, including being a ‘reserve’, are less important, or auxiliary, and do not need immediate recovery. Thus, inactive workers act as a reserve labor force and may still play a role as food stores for the colony, but a role in facilitating colony-wide communication is unlikely. Our results are consistent with the often cited

  20. Enhancers of Conidiation Mutants in Aspergillus Nidulans

    PubMed Central

    Gems, D. H.; Clutterbuck, A. J.

    1994-01-01

    Mutants at a number of loci, designated sthenyo, have been isolated as enhancers of the oligoconidial mutations at the medA locus. Two loci have been mapped: sthA on linkage group I, and sthB on linkage group V. Two probable alleles have been identified at each locus but two further mutants were unlinked to either sthA or sthB. Neither sthA nor sthB mutants have conspicuous effects on morphology on their own, nor could the sthA1 sthB2 double mutant be distinguished from wild type. Mutants at both loci also interact with the temperature-sensitive brlA42 mutant at the permissive temperature to give a phenotype described as ``Abacoid.'' sthA1 also induces a slight modification of the phenotype of an abaA mutant. We conclude that sthenyo genes act mainly at the phialide stage of conidiation. We also describe the isolation of new medA mutants arising spontaneously as outgrowths on brlA42 colonies. PMID:8056325

  1. Regulation of Mutant p53 Protein Expression.

    PubMed

    Vijayakumaran, Reshma; Tan, Kah Hin; Miranda, Panimaya Jeffreena; Haupt, Sue; Haupt, Ygal

    2015-01-01

    For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be explained in mutant p53-expressing cells by the lack of an auto-regulatory loop with Mdm2 and other negative regulators, which are pivotal for wt p53 regulation. Further, additional protective mechanisms are acquired by mutant p53, largely mediated by the co-chaperones and their paralogs, the stress-induced heat shock proteins. Consequently, mutant p53 is accumulated in cancer cells in response to chronic stress and this accumulation is critical for its oncogenic gain of functions (GOF). Building on the extensive knowledge regarding wt p53, the regulation of mutant p53 is unraveling. In this review, we describe the current understanding on the major levels at which mutant p53 is regulated. These include the regulation of p53 protein levels by microRNA and by enzymes controlling p53 proteasomal degradation.

  2. Eyespot-assembly mutants in Chlamydomonas reinhardtii.

    PubMed Central

    Lamb, M R; Dutcher, S K; Worley, C K; Dieckmann, C L

    1999-01-01

    Chlamydomonas reinhardtii is a single-celled green alga that phototaxes toward light by means of a light-sensitive organelle, the eyespot. The eyespot is composed of photoreceptor and Ca(++)-channel signal transduction components in the plasma membrane of the cell and reflective carotenoid pigment layers in an underlying region of the large chloroplast. To identify components important for the positioning and assembly of a functional eyespot, a large collection of nonphototactic mutants was screened for those with aberrant pigment spots. Four loci were identified. eye2 and eye3 mutants have no pigmented eyespots. min1 mutants have smaller than wild-type eyespots. mlt1(ptx4) mutants have multiple eyespots. The MIN1, MLT1(PTX4), and EYE2 loci are closely linked to each other; EYE3 is unlinked to the other three loci. The eye2 and eye3 mutants are epistatic to min1 and mlt1 mutations; all double mutants are eyeless. min1 mlt1 double mutants have a synthetic phenotype; they are eyeless or have very small, misplaced eyespots. Ultrastructural studies revealed that the min1 mutants are defective in the physical connection between the plasma membrane and the chloroplast envelope membranes in the region of the pigment granules. Characterization of these four loci will provide a beginning for the understanding of eyespot assembly and localization in the cell. PMID:10511552

  3. A halotolerant mutant of Saccharomyces cerevisiae.

    PubMed Central

    Gaxiola, R; Corona, M; Zinker, S

    1996-01-01

    FRD, a nuclear and dominant spontaneous mutant of Saccharomyces cerevisiae capable of growing in up to 2 M NaCl, was isolated. Compared with parental cells, the mutant cells have a lower intracellular Na+/K+ ratio, shorter generation times in the presence of 1 M NaCl, and alterations in gene expression. PMID:8631691

  4. Saint Louis Encephalitis Temperature-Sensitive Mutants.

    DTIC Science & Technology

    1979-09-01

    Several mutants have been used in pairwise crosses to determine complementation Accessionl For VTIS G!RA& DTIC T %B 3 fl!, -r,. AD) Av ’Di [ Annual...Ghendon (1973) indicate that a large number of polio virus ts mutants producing a pathologic change in infected monkeys were assayed for virus produccion

  5. Depressive symptoms are associated with physical inactivity in patients with type 2 diabetes. The DIAZOB Primary Care Diabetes study.

    PubMed

    Koopmans, Berber; Pouwer, François; de Bie, Robert A; van Rooij, Elisabeth S; Leusink, Geraline L; Pop, Victor J

    2009-06-01

    Depression is a common complication of type 2 diabetes, associated with poor disease outcomes such as impaired glycaemic control, cardiovascular disease and increased mortality. The mechanisms behind these associations are unclear. Depression might contribute to poor disease outcomes through decreased physical activity. To test whether type 2 diabetes patients with elevated depression scores are more often physically inactive. Demographic features, clinical factors, level of physical inactivity and depressive symptoms were assessed in 2646 primary care patients with type 2 diabetes. Sequential multiple logistic regression analyses [odds ratio, 95% confidence interval (CI)] were performed to test the association between depressive symptoms and physical inactivity. About 48% of the respondents were physically inactive. Elevated depressive symptoms were found in 14% of the respondents. After adjustment for potential confounders, the odds for being physically inactive were almost doubled in depressed patients with type 2 diabetes 1.74 (95% CI 1.32-2.31). Presence of depressive symptoms almost doubles the likelihood of physical inactivity in patients with type 2 diabetes. Longitudinal studies are needed to investigate whether physical inactivity forms the link between depression and poor disease outcomes.

  6. Radiation-sensitive mutants of Arabidopsis thaliana

    SciTech Connect

    Jenkins, M.E.; Harlow, G.R.; Liu, Z.

    1995-06-01

    Five Arabidopsis mutants have been isolated on the basis of hypersensitivity of leaf tissue to UV light. For each mutant, the UV-hypersensitive phenotype (uvh) was inherited as a single recessive Mendelian trait. In addition, each uvh mutant represented a separate complementation group. Three of the mutations producing the UV hypersensitive phenotype have been mapped relative to either genetic markers or physical microsatellite polymorphisms. Locus UVH1 is linked to nga76 on chromosome 5, UVH3 to GL1 on chromosome three, and UVH6 to nga59 on chromosome 1. Each uvh mutant has a characteristic pattern of sensitivity based on UV sensitivity of leaf tissue, UV sensitivity of root tissue, and ionizing radiation sensitivity of seeds. On the basis of these patterns, possible molecular defects in these mutants are discussed. 30 refs., 3 figs., 5 tabs.

  7. Effects of optical and geometrical properties on YORP effect for inactive satellites

    NASA Astrophysics Data System (ADS)

    Albuja, A.; Scheeres, D.

    2014-09-01

    With the increasing number of space debris in Earth orbit, it is important to understand the dynamics of these objects. Initial studies have demonstrated that the Yarkovsky, O'Keefe, Radzievskii, Paddack (YORP) effect on inactive satellite needs to be further explored as it could be noticeably affecting the rotational dynamics of these Earth orbiting objects. The YORP effect is created by torques resulting from light and thermal energy being re-emitted from the surface of a body. This effect has been well studied and observed to affect the spin states of asteroids. The purpose of this paper is to further investigate YORP in the realm of large inactive Geosynchronous Earth Orbit (GEO) satellites. The forces that cause the YORP effect are highly dependent on the optical, thermal and geometrical properties of the facets making up the surface of the body being analyzed. This paper focuses on exploring the effect of these properties on the YORP effect for inactive satellite. Two different satellite models that represent bus types of inactive satellites in GEO are used for this study. By varying the optical, thermal and geometrical properties of these models, in a manner that remains consistent with realistic satellite parameters, we can understand the relationship between these properties and the torques created by YORP. Having this knowledge allows for better understanding of the possible attitude states (spin rate and obliquity) for uncontrolled satellites in GEO. This information can then be used to make predictions of the long-term behavior of the rotation rate and obliquity of these objects. Categories of potential final states for defunct GEO satellites can then be created based on geometrical and optical properties (e.g. spin up continuously, spin down continuously, etc.). This allows the population of inactive GEO satellites to be studied in a more general sense and final attitude states for these objects can be quickly identified. Furthermore, an understanding

  8. The economic burden of physical inactivity: a systematic review and critical appraisal.

    PubMed

    Ding, Ding; Kolbe-Alexander, Tracy; Nguyen, Binh; Katzmarzyk, Peter T; Pratt, Michael; Lawson, Kenny D

    2017-10-01

    To summarise the literature on the economic burden of physical inactivity in populations, with emphases on appraising the methodologies and providing recommendations for future studies. Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number CRD42016047705). Electronic databases for peer-reviewed and grey literature were systematically searched, followed by reference searching and consultation with experts. Studies that examined the economic consequences of physical inactivity in a population/population-based sample, with clearly stated methodologies and at least an abstract/summary written in English. Of the 40 eligible studies, 27 focused on direct healthcare costs only, 13 also estimated indirect costs and one study additionally estimated household costs. For direct costs, 23 studies used a population attributable fraction (PAF) approach with estimated healthcare costs attributable to physical inactivity ranging from 0.3% to 4.6% of national healthcare expenditure; 17 studies used an econometric approach, which tended to yield higher estimates than those using a PAF approach. For indirect costs, 10 studies used a human capital approach, two used a friction cost approach and one used a value of a statistical life approach. Overall, estimates varied substantially, even within the same country, depending on analytical approaches, time frame and other methodological considerations. Estimating the economic burden of physical inactivity is an area of increasing importance that requires further development. There is a marked lack of consistency in methodological approaches and transparency of reporting. Future studies could benefit from cross-disciplinary collaborations involving economists and physical activity experts, taking a societal perspective and following best practices in conducting and reporting analysis, including accounting for potential confounding, reverse causality and

  9. Is Moderate Red Wine Consumption Safe in Inactive Inflammatory Bowel Disease?

    PubMed Central

    Swanson, Garth R.; Tieu, Vanessa; Shaikh, Maliha; Forsyth, Chris; Keshavarzian, Ali

    2011-01-01

    Background Alcohol consumption is a potential trigger for inflammatory bowel disease (IBD) flare because of alcohol-induced oxidative stress and its deleterious effects on gut barrier function. Additionally, we have recently shown that alcohol consumption is associated with more symptoms in IBD. However, it is not known whether moderate daily alcohol consumption can modify IBD disease activity. To test what effects alcohol may have on patients with IBD, we evaluated the effect of moderate daily red wine for 1 week on two factors associated with recurrent IBD disease activity: intestinal permeability and stool calprotectin. Methods To assess the effects of moderate daily alcohol consumption on intestinal permeability and inflammation, we recruited 21 patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's disease (CD), and 7 healthy controls. All participants with IBD completed a validated questionnaire on disease activity (Crohn's disease activity index or ulcerative colitis clinical activity index), to confirm they had inactive disease. All subjects then underwent a baseline assessment that included a blood draw, urine collection after sugar challenge, and stool collection. Subjects then consumed 1–3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and repeated the three measures. Results No subjects flared during the study. Moderate alcohol consumption did not significantly change either clinical disease activity scores or C-reactive protein. In contrast to healthy subjects, daily consumption of red wine significantly (1) decreased stool calprotectin in IBD subjects from baseline (p = 0.001) and (2) increased intestinal permeability as measured by urinary lactulose/mannitol excretion (marker of small bowel permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large bowel permeability) in UC (p = 0.012). Conclusions One week of moderate consumption of red wine in inactive IBD was associated with a significant

  10. crl mutants of Saccharomyces cerevisiae resemble both mutants affecting general control of amino acid biosynthesis and omnipotent translational suppressor mutants.

    PubMed

    McCusker, J H; Haber, J E

    1988-06-01

    Cyocloheximide resistant lethal (crl) mutants of Saccharomyces cerevisiae, defining 22 unlinked complementation groups, are unable to grow at 37 degrees. They are also highly pleiotropic at their permissive temperature of 25 degrees. The mutants are all unable to arrest at the G1 stage of the cell cycle when grown to stationary phase or when starved for a single amino acid, though they do arrest at G1 when deprived of all nitrogen. The crl mutants are also hypersensitive to various amino acid analogs and to 3-aminotriazole. These mutants also "tighten" leaky auxotrophic mutations that permit wild-type cells to grow in the absence of the appropriate amino acid. All of these phenotypes are also exhibited by gcn mutants affecting general control of amino acid biosynthesis. In addition, the crl mutants are all hypersensitive to hygromycin B, an aminoglycoside antibiotic that stimulates translational misreading. The crl mutations also suppress one nonsense mutation which is phenotypically suppressed by hygromycin B. Many crl mutants are also osmotically sensitive. These are phenotypes which the crl mutations have in common with previously isolated omnipotent suppressors. We suggest that the the crl mutations all affect the fidelity of protein translation.

  11. Using the CRISPR-Cas System to Positively Select Mutants in Genes Essential for Its Function.

    PubMed

    Yosef, Ido; Goren, Moran G; Edgar, Rotem; Qimron, Udi

    2015-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated proteins (Cas) comprise a prokaryotic adaptive defense system against foreign nucleic acids. This defense is mediated by Cas proteins, which are guided by sequences flanked by the repeats, called spacers, to target nucleic acids. Spacers designed against the prokaryotic self chromosome are lethal to the prokaryotic cell. This self-killing of the bacterium by its own CRISPR-Cas system can be used to positively select genes that participate in this killing, as their absence will result in viable cells. Here we describe a positive selection assay that uses this feature to identify E. coli mutants encoding an inactive CRISPR-Cas system. The procedure includes establishment of an assay that detects this self-killing, generation of transposon insertion mutants in random genes, and selection of viable mutants, suspected as required for this lethal activity. This procedure enabled us to identify a novel gene, htpG, that is required for the activity of the CRISPR-Cas system. The procedures described here can be adjusted to various organisms to identify genes required for their CRISPR-Cas activity.

  12. Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2

    PubMed Central

    Andreotti, Giuseppina; Monti, Maria Chiara; Citro, Valentina; Cubellis, Maria Vittoria

    2015-01-01

    The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces the protein found in patients, has the same activity of wild type/R141H, which reproduces the protein found in healthy carriers. On the other hand the stability of R141H/F119L appears to be reduced both in vitro and in vivo. These findings suggest that a therapy designed to enhance protein stability such as those based on pharmacological chaperones or modulation of proteostasis could be beneficial for PMM2-CDG patients carrying R141H/F119L genotype as well as for other genotypes where protein stability rather than specific activity is affected by mutations. PMID:26488408

  13. Unusual thermal and conformational properties of the rhodopsin congenital night blindness mutant Thr-94 --> Ile.

    PubMed

    Ramon, Eva; del Valle, Luis J; Garriga, Pere

    2003-02-21

    Naturally occurring point mutations in the opsin gene cause the retinal diseases retinitis pigmentosa and congenital night blindness. Although these diseases involve similar mutations in very close locations in rhodopsin, their progression is very different, with retinitis pigmentosa being severe and causing retinal degeneration. We report on the expression and characterization of the recently found T94I mutation associated with congenital night blindness, in the second transmembrane helix or rhodopsin, and mutations at the same site. T94I mutant rhodopsin folded properly and was able to bind 11-cis-retinal to form chromophore, but it showed a blue-shifted visible band at 478 nm and reduced molar extinction coefficient. Furthermore, T94I showed dramatically reduced thermal stability, extremely long lived metarhodopsin II intermediate, and highly increased reactivity toward hydroxylamine in the dark, when compared with wild type rhodopsin. The results are consistent with the location of Thr-94 in close proximity to Glu-113 counterion in the vicinity of the Schiff base linkage and suggest a role for this residue in maintaining the correct dark inactive conformation of the receptor. The reported results, together with previously published data on the other two known congenital night blindness mutants, suggest that the molecular mechanism underlying this disease may not be structural misfolding, as proposed for retinitis pigmentosa mutants, but abnormal functioning of the receptor by decreased thermal stability and/or constitutive activity.

  14. Macrobenthos community structure and trophic relationships within active and inactive Pacific hydrothermal sediments

    NASA Astrophysics Data System (ADS)

    Levin, Lisa A.; Mendoza, Guillermo F.; Konotchick, Talina; Lee, Raymond

    2009-09-01

    Hydrothermal fluids passing through sediments create a habitat hypothesized to influence the community structure of infaunal macrobenthos. Here we characterize the density, biomass, species composition, diversity, distributions, lifestyle, and nutritional sources of macroinfauna in hydrothermal sediments in NE and SW Pacific settings, and draw comparisons in search of faunal attributes characteristic of this habitat. There is increasing likelihood that seafloor massive sulfide deposits, associated with active and inactive hydrothermal venting, will be mined commercially. This creates a growing imperative for a more thorough understanding of the structure, dynamics, and resilience of the associated sediment faunas, and has stimulated the research presented here. Macrobenthic assemblages were studied at Manus Basin (1430-1634 m, Papua New Guinea [PNG]) as a function of location (South Su vs. Solwara 1), and hydrothermal activity (active vs. inactive), and at Middle Valley (2406-2411 m, near Juan de Fuca Ridge) as a function of habitat (active clam bed, microbial mat, hot mud, inactive background sediment). The studies conducted in PNG formed part of the environmental impact assessment work for the Solwara 1 Project of Nautilus Minerals Niugini Limited. We hypothesized that hydrothermally active sites should support (a) higher densities and biomass, (b) greater dominance and lower diversity, (c) a higher fraction of deposit feeders, and (d) greater isotopic evidence for chemosynthetic food sources than inactive sites. Manus Basin macrofauna generally had low density (<1000 ind. m -2) and low biomass (0.1-1.07 g m -2), except for the South Su active site, which had higher density (3494 ind. m -2) and biomass (11.94 g m -2), greater dominance (R1D=76%), lower diversity and more spatial (between-core) homogeneity than the Solwara 1 and South Su inactive sites. Dominant taxa at Manus Basin were Spionidae ( Prionospio sp.) in active sediments, and tanaids and deposit

  15. Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: use of a mutant D(2) dopamine receptor that adopts the activated conformation.

    PubMed

    Wilson, J; Lin, H; Fu, D; Javitch, J A; Strange, P G

    2001-04-01

    The antipsychotic drugs have been shown to be inverse agonists at the D(2) dopamine receptor. We have examined the mechanism of this inverse agonism by making mutations in residue T343 in the base of the sixth transmembrane spanning region of the receptor. T343R, T343S and T343K mutant D(2) dopamine receptors were made and the T343R mutant characterized in detail. The T343R mutant D(2) dopamine receptor exhibits properties of a receptor that resides more in the activated state, namely increased agonist binding affinity (independent of G-protein coupling and dependent on agonist efficacy), increased agonist potency in functional tests (adenylyl cyclase inhibition) and increased inverse agonist effects. The binding of agonists to the mutant receptor also shows sensitivity to sodium ions, unlike the native receptor, so that isomerization of the receptor to its inactive state may be driven by sodium ions. The binding of inverse agonists to the receptor is, however, unaffected by the mutation. We conclude that inverse agonism at this receptor is not achieved by the inverse agonist binding preferentially to the non-activated state of the receptor over the activated state. Rather the inverse agonist appears to bind to all forms of the receptor but then renders the receptor inactive.

  16. Endonuclease IV (nfo) mutant of Escherichia coli.

    PubMed Central

    Cunningham, R P; Saporito, S M; Spitzer, S G; Weiss, B

    1986-01-01

    A cloned gene, designated nfo, caused overproduction of an EDTA-resistant endonuclease specific for apurinic-apyrimidinic sites in DNA. The sedimentation coefficient of the enzyme was similar to that of endonuclease IV. An insertion mutation was constructed in vitro and transferred from a plasmid to the Escherichia coli chromosome. nfo mutants had an increased sensitivity to the alkylating agents methyl methanesulfonate and mitomycin C and to the oxidants tert-butyl hydroperoxide and bleomycin. The nfo mutation enhanced the killing of xth (exonuclease III) mutants by methyl methanesulfonate, H2O2, tert-butyl hydroperoxide, and gamma rays, and it enhanced their mutability by methyl methanesulfonate. It also increased the temperature sensitivity of an xth dut (dUTPase) mutant that is defective in the repair of uracil-containing DNA. These results are consistent with earlier findings that endonuclease IV and exonuclease III both cleave DNA 5' to an apurinic-apyrimidinic site and that exonuclease III is more active. However, nfo mutants were more sensitive to tert-butyl hydroperoxide and to bleomycin than were xth mutants, suggesting that endonuclease IV might recognize some lesions that exonuclease III does not. The mutants displayed no marked increase in sensitivity to 254-nm UV radiation, and the addition of an nth (endonuclease III) mutation to nfo or nfo xth mutants did not significantly increase their sensitivity to any of the agents tested. Images PMID:2430946

  17. Salmonella typhimurium mutants lacking NAD pyrophosphatase.

    PubMed Central

    Park, U E; Roth, J R; Olivera, B M

    1988-01-01

    NAD can serve as both a purine and a pyridine source for Salmonella typhimurium. Exogenous NAD is rapidly broken down into nicotinamide mononucleotide and AMP by an NAD pyrophosphatase, the first step in the pathway for the assimilation of exogenous NAD. We isolated and characterized mutants of S. typhimurium lacking NAD pyrophosphatase activity; such mutants were identified by their failure to use exogenous NAD as a purine source. These mutants carry mutations that map at a new locus, designated pnuE, between 86 and 87 min on the Salmonella chromosome. PMID:2841298

  18. 40 CFR 61.151 - Standard for inactive waste disposal sites for asbestos mills and manufacturing and fabricating...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactive waste disposal sites for asbestos tailings, a resinous or petroleum-based dust suppression agent... the particular asbestos tailings by the manufacturer of the dust suppression agent to achieve and...

  19. Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity

    PubMed Central

    Bey, Lionel; Hamilton, Marc T

    2003-01-01

    We have examined the regulation of lipoprotein lipase (LPL) activity in skeletal muscle during physical inactivity in comparison to low-intensity contractile activity of ambulatory controls. From studies acutely preventing ambulatory activity of one or both the hindlimbs in rats, it was shown that ≈90–95 % of the heparin-releasable (HR) LPL activity normally present in rat muscle with ambulatory activity is lost, and thus dependent on local contractile activity. Similarly, ≈95 % of the differences in LPL activity between muscles of different fibre types was dependent on ambulatory activity. The robustness of the finding that physical inactivity significantly decreases muscle LPL activity was evident from confirmatory studies with different models of inactivity, in many rats and mice, both sexes, three muscle types and during both acute and chronic (11 days) treatment. Inactivity caused a local reduction of plasma [3H]triglyceride uptake into muscle and a decrease in high density lipoprotein cholesterol concentration. LPL mRNA was not differentially expressed between ambulatory controls and either the acutely or chronically inactive groups. Instead, the process involved a rapid loss of the HR-LPL protein mass (the portion of LPL largely associated with the vascular endothelium) by an actinomycin D-sensitive signalling mechanism (i.e. transcriptionally dependent process). Significant decreases of intracellular LPL protein content lagged behind the loss of HR-LPL protein. Treadmill walking raised LPL activity ≈8-fold (P < 0.01) within 4 h after inactivity. The striking sensitivity of muscle LPL to inactivity and low-intensity contractile activity may provide one piece of the puzzle for why inactivity is a risk factor for metabolic diseases and why even non-vigorous activity provides marked protection against disorders involving poor lipid metabolism. PMID:12815182

  20. Predictors of hazardous drinking, tobacco smoking and physical inactivity in vocational school students

    PubMed Central

    2013-01-01

    Background Tobacco smoking, hazardous drinking and physical inactivity during adolescence are risk factors that are associated with poorer health in adulthood. The identification of subgroups of young people with a high prevalence of one or more of these risk factors allows an optimised allocation of preventive measures. This study aimed at investigating hazardous drinking, tobacco smoking and physical inactivity as well as their associations and demographic predictors in vocational school students. Methods Out of 57 contacted vocational schools in Switzerland, a total of 24 schools participated in a survey assessing gender, age, immigrant background, educational attainment and vocational field as well as the above mentioned health risk factors. Out of the 2659 students present in 177 included vocational school classes, 2647 (99.5%) completed the survey. Binary logistic regression analyses were conducted to investigate the demographic predictors of each health risk factor and a multinomial logistic regression analysis was conducted to investigate predictors of different risk factor combinations. Results Of the surveyed students, 79.4% showed at least one risk factor, 43.6% showed two or more and 9.6% showed all three health risk factors. Hazardous drinking was more prevalent in male, physical inactivity was more prevalent in female vocational school students. The proportion of students with low physical activity and tobacco smoking increased with increasing age. While the combination of hazardous drinking and tobacco smoking was higher in males, the other risk factor combinations were observed particularly among females. Conclusions Multiple risk factors were ascertained in a significant proportion of vocational school students. Specifically, tobacco smoking and hazardous drinking were coexistent. The study underlines the need for preventive measures in specific subpopulations of adolescents and young adults with lower educational level. PMID:23672294

  1. Chemically Linked Vemurafenib Inhibitors Promote an Inactive BRAFV600E Conformation

    PubMed Central

    Grasso, Michael; Estrada, Michelle A.; Ventocilla, Christian; Samanta, Minu; Maksimoska, Jasna; Villanueva, Jessie; Winkler, Jeffrey D.; Marmorstein, Ronen

    2016-01-01

    The BRAF kinase, within the mitogen activated protein kinase (MAPK) signaling pathway, harbors activating mutations in about half of melanomas and to a significant extent in many other cancers. A single valine to glutamic acid substitution at residue 600 (BRAFV600E) accounts for about 90% of these activating mutations. While BRAFV600E-selective small molecule inhibitors, such as debrafenib and vemurafenib, have shown therapeutic benefit, almost all patients develop resistance. Resistance often arises through reactivation of the MAPK pathway, typically through mutation of upstream RAS, downstream MEK or splicing variants. RAF kinases signal as homo- and hetero-dimers, and another complication associated with small molecule BRAFV600E inhibition is drug-induced allosteric activation of a wild-type RAF subunit (BRAF or CRAF) of the kinase dimer, a process called ‘transactivation’ or ‘paradoxical activation.’ Here we used BRAFV600E and vemurafenib as a model system to develop chemically linked kinase inhibitors to lock RAF dimers in an inactive conformation that cannot undergo transactivation. This structure-based design effort resulted in the development of Vem-BisAmide-2, a compound containing two vemurafenib molecules connected by a bis amide linker. We show that Vem-BisAmide-2 has comparable inhibitory potency as vemurafenib to BRAFV600E both in vitro and in cells, but promotes an inactive dimeric BRAFV600E conformation unable to undergo transactivation. The crystal structure of a BRAFV600E/Vem-BisAmide-2 complex and associated biochemical studies reveal the molecular basis for how Vem-BisAmide-2 mediates selectivity for an inactive over active dimeric BRAFV600E conformation. These studies have implications for targeting BRAFV600E/RAF heterodimers and other kinase dimers for therapy. PMID:27571413

  2. Population-attributable causes of cancer in Korea: obesity and physical inactivity.

    PubMed

    Park, Sohee; Kim, Yeonju; Shin, Hai-Rim; Lee, Boram; Shin, Aesun; Jung, Kyu-Won; Jee, Sun Ha; Kim, Dong Hyun; Yun, Young Ho; Park, Sue Kyung; Boniol, Mathieu; Boffetta, Paolo

    2014-01-01

    Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992-1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry. Excess body weight was responsible for 1,444 (1.5%) and 2,004 (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020. With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea.

  3. Mutations of CB1 T210 Produce Active and Inactive Receptor Forms

    PubMed Central

    D’Antona, Aaron M.; Ahn, Kwang H.; Kendall, Debra A.

    2008-01-01

    Human cannabinoid receptor 1 (CB1) has attracted substantial interest as a potential therapeutic target for treating obesity and other obsessive disorders. An understanding of the mechanism governing the transition of the CB1 receptor between its inactive and active states is critical for understanding how therapeutics can selectively regulate receptor activity. We have examined the importance of the Thr at position 210 in CB1 in this transition, a residue predicted to be on the same face of the helix as the Arg of the DRY motif highly conserved in the G protein-coupled receptor superfamily. This Thr was substituted with Ile and Ala via mutagenesis, and the receptors, T210I and T210A, were expressed in HEK 293 cells. The T210I receptor exhibited enhanced agonist and diminished inverse agonist affinity relative to the wild type, consistent with a shift toward the active form. However, treatment with GTPγS to inhibit G protein coupling diminished the affinity change for the inverse agonist SR141716A. The decreased thermal stability of the T210I receptor and increased level of internalization of a T210I receptor—GFP chimera were also observed, consistent with constitutive activity. In contrast, the T210A receptor exhibited the opposite profile: diminished agonist and enhanced inverse agonist affinity. The T210A receptor was found to be more thermally stable than the wild type, and high levels of a T210A receptor—GFP chimera were localized to the cell surface as predicted for an inactive receptor form. These results suggest that T210 plays a key role in governing the transition between inactive and active CB1 receptor states. PMID:16634642

  4. Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity

    PubMed Central

    Roberts, Michael D.; Company, Joseph M.; Brown, Jacob D.; Toedebusch, Ryan G.; Padilla, Jaume; Jenkins, Nathan T.; Laughlin, M. Harold

    2012-01-01

    According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2–19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6–11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity. PMID:22696577

  5. Comparative Effectiveness Research Using Observational Data: Active Comparators to Emulate Target Trials with Inactive Comparators

    PubMed Central

    Huitfeldt, Anders; Hernan, Miguel A.; Kalager, Mette; Robins, James M.

    2016-01-01

    Introduction: Because a comparison of noninitiators and initiators of treatment may be hopelessly confounded, guidelines for the conduct of observational research often recommend using an “active” comparator group consisting of people who initiate a treatment other than the medication of interest. In this paper, we discuss the conditions under which this approach is valid if the goal is to emulate a trial with an inactive comparator. Identification of Effects: We provide conditions under which a target trial in a subpopulation can be validly emulated from observational data, using an active comparator that is known or believed to be inactive for the outcome of interest. The average treatment effect in the population as a whole is not identified, but under certain conditions this approach can be used to emulate a trial in the subset of individuals who were treated with the treatment of interest, in the subset of individuals who were treated with the treatment of interest but not with the comparator, or in the subset of individuals who were treated with both the treatment of interest and the active comparator. The Plausibility of the Comparability Conditions: We discuss whether the required conditions can be expected to hold in pharmacoepidemiologic research, with a particular focus on whether the conditions are plausible in situations where the standard analysis fails due to unmeasured confounding by access to health care or health seeking behaviors. Discussion: The conditions discussed in this paper may at best be approximately true. Investigators using active comparator designs to emulate trials with inactive comparators should exercise caution. PMID:27891526

  6. Same origins of DNA replication function on the active and inactive human X chromosomes.

    PubMed

    Cohen, Stephanie M; Brylawski, Bruna P; Cordeiro-Stone, Marila; Kaufman, David G

    2003-04-01

    We previously characterized a functional origin of DNA replication at the transcriptional promoter of the human hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene (Cohen et al. [2002] J. Cell. Biochem. 85:346-356). This origin was mapped using a quantitative PCR assay to evaluate the relative abundance of HPRT markers in short nascent DNA strands isolated from asynchronous cultures of male fibroblasts. The HPRT gene on the X chromosome is transcriptionally active in male human fibroblasts. It is known that on the heterochromatic X chromosome in female cells the HPRT gene is transcriptionally silenced and its replication timing changes from early to late in S phase. This change in replication timing could indicate that replication of the HPRT gene is under the control of different origins of DNA replication in the active (euchromatic, early replicating) and the inactive (heterochromatic, late replicating) X chromosomes. In the present study, we identified the location of the origin of replication of a second X chromosome gene, glucose-6-phosphate dehydrogenase (G6PD), which we mapped to its transcriptional promoter, in normal male human fibroblasts. Then, we determined the activity of the previously identified HPRT and the G6PD human origins in hybrid hamster cells carrying either the active or the inactive human X chromosome. The results of these studies clearly demonstrated that the human HPRT and G6PD origins of replication were utilized to the same extent in the active and the inactive X chromosomes. Therefore, transcription activity at the HPRT and G6PD genes is not necessary for initiation of DNA replication at the origins mapped to these chromosomal loci.

  7. Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS*

    PubMed Central

    Demory Beckler, Michelle; Higginbotham, James N.; Franklin, Jeffrey L.; Ham, Amy-Joan; Halvey, Patrick J.; Imasuen, Imade E.; Whitwell, Corbin; Li, Ming; Liebler, Daniel C.; Coffey, Robert J.

    2013-01-01

    Activating mutations in KRAS occur in 30% to 40% of colorectal cancers. How mutant KRAS alters cancer cell behavior has been studied intensively, but non-cell autonomous effects of mutant KRAS are less understood. We recently reported that exosomes isolated from mutant KRAS-expressing colon cancer cells enhanced the invasiveness of recipient cells relative to exosomes purified from wild-type KRAS-expressing cells, leading us to hypothesize mutant KRAS might affect neighboring and distant cells by regulating exosome composition and behavior. Herein, we show the results of a comprehensive proteomic analysis of exosomes from parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only). Mutant KRAS status dramatically affects the composition of the exosome proteome. Exosomes from mutant KRAS cells contain many tumor-promoting proteins, including KRAS, EGFR, SRC family kinases, and integrins. DKs-8 cells internalize DKO-1 exosomes, and, notably, DKO-1 exosomes transfer mutant KRAS to DKs-8 cells, leading to enhanced three-dimensional growth of these wild-type KRAS-expressing non-transformed cells. These results have important implications for non-cell autonomous effects of mutant KRAS, such as field effect and tumor progression. PMID:23161513

  8. A Gyrase Mutant with Low Activity Disrupts Supercoiling at the Replication Terminus

    PubMed Central

    Pang, Zhenhua; Chen, Ray; Manna, Dipankar; Higgins, N. Patrick

    2005-01-01

    When a mutation in an essential gene shows a temperature-sensitive phenotype, one usually assumes that the protein is inactive at nonpermissive temperature. DNA gyrase is an essential bacterial enzyme composed of two subunits, GyrA and GyrB. The gyrB652 mutation results from a single base change that substitutes a serine residue for arginine 436 (R436-S) in the GyrB protein. At 42°C, strains with the gyrB652 allele stop DNA replication, and at 37°C, such strains grow but have RecA-dependent SOS induction and show constitutive RecBCD-dependent DNA degradation. Surprisingly, the GyrB652 protein is not inactive at 42°C in vivo or in vitro and it doesn't directly produce breaks in chromosomal DNA. Rather, this mutant has a low kcat compared to wild-type GyrB subunit. With more than twice the normal mean number of supercoil domains, this gyrase hypomorph is prone to fork collapse and topological chaos near the terminus of DNA replication. PMID:16267301

  9. Rotational Dynamics of Inactive Satellites as a Result of the YORP Effect

    NASA Astrophysics Data System (ADS)

    Albuja, Antonella A.

    Observations of inactive satellites in Earth orbit show that these objects are generally rotating, some with very fast rotation rates. In addition, observations indicate that the rotation rate at which defunct satellites spin tends to evolve over time. However, the cause for this behavior is unknown. The observed secular change in the spin rate and spin axis orientation of asteroids is known to be caused by the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect, which results in a torque that is created from reflected thermal energy and sunlight from the surface of an asteroid. This thesis explores the effect of YORP on defunct satellites in Earth orbit and offers this as a potential cause for the observed rotation states of inactive satellites. In this work, several different satellite models are developed to represent inactive satellites in Geostationary Earth Orbit (GEO). The evolution of the spin rate and obliquity for each satellite is then explored using Euler's equations of motion as well as spin and year averaged dynamics. This results in the dynamics being analyzed to understand the secular changes that occur, as well as the variations that result from short period terms over the course of a year. Some of the model satellites have asymmetric geometries, leading to the classical YORP effect as originally formulated for asteroids. One model satellite is geometrically symmetric, but relies on mass distribution asymmetry to generate the YORP effect. Because the YORP effect is directly dependent on geometric, optical and thermal properties of the satellite, varying these parameters can lead to different long-term rotational behavior. A sensitivity study is done by varying these parameters and analyzing its effect on the long-term dynamics of a satellite. Additionally, available observation data of inactive GEO satellites are used to estimate the YORP torque acting on those bodies. A comparison between this torque and the expected torque on a defunct satellite

  10. Remedial action plan for stabilization of the inactive uranium mill tailings site at Monument Valley, Arizona

    SciTech Connect

    1986-02-01

    This Remedial Action Plan (RAP) has been developed to serve a two-fold purpose. It presents the series of activities which are proposed by the U.S. Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uranium processing site located near Monument Valley, Arizona It also serves to document the concurrence of both the Navajo Nation and the U.S. Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by NRC, becomes Appendix B of the Cooperative Agreement.

  11. Risk assessment as a management tool for inactive hazardous materials disposal sites

    NASA Astrophysics Data System (ADS)

    Chrostowski, Paul C.; Pearsall, Lorraine J.; Shaw, Charles

    1985-09-01

    A protocol for risk assessment at inactive hazardous material disposal sites has been developed by using mathematical modeling and estimation techniques. Compared with ranking models, the protocol yields quantitative results with a minimum of input data that may be used to select among management, scientific, or engineering alternatives for the site. This article reviews the background, presents the protocol, illustrates the application of the protocol, and demonstrates the use of the protocol in conjunction with the critical environmental area concept. Comparisons are also presented with other model systems such as the EPA HRS.

  12. Increasing prevalence of overweight, obesity and physical inactivity: two population-based studies 1986 and 1994.

    PubMed

    Lindström, Martin; Isacsson, Sven-Olof; Merlo, Juan

    2003-12-01

    The aim of this study was to investigate the 1986-1994 trend in obesity, overweight and sedentary leisure-time physical activity status, and the educational gradient in overweight and obesity in the city of Malmö, Sweden. The public health surveys in Malmö 1986 and 1994 are cross-sectional studies. A total of 4,800 and 5,600 individuals aged 20-80 years were randomly chosen to be interviewed by a postal questionnaire. The participation rates were 74% and 71%. Obesity was defined as BMI 30.0 or more and overweight as BMI 25.0-29.9. The prevalences of leisure-time physical inactivity, obesity and overweight were computed, and the differences between 1986 and 1994 as well as educational gradients in overweight and obesity were assessed. The prevalence of obesity increased from 4.6% to 11.4% (p<0.001) among men and from 6.1% to 9.8% (p<0.001) among women. The prevalence of overweight (BMI 25.0-29.9) increased from 33.9% to 45.2% (p<0.001) among men, and from 19.6% to 29.1% (p<0.001) among women. The prevalence of leisure time physical inactivity increased among men from 14.7% to 18.1% (p<0.001) among men and from 19.4% to 26.7% (p<0.001) among women. The increasing prevalences of obesity, overweight and physical inactivity were observed in all age, country of origin and educational status groups. The educational differences in BMI 25.0+ observed among both men and women in 1986 disappeared among men in 1994. In contrast, educational differences in obesity (BMI 30.0+), not seen in 1986, appeared in 1994 among men. The proportions of the population with obesity and overweight increased significantly between 1986 and 1994 for both men and women. The increasing prevalence of physical inactivity seems to be an important explanation.

  13. Methylation of the mouse hprt gene differs on the active and inactive X chromosomes.

    PubMed Central

    Lock, L F; Melton, D W; Caskey, C T; Martin, G R

    1986-01-01

    It has been proposed that DNA methylation is involved in the mechanism of X inactivation, the process by which equivalence of levels of X-linked gene products is achieved in female (XX) and male (XY) mammals. In this study, Southern blots of female and male DNA digested with methylation-sensitive restriction endonucleases and hybridized to various portions of the cloned mouse hprt gene were compared, and sites within the mouse hprt gene were identified that are differentially methylated in female and male cells. The extent to which these sites are methylated when carried on the active and inactive X chromosomes was directly determined in a similar analysis of DNA from clonal cell lines established from a female embryo derived from a mating of two species of mouse, Mus musculus and Mus caroli. The results revealed two regions of differential methylation in the mouse hprt gene. One region, in the first intron of the gene, includes four sites that are completely unmethylated when carried on the active X and extensively methylated when carried on the inactive X. These same sites are extensively demethylated in hprt genes reactivated either spontaneously or after 5-azacytidine treatment. The second region includes several sites in the 3' 20kilobases of the gene extending from exon 3 to exon 9 that show the converse pattern; i.e., they are completely methylated when carried on the active X and completely unmethylated when carried on the inactive X. At least one of these sites does not become methylated after reactivation of the gene. The results of this study, together with the results of previous studies by others of the human hprt gene, indicate that these regions of differential methylation on the active and inactive X are conserved between mammalian species. Furthermore, the data described here are consistent with the idea that at least the sites in the 5' region of the gene play a role in the X inactivation phenomenon and regulation of expression of the mouse hprt

  14. Living in a Box or Call of the Wild? Revisiting Lifetime Inactivity and Sarcopenia

    PubMed Central

    Hindle, Allyson

    2011-01-01

    Abstract Significance The accepted effects of aging in mammalian skeletal muscle are progressive atrophy and weakening, or sarcopenia. Canonical hallmarks of aging in skeletal muscle include a reduction in muscle fiber cross-sectional area, a loss in muscle fibers through apoptosis and denervation, and infiltration of connective tissue or fibrosis. Emerging thought suggests that pro-inflammatory signaling and oxidative stress may contribute to sarcopenia. Critical Issues Unfortunately, most of the mammalian models used to examine and understand sarcopenia are confounded by the pervasive influence of prolonged physical inactivity. Further, the potential for underlying metabolic disorder and chronic disease (e.g., type II diabetes and cardiovascular disease) may accelerate skeletal muscle wasting. Because physical inactivity may share elevated pro-inflammatory (tumor necrosis factor-alpha and inducible nitric oxide synthase) and insufficient stress response (insulin-like growth factor-1 [IGF-1], heat-shock protein 25 [HSP25], NAD-dependent deacetylase sirtuin-3 [SIRT-3], and peroxisome proliferator-activated receptor-gamma coactivator 1[PGC-1α]) signaling with aging and chronic disease, it is critical to distinguish true aging from chronic inactivity or underlying disease. Conversely, the efficacy of exercise and caloric restrictive interventions against sarcopenia in aging populations appears highly effective when (a) conducted across the lifespan, or (b) at higher intensities when commenced in middle age or later. Recent Advances While the prospective mechanisms by which exercise or daily activity provide have not been elucidated, upregulation of HSPs, PGC-1α, and IGF-1 may ameliorate inflammatory signaling, apoptosis, and sarcopenia. Limited data indicate that the aging phenotype exhibited by mammals living in their natural habitat (Weddell seal and shrews) express limited apoptosis and fiber atrophy, whereas significant collagen accumulation remains. In

  15. Yeast mutants auxotrophic for choline or ethanolamine.

    PubMed Central

    Atkinson, K D; Jensen, B; Kolat, A I; Storm, E M; Henry, S A; Fogel, S

    1980-01-01

    Three mutants of the yeast Saccharomyces cerevisiae which require exogenous ethanolamine or choline were isolated. The mutants map to a single locus (cho1) on chromosome V. The lipid composition suggests that cho1 mutants do not synthesize phosphatidylserine under any growth conditions. If phosphatidylethanolamine or phosphatidylcholine, which are usually derived from phosphatidylserine, were synthesized from exogenous ethanolamine or choline, the mutants grew and divided relatively normally. However, mitochondrial abnormalities were evident even when ethanolamine and choline were supplied. Diploids homozygous for the cho1 mutation were defective in sporulation. Growth on nonfermentable carbon sources was slow, and a high proportion of respiratory-deficient (petite) cells were generated in cho1 cultures. PMID:6988386

  16. Characterization of rag1 mutant zebrafish leukocytes

    PubMed Central

    Petrie-Hanson, Lora; Hohn, Claudia; Hanson, Larry

    2009-01-01

    Background Zebrafish may prove to be one of the best vertebrate models for innate immunology. These fish have sophisticated immune components, yet rely heavily on innate immune mechanisms. Thus, the development and characterization of mutant and/or knock out zebrafish are critical to help define immune cell and immune gene functions in the zebrafish model. The use of Severe Combined Immunodeficient (SCID) and recombination activation gene 1 and 2 mutant mice has allowed the investigation of the specific contribution of innate defenses in many infectious diseases. Similar zebrafish mutants are now being used in biomedical and fish immunology related research. This report describes the leukocyte populations in a unique model, recombination activation gene 1-/- mutant zebrafish (rag1 mutants). Results Differential counts of peripheral blood leukocytes (PBL) showed that rag1 mutants had significantly decreased lymphocyte-like cell populations (34.7%) compared to wild-types (70.5%), and significantly increased granulocyte populations (52.7%) compared to wild-types (17.6%). Monocyte/macrophage populations were similar between mutants and wild-types, 12.6% and 11.3%, respectively. Differential leukocyte counts of rag1 mutant kidney hematopoietic tissue showed a significantly reduced lymphocyte-like cell population (8%), a significantly increased myelomonocyte population (57%), 34.8% precursor cells, and 0.2% thrombocytes, while wild-type hematopoietic kidney tissue showed 29.4% lymphocytes/lymphocyte-like cells, 36.4% myelomonocytes, 33.8% precursors and 0.5% thrombocytes. Flow cytometric analyses of kidney hematopoietic tissue revealed three leukocyte populations. Population A was monocytes and granulocytes and comprised 34.7% of the gated cells in rag1 mutants and 17.6% in wild-types. Population B consisted of hematopoietic precursors, and comprised 50% of the gated cells for rag1 mutants and 53% for wild-types. Population C consisted of lymphocytes and lymphocyte

  17. Muscle development in mdx mutant mice.

    PubMed

    Dangain, J; Vrbova, G

    1984-01-01

    Mechanical and contractile properties of tibialis anterior (TA) muscles from X-linked muscular dystrophic (mdx) mutant mice at different stages of development are compared to those of muscles from normal control animals. There is no difference between the tension output, speeds of contraction and relaxation, and weight of TA muscles from mutant adults and normal control animals. However, it is found that in 3-4-week-old mutant animals, tension output and muscle weight are very much reduced, and half relaxation time is prolonged. Thus, during this stage of development, muscles from mdx mice do not function properly. Histological examination of these muscles provides further evidence that, in these animals, rapid muscle destruction occurs at a particular time of development and that it is followed by complete recovery. This new mutant therefore presents an interesting case of muscle destruction and rapid regeneration. However, it is not an adequate model for Duchenne muscular dystrophy.

  18. Characteristics of Agrobacterium tumefaciens auxotrophic mutant infectivity.

    PubMed

    Lippincott, B B; Lippincott, J A

    1966-10-01

    Lippincott, Barbara B. (Northwestern University, Evanston, Ill.), and James A. Lippincott. Characteristics of Agrobacterium tumefaciens auxotrophic mutant infectivity. J. Bacteriol. 92:937-945. 166.-Mutants of Agrobacterium tumefaciens auxotrophic for adenine, methionine, or asparagine are less infectious than the wild-type strain B6 from which they were derived and show increased infectivity on pinto bean leaves when the specific compounds required for growth of the mutants are added to the infected leaf. Reversion to a prototrophic form of nutrition is accompanied by increased infectivity. Tumors initiated by these auxotrophic mutants are shown to arise only at large wound sites where nutritional conditions may be less restricting. The data indicate that, after inoculation, the bacteria pass through a phase in which host-supplied nutrients are utilized for the production of one or more factors necessary for successful tumor initiation.

  19. Targeting ESR1-Mutant Breast Cancer

    DTIC Science & Technology

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1-Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1-Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...mutations found in breast cancer using both structural and cell based assays. We have now have evidence for the effects of the most recurrent

  20. Mutant IDH1 and thrombosis in gliomas.

    PubMed

    Unruh, Dusten; Schwarze, Steven R; Khoury, Laith; Thomas, Cheddhi; Wu, Meijing; Chen, Li; Chen, Rui; Liu, Yinxing; Schwartz, Margaret A; Amidei, Christina; Kumthekar, Priya; Benjamin, Carolina G; Song, Kristine; Dawson, Caleb; Rispoli, Joanne M; Fatterpekar, Girish; Golfinos, John G; Kondziolka, Douglas; Karajannis, Matthias; Pacione, Donato; Zagzag, David; McIntyre, Thomas; Snuderl, Matija; Horbinski, Craig

    2016-12-01

    Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

  1. Targeting ESR1-Mutant Breast Cancer

    DTIC Science & Technology

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1-Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...ORGANIZATION: Sloan Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: September 2015 TYPE OF REPORT: Annual Technical Report...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1-Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT

  2. Quantitative Analysis of Triple Mutant Genetic Interactions

    PubMed Central

    Braberg, Hannes; Alexander, Richard; Shales, Michael; Xu, Jiewei; Franks-Skiba, Kathleen E.; Wu, Qiuqin; Haber, James E.; Krogan, Nevan J.

    2014-01-01

    The quantitative analysis of genetic interactions between pairs of gene mutations has proven effective for characterizing cellular functions but can miss important interactions for functionally redundant genes. To address this limitation, we have developed an approach termed Triple Mutant Analysis (TMA). The procedure relies on a query strain that contains two deletions in a pair of redundant or otherwise related genes, that is crossed against a panel of candidate deletion strains to isolate triple mutants and measure their growth. A central feature of TMA is to interrogate mutants that are synthetically sick when two other genes are deleted but interact minimally with either single deletion. This approach has been valuable for discovering genes that restore critical functions when the principle actors are deleted. TMA has also uncovered double mutant combinations that produce severe defects because a third protein becomes deregulated and acts in a deleterious fashion, and it has revealed functional differences between proteins presumed to act together. The protocol is optimized for Singer ROTOR pinning robots, takes 3 weeks to complete, and measures interactions for up to 30 double mutants against a library of 1536 single mutants. PMID:25010907

  3. Isolation and characterization of unusual gin mutants.

    PubMed Central

    Klippel, A; Cloppenborg, K; Kahmann, R

    1988-01-01

    Site-specific inversion of the G segment in phage Mu DNA is promoted by two proteins, the DNA invertase Gin and the host factor FIS. Recombination occurs if the recombination sites (IR) are arranged as inverted repeats and a recombinational enhancer sequence is present in cis. Intermolecular reactions as well as deletions between direct repeats of the IRs rarely occur. Making use of a fis- mutant of Escherichia coli we have devised a scheme to isolate gin mutants that have a FIS independent phenotype. This mutant phenotype is caused by single amino acid changes at five different positions of gin. The mutant proteins display a whole set of new properties in vivo: they promote inversions, deletions and intermolecular recombination in an enhancer- and FIS-independent manner. The mutants differ in recombination activity. The most active mutant protein was analysed in vitro. The loss of site orientation specificity was accompanied with the ability to recombine even linear substrates. We discuss these results in connection with the role of the enhancer and FIS protein in the wild-type situation. Images PMID:2974801

  4. Short stature caused by a mutant growth hormone with an antagonistic effect.

    PubMed

    Takahashi, Y; Kaji, H; Okimura, Y; Goji, K; Abe, H; Chihara, K

    1996-10-01

    The molecular basis of biologically inactive GH remained unclear until recently. We have very recently reported a child with short stature and a mutant GH caused by a single missense mutation in the GH-1 gene, which itself cannot transduce the GH-signal to the cells but can blunt the action of wild-type GH by virtue of its greater affinity for the GH binding protein (GHBP)/GH receptor. Briefly the clinical features of the patient are: At the age of 4.9 years his height was 81.7 cm (-6.1 SD) and bone age was 2 years. The patient's serum insulin-like growth factor-1 (IGF-1) concentration was 34 ng/ml. The basal serum GH concentration ranged from 7.0 to 14.0 ng/ml and peak concentrations after insulin hypoglycemia, arginine and L-dopa were 38.0, 15.0 and 35.0 ng/ml, respectively. A heterozygous single base substitution was identified in the GH-1 gene of the proband, predicted to convert codon 77 from arginine to cysteine. Isoelectric focusing revealed the presence of an abnormal GH peak in addition to a normal GH peak. The affinity of expressed mutant GH to GHBP was approximately 6 times higher than that of wild-type GH. The mutant GH not only failed to stimulate tyrosine phosphorylation by itself, but it also inhibited the activity of wild-type GH when added simultaneously even in a one tenth dose of wild-type GH. The child whom we reported is therefore the first case of short stature caused by mutant GH with an antagonistic effect.

  5. [High prevalence of physical inactivity among adolescents living with HIV/Aids].

    PubMed

    Tanaka, Luana Fiengo; Latorre, Maria do Rosário Dias de Oliveira; Silva, Aline Medeiros; Konstantyner, Thais Claudia Roma de Oliveira; Peres, Stela Verzinhasse; Marques, Heloisa Helena de Sousa

    2015-01-01

    To assess the prevalence of physical inactivity among adolescents with HIV/AIDS, as well as associated factors. Ninety-one adolescents (from 10 to 19 years old) with HIV/AIDS who are patients at a university follow-up service were interviewed. Anthropometric data (weight, height, and waist circumference) were measured twice; clinical information was obtained from medical records, and habitual physical activity was assessed by a questionnaire proposed by Florindo et al. The cutoff point for sedentariness was 300minutes/week. The prevalence of inadequate height for age, malnutrition, and overweight/obesity was 15.4%, 9.9% and 12.1%, respectively. The most common physical activities were soccer (44.4%), volleyball (14.4%) and cycling (7.8%). The median times spent with physical activity and walking/bicycling to school were 141minutes and 39minutes, respectively. Most adolescents (71.4%) were sedentary and this proportion was higher among girls (p=0.046). A high prevalence of physical inactivity among adolescents with HIV/AIDS was observed, similarly to the general population. Promoting physical activity among adolescents, especially among girls with HIV/AIDS, as well as monitoring it should be part of the follow-up routine of these patients. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  6. Overweight, obesity, and inactivity and urban design in rapidly growing Chinese cities.

    PubMed

    Day, Kristen; Alfonzo, Mariela; Chen, Yufei; Guo, Zhan; Lee, Karen K

    2013-05-01

    China faces rising rates of overweight, obesity, and physical inactivity among its citizens. Risk is highest in China's rapidly growing cities and urban populations. Current urban development practices and policies in China heighten this risk. These include policies that support decentralization in land use planning; practices of neighborhood gating; and policies and practices tied to motor vehicle travel, transit planning, and bicycle and pedestrian infrastructure. In this paper, we review cultural, political, and economic issues that influence overweight, obesity, and inactivity in China. We examine key urban planning features and policies that shape urban environments that may compromise physical activity as part of everyday life, including walking and bicycling. We review the empirical research to identify planning and design strategies that support physical activity in other high-density cities in developing and developed countries. Finally, we identify successful strategies to increase physical activity in another growing, high-density city - New York City - to suggest strategies that may have relevance for rapidly urbanizing Chinese cities.

  7. Major initiatives related to childhood obesity and physical inactivity in Canada: the year in review.

    PubMed

    Tremblay, Mark S

    2012-01-01

    This manuscript briefly reviews 15 significant initiatives related to childhood obesity and physical inactivity in Canada between September 2010 and September 2011. These include the: announcement of a Federal-Provincial-Territorial framework for action to promote healthy weights; implementation of the nutrition labeling initiative; launch of the CBC "Live Right Now" campaign; announcement of the Public Health Agency of Canada's innovation strategy funding related to obesity; publication of the Canadian Health Measures Survey physical activity findings; release of new Canadian physical activity and sedentary behaviour guidelines; launch of ParticipACTION's "Think Again" campaign; workshop on building trust to address the epidemic of obesity; start of the Canadian Pediatric Weight Management Registry; initiation of "Our Health Our Future: A National Dialogue on Healthy Weights"; release of the Active Healthy Kids Canada Report Card on Physical Activity for Children and Youth; National Obesity Summit; Nature Play Day and Sports Day in Canada; development of the Canadian Assessment of Physical Literacy; and the creation of Active Canada 20/20--A National Physical Activity Plan. The diversity and intensity of activity addressing the childhood obesity and physical inactivity "epidemic" in Canada is encouraging and must be maintained and enhanced.

  8. Aerobic capacity testing with inactive individuals: the role of subjective experience.

    PubMed

    Magnan, Renee E; Kwan, Bethany M; Ciccolo, Joseph T; Gurney, Burke; Mermier, Christine M; Bryan, Angela D

    2013-02-01

    Maximal oxygen uptake (VO2max), an assessment of cardiorespiratory fitness, is regularly used as the primary outcome in exercise interventions. Many criteria have been suggested for validating such tests-most commonly, a plateau in oxygen consumption. The current study investigated the proportion of inactive individuals who reached a plateau in oxygen uptake and who achieved a valid test as assessed by secondary criteria (RERmax ≥ 1.1; RPEmax ≥ 18; age predicted HRmax ±10bpm), and the correlates of a successful plateau or achievement of secondary criteria during a VO2max session. Participants (n = 240) were inactive individuals who completed VO2max assessments using an incremental treadmill test. We explored physical, behavioral, and motivational factors as predictors of meeting criteria for meeting a valid test. Approximately 59% of the sample achieved plateau using absolute (increase of VO2 of 150ml O2 or less) and 37% achieved plateau using relative (increase of VO2 of 1.5ml/kg O2 or less) criteria. Being male, having a higher BMI, a greater waist-to-hip ratio, and increased self-efficacy were associated with lower odds of achieving an absolute plateau, whereas none of these factors predicted odds of achieving relative plateau. Findings raise questions about the validity of commonly used criteria with less active populations.

  9. Any link between sexual inactivity and treadle pump performance characteristics: The Malawi case

    NASA Astrophysics Data System (ADS)

    Joseph, Chidanti-Malunga; Yamikani, Malunga

    In mitigating the effects of climate change in Malawi, government promotes the use of low cost irrigation technologies to small-scale farmers, especially in wetlands where water is available. The treadle pump is one such technology. The pump is a manual water lifting device operated by feet. Although the technology has been widely accepted by small-scale farmers, there are documented reports that some farmers abandon the technology, preferring other technologies such as river diversion. One theory for the abandonment is that female farmers claim that the technology makes their male counterparts sexually inactive. This research seeks to find an explanation to the misconception. The study analyzed the physical characteristics of the treadle pump and its users. The results show that the technology is male-dominated (30% were females out of a sample of 40). The results also show that the technology is labor-intensive with very small discharge rates (an average of 0.78 l/s) achieved regardless of the BMI of the operator. With such small discharge rates, in order to fulfill irrigation requirements of a crop, the operator has to pump for long hours. This exercise makes men naturally tired, perhaps making them sexually inactive as well.

  10. Intestinal pseudo-obstruction in inactive systemic lupus erythematosus: An unusual finding

    PubMed Central

    Leonardi, Giulia; de Bortoli, Nicola; Bellini, Massimo; Mumolo, Maria Gloria; Costa, Francesco; Ricchiuti, Angelo; Bombardieri, Stefano; Marchi, Santino

    2010-01-01

    Chronic intestinal pseudo-obstruction (CIP) is an infrequent complication of an active systemic lupus erythematosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (ECLAM score 2) was hospitalized with postprandial fullness, vomiting, abdominal bloating and abdominal pain. She had had no bowel movements for five days. Plain abdominal X-ray revealed multiple fluid levels and dilated small and large bowel loops with air-fluid levels. Intestinal contrast radiology detected dilated loops. CIP was diagnosed. The patient was treated with prokinetics, octreotide, claritromycin, rifaximin, azathioprine and tegaserod without any clinical improvement. Then methylprednisolone (500 mg iv daily) was started. After the first administration, the patient showed peristaltic movements. A bowel movement was reported after the second administration. A plain abdominal X-ray revealed no air-fluid levels. Steroid therapy was slowly reduced with complete resolution of the symptoms. The patient is still in a good clinical condition. SLE-related CIP is generally reported as a complication of an active disease. In our case, CIP was the only clinical demonstration of the SLE. PMID:21577309

  11. Flavonoid-induced conversion of catalase to its inactive form--Compound II.

    PubMed

    Krych, J; Gebicki, J L; Gebicka, L

    2014-11-01

    Flavonoids (FlaOHs), plant polyphenols, are ubiquitous components of human diet and are known as antioxidants. However, their prooxidant activity has also been reported. We have recently found that FlaOHs inhibit catalase, the heme enzyme which catalyzes the decomposition of hydrogen peroxide (H2O2) into water and molecular oxygen. The catalytic cycle proceeds with the formation of the intermediate, Compound I (Cpd I), an oxoferryl porphyrin π-cation radical, the two-electron oxidation product of a heme group. Under conditions of low H2O2 fluxes and in the presence of an appropriate substrate, Cpd I can undergo one-electron reduction to inactive Compound II (Cpd II), oxoferryl derivative without radical site. Here we show that in vitro, under low fluxes of H2O2, FlaOHs reduce Cpd I to inactive Cpd II. Measurable amounts of Cpd II can be formed even in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) at concentration comparable with the investigated FlaOHs. Possible mechanisms of electron transfer from FlaOH molecule to the heme are discussed.

  12. [Impact of physical inactivity on mortality and the economic costs of cardiovascular deaths: evidence from Argentina].

    PubMed

    García, Christian Martín; González-Jurado, José Antonio

    2017-08-21

    Estimate mortality and economic costs from cardiovascular diseases attributable to physical inactivity in Argentina. Attributable mortality (AM) from physical inactivity was estimated as the product of the population attributable fraction and the number of deaths caused by associated cardiovascular diseases. Value of statistical life (VSL) was calculated using the human capital approach, in which VSL was estimated through lost productivity from premature death. Economic costs were calculated using AM and VSL, stratifying by sex, age group, and physical activity level. A sensitivity analysis was used to evaluate how costs vary in three possible scenarios. AM from low and moderate physical activity ranged from 33 (18 to 24 years) to 7 857 (>84 years) deaths annually in both sexes. VSL ranged from I$441 005 (international dollars) (18 to 24 years) to I$4,121 (>84 years). Assessment of total costs by sex indicates that economic losses amounted to I$752.5 million for men and I$444.5 million for women. Economic losses ranged from 0.61% of GDP for the minimum scenario, 0.85% for the average scenario, and 1.48% for the maximum scenario. Stronger public policy-making aimed at reduction of sedentary lifestyles in Argentina is recommended.

  13. Detection of (In)activity Periods in Human Body Motion Using Inertial Sensors: A Comparative Study

    PubMed Central

    Olivares, Alberto; Ramírez, Javier; Górriz, Juan M.; Olivares, Gonzalo; Damas, Miguel

    2012-01-01

    Determination of (in)activity periods when monitoring human body motion is a mandatory preprocessing step in all human inertial navigation and position analysis applications. Distinction of (in)activity needs to be established in order to allow the system to recompute the calibration parameters of the inertial sensors as well as the Zero Velocity Updates (ZUPT) of inertial navigation. The periodical recomputation of these parameters allows the application to maintain a constant degree of precision. This work presents a comparative study among different well known inertial magnitude-based detectors and proposes a new approach by applying spectrum-based detectors and memory-based detectors. A robust statistical comparison is carried out by the use of an accelerometer and angular rate signal synthesizer that mimics the output of accelerometers and gyroscopes when subjects are performing basic activities of daily life. Theoretical results are verified by testing the algorithms over signals gathered using an Inertial Measurement Unit (IMU). Detection accuracy rates of up to 97% are achieved. PMID:22778613

  14. Cold-active alkaline phosphatase is irreversibly transformed into an inactive dimer by low urea concentrations.

    PubMed

    Hjörleifsson, Jens Guðmundur; Ásgeirsson, Bjarni

    2016-07-01

    Alkaline phosphatase is a homodimeric metallo-hydrolase where both Zn(2+) and Mg(2+) are important for catalysis and stability. Cold-adapted alkaline phosphatase variants have high activity at low temperatures and lower thermal stability compared with variants from mesophilic hosts. The instability, and thus inactivation, could be due to loose association of the dimers and/or loosely bound Mg(2)(+) in the active site, but this has not been studied in detail for the cold-adapted variants. Here, we focus on using the intrinsic fluorescence of Trp in alkaline phosphatase from the marine bacterium Vibrio splendidus (VAP) to probe for dimerization. Trp→Phe substitutions showed that two out of the five native Trp residues contributed mostly to the fluorescence emission. One residue, 15Å away from the active site (W460) and highly solvent excluded, was phosphorescent and had a distant role in substrate binding. An additional Trp residue was introduced to the dimer interface to act as a possible probe for dimerization. Urea denaturation curves indicated that an inactive dimer intermediate, structurally equivalent to the native state, was formed before dimer dissociation took place. This is the first example of the transition of a native dimer to an inactive dimer intermediate for alkaline phosphatase without using mutagenesis, ligands, or competitive inhibition.

  15. Small intestinal bacterial overgrowth in inactive Crohn’s disease: Influence of thiopurine and biological treatment

    PubMed Central

    Sánchez-Montes, Cristina; Ortiz, Vicente; Bastida, Guillermo; Rodríguez, Ester; Yago, María; Beltrán, Belén; Aguas, Mariam; Iborra, Marisa; Garrigues, Vicente; Ponce, Julio; Nos, Pilar

    2014-01-01

    AIM: To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn’s disease (CD). METHODS: This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test. RESULTS: One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P < 0.05). Multivariate analysis revealed that the presence of meteorism and a fistulizing pattern were associated with the presence of SIBO (P < 0.05). CONCLUSION: Immunosuppressants and/or biological drugs do not induce SIBO in inactive CD. Fistulizing disease pattern and meteorism are associated with SIBO. PMID:25320539

  16. Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive

    PubMed Central

    Maupetit-Méhouas, Stéphanie; Montibus, Bertille; Nury, David; Tayama, Chiharu; Wassef, Michel; Kota, Satya K.; Fogli, Anne; Cerqueira Campos, Fabiana; Hata, Kenichiro; Feil, Robert; Margueron, Raphael; Nakabayashi, Kazuhiko; Court, Franck; Arnaud, Philippe

    2016-01-01

    Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked by DNA methylation imprints on the maternal or paternal allele. Mono-allelic DNA methylation is strictly required for the process of imprinting and has to be faithfully maintained during the entire life-span. While the regulation of DNA methylation itself is well understood, the mechanisms whereby the opposite allele remains unmethylated are unclear. Here, we show that in the mouse, at maternally methylated ICRs, the paternal allele, which is constitutively associated with H3K4me2/3, is marked by default by H3K27me3 when these ICRs are transcriptionally inactive, leading to the formation of a bivalent chromatin signature. Our data suggest that at ICRs, chromatin bivalency has a protective role by ensuring that DNA on the paternal allele remains unmethylated and protected against spurious and unscheduled gene expression. Moreover, they provide the proof of concept that, beside pluripotent cells, chromatin bivalency is the default state of transcriptionally inactive CpG island promoters, regardless of the developmental stage, thereby contributing to protect cell identity. PMID:26400168

  17. Reduction potentials of heterometallic manganese-oxido cubane complexes modulated by redox-inactive metals.

    PubMed

    Tsui, Emily Y; Agapie, Theodor

    2013-06-18

    Understanding the effect of redox-inactive metals on the properties of biological and heterogeneous water oxidation catalysts is important both fundamentally and for improvement of future catalyst designs. In this work, heterometallic manganese-oxido cubane clusters [MMn3O4] (M = Sr(2+), Zn(2+), Sc(3+), Y(3+)) structurally relevant to the oxygen-evolving complex (OEC) of photosystem II were prepared and characterized. The reduction potentials of these clusters and other related mixed metal manganese-tetraoxido complexes are correlated with the Lewis acidity of the apical redox-inactive metal in a manner similar to a related series of heterometallic manganese-dioxido clusters. The redox potentials of the [SrMn3O4] and [CaMn3O4] clusters are close, which is consistent with the observation that the OEC is functional only with one of these two metals. Considering our previous studies of [MMn3O2] moieties, the present results with more structurally accurate models of the OEC ([MMn3O4]) suggest a general relationship between the reduction potentials of heterometallic oxido clusters and the Lewis acidities of incorporated cations that applies to diverse structural motifs. These findings support proposals that one function of calcium in the OEC is to modulate the reduction potential of the cluster to allow electron transfer.

  18. Physical inactivity and platelet function in humans and brown bears: A comparative study.

    PubMed

    Arinell, K; Blanc, S; Welinder, K G; Støen, O-G; Evans, A L; Fröbert, O

    2017-07-31

    Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few. Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

  19. High prevalence of physical inactivity among adolescents living with HIV/AIDS

    PubMed Central

    Tanaka, Luana Fiengo; Latorre, Maria do Rosário Dias de Oliveira; da Silva, Aline Medeiros; Konstantyner, Thais Claudia Roma de Oliveira; Peres, Stela Verzinhasse; Marques, Heloisa Helena de Sousa

    2015-01-01

    Objective: To assess the prevalence of physical inactivity among adolescents with HIV/AIDS, as well as associated factors. Methods: Ninety-one adolescents (from 10 to 19 years old) with HIV/AIDS who are patients at a university follow-up service were interviewed. Anthropometric data (weight, height, and waist circumference) were measured twice; clinical information was obtained from medical records, and habitual physical activity was assessed by a questionnaire proposed by Florindo et al. The cutoff point for sedentariness was 300 minutes/week. Results: The prevalence of inadequate height for age, malnutrition, and overweight/obesity was 15.4%, 9.9% and 12.1%, respectively. The most common physical activities were soccer (44.4%), volleyball (14.4%) and cycling (7.8%). The median times spent with physical activity and walking/bicycling to school were 141 min and 39 min, respectively. Most adolescents (71.4%) were sedentary and this proportion was higher among girls (p=0.046). Conclusions: A high prevalence of physical inactivity among adolescents with HIV/AIDS was observed, similar to the general population. Promoting physical activity among adolescents, especially among girls with HIV/AIDS, as well as monitoring it should be part of the follow-up routine of these patients. PMID:25907024

  20. Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive.

    PubMed

    Maupetit-Méhouas, Stéphanie; Montibus, Bertille; Nury, David; Tayama, Chiharu; Wassef, Michel; Kota, Satya K; Fogli, Anne; Cerqueira Campos, Fabiana; Hata, Kenichiro; Feil, Robert; Margueron, Raphael; Nakabayashi, Kazuhiko; Court, Franck; Arnaud, Philippe

    2016-01-29

    Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked by DNA methylation imprints on the maternal or paternal allele. Mono-allelic DNA methylation is strictly required for the process of imprinting and has to be faithfully maintained during the entire life-span. While the regulation of DNA methylation itself is well understood, the mechanisms whereby the opposite allele remains unmethylated are unclear. Here, we show that in the mouse, at maternally methylated ICRs, the paternal allele, which is constitutively associated with H3K4me2/3, is marked by default by H3K27me3 when these ICRs are transcriptionally inactive, leading to the formation of a bivalent chromatin signature. Our data suggest that at ICRs, chromatin bivalency has a protective role by ensuring that DNA on the paternal allele remains unmethylated and protected against spurious and unscheduled gene expression. Moreover, they provide the proof of concept that, beside pluripotent cells, chromatin bivalency is the default state of transcriptionally inactive CpG island promoters, regardless of the developmental stage, thereby contributing to protect cell identity.

  1. Physical (in)activity and endothelium-derived constricting factors: overlooked adaptations.

    PubMed

    Thijssen, D H J; Rongen, G A; Smits, P; Hopman, M T E

    2008-01-15

    The inner surrounding of arterial vessels, the endothelium, is optimally located to detect changes in blood characteristics or blood flow that may result from changes in physical activity or from diseases. In response to physical stimuli, the endothelium varies its release of circulating vasoactive substances and serves as a source of local and systemic endothelium-derived dilator and vasoconstrictor factors. Endothelial dysfunction is one of the earliest markers of vascular abnormalities observed in cardiovascular disease and ageing. Exercise training is an efficient therapeutic strategy to improve endothelial function. Traditionally, studies on endothelial dysfunction and physical (in)activity-related effects on vascular adaptations are primarily focused on vasodilator substances (i.e. nitric oxide). One may suggest that augmentation of vasoconstrictor pathways (such as endothelin-1 and angiotensin II) contributes to the endothelial dysfunction observed after physical inactivity. Moreover, these pathways may also explain the exercise-induced beneficial cardiovascular adaptations. This review summarizes the current knowledge on the effects of physical (in)activity on several endothelium-derived vasoconstrictor substances.

  2. Inactive corrinoid-compound significantly decreases in Spirulina platensis grown in a cobalt-deficient medium.

    PubMed

    Watanabe, F; Miyamoto, E; Nakano, Y

    2001-11-01

    Spirulina platensis NIES-39 was grown under open culture system in the presence or absence of CoSO(4) (12 microg/L) and/or vitamin B(12) (10 microg/L) to confirm whether CoSO(4) and/or vitamin B(12) stimulate or are essential for growth of the algal cells and for accumulation of vitamin B(12). The addition of CoSO(4) and/or vitamin B(12) could not affect both cell growth and cell yield of the alga. The amount of corrinoid-compound was increased significantly by the addition of CoSO(4) but not by vitamin B(12). A C18 reversed-phase HPLC pattern of the Spirulina corrinoid-compound increased by the addition of CoSO(4) was identical to that of authentic pseudovitamin B(12), which is inactive for human. These results indicate that the algal cells grown in the absence of CoSO(4) are suitable for use of human health foods because the inactive corrinoid-compound can be reduced significantly.

  3. Detection of (in)activity periods in human body motion using inertial sensors: a comparative study.

    PubMed

    Olivares, Alberto; Ramírez, Javier; Górriz, Juan M; Olivares, Gonzalo; Damas, Miguel

    2012-01-01

    Determination of (in)activity periods when monitoring human body motion is a mandatory preprocessing step in all human inertial navigation and position analysis applications. Distinction of (in)activity needs to be established in order to allow the system to recompute the calibration parameters of the inertial sensors as well as the Zero Velocity Updates (ZUPT) of inertial navigation. The periodical recomputation of these parameters allows the application to maintain a constant degree of precision. This work presents a comparative study among different well known inertial magnitude-based detectors and proposes a new approach by applying spectrum-based detectors and memory-based detectors. A robust statistical comparison is carried out by the use of an accelerometer and angular rate signal synthesizer that mimics the output of accelerometers and gyroscopes when subjects are performing basic activities of daily life. Theoretical results are verified by testing the algorithms over signals gathered using an Inertial Measurement Unit (IMU). Detection accuracy rates of up to 97% are achieved.

  4. Protective effect of inactive ingredients against nephrotoxicity of vancomycin hydrochloride in rats.

    PubMed

    Hodoshima, Naoko; Nakano, Yoshihisa; Izumi, Masaaki; Mitomi, Nayu; Nakamura, Yukari; Aoki, Makoto; Gyobu, Akiko; Shibasaki, Shigeki; Kurosawa, Toru

    2004-02-01

    A generic form of vancomycin for I.V. infusion (MEEK) is more soluble and stable than the brand-name form of vancomycin hydrochloride (VCM) due to the addition of two inactive ingredients: D-mannitol and Macrogol400 (PEG400). The aim of the present study was to compare the nephrotoxicity of MEEK with that of brand-name VCM (S-VCM) and to analyze the pharmacokinetics of these preparations. Following administration to rats at the clinical dose of 40 mg/kg, there was no difference between MEEK and S-VCM with regard to pharmacokinetics and effects on the kidneys, indicating that MEEK should be as effective as S-VCM. When administered at the nephrotoxic dose of 400 mg/kg, S-VCM caused impairment of renal function and kidney damage, and an increase of the plasma concentration due to decreased renal clearance was observed. In contrast, MEEK had virtually no effect on renal function or the kidneys and did not cause a marked change of renal clearance. These findings suggest that the inactive ingredients in MEEK play a role in reducing the nephrotoxicity of VCM.

  5. Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin

    PubMed Central

    Hanley, Mariah L.; Yoo, Tae Yeon; Sonnett, Matthew; Needleman, Daniel J.; Mitchison, Timothy J.

    2017-01-01

    The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti–cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy. We found that autophosphorylation of the CPC decreases its sedimentation coefficient in egg cytosol and increases its diffusion coefficient in live cells, indicating a decrease in mass. Using immunoprecipitation coupled with mass spectrometry and immunoblots, we discovered that inactive, unphosphorylated CPC interacts with nucleophosmin/nucleoplasmin proteins, which are known to oligomerize into pentamers and decamers. Autophosphorylation of the CPC causes it to dissociate from nucleophosmin/nucleoplasmin. We propose that nucleophosmin/nucleoplasmin complexes serve as chaperones that negatively regulate the CPC and/or stabilize its inactive form, preventing CPC autophosphorylation and recruitment to chromatin and microtubules in mitosis. PMID:28404751

  6. "Spatial Energetics": Integrating Data From GPS, Accelerometry, and GIS to Address Obesity and Inactivity.

    PubMed

    James, Peter; Jankowska, Marta; Marx, Christine; Hart, Jaime E; Berrigan, David; Kerr, Jacqueline; Hurvitz, Philip M; Hipp, J Aaron; Laden, Francine

    2016-11-01

    To address the current obesity and inactivity epidemics, public health researchers have attempted to identify spatial factors that influence physical inactivity and obesity. Technologic and methodologic developments have led to a revolutionary ability to examine dynamic, high-resolution measures of temporally matched location and behavior data through GPS, accelerometry, and GIS. These advances allow the investigation of spatial energetics, high-spatiotemporal resolution data on location and time-matched energetics, to examine how environmental characteristics, space, and time are linked to activity-related health behaviors with far more robust and detailed data than in previous work. Although the transdisciplinary field of spatial energetics demonstrates promise to provide novel insights on how individuals and populations interact with their environment, there remain significant conceptual, technical, analytical, and ethical challenges stemming from the complex data streams that spatial energetics research generates. First, it is essential to better understand what spatial energetics data represent, the relevant spatial context of analysis for these data, and if spatial energetics can establish causality for development of spatially relevant interventions. Second, there are significant technical problems for analysis of voluminous and complex data that may require development of spatially aware scalable computational infrastructures. Third, the field must come to agreement on appropriate statistical methodologies to account for multiple observations per person. Finally, these challenges must be considered within the context of maintaining participant privacy and security. This article describes gaps in current practice and understanding and suggests solutions to move this promising area of research forward.

  7. Arabian Oryx (Oryx leucoryx) Respond to Increased Ambient Temperatures with a Seasonal Shift in the Timing of Their Daily Inactivity Patterns.

    PubMed

    Davimes, Joshua G; Alagaili, Abdulaziz N; Gravett, Nadine; Bertelsen, Mads F; Mohammed, Osama B; Ismail, Khairy; Bennett, Nigel C; Manger, Paul R

    2016-08-01

    The Arabian oryx inhabits an environment where summer ambient temperatures can exceed 40 °C for extended periods of time. While the oryx uses a suite of adaptations that aid survival, the effects of this extreme environment on inactivity are unknown. To determine how the oryx manages inactivity seasonally, we measured the daily rhythm of body temperature and used fine-grain actigraphy, in 10 animals, to reveal when the animals were inactive in relation to ambient temperature and photoperiod. We demonstrate that during the cooler winter months, the oryx was inactive during the cooler parts of the 24-h day (predawn hours), showing a nighttime (nocturnal) inactivity pattern. In contrast, in the warmer summer months, the oryx displayed a bimodal inactivity pattern, with major inactivity bouts (those greater than 1 h) occurring equally during both the coolest part of the night (predawn hours) and the warmest part of the day (afternoon hours). Of note, the timing of the daily rhythm of body temperature did not vary seasonally, although the amplitude did change, leading to a seasonal alteration in the phase relationship between inactivity and the body temperature rhythm. Because during periods of inactivity the oryx were presumably asleep for much of the time, we speculate that the daytime shift in inactivity may allow the oryx to take advantage of the thermoregulatory physiology of sleep, which likely occurs when the animal is inactive for more than 1 h, to mitigate environmentally induced increases in body temperature.

  8. Denitrification and ammonia oxidation by Nitrosomonas europaea wild-type, and NirK- and NorB-deficient mutants.

    PubMed

    Schmidt, Ingo; van Spanning, Rob J M; Jetten, Mike S M

    2004-12-01

    The phenotypes of three different Nitrosomonas europaea strains--wild-type, nitrite reductase (NirK)-deficient and nitric oxide reductase (NorB)-deficient strains--were characterized in chemostat cell cultures, and the effect of nitric oxide (NO) on metabolic activities was evaluated. All strains revealed similar aerobic ammonia oxidation activities, but the growth rates and yields of the knock-out mutants were significantly reduced. Dinitrogen (N2) was the main gaseous product of the wild-type, produced via its denitrification activity. The mutants were unable to reduce nitrite to N2, but excreted more hydroxylamine leading to the formation of almost equal amounts of NO, nitrous oxide (N2O) and N2 by chemical auto-oxidation and chemodenitrification of hydroxylamine. Under anoxic conditions Nsm. europaea wild-type gains energy for growth via nitrogen dioxide (NO2)-dependent ammonia oxidation or hydrogen-dependent denitrification using nitrite as electron acceptor. The mutant strains were restricted to NO and/or N2O as electron acceptor and consequently their growth rates and yields were much lower compared with the wild-type. When cells were transferred from anoxic (denitrification) to oxic conditions, the wild-type strain endogenously produced NO and recovered ammonia oxidation within 8 h. In contrast, the mutant strains remained inactive. For recovery of ammonia oxidation activity the NO concentration had to be adjusted to about 10 p.p.m. in the aeration gas.

  9. Stabilization of physical RAF/14-3-3 interaction by cotylenin A as treatment strategy for RAS mutant cancers.

    PubMed

    Molzan, Manuela; Kasper, Stefan; Röglin, Lars; Skwarczynska, Malgorzata; Sassa, Takeshi; Inoue, Takatsugu; Breitenbuecher, Frank; Ohkanda, Junko; Kato, Nobuo; Schuler, Martin; Ottmann, Christian

    2013-09-20

    One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAF(V600) mutant melanomas. However, they paradoxically promote the growth of RAS mutant tumors, partly due to the complex interplay between different homo- and heterodimers of A-RAF, B-RAF, and C-RAF. Based on pathway analysis and structure-guided compound identification, we describe the natural product cotylenin-A (CN-A) as stabilizer of the physical interaction of C-RAF with 14-3-3 proteins. CN-A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259, but not to the activating interaction site, pSer621. While CN-A alone is inactive in RAS mutant cancer models, combined treatment with CN-A and an anti-EGFR antibody synergistically suppresses tumor growth in vitro and in vivo. This defines a novel pharmacologic strategy for treatment of RAS mutant cancers.

  10. Does guasha offer hepatoprotective effect to chronic inactive hepatitis B carriers? A built-in design to control subject expectation.

    PubMed

    Chan, Suk-tak; Yuen, John W M; Gohel, Mayur-Danny I; Wong, Ho-cheong; Chung, Chi-ping; Sun, Yu; Ng, Jia-nian; Lie, Rosalind; Kwong, Kenneth K

    2013-09-01

    A previous case study showed that Guasha, an ancient manual therapeutic technique, could exert hepatoprotective effect in a human chronic active hepatitis B carrier (active-CHB) by modulating the liver enzymes, cytokines, and heme oxygenase-1 (HO-1). The present study serves as a control to the aforementioned case report. The controls were chronic inactive carriers (inactive-CHB) and noncarriers of hepatitis B (NCs). Besides showing a difference in biochemical markers between controls and the previously reported active-CHB case, the asymptomatic condition in both inactive- and active-CHB offers an excellent control for the patient's expectation about Guasha's efficacy. The purpose of this case study was to investigate whether hepatoprotective biochemical markers previously measured in active-CHB in response to Guasha were also present in controls. Four inactive-CHB and nine NC participants were included. Each participant received a 15-minute Guasha treatment. Blood samples were obtained immediately before Guasha (day 0) and after Guasha (days 2, 5, and 7). Biochemistry values for liver function, HO-1, and T-helper (Th) cytokines were determined from blood tests. Neither the participants nor the investigator who administered Guasha were aware of the blood test results until after all data were collected for all participants. In both inactive-CHB and NC participants, liver function, serum HO-1, and Th1/Th2 cytokines did not significantly differ before and after Guasha. In contrast to results in active-CHB patients, Guasha did not induce any significant modulation of liver enzymes, HO-1, or cytokines in inactive-CHB and NC participants. The current results suggest that a Guasha-induced hepatoprotective effect depends on the inflammatory event or clinical stage of chronic hepatitis B. Because both active and inactive carriers were completely unaware of their liver status at the time of receiving Guasha, the research protocol is effective in discounting the model that

  11. In silico screening for agonists and blockers of the β2 adrenergic receptor: implications of inactive and activated state structures

    PubMed Central

    Costanzi, Stefano; Vilar, Santiago

    2011-01-01

    Ten crystal structures of the β2 adrenergic receptor (β2AR) have been published, reflecting different signaling states. Here, through controlled docking experiments, we examined the implications of using inactive or activated structures on the in silico screening for agonists and blockers of the receptor. Specifically, we targeted the crystal structures solved in complex with carazolol (2RH1), the neutral antagonist alprenalol (3NYA), the irreversible agonist FAUC50 (3PDS) and the full agonist BI-167017 (3P0G). Our results indicate that activated structures favor agonists over blockers while inactive structures favor blockers over agonists. This tendency is more marked for activated than for inactive structures. Additionally, agonists tend to receive more favorable docking scores when docked at activated rather than inactive structures, while blockers do the opposite. Hence, the difference between the docking scores attained with an activated and an inactive structure is an excellent means for the classification of ligands into agonists and blockers, as we determined through receiver operating characteristic (ROC) curves and linear discriminant analysis (LDA). With respect to virtual screening, all structures prioritized well agonists and blockers over non-binders. However, inactive structures worked better for blockers and activated structures worked better for agonists. Notably, the combination of individual docking experiments through receptor ensemble docking (RED) resulted in an excellent performance in the retrieval of both agonists and blockers. Finally, we demonstrated that the induced fit docking of agonists is a viable way of modifying an inactive crystal structure and bias it towards the in silico recognition of agonists rather than blockers. PMID:22170280

  12. Characteristics of the activity-affect association in inactive people: an ambulatory assessment study in daily life.

    PubMed

    von Haaren, Birte; Loeffler, Simone Nadine; Haertel, Sascha; Anastasopoulou, Panagiota; Stumpp, Juergen; Hey, Stefan; Boes, Klaus

    2013-01-01

    Acute and regular exercise as well as physical activity (PA) is related to well-being and positive affect. Recent studies have shown that even daily, unstructured physical activities increase positive affect. However, the attempt to achieve adherence to PA or exercise in inactive people through public health interventions has often been unsuccessful. Most studies analyzing the activity-affect association in daily life, did not report participants' habitual activity behavior. Thus, samples included active and inactive people, but they did not necessarily exhibit the same affective reactions to PA in daily life. Therefore the present study investigated whether the association between PA and subsequent affective state in daily life can also be observed in inactive individuals. We conducted a pilot study with 29 inactive university students (mean age 21.3 ± 1.7 years) using the method of ambulatory assessment. Affect was assessed via electronic diary and PA was measured with accelerometers. Participants had to rate affect every 2 h on a six item bipolar scale reflecting the three basic mood dimensions energetic arousal, valence, and calmness. We calculated activity intensity level [mean Metabolic Equivalent (MET) value] and the amount of time spent in light activity over the last 15 min before every diary prompt and conducted within-subject correlations. We did not find significant associations between activity intensity and the three mood dimensions. Due to the high variability in within-subject correlations we conclude that not all inactive people show the same affective reactions to PA in daily life. Analyzing the PA-affect association of inactive people was difficult due to little variance and distribution of the assessed variables. Interactive assessment and randomized controlled trials might help solving these problems. Future studies should examine characteristics of affective responses of inactive people to PA in daily life. General assumptions

  13. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors.

    PubMed

    Jia, Yong; Yun, Cai-Hong; Park, Eunyoung; Ercan, Dalia; Manuia, Mari; Juarez, Jose; Xu, Chunxiao; Rhee, Kevin; Chen, Ting; Zhang, Haikuo; Palakurthi, Sangeetha; Jang, Jaebong; Lelais, Gerald; DiDonato, Michael; Bursulaya, Badry; Michellys, Pierre-Yves; Epple, Robert; Marsilje, Thomas H; McNeill, Matthew; Lu, Wenshuo; Harris, Jennifer; Bender, Steven; Wong, Kwok-Kin; Jänne, Pasi A; Eck, Michael J

    2016-06-02

    The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase, but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor. Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant, but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond. All current EGFR TKIs target the ATP-site of the kinase, highlighting the need for therapeutic agents with alternative mechanisms of action. Here we describe the rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. The crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. However, as a single agent it is not effective in blocking EGFR-driven proliferation in cells owing to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state. We observe marked synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization, rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR(L858R/T790M) and by EGFR(L858R/T790M/C797S), a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors.

  14. Characterization of shrunken endosperm mutants in barley.

    PubMed

    Ma, Jian; Jiang, Qian-Tao; Wei, Long; Wang, Ji-Rui; Chen, Guo-Yue; Liu, Ya-Xi; Li, Wei; Wei, Yu-Ming; Liu, Chunji; Zheng, You-Liang

    2014-04-10

    Despite numerous studies on shrunken endosperm mutants caused by either maternal tissues (seg) or kernel per se (sex) in barley, the molecular mechanism for all of the eight seg mutants (seg1-seg8) and some sex mutants is yet to be uncovered. In this study, we determined the amylose content, characterized granule-binding proteins, analyzed the expression of key genes involved in starch synthesis, and examined starch granule structure of both normal (Bowman and Morex) and shrunken endosperm (seg1, seg3, seg4a, seg4b, seg5, seg6, seg7, and sex1) barley accessions. Our results showed that amylose contents of shrunken endosperm mutants ranged from 8.9% (seg4a) to 25.8% (seg1). SDS-PAGE analysis revealed that 87 kDa proteins corresponding to the starch branching enzyme II (SBEII) and starch synthase II (SSII) were not present in seg1, seg3, seg6, and seg7 mutants. Real-time quantitative PCR (RT-qPCR) analysis indicated that waxy expression levels of seg1, seg3, seg6, and seg7 mutants decreased in varying degrees to lower levels until 27 days after anthesis (DAA) after reaching the peak at 15-21 DAA, which differed from the pattern of normal barley accessions. Further characterization of waxy alleles revealed 7 non-synonymous single nucleotide polymorphisms (SNPs) in the coding sequences and 16 SNPs and 8 indels in the promoter sequences of the mutants. Results from starch granule by scanning electron microscopy (SEM) indicated that, in comparison with normal barley accessions, seg4a, seg4b, and sex1 had fewer starch granules per grain; seg3 and seg6 had less small B-type granules; some large A-type granules in seg7 had a hollow surface. These results improve our understanding about effects of seg and sex mutants on starch biosynthesis and granule structure during endosperm development and provide information for identification of key genes responsible for these shrunken endosperm mutants.

  15. Phanerochaete mutants with enhanced ligninolytic activity

    SciTech Connect

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1993-06-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organopollutants in soils and aqueous media. Although some of the organic compounds are degraded under nonligninolytic conditions, most are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, biopulping, biobleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated or are hyperproducers or supersecretors of key enzymes under enriched conditions. Through ultraviolet-light and gamma-rays mutagenesis we have isolated a variety of mutants, some of which produce key enzymes of the ligninolytic system under high-nitrogen growth conditions. One of the mutants produced 272 units (U) of lignin peroxidases enzyme activity per liter after nine days under high nitrogen. The mutant and the parent strains produced up to 54 U/L and 62 U/L, respectively, of the enzyme activity under low-nitrogen growth conditions during this period. In some experiments the mutant showed 281 U/L of enzyme activity under high nitrogen after 17 days.

  16. Computing border bases using mutant strategies

    NASA Astrophysics Data System (ADS)

    Ullah, E.; Abbas Khan, S.

    2014-01-01

    Border bases, a generalization of Gröbner bases, have actively been addressed during recent years due to their applicability to industrial problems. In cryptography and coding theory a useful application of border based is to solve zero-dimensional systems of polynomial equations over finite fields, which motivates us for developing optimizations of the algorithms that compute border bases. In 2006, Kehrein and Kreuzer formulated the Border Basis Algorithm (BBA), an algorithm which allows the computation of border bases that relate to a degree compatible term ordering. In 2007, J. Ding et al. introduced mutant strategies bases on finding special lower degree polynomials in the ideal. The mutant strategies aim to distinguish special lower degree polynomials (mutants) from the other polynomials and give them priority in the process of generating new polynomials in the ideal. In this paper we develop hybrid algorithms that use the ideas of J. Ding et al. involving the concept of mutants to optimize the Border Basis Algorithm for solving systems of polynomial equations over finite fields. In particular, we recall a version of the Border Basis Algorithm which is actually called the Improved Border Basis Algorithm and propose two hybrid algorithms, called MBBA and IMBBA. The new mutants variants provide us space efficiency as well as time efficiency. The efficiency of these newly developed hybrid algorithms is discussed using standard cryptographic examples.

  17. Factors increasing the risk of inactivity among administrative, technical, and manual workers in Warszawa public institutions.

    PubMed

    Biernat, Elżbieta

    2015-01-01

    The research aims to assess the level of physical activity among administrative, technical, and manual workers employed in Warszawa public institutions and to analyze the factors that increase the risk of failing to meet World Health Organization (WHO) recommendations. The study comprised 373 employees of randomly selected institutions. A short version of International Physical Activity Questionnaire (IPAQ) was applied. The correlation between the mean values of duration, days, MET-min/week of efforts, gender, and type of work was analyzed using the Tukey's honest significant difference (HSD) test, while the correlation between the level of physical activity and the socio-demographic characteristics was assessed with the Chi2 test. The strength of the relationship between socio-demographic characteristics and fulfilment of WHO standards was expressed by the odds ratio (OR) and 95% confidence interval (95% CI). The significance level was p = 0.05. High levels of physical activity were declared by 41.8% of the manual workers, 14.7% of the administration staff, and 7.3% of the technicians; 19%, 31.5% and 54.5%, respectively, reported low levels of physical activity. Factors determining the fulfilment of the WHO recommendations include: the nature of work (p = 0.003), education (p = 0.004), and income (p = 0.003). The risk of being inactive nearly doubles in the case of administration staff (31.5%) and increases more than 4 times in the case of technicians (54.5%). Respondents with secondary school education (31.6%) are exposed to a 3-fold higher risk of inactivity, while in respondents with higher education (37.2%), the level of the risk is 4-fold higher. Compared to those in the highest income group (23.4%), people who earn less (34.1%) are inactive almost twice as often. Urgent intervention is necessary in all studied groups: increased energy expenditure for recreation and locomotion, educational offers of employers to promote healthy lifestyle

  18. Population-Attributable Causes of Cancer in Korea: Obesity and Physical Inactivity

    PubMed Central

    Shin, Hai-Rim; Lee, Boram; Shin, Aesun; Jung, Kyu-Won; Jee, Sun Ha; Kim, Dong Hyun; Yun, Young Ho; Park, Sue Kyung; Boniol, Mathieu; Boffetta, Paolo

    2014-01-01

    Background Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. Methodology/Principal Findings Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992–1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated usin