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Sample records for catalytically inactive rnase

  1. Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP.

    Science.gov (United States)

    Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S

    2011-10-01

    Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed.

  2. Basic RNases of wild almond (Prunus webbii): cloning and characterization of six new S-RNase and one "non-S RNase" genes.

    Science.gov (United States)

    Banović, Bojana; Surbanovski, Nada; Konstantinović, Miroslav; Maksimović, Vesna

    2009-03-01

    In order to investigate the S-RNase allele structure of a Prunus webbii population from the Montenegrin region of the Balkans, we analyzed 10 Prunus webbii accessions. We detected 10 different S-RNase allelic variants and obtained the nucleotide sequences for six S-RNases. The BLAST analysis showed that these six sequences were new Prunus webbii S-RNase alleles. It also revealed that one of sequenced alleles, S(9)-RNase, coded for an amino acid sequence identical to that for Prunus dulcis S(14)-RNase, except for a single conservative amino acid replacement in the signal peptide region. Another, S(3)-RNase, was shown to differ by only three amino acid residues from Prunus salicina Se-RNase. The allele S(7)-RNase was found to be inactive by stylar protein isoelectric focusing followed by RNase-specific staining, but the reason for the inactivity was not at the coding sequence level. Further, in five of the 10 analyzed accessions, we detected the presence of one active basic RNase (marked PW(1)) that did not amplify with S-RNase-specific DNA primers. However, it was amplified with primers designed from the PA1 RNase nucleotide sequence (basic "non-S RNase" of Prunus avium) and the obtained sequence showed high homology (80%) with the PA1 allele. Although homologs of PA1 "non-S RNases" have been reported in four other Prunus species, this is the first recorded homolog in Prunus webbii. The evolutionary implications of the data are discussed.

  3. RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry

    Science.gov (United States)

    Siddiqui, Mohammad Adnan; Dayal, Shubham; Naji, Merna; Ezelle, Heather J.; Zeng, Chun; Zhou, Aimin; Hassel, Bret A.

    2014-01-01

    ABSTRACT The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents. PMID:25352621

  4. Footprinting analysis of interactions between the largest eukaryotic RNase P/MRP protein Pop1 and RNase P/MRP RNA components.

    Science.gov (United States)

    Fagerlund, Robert D; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2015-09-01

    Ribonuclease (RNase) P and RNase MRP are closely related catalytic ribonucleoproteins involved in the metabolism of a wide range of RNA molecules, including tRNA, rRNA, and some mRNAs. The catalytic RNA component of eukaryotic RNase P retains the core elements of the bacterial RNase P ribozyme; however, the peripheral RNA elements responsible for the stabilization of the global architecture are largely absent in the eukaryotic enzyme. At the same time, the protein makeup of eukaryotic RNase P is considerably more complex than that of the bacterial RNase P. RNase MRP, an essential and ubiquitous eukaryotic enzyme, has a structural organization resembling that of eukaryotic RNase P, and the two enzymes share most of their protein components. Here, we present the results of the analysis of interactions between the largest protein component of yeast RNases P/MRP, Pop1, and the RNA moieties of the enzymes, discuss structural implications of the results, and suggest that Pop1 plays the role of a scaffold for the stabilization of the global architecture of eukaryotic RNase P RNA, substituting for the network of RNA-RNA tertiary interactions that maintain the global RNA structure in bacterial RNase P. © 2015 Fagerlund et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  5. RNase MRP RNA and RNase P activity in plants are associated with a Pop1p containing complex.

    Science.gov (United States)

    Krehan, Mario; Heubeck, Christian; Menzel, Nicolas; Seibel, Peter; Schön, Astrid

    2012-09-01

    RNase P processes the 5'-end of tRNAs. An essential catalytic RNA has been demonstrated in Bacteria, Archaea and the nuclei of most eukaryotes; an organism-specific number of proteins complement the holoenzyme. Nuclear RNase P from yeast and humans is well understood and contains an RNA, similar to the sister enzyme RNase MRP. In contrast, no protein subunits have yet been identified in the plant enzymes, and the presence of a nucleic acid in RNase P is still enigmatic. We have thus set out to identify and characterize the subunits of these enzymes in two plant model systems. Expression of the two known Arabidopsis MRP RNA genes in vivo was verified. The first wheat MRP RNA sequences are presented, leading to improved structure models for plant MRP RNAs. A novel mRNA encoding the central RNase P/MRP protein Pop1p was identified in Arabidopsis, suggesting the expression of distinct protein variants from this gene in vivo. Pop1p-specific antibodies precipitate RNase P activity and MRP RNAs from wheat extracts. Our results provide evidence that in plants, Pop1p is associated with MRP RNAs and with the catalytic subunit of RNase P, either separately or in a single large complex.

  6. Structural organizations of yeast RNase P and RNase MRP holoenzymes as revealed by UV-crosslinking studies of RNA-protein interactions.

    Science.gov (United States)

    Khanova, Elena; Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2012-04-01

    Eukaryotic ribonuclease (RNase) P and RNase MRP are closely related ribonucleoprotein complexes involved in the metabolism of various RNA molecules including tRNA, rRNA, and some mRNAs. While evolutionarily related to bacterial RNase P, eukaryotic enzymes of the RNase P/MRP family are much more complex. Saccharomyces cerevisiae RNase P consists of a catalytic RNA component and nine essential proteins; yeast RNase MRP has an RNA component resembling that in RNase P and 10 essential proteins, most of which are shared with RNase P. The structural organizations of eukaryotic RNases P/MRP are not clear. Here we present the results of RNA-protein UV crosslinking studies performed on RNase P and RNase MRP holoenzymes isolated from yeast. The results indicate locations of specific protein-binding sites in the RNA components of RNase P and RNase MRP and shed light on the structural organizations of these large ribonucleoprotein complexes.

  7. Structural organizations of yeast RNase P and RNase MRP holoenzymes as revealed by UV-crosslinking studies of RNA–protein interactions

    Science.gov (United States)

    Khanova, Elena; Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S.

    2012-01-01

    Eukaryotic ribonuclease (RNase) P and RNase MRP are closely related ribonucleoprotein complexes involved in the metabolism of various RNA molecules including tRNA, rRNA, and some mRNAs. While evolutionarily related to bacterial RNase P, eukaryotic enzymes of the RNase P/MRP family are much more complex. Saccharomyces cerevisiae RNase P consists of a catalytic RNA component and nine essential proteins; yeast RNase MRP has an RNA component resembling that in RNase P and 10 essential proteins, most of which are shared with RNase P. The structural organizations of eukaryotic RNases P/MRP are not clear. Here we present the results of RNA–protein UV crosslinking studies performed on RNase P and RNase MRP holoenzymes isolated from yeast. The results indicate locations of specific protein-binding sites in the RNA components of RNase P and RNase MRP and shed light on the structural organizations of these large ribonucleoprotein complexes. PMID:22332141

  8. RNase MRP and disease.

    Science.gov (United States)

    Mattijssen, Sandy; Welting, Tim J M; Pruijn, Ger J M

    2010-01-01

    The human RNase MRP complex consists of a catalytic RNA and several protein components. RNase MRP is a ubiquitously expressed eukaryotic endoribonuclease that cleaves various RNAs, including ribosomal, messenger, and mitochondrial RNAs, in a highly specific fashion. In several autoimmune diseases autoantibodies targeting RNase MRP have been found. These so-called anti-Th/To autoantibodies, which most frequently can be detected in the sera of scleroderma patients, are directed to several protein components of the RNase MRP and the evolutionarily related RNase P complex. It is not yet known whether the anti-Th/To immune response is an epiphenomenon or whether these autoantibodies play a role in the pathophysiology of the disease. The gene encoding the RNase MRP RNA was the first nuclear non-coding RNA gene demonstrated to be associated with a genetic disease. Mutations in this gene are causing the highly pleiotropic disease cartilage-hair hypoplasia (CHH). CHH patients are characterized by a short stature, hypoplastic hair, and short limbs. In addition, they show a predisposition to lymphomas and other cancers and suffer from defective T-cell immunity. Since the identification of the first CHH-associated mutations in 2001, many distinct mutations have been found in different patients. These mutations either affect the structure of the RNase MRP RNA or are located in the promoter region and reduce the expression levels. In this review article we will, after describing the biochemical aspects of RNase MRP, discuss the targeting of RNase MRP in autoimmunity and the role of mutations in the RNase MRP RNA gene in CHH. 2010 John Wiley & Sons, Ltd.

  9. Substitutions in conserved regions preceding and within the linker affect activity and flexibility of tRNase ZL, the long form of tRNase Z.

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    Makenzie Saoura

    Full Text Available The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether and functions as a monomer. The amino domain retains the flexible arm responsible for substrate recognition and binding while the carboxy domain retains the active site. The linker region was explored by Ala-scanning through two conserved regions of D. melanogaster tRNase Z: NdomTprox, located at the carboxy end of the amino domain proximal to the linker, and Tflex, a flexible site in the linker. Periodic substitutions in a hydrophobic patch (F329 and L332 at the carboxy end of NdomTprox show 2,700 and 670-fold impairment relative to wild type, respectively, accompanied by reduced linker flexibility at N-T inside the Ndom- linker boundary. The Ala substitution for N378 in the Tflex region has 10-fold higher catalytic efficiency than wild type and locally decreased flexibility, while the Ala substitution at R382 reduces catalytic efficiency ~50-fold. These changes in pre-tRNA processing kinetics and protein flexibility are interpreted in light of a recent crystal structure for S. cerevisiae tRNase Z, suggesting transmission of local changes in hydrophobicity into the skeleton of the amino domain.

  10. Active Yeast Telomerase Shares Subunits with Ribonucleoproteins RNase P and RNase MRP.

    Science.gov (United States)

    Lemieux, Bruno; Laterreur, Nancy; Perederina, Anna; Noël, Jean-François; Dubois, Marie-Line; Krasilnikov, Andrey S; Wellinger, Raymund J

    2016-05-19

    Telomerase is the ribonucleoprotein enzyme that replenishes telomeric DNA and maintains genome integrity. Minimally, telomerase activity requires a templating RNA and a catalytic protein. Additional proteins are required for activity on telomeres in vivo. Here, we report that the Pop1, Pop6, and Pop7 proteins, known components of RNase P and RNase MRP, bind to yeast telomerase RNA and are essential constituents of the telomerase holoenzyme. Pop1/Pop6/Pop7 binding is specific and involves an RNA domain highly similar to a protein-binding domain in the RNAs of RNase P/MRP. The results also show that Pop1/Pop6/Pop7 function to maintain the essential components Est1 and Est2 on the RNA in vivo. Consistently, addition of Pop1 allows for telomerase activity reconstitution with wild-type telomerase RNA in vitro. Thus, the same chaperoning module has allowed the evolution of functionally and, remarkably, structurally distinct RNPs, telomerase, and RNases P/MRP from unrelated progenitor RNAs. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. RNase MRP cleaves pre-tRNASer-Met in the tRNA maturation pathway.

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    Saito, Yuichiro; Takeda, Jun; Adachi, Kousuke; Nobe, Yuko; Kobayashi, Junya; Hirota, Kouji; Oliveira, Douglas V; Taoka, Masato; Isobe, Toshiaki

    2014-01-01

    Ribonuclease mitochondrial RNA processing (RNase MRP) is a multifunctional ribonucleoprotein (RNP) complex that is involved in the maturation of various types of RNA including ribosomal RNA. RNase MRP consists of a potential catalytic RNA and several protein components, all of which are required for cell viability. We show here that the temperature-sensitive mutant of rmp1, the gene for a unique protein component of RNase MRP, accumulates the dimeric tRNA precursor, pre-tRNA(Ser-Met). To examine whether RNase MRP mediates tRNA maturation, we purified the RNase MRP holoenzyme from the fission yeast Schizosaccharomyces pombe and found that the enzyme directly and selectively cleaves pre-tRNA(Ser-Met), suggesting that RNase MRP participates in the maturation of specific tRNA in vivo. In addition, mass spectrometry-based ribonucleoproteomic analysis demonstrated that this RNase MRP consists of one RNA molecule and 11 protein components, including a previously unknown component Rpl701. Notably, limited nucleolysis of RNase MRP generated an active catalytic core consisting of partial mrp1 RNA fragments, which constitute "Domain 1" in the secondary structure of RNase MRP, and 8 proteins. Thus, the present study provides new insight into the structure and function of RNase MRP.

  12. Crystal structure of the RNase T1 Gp c U complex

    International Nuclear Information System (INIS)

    Arni, R.K.

    1996-01-01

    Full text. Ribonuclease T 1 (RNase T 1 ; EC 3.1.27.3) a member of an extensive gene family of orthologous enzymes from fungi and bacteria that display sequence and structural homology. RNase T 1 is a guanine specific extracellular enzyme from Aspergillus oryzae that cleaves single stranded RNA by catalytic transesterification of 3,5 diester links to 2,3 cyclic diesters at guanylyl residues followed by their catalytic hydrolysis to corresponding 3 monoester. It has been suggested that subsites at both the 5 and 3 sides of a cleavable guanylyl residue in RNA substrates exist. The structure of the monomeric RNase T 1 2 guanosine mono phosphate was determined at 1.9 A resolution using syncrotron radiation (Arni et al. 1987) and revealed the specific interactions at the base recognition and catalytic sites (Arni et al., 1988). The structure of native RNase T 1 indicated the conformational changes of the amino acids forming the base recognition site (Arni et al., 1992). This protein has now been crystallized with Gpc U (Guanylyl (3,6) 6 deoxyhomouridine) which is an isosteric phosphonate analogue of the RNA fragment GpU (Guanylyl (3,5) Uridine), with the 5 oxygen of the uridine moiety replaced by a methylene. The structure has been determined and refined at 2.0 A resolution and indicates the existence of subsites and a novel ribose interaction. (author)

  13. Structural Basis for the Inhibition of RNase H Activity of HIV-1 Reverse Transcriptase by RNase H Active Site-Directed Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Su, Hua-Poo; Yan, Youwei; Prasad, G. Sridhar; Smith, Robert F.; Daniels, Christopher L.; Abeywickrema, Pravien D.; Reid, John C.; Loughran, H. Marie; Kornienko, Maria; Sharma, Sujata; Grobler, Jay A.; Xu, Bei; Sardana, Vinod; Allison, Timothy J.; Williams, Peter D.; Darke, Paul L.; Hazuda, Daria J.; Munshi, Sanjeev (Merck)

    2010-09-02

    HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H inhibitors.

  14. Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA

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    Zhu, Yanglong; Stribinskis, Vilius; Ramos, Kenneth S.; Li, Yong

    2006-01-01

    RNase MRP is a eukaryote-specific endoribonuclease that generates RNA primers for mitochondrial DNA replication and processes precursor rRNA. RNase P is a ubiquitous endoribonuclease that cleaves precursor tRNA transcripts to produce their mature 5′ termini. We found extensive sequence homology of catalytic domains and specificity domains between their RNA subunits in many organisms. In Candida glabrata, the internal loop of helix P3 is 100% conserved between MRP and P RNAs. The helix P8 of MRP RNA from microsporidia Encephalitozoon cuniculi is identical to that of P RNA. Sequence homology can be widely spread over the whole molecule of MRP RNA and P RNA, such as those from Dictyostelium discoideum. These conserved nucleotides between the MRP and P RNAs strongly support the hypothesis that the MRP RNA is derived from the P RNA molecule in early eukaryote evolution. PMID:16540690

  15. The human core exosome interacts with differentially localized processive RNases

    DEFF Research Database (Denmark)

    Tomecki, Rafal; Kristiansen, Maiken Søndergaard; Lykke-Andersen, Søren

    2010-01-01

    The eukaryotic RNA exosome is a ribonucleolytic complex involved in RNA processing and turnover. It consists of a nine-subunit catalytically inert core that serves a structural function and participates in substrate recognition. Best defined in Saccharomyces cerevisiae, enzymatic activity comes...... from the associated subunits Dis3p (Rrp44p) and Rrp6p. The former is a nuclear and cytoplasmic RNase II/R-like enzyme, which possesses both processive exo- and endonuclease activities, whereas the latter is a distributive RNase D-like nuclear exonuclease. Although the exosome core is highly conserved......, identity and arrangements of its catalytic subunits in different vertebrates remain elusive. Here, we demonstrate the association of two different Dis3p homologs--hDIS3 and hDIS3L--with the human exosome core. Interestingly, these factors display markedly different intracellular localizations: hDIS3...

  16. Structure of Pfu Pop5, an archaeal RNase P protein.

    Science.gov (United States)

    Wilson, Ross C; Bohlen, Christopher J; Foster, Mark P; Bell, Charles E

    2006-01-24

    We have used NMR spectroscopy and x-ray crystallography to determine the three-dimensional structure of PF1378 (Pfu Pop5), one of four protein subunits of archaeal RNase P that shares a homolog in the eukaryotic enzyme. RNase P is an essential and ubiquitous ribonucleoprotein enzyme required for maturation of tRNA. In bacteria, the enzyme's RNA subunit is responsible for cleaving the single-stranded 5' leader sequence of precursor tRNA molecules (pre-tRNA), whereas the protein subunit assists in substrate binding. Although in bacteria the RNase P holoenzyme consists of one large catalytic RNA and one small protein subunit, in archaea and eukarya the enzyme contains several (> or =4) protein subunits, each of which lacks sequence similarity to the bacterial protein. The functional role of the proteins is poorly understood, as is the increased complexity in comparison to the bacterial enzyme. Pfu Pop5 has been directly implicated in catalysis by the observation that it pairs with PF1914 (Pfu Rpp30) to functionally reconstitute the catalytic domain of the RNA subunit. The protein adopts an alpha-beta sandwich fold highly homologous to the single-stranded RNA binding RRM domain. Furthermore, the three-dimensional arrangement of Pfu Pop5's structural elements is remarkably similar to that of the bacterial protein subunit. NMR spectra have been used to map the interaction of Pop5 with Pfu Rpp30. The data presented permit tantalizing hypotheses regarding the role of this protein subunit shared by archaeal and eukaryotic RNase P.

  17. Mechanistic and Structural Studies of Protein-Only RNase P Compared to Ribonucleoproteins Reveal the Two Faces of the Same Enzymatic Activity

    Directory of Open Access Journals (Sweden)

    Cédric Schelcher

    2016-06-01

    Full Text Available RNase P, the essential activity that performs the 5′ maturation of tRNA precursors, can be achieved either by ribonucleoproteins containing a ribozyme present in the three domains of life or by protein-only enzymes called protein-only RNase P (PRORP that occur in eukaryote nuclei and organelles. A fast growing list of studies has investigated three-dimensional structures and mode of action of PRORP proteins. Results suggest that similar to ribozymes, PRORP proteins have two main domains. A clear functional analogy can be drawn between the specificity domain of the RNase P ribozyme and PRORP pentatricopeptide repeat domain, and between the ribozyme catalytic domain and PRORP N4BP1, YacP-like Nuclease domain. Moreover, both types of enzymes appear to dock with the acceptor arm of tRNA precursors and make specific contacts with the corner of pre-tRNAs. While some clear differences can still be delineated between PRORP and ribonucleoprotein (RNP RNase P, the two types of enzymes seem to use, fundamentally, the same catalytic mechanism involving two metal ions. The occurrence of PRORP and RNP RNase P represents a remarkable example of convergent evolution. It might be the unique witness of an ongoing replacement of catalytic RNAs by proteins for enzymatic activities.

  18. Evidence of surface migration and formation of catalytically inactive Pt in corrosion studies of Pt+ implanted Ti

    International Nuclear Information System (INIS)

    Appleton, B.R.; Kelly, E.J.; White, C.W.; Thompson, N.G.; Lichter, B.D.

    1980-08-01

    This investigation is part of an ongoing research project directed at applying the techniques of ion implantation doping and ion scattering analysis to identify the mechanisms associated with the anodic dissolution of Ti-Pt alloys. The Ti-Pt alloys produced by ion implantation were electrochemically examined in hydrogen saturated 1 N H 2 SO 4 by both potentiostatic polarization and open-circuit potential methods. In this study, Ti samples implanted to relatively high doses (5.4 x 10 15 to 2.9 x 10 16 atoms/cm 2 ) were examined by ion scattering analysis at various stages in the electrochemical measurements. Quantitative measurements showed that the majority of the implanted Pt accumulated on the surface during anodic dissolution and underwent large scale surface migration. Evidence is also presented for the transition of the Pt on the surface from a catalytically active to inactive state. Possible mechanisms for the observed catalytically inactive Pt are discussed

  19. Modular architecture of eukaryotic RNase P and RNase MRP revealed by electron microscopy.

    Science.gov (United States)

    Hipp, Katharina; Galani, Kyriaki; Batisse, Claire; Prinz, Simone; Böttcher, Bettina

    2012-04-01

    Ribonuclease P (RNase P) and RNase MRP are closely related ribonucleoprotein enzymes, which process RNA substrates including tRNA precursors for RNase P and 5.8 S rRNA precursors, as well as some mRNAs, for RNase MRP. The structures of RNase P and RNase MRP have not yet been solved, so it is unclear how the proteins contribute to the structure of the complexes and how substrate specificity is determined. Using electron microscopy and image processing we show that eukaryotic RNase P and RNase MRP have a modular architecture, where proteins stabilize the RNA fold and contribute to cavities, channels and chambers between the modules. Such features are located at strategic positions for substrate recognition by shape and coordination of the cleaved-off sequence. These are also the sites of greatest difference between RNase P and RNase MRP, highlighting the importance of the adaptation of this region to the different substrates.

  20. HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain.

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    Marie-Claude Gingras

    Full Text Available The HD-PTP protein has been described as a tumor suppressor candidate and based on its amino acid sequence, categorized as a classical non-transmembrane protein tyrosine phosphatase (PTP. To date, no HD-PTP phosphorylated substrate has been identified and controversial results concerning its catalytic activity have been recently reported.Here we report a rigorous enzymatic analysis demonstrating that the HD-PTP protein does not harbor tyrosine phosphatase or lipid phosphatase activity using the highly sensitive DiFMUP substrate and a panel of different phosphatidylinositol phosphates. We found that HD-PTP tyrosine phosphatase inactivity is caused by an evolutionary conserved amino acid divergence of a key residue located in the HD-PTP phosphatase domain since its back mutation is sufficient to restore the HD-PTP tyrosine phosphatase activity. Moreover, in agreement with a tumor suppressor activity, HD-PTP expression leads to colony growth reduction in human cancer cell lines, independently of its catalytic PTP activity status.In summary, we demonstrate that HD-PTP is a catalytically inactive protein tyrosine phosphatase. As such, we identify one residue involved in its inactivation and show that its colony growth reduction activity is independent of its PTP activity status in human cancer cell lines.

  1. Catalysis by Glomerella cingulata cutinase requires conformational cycling between the active and inactive states of its catalytic triad.

    Science.gov (United States)

    Nyon, Mun Peak; Rice, David W; Berrisford, John M; Hounslow, Andrea M; Moir, Arthur J G; Huang, Huazhang; Nathan, Sheila; Mahadi, Nor Muhammad; Bakar, Farah Diba Abu; Craven, C Jeremy

    2009-01-09

    Cutinase belongs to a group of enzymes that catalyze the hydrolysis of esters and triglycerides. Structural studies on the enzyme from Fusarium solani have revealed the presence of a classic catalytic triad that has been implicated in the enzyme's mechanism. We have solved the crystal structure of Glomerella cingulata cutinase in the absence and in the presence of the inhibitors E600 (diethyl p-nitrophenyl phosphate) and PETFP (3-phenethylthio-1,1,1-trifluoropropan-2-one) to resolutions between 2.6 and 1.9 A. Analysis of these structures reveals that the catalytic triad (Ser136, Asp191, and His204) adopts an unusual configuration with the putative essential histidine His204 swung out of the active site into a position where it is unable to participate in catalysis, with the imidazole ring 11 A away from its expected position. Solution-state NMR experiments are consistent with the disrupted configuration of the triad observed crystallographically. H204N, a site-directed mutant, was shown to be catalytically inactive, confirming the importance of this residue in the enzyme mechanism. These findings suggest that, during its catalytic cycle, cutinase undergoes a significant conformational rearrangement converting the loop bearing the histidine from an inactive conformation, in which the histidine of the triad is solvent exposed, to an active conformation, in which the triad assumes a classic configuration.

  2. Ire1 Has Distinct Catalytic Mechanisms for XBP1/HAC1 Splicing and RIDD

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    Arvin B. Tam

    2014-11-01

    Full Text Available An evolutionarily conserved unfolded protein response (UPR component, IRE1, cleaves XBP1/HAC1 introns in order to generate spliced mRNAs that are translated into potent transcription factors. IRE1 also cleaves endoplasmic-reticulum-associated RNAs leading to their decay, an activity termed regulated IRE1-dependent decay (RIDD; however, the mechanism by which IRE1 differentiates intron cleavage from RIDD is not well understood. Using in vitro experiments, we found that IRE1 has two different modes of action: XBP1/HAC1 is cleaved by IRE1 subunits acting cooperatively within IRE1 oligomers, whereas a single subunit of IRE1 performs RIDD without cooperativity. Furthermore, these distinct activities can be separated by complementation of catalytically inactive IRE1 RNase and mutations at oligomerization interfaces. Using an IRE1 RNase inhibitor, STF-083010, selective inhibition of XBP1 splicing indicates that XBP1 promotes cell survival, whereas RIDD leads to cell death, revealing modulation of IRE1 activities as a drug-development strategy.

  3. Differential association of protein subunits with the human RNase MRP and RNase P complexes.

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    Welting, Tim J M; Kikkert, Bastiaan J; van Venrooij, Walther J; Pruijn, Ger J M

    2006-07-01

    RNase MRP is a eukaryotic endoribonuclease involved in nucleolar and mitochondrial RNA processing events. RNase MRP is a ribonucleoprotein particle, which is structurally related to RNase P, an endoribonuclease involved in pre-tRNA processing. Most of the protein components of RNase MRP have been reported to be associated with RNase P as well. In this study we determined the association of these protein subunits with the human RNase MRP and RNase P particles by glycerol gradient sedimentation and coimmunoprecipitation. In agreement with previous studies, RNase MRP sedimented at 12S and 60-80S. In contrast, only a single major peak was observed for RNase P at 12S. The analysis of individual protein subunits revealed that hPop4 (also known as Rpp29), Rpp21, Rpp20, and Rpp25 only sedimented in 12S fractions, whereas hPop1, Rpp40, Rpp38, and Rpp30 were also found in 60-80S fractions. In agreement with their cosedimentation with RNase P RNA in the 12S peak, coimmunoprecipitation with VSV-epitope-tagged protein subunits revealed that hPop4, Rpp21, and in addition Rpp14 preferentially associate with RNase P. These data show that hPop4, Rpp21, and Rpp14 may not be associated with RNase MRP. Furthermore, Rpp20 and Rpp25 appear to be associated with only a subset of RNase MRP particles, in contrast to hPop1, Rpp40, Rpp38, and Rpp30 (and possibly also hPop5), which are probably associated with all RNase MRP complexes. Our data are consistent with a transient association of Rpp20 and Rpp25 with RNase MRP, which may be inversely correlated to its involvement in pre-rRNA processing.

  4. Conserved and variable domains of RNase MRP RNA.

    Science.gov (United States)

    Dávila López, Marcela; Rosenblad, Magnus Alm; Samuelsson, Tore

    2009-01-01

    Ribonuclease MRP is a eukaryotic ribonucleoprotein complex consisting of one RNA molecule and 7-10 protein subunits. One important function of MRP is to catalyze an endonucleolytic cleavage during processing of rRNA precursors. RNase MRP is evolutionary related to RNase P which is critical for tRNA processing. A large number of MRP RNA sequences that now are available have been used to identify conserved primary and secondary structure features of the molecule. MRP RNA has structural features in common with P RNA such as a conserved catalytic core, but it also has unique features and is characterized by a domain highly variable between species. Information regarding primary and secondary structure features is of interest not only in basic studies of the function of MRP RNA, but also because mutations in the RNA give rise to human genetic diseases such as cartilage-hair hypoplasia.

  5. RNaseI from Escherichia coli cannot substitute for S-RNase in rejection of Nicotiana plumbaginifolia pollen.

    Science.gov (United States)

    Beecher, B; Murfett, J; McClure, B A

    1998-03-01

    Unilateral incompatibility often occurs between self-incompatible (SI) species and their self-compatible (SC) relatives. For example, SI Nicotiana alata rejects pollen from SC N. plumbaginifolia, but the reciprocal pollination is compatible. This interspecific pollen rejection system closely resembles intraspecific S-allele-specific pollen rejection. However, the two systems differ in degree of specificity. In SI, rejection is S-allele-specific, meaning that only a single S-RNase causes rejection of pollen with a specific S genotype. Rejection of N. plumbaginifolia pollen is less specific, occurring in response to almost any S-RNase. Here, we have tested whether a non-S-RNase can cause rejection of N. plumbaginifolia pollen. The Escherichia coli rna gene encoding RNAseI was engineered for expression in transgenic (N. plumbaginifolia x SC N. alata) hybrids. Expression levels and pollination behavior of hybrids expressing E. coli RNaseI were compared to controls expressing SA2-RNase from N. alata. Immunoblot analysis and RNase activity assays showed that RNaseI and SA2-RNase were expressed at comparable levels. However, expression of SA2-RNase caused rejection of N. plumbaginifolia pollen, whereas expression of RNaseI did not. Thus, in this system, RNase activity alone is not sufficient for rejection of N. plumbaginifolia pollen. The results suggest that S-RNases may be specially adapted to function in pollen rejection.

  6. Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease.

    Science.gov (United States)

    Mattijssen, Sandy; Hinson, Ella R; Onnekink, Carla; Hermanns, Pia; Zabel, Bernhard; Cresswell, Peter; Pruijn, Ger J M

    2011-07-01

    RNase MRP is a conserved endoribonuclease, in humans consisting of a 267-nucleotide RNA associated with 7-10 proteins. Mutations in its RNA component lead to several autosomal recessive skeletal dysplasias, including cartilage-hair hypoplasia (CHH). Because the known substrates of mammalian RNase MRP, pre-ribosomal RNA, and RNA involved in mitochondrial DNA replication are not likely involved in CHH, we analyzed the effects of RNase MRP (and the structurally related RNase P) depletion on mRNAs using DNA microarrays. We confirmed the upregulation of the interferon-inducible viperin mRNA by RNAi experiments and this appeared to be independent of the interferon response. We detected two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. This is the first study providing direct evidence for the cleavage of a mRNA by RNase MRP/RNase P in human cells. Implications for the involvement in the pathophysiology of CHH are discussed.

  7. The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response.

    Science.gov (United States)

    Ezelle, Heather J; Malathi, Krishnamurthy; Hassel, Bret A

    2016-01-08

    The interferon (IFN)-regulated endoribonuclease RNase-L is involved in multiple aspects of the antimicrobial innate immune response. It is the terminal component of an RNA cleavage pathway in which dsRNA induces the production of RNase-L-activating 2-5A by the 2'-5'-oligoadenylate synthetase. The active nuclease then cleaves ssRNAs, both cellular and viral, leading to downregulation of their expression and the generation of small RNAs capable of activating retinoic acid-inducible gene-I (RIG-I)-like receptors or the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome. This leads to IFNβ expression and IL-1β activation respectively, in addition to broader effects on immune cell function. RNase-L is also one of a growing number of innate immune components that interact with the cell cytoskeleton. It can bind to several cytoskeletal proteins, including filamin A, an actin-binding protein that collaborates with RNase-L to maintain the cellular barrier to viral entry. This antiviral activity is independent of catalytic function, a unique mechanism for RNase-L. We also describe here the interaction of RNase-L with the E3 ubiquitin ligase and scaffolding protein, ligand of nump protein X (LNX), a regulator of tight junction proteins. In order to better understand the significance and context of these novel binding partners in the antimicrobial response, other innate immune protein interactions with the cytoskeleton are also discussed.

  8. Effect of the replacement of aspartic acid/glutamic acid residues with asparagine/glutamine residues in RNase He1 from Hericium erinaceus on inhibition of human leukemia cell line proliferation.

    Science.gov (United States)

    Kobayashi, Hiroko; Motoyoshi, Naomi; Itagaki, Tadashi; Suzuki, Mamoru; Inokuchi, Norio

    2015-01-01

    RNase He1 from Hericium erinaceus, a member of the RNase T1 family, has high identity with RNase Po1 from Pleurotus ostreatus with complete conservation of the catalytic sequence. However, the optimal pH for RNase He1 activity is lower than that of RNase Po1, and the enzyme shows little inhibition of human tumor cell proliferation. Hence, to investigate the potential antitumor activity of recombinant RNase He1 and to possibly enhance its optimum pH, we generated RNase He1 mutants by replacing 12 Asn/Gln residues with Asp/Glu residues; the amino acid sequence of RNase Po1 was taken as reference. These mutants were then expressed in Escherichia coli. Using site-directed mutagenesis, we successfully modified the optimal pH for enzyme activity and generated a recombinant RNase He1 that inhibited the proliferation of cells in the human leukemia cell line. These properties are extremely important in the production of anticancer biologics that are based on RNase activity.

  9. The RNase PD2 gene of almond (Prunus dulcis) represents an evolutionarily distinct class of S-like RNase genes.

    Science.gov (United States)

    Ma, R C; Oliveira, M M

    2000-07-01

    A cDNA for an S-like RNase (RNase PD2) has been isolated from a pistil cDNA library of Prunus dulcis cv. Ferragnés. The cDNA encodes an acidic protein of 226 amino acid residues with a molecular weight of 25 kDa. A potential N-glycosylation site is present at the N-terminus in RNase PD2. A signal peptide of 23 amino acid residues and a transmembrane domain are predicted. The two active-site histidines present in enzymes of the T2/S RNase superfamily were detected in RNase PD2. Its amino acid sequence shows 71.2% similarity to RNSI of Arabidopsis and RNase T2 of chickpea, respectively. Northern blotting and RT-PCR analyses indicate that PD2 is expressed predominantly in petals, pistils of open flowers and leaves of the almond tree. Analyses of shoots cultured in vitro suggested that the expression of RNase PD2 is associated with phosphate starvation. Southern analysis detected two sequences related to RNase PD2 in the P. dulcis genome. RFLP analysis showed that S-like RNase genes are polymorphic in different almond cultivars. The PD2 gene sequence was amplified by PCR and two introns were shown to interrupt the coding region. Based on sequence analysis, we have defined three classes of S-like RNase genes, with the PD2 RNase gene representing a distinct class. The significance of the structural divergence of S-like RNase genes is further discussed.

  10. Evolutionary relationships among self-incompatibility RNases

    Science.gov (United States)

    Igic, Boris; Kohn, Joshua R.

    2001-01-01

    T2-type RNases are responsible for self-pollen recognition and rejection in three distantly related families of flowering plants—the Solanaceae, Scrophulariaceae, and Rosaceae. We used phylogenetic analyses of 67 T2-type RNases together with information on intron number and position to determine whether the use of RNases for self-incompatibility in these families is homologous or convergent. All methods of phylogenetic reconstruction as well as patterns of variation in intron structure find that all self-incompatibility RNases along with non-S genes from only two taxa form a monophyletic clade. Several lines of evidence suggest that the best interpretation of this pattern is homology of self-incompatibility RNases from the Scrophulariaceae, Solanaceae, and Rosaceae. Because the most recent common ancestor of these three families is the ancestor of ≈75% of dicot families, our results indicate that RNase-based self-incompatibility was the ancestral state in the majority of dicots. PMID:11698683

  11. Nickel affects Xlem Sap RNase A and converts RNase A to a Urease

    Science.gov (United States)

    Nickel (Ni) is an essential micronutrient; however, its metabolic or physiological functions in plants and animals are largely uncharacterized. The ribonucleases (RNase, e.g., RNase A) are a large family of hydrolases found in one form or many forms facilitating nitrogen (N) cycling. It is current...

  12. RNases and Helicases in Gram-Positive Bacteria.

    Science.gov (United States)

    Durand, Sylvain; Condon, Ciaran

    2018-04-01

    RNases are key enzymes involved in RNA maturation and degradation. Although they play a crucial role in all domains of life, bacteria, archaea, and eukaryotes have evolved with their own sets of RNases and proteins modulating their activities. In bacteria, these enzymes allow modulation of gene expression to adapt to rapidly changing environments. Today, >20 RNases have been identified in both Escherichia coli and Bacillus subtilis , the paradigms of the Gram-negative and Gram-positive bacteria, respectively. However, only a handful of these enzymes are common to these two organisms and some of them are essential to only one. Moreover, although sets of RNases can be very similar in closely related bacteria such as the Firmicutes Staphylococcus aureus and B. subtilis , the relative importance of individual enzymes in posttranscriptional regulation in these organisms varies. In this review, we detail the role of the main RNases involved in RNA maturation and degradation in Gram-positive bacteria, with an emphasis on the roles of RNase J1, RNase III, and RNase Y. We also discuss how other proteins such as helicases can modulate the RNA-degradation activities of these enzymes.

  13. RNase P RNA from the Recently Evolved Plastid of Paulinella and from Algae

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    Pilar Bernal-Bayard

    2014-11-01

    Full Text Available The RNase P RNA catalytic subunit (RPR encoded in some plastids has been found to be functionally defective. The amoeba Paulinella chromatophora contains an organelle (chromatophore that is derived from the recent endosymbiotic acquisition of a cyanobacterium, and therefore represents a model of the early steps in the acquisition of plastids. In contrast with plastid RPRs the chromatophore RPR retains functionality similar to the cyanobacterial enzyme. The chromatophore RPR sequence deviates from consensus at some positions but those changes allow optimal activity compared with mutated chromatophore RPR with the consensus sequence. We have analyzed additional RPR sequences identifiable in plastids and have found that it is present in all red algae and in several prasinophyte green algae. We have assayed in vitro a subset of the plastid RPRs not previously analyzed and confirm that these organelle RPRs lack RNase P activity in vitro.

  14. Impaired Sperm Maturation in Rnase9 Knockout Mice1

    Science.gov (United States)

    Westmuckett, Andrew D.; Nguyen, Edward B.; Herlea-Pana, Oana M.; Alvau, Antonio; Salicioni, Ana M.; Moore, Kevin L.

    2014-01-01

    ABSTRACT Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease A superfamily member that is expressed only in the epididymis. It is a small, secreted polypeptide, it lacks ribonuclease activity, and its function(s) is unknown. However, epididymis-specific expression suggests a role in sperm maturation. We generated Rnase9−/− mice to study RNASE9 function in vivo. We confirm that RNASE9 expression is restricted to the epididymis. Within the epididymis, RNASE9 is first detected in midcaput, persists through the distal caput and corpus, and wanes in the cauda. Rnase9−/− mice are born at the expected Mendelian ratio, have normal postnatal growth and development, and have no outwardly apparent phenotype. Spermatogenesis is normal, and Rnase9-null sperm are morphologically normal. Rnase9−/− males have normal fertility in unrestricted mating trials, and fertilization rates in in vitro fertilization assays are indistinguishable from wild-type mice. Visual observations coupled with analyses of sperm velocities shortly after swim out from the corpus shows that motility of Rnase9-null sperm is significantly impaired. However, no differences between wild-type and Rnase9-null sperm are detected by computer-assisted sperm analysis 10–90 min after sperm isolation from the corpus or cauda. Assessment of capacitation-dependent signaling pathways in Rnase9-null sperm showed that, while levels of tyrosine phosphorylation of sperm proteins were normal, there was decreased phosphorylation of protein kinase A substrates upon capacitation compared to wild-type mice. In conclusion, RNASE9 is dispensable for fertility, but the absence of RNASE9 during epididymal transit results in impaired sperm maturation. PMID:24719258

  15. Triose phosphate isomerase deficiency is caused by altered dimerization--not catalytic inactivity--of the mutant enzymes.

    Directory of Open Access Journals (Sweden)

    Markus Ralser

    Full Text Available Triosephosphate isomerase (TPI deficiency is an autosomal recessive disorder caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A drastic decrease in TPI activity and an increased level of its substrate, dihydroxyacetone phosphate, have been measured in unpurified cell extracts of affected individuals. These observations allowed concluding that the different mutations in the TPI alleles result in catalytically inactive enzymes. However, despite a high occurrence of TPI null alleles within several human populations, the frequency of this disorder is exceptionally rare. In order to address this apparent discrepancy, we generated a yeast model allowing us to perform comparative in vivo analyses of the enzymatic and functional properties of the different enzyme variants. We discovered that the majority of these variants exhibit no reduced catalytic activity per se. Instead, we observed, the dimerization behavior of TPI is influenced by the particular mutations investigated, and by the use of a potential alternative translation initiation site in the TPI gene. Additionally, we demonstrated that the overexpression of the most frequent TPI variant, Glu104Asp, which displays altered dimerization features, results in diminished endogenous TPI levels in mammalian cells. Thus, our results reveal that enzyme deregulation attributable to aberrant dimerization of TPI, rather than direct catalytic inactivation of the enzyme, underlies the pathogenesis of TPI deficiency. Finally, we discovered that yeast cells expressing a TPI variant exhibiting reduced catalytic activity are more resistant against oxidative stress caused by the thiol-oxidizing reagent diamide. This observed advantage might serve to explain the high allelic frequency of TPI null alleles detected among human populations.

  16. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Koc, Hasan; Schmitt, Mark E; Krasilnikov, Andrey S

    2007-10-01

    Pop6 and Pop7 are protein subunits of Saccharomyces cerevisiae RNase MRP and RNase P. Here we show that bacterially expressed Pop6 and Pop7 form a soluble heterodimer that binds the RNA components of both RNase MRP and RNase P. Footprint analysis of the interaction between the Pop6/7 heterodimer and the RNase MRP RNA, combined with gel mobility assays, demonstrates that the Pop6/7 complex binds to a conserved region of the P3 domain. Binding of these proteins to the MRP RNA leads to local rearrangement in the structure of the P3 loop and suggests that direct interaction of the Pop6/7 complex with the P3 domain of the RNA components of RNases MRP and P may mediate binding of other protein components. These results suggest a role for a key element in the RNase MRP and RNase P RNAs in protein binding, and demonstrate the feasibility of directly studying RNA-protein interactions in the eukaryotic RNases MRP and P complexes.

  17. Interactions between subunits of Saccharomyces cerevisiae RNase MRP support a conserved eukaryotic RNase P/MRP architecture.

    Science.gov (United States)

    Aspinall, Tanya V; Gordon, James M B; Bennett, Hayley J; Karahalios, Panagiotis; Bukowski, John-Paul; Walker, Scott C; Engelke, David R; Avis, Johanna M

    2007-01-01

    Ribonuclease MRP is an endonuclease, related to RNase P, which functions in eukaryotic pre-rRNA processing. In Saccharomyces cerevisiae, RNase MRP comprises an RNA subunit and ten proteins. To improve our understanding of subunit roles and enzyme architecture, we have examined protein-protein and protein-RNA interactions in vitro, complementing existing yeast two-hybrid data. In total, 31 direct protein-protein interactions were identified, each protein interacting with at least three others. Furthermore, seven proteins self-interact, four strongly, pointing to subunit multiplicity in the holoenzyme. Six protein subunits interact directly with MRP RNA and four with pre-rRNA. A comparative analysis with existing data for the yeast and human RNase P/MRP systems enables confident identification of Pop1p, Pop4p and Rpp1p as subunits that lie at the enzyme core, with probable addition of Pop5p and Pop3p. Rmp1p is confirmed as an integral subunit, presumably associating preferentially with RNase MRP, rather than RNase P, via interactions with Snm1p and MRP RNA. Snm1p and Rmp1p may act together to assist enzyme specificity, though roles in substrate binding are also indicated for Pop4p and Pop6p. The results provide further evidence of a conserved eukaryotic RNase P/MRP architecture and provide a strong basis for studies of enzyme assembly and subunit function.

  18. Detection of Intracellular Reduced (Catalytically Active) SHP-1 and Analyses of Catalytically Inactive SHP-1 after Oxidation by Pervanadate or H2O2.

    Science.gov (United States)

    Choi, Seeyoung; Love, Paul E

    2018-01-05

    Oxidative inactivation of cysteine-dependent Protein Tyrosine Phosphatases (PTPs) by cellular reactive oxygen species (ROS) plays a critical role in regulating signal transduction in multiple cell types. The phosphatase activity of most PTPs depends upon a 'signature' cysteine residue within the catalytic domain that is maintained in the de-protonated state at physiological pH rendering it susceptible to ROS-mediated oxidation. Direct and indirect techniques for detection of PTP oxidation have been developed (Karisch and Neel, 2013). To detect catalytically active PTPs, cell lysates are treated with iodoacetyl-polyethylene glycol-biotin (IAP-biotin), which irreversibly binds to reduced (S - ) cysteine thiols. Irreversible oxidation of SHP-1 after treatment of cells with pervanadate or H 2 O 2 is detected with antibodies specific for the sulfonic acid (SO 3 H) form of the conserved active site cysteine of PTPs. In this protocol, we describe a method for the detection of the reduced (S - ; active) or irreversibly oxidized (SO 3 H; inactive) form of the hematopoietic PTP SHP-1 in thymocytes, although this method is applicable to any cysteine-dependent PTP in any cell type.

  19. SCFSLF-mediated cytosolic degradation of S-RNase is required for cross-pollen compatibility in S-RNase-based self-incompatibility in Petunia hybrida

    Directory of Open Access Journals (Sweden)

    Yongbiao eXue

    2014-07-01

    Full Text Available Many flowering plants adopt self-incompatibility (SI to maintain their genetic diversity. In species of Solanaceae, Plantaginaceae and Rosaceae, SI is genetically controlled by a single S-locus with multiple haplotypes. The S-locus has been shown to encode S-RNases expressed in pistil and multiple SLF (S-locus F-box proteins in pollen controlling the female and male specificity of SI, respectively. S-RNases appear to function as a cytotoxin to reject self-pollen. In addition, SLFs have been shown to form SCF (SKP1/Cullin1/F-box complexes to serve as putative E3 ubiquitin ligase to interact with S-RNases. Previously, two different mechanisms, the S-RNase degradation and the S-RNase compartmentalization, have been proposed as the restriction mechanisms of S-RNase cytotoxicity allowing compatible pollination. In this study, we have provided several lines of evidence in support of the S-RNase degradation mechanism by a combination of cellular, biochemical and molecular biology approaches. First, both immunogold labeling and subcellular fractionation assays showed that two key pollen SI factors, PhSLF-S3L and PhSSK1 (SLF-interacting SKP1-like1 from Petunia hybrida, a Solanaceous species, are co-localized in cytosols of both pollen grains and tubes. Second, PhS3L-RNases are mainly detected in the cytosols of both self and non-self pollen tubes after pollination. Third, we found that both PhS3-RNases and PhS3L-RNases directly interact with PhSLF-S3L by yeast two-hybrid and co-immunoprecipitation assays. Fourth, S-RNases are specifically degraded in compatible pollen tubes by non-self SLF action. Taken together, our results demonstrate that SCFSLF-mediated non-self S-RNase degradation occurs in the cytosol of pollen tube through the ubiquitin/26S proteasome system serving as the major mechanism to neutralize S-RNase cytotoxicity during compatible pollination in P. hybrida.

  20. A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L

    Science.gov (United States)

    Drappier, Melissa; Elliott, Ruth; Zhang, Rong; Weiss, Susan R.; Silverman, Robert H.

    2018-01-01

    The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A. PMID:29652922

  1. Lack of RNase L attenuates macrophage functions.

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    Xin Yi

    Full Text Available Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α, interleukin (IL-1β, IL-6, and cyclooxygenase-2 (Cox-2 by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown.Bone marrow-derived macrophages (BMMs were generated from RNase L(+/+and (-/- mice. The migration of BMMs was analyzed by using Transwell migration assays. Endocytosis and phagocytosis of macrophages were assessed by using fluorescein isothiocyanate (FITC-Dextran 40,000 and FITC-E. coli bacteria, respectively. The expression of inflammatory genes was determined by Western Blot and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter assays.Lack of RNase L significantly decreased the migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine C-C motif ligand-2 (CCL2. Interestingly, RNase L deficient BMMs showed a significant reduction of endocytic activity to FITC-Dextran 40,000, but no any obvious effect on their phagocytic activity to FITC-bacteria under the same condition. RNase L impacts the expression of certain genes related to cell migration and inflammation such as transforming growth factor (TGF-β, IL-1β, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2 promoter revealed that RNase L regulated the expression of Cox-2 in macrophages at its transcriptional level. Taken together, our findings provide direct evidence showing that RNase L contributes to innate immunity through regulating macrophage functions.

  2. Cooperative RNP assembly: Complementary rescue of structural defects by protein and RNA subunits of archaeal RNase P

    Science.gov (United States)

    Chen, Wen-Yi; Xu, Yiren; Cho, I-Ming; Oruganti, Sri Vidya; Foster, Mark P.; Gopalan, Venkat

    2011-01-01

    RNase P is a ribonucleoprotein (RNP) complex that utilizes a Mg2+-dependent RNA catalyst to cleave the 5′-leader of precursor tRNAs (pre-tRNAs) and generate mature tRNAs. The bacterial RNase P protein (RPP) aids RNase P RNA (RPR) catalysis by promoting substrate binding, Mg2+ coordination, and product release. Archaeal RNase P comprises an RPR and at least four RPPs, which have eukaryal homologs and function as two binary complexes (POP5•RPP30 and RPP21•RPP29). In this study, we employed a previously characterized substrate-enzyme conjugate [pre-tRNATyr-Methanocaldococcus jannaschii (Mja) RPR] to investigate the functional role of a universally conserved uridine in a bulge-helix structure in archaeal RPRs. Deletion of this bulged uridine resulted in an 80-fold decrease in the self-cleavage rate of pre-tRNATyr-MjaΔU RPR compared to the wildtype, and this defect was partially ameliorated upon addition of either RPP pair. The catalytic defect in the archaeal mutant RPR mirrors that reported in a bacterial RPR and highlights a parallel in their active sites. Furthermore, an N-terminal deletion mutant of Pyrococcus furiosus (Pfu) RPP29 that is defective in assembling with its binary partner RPP21, as assessed by isothermal titration calorimetry and NMR spectroscopy, is functional when reconstituted with the cognate Pfu RPR. Collectively, these results indicate that archaeal RPPs are able to compensate for structural defects in their cognate RPR and vice-versa, and provide striking examples of the cooperative subunit interactions critical for driving archaeal RNase P towards its functional conformation. (236 words) PMID:21683084

  3. Cloning, expression and location of RNase9 in human epididymis

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    Lin YQ

    2008-11-01

    Full Text Available Abstract Background Mammalian spermatozoa become fully motile and fertile during transit through the luminal fluid of the epididymis. At least 200 proteins are present in the epididymal lumen, but the potential roles of these luminal proteins in male fertility are unknown. Investigation of the function of these proteins will elucidate the mechanism of sperm maturation, and also provide new drug targets for male contraception. We cloned RNase9 from a human epididymis cDNA library for characterization and analysis of its functions. Findings It was predicted that human RNase9 gene was located on chromosome 14q11.2 and encoded a 205 amino acids protein with a signal peptide of 26 amino acids at the N-terminus. The protein had eight conserved cysteine residues characteristic of the RNase A family members and several potential post-translational modification sites. At the transcriptional level, RNase9 was expressed in a wide variety of tissues, and the expression was higher in men than in boys. RNase9 was localized to the post-equatorial region of the sperms' head. Immunofluorescence staining showed that RNase9 protein was present mostly in the epithelium of the epididymal tubule. Recombinant RNase9 had no ribonuclease activity. In addition, RNase9 had no detectable effect on sperm motility and fertilization as demonstrated by blocking spermatozoa with anti-RNase9 polyclonal serum. Conclusion RNase9 is expressed in a wide variety of tissues. It is located on the post-equatorial region of the sperm head and the epithelium of epididymal tubule. Although RNase9 belongs to the RNase A family, it has no ribonuclease activity.

  4. Self-(in)compatibility of the almonds P. dulcis and P. webbii: detection and cloning of 'wild-type Sf ' and new self-compatibility alleles encoding inactive S-RNases.

    Science.gov (United States)

    Bosković, Radovan I; Tobutt, Kenneth R; Ortega, Encarnación; Sutherland, Bruce G; Godini, Angelo

    2007-12-01

    Prunus dulcis, the almond, is a predominantly self-incompatible (SI) species with a gametophytic self-incompatibility system mediated by S-RNases. The economically important allele Sf, which results in self-compatibility in P. dulcis, is said to have arisen by introgression from Prunus webbii in the Italian region of Apulia. We investigated the range of self-(in)compatibility alleles in Apulian material of the two species. About 23 cultivars of P. dulcis (14 self-compatible (SC) and nine SI) and 33 accessions of P. webbii (16 SC, two SI and 15 initially of unknown status), all from Apulia, were analysed using PCR of genomic DNA to amplify S-RNase alleles and, in most cases, IEF and staining of stylar protein extracts to detect S-RNase activity. Some amplification products were cloned and sequenced. The allele Sf was present in nearly all the SC cultivars of P. dulcis but, surprisingly, was absent from nearly all SC accessions of P. webbii. And of particular interest was the presence in many SI cultivars of P. dulcis of a new active allele, labelled S30, the sequence of which showed it to be the wild-type of Sf so that Sf can be regarded as a stylar part mutant S30 degrees . These findings indicate Sf may have arisen within P. dulcis, by mutation. One SC cultivar of P. dulcis, 'Patalina', had a new self-compatibility allele lacking RNase activity, Sn5, which could be useful in breeding programmes. In the accessions of P. webbii, some of which were known to be SC, three new alleles were found which lacked RNase activity but had normal DNA sequences.

  5. Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Abdur, Rob; Gerlits, Oksana O.; Gan, Jianhua; Jiang, Jiansheng; Salon, Jozef; Kovalevsky, Andrey Y.; Chumanevich, Alexander A.; Weber, Irene T.; Huang, Zhen, E-mail: huang@gsu.edu [Georgia State University, Atlanta, GA 30303 (United States)

    2014-02-01

    Selenium-derivatized oligonucleotides may facilitate phase determination and high-resolution structure determination for protein–nucleic acid crystallography. The Se atom-specific mutagenesis (SAM) strategy may also enhance the study of nuclease catalysis. The crystal structures of protein–nucleic acid complexes are commonly determined using selenium-derivatized proteins via MAD or SAD phasing. Here, the first protein–nucleic acid complex structure determined using selenium-derivatized nucleic acids is reported. The RNase H–RNA/DNA complex is used as an example to demonstrate the proof of principle. The high-resolution crystal structure indicates that this selenium replacement results in a local subtle unwinding of the RNA/DNA substrate duplex, thereby shifting the RNA scissile phosphate closer to the transition state of the enzyme-catalyzed reaction. It was also observed that the scissile phosphate forms a hydrogen bond to the water nucleophile and helps to position the water molecule in the structure. Consistently, it was discovered that the substitution of a single O atom by a Se atom in a guide DNA sequence can largely accelerate RNase H catalysis. These structural and catalytic studies shed new light on the guide-dependent RNA cleavage.

  6. The helicase and RNaseIIIa domains of Arabidopsis Dicer-Like1 modulate catalytic parameters during MicroRNA biogenesis

    KAUST Repository

    Liu, Chenggang; Axtell, Michael J.; Fedoroff, Nina V.

    2012-01-01

    Dicer-Like1 (DCL1), an RNaseIII endonuclease, and Hyponastic Leaves1 (HYL1), a double-stranded RNA-binding protein, are core components of the plant microRNA (miRNA) biogenesis machinery. hyl1 mutants accumulate low levels of miRNAs and display

  7. The L7Ae protein binds to two kink-turns in the Pyrococcus furiosus RNase P RNA

    Science.gov (United States)

    Lai, Stella M.; Lai, Lien B.; Foster, Mark P.; Gopalan, Venkat

    2014-01-01

    The RNA-binding protein L7Ae, known for its role in translation (as part of ribosomes) and RNA modification (as part of sn/oRNPs), has also been identified as a subunit of archaeal RNase P, a ribonucleoprotein complex that employs an RNA catalyst for the Mg2+-dependent 5′ maturation of tRNAs. To better understand the assembly and catalysis of archaeal RNase P, we used a site-specific hydroxyl radical-mediated footprinting strategy to pinpoint the binding sites of Pyrococcus furiosus (Pfu) L7Ae on its cognate RNase P RNA (RPR). L7Ae derivatives with single-Cys substitutions at residues in the predicted RNA-binding interface (K42C/C71V, R46C/C71V, V95C/C71V) were modified with an iron complex of EDTA-2-aminoethyl 2-pyridyl disulfide. Upon addition of hydrogen peroxide and ascorbate, these L7Ae-tethered nucleases were expected to cleave the RPR at nucleotides proximal to the EDTA-Fe–modified residues. Indeed, footprinting experiments with an enzyme assembled with the Pfu RPR and five protein cofactors (POP5, RPP21, RPP29, RPP30 and L7Ae–EDTA-Fe) revealed specific RNA cleavages, localizing the binding sites of L7Ae to the RPR's catalytic and specificity domains. These results support the presence of two kink-turns, the structural motifs recognized by L7Ae, in distinct functional domains of the RPR and suggest testable mechanisms by which L7Ae contributes to RNase P catalysis. PMID:25361963

  8. Crystallization and preliminary X-ray analysis of Escherichia coli RNase G

    International Nuclear Information System (INIS)

    Fang, Pengfei; Wang, Jing; Li, Xu; Guo, Min; Xing, Li; Cao, Xu; Zhu, Yi; Gao, Yan; Niu, Liwen; Teng, Maikun

    2009-01-01

    Full-length E. coli RNase G was overexpressed, purified and crystallized. Diffraction data were collected to a resolution of 3.4 Å. The homologous RNases RNase E and RNase G are widely distributed in bacteria and function in many important physiological processes, including mRNA degradation, rRNA maturation and so on. In this study, the crystallization and preliminary X-ray analysis of RNase G from Escherichia coli is described. Purified recombinant E. coli RNase G, which has 497 amino acids, was crystallized in the cubic space group F432, with unit-cell parameters a = b = c = 219.84 Å. X-ray diffraction data were collected to a resolution of 3.4 Å

  9. Genetic and genomic analysis of RNases in model cyanobacteria.

    Science.gov (United States)

    Cameron, Jeffrey C; Gordon, Gina C; Pfleger, Brian F

    2015-10-01

    Cyanobacteria are diverse photosynthetic microbes with the ability to convert CO2 into useful products. However, metabolic engineering of cyanobacteria remains challenging because of the limited resources for modifying the expression of endogenous and exogenous biochemical pathways. Fine-tuned control of protein production will be critical to optimize the biological conversion of CO2 into desirable molecules. Messenger RNAs (mRNAs) are labile intermediates that play critical roles in determining the translation rate and steady-state protein concentrations in the cell. The majority of studies on mRNA turnover have focused on the model heterotrophic bacteria Escherichia coli and Bacillus subtilis. These studies have elucidated many RNA modifying and processing enzymes and have highlighted the differences between these Gram-negative and Gram-positive bacteria, respectively. In contrast, much less is known about mRNA turnover in cyanobacteria. We generated a compendium of the major ribonucleases (RNases) and provide an in-depth analysis of RNase III-like enzymes in commonly studied and diverse cyanobacteria. Furthermore, using targeted gene deletion, we genetically dissected the RNases in Synechococcus sp. PCC 7002, one of the fastest growing and industrially attractive cyanobacterial strains. We found that all three cyanobacterial homologs of RNase III and a member of the RNase II/R family are not essential under standard laboratory conditions, while homologs of RNase E/G, RNase J1/J2, PNPase, and a different member of the RNase II/R family appear to be essential for growth. This work will enhance our understanding of native control of gene expression and will facilitate the development of an RNA-based toolkit for metabolic engineering in cyanobacteria.

  10. Solution Structure of Pfu RPP21, a Component of the Archaeal RNase P Holoenzyme, and Interactions with its RPP29 Protein Partner

    Science.gov (United States)

    Amero, Carlos D; Boomershine, William P; Xu, Yiren; Foster, Mark

    2009-01-01

    RNase P is the ubiquitous ribonucleoprotein metalloenzyme responsible for cleaving the 5′-leader sequence of precursor tRNAs during their maturation. While the RNA subunit is catalytically active on its own at high monovalent and divalent ion concentration, four proteins subunits are associated with archaeal RNase P activity in vivo: RPP21, RPP29, RPP30 and POP5. These proteins have been shown to function in pairs: RPP21-RPP29 and POP5-RPP30. We have determined the solution structure of RPP21 from the hyperthermophilic archaeon Pyrococcus furiosus (Pfu) using conventional and paramagnetic NMR techniques. Pfu RPP21 in solution consists of an unstructured N-terminus, two alpha helices, a zinc binding motif, and an unstructured C-terminus. Moreover, we have used chemical shift perturbations to characterize the interaction of RPP21 with Pfu RPP29. The data show that the primary contact with RPP29 is localized to the two helices of RPP21. This information represents a fundamental step towards understanding structure-function relationships of the archaeal RNase P holoenzyme. PMID:18922021

  11. Comparison of mitochondrial and nucleolar RNase MRP reveals identical RNA components with distinct enzymatic activities and protein components.

    Science.gov (United States)

    Lu, Qiaosheng; Wierzbicki, Sara; Krasilnikov, Andrey S; Schmitt, Mark E

    2010-03-01

    RNase MRP is a ribonucleoprotein endoribonuclease found in three cellular locations where distinct substrates are processed: the mitochondria, the nucleolus, and the cytoplasm. Cytoplasmic RNase MRP is the nucleolar enzyme that is transiently relocalized during mitosis. Nucleolar RNase MRP (NuMRP) was purified to homogeneity, and we extensively purified the mitochondrial RNase MRP (MtMRP) to a single RNA component identical to the NuMRP RNA. Although the protein components of the NuMRP were identified by mass spectrometry successfully, none of the known NuMRP proteins were found in the MtMRP preparation. Only trace amounts of the core NuMRP protein, Pop4, were detected in MtMRP by Western blot. In vitro activity of the two enzymes was compared. MtMRP cleaved only mitochondrial ORI5 substrate, while NuMRP cleaved all three substrates. However, the NuMRP enzyme cleaved the ORI5 substrate at sites different than the MtMRP enzyme. In addition, enzymatic differences in preferred ionic strength confirm these enzymes as distinct entities. Magnesium was found to be essential to both enzymes. We tested a number of reported inhibitors including puromycin, pentamidine, lithium, and pAp. Puromycin inhibition suggested that it binds directly to the MRP RNA, reaffirming the role of the RNA component in catalysis. In conclusion, our study confirms that the NuMRP and MtMRP enzymes are distinct entities with differing activities and protein components but a common RNA subunit, suggesting that the RNA must be playing a crucial role in catalytic activity.

  12. Chemically modified oligonucleotides with efficient RNase H response

    DEFF Research Database (Denmark)

    Vester, Birte; Boel, Anne Marie; Lobedanz, Sune

    2008-01-01

    Ten different chemically modified nucleosides were incorporated into short DNA strands (chimeric oligonucleotides ON3-ON12 and ON15-ON24) and then tested for their capacity to mediate RNAse H cleavage of the complementary RNA strand. The modifications were placed at two central positions directly...... in the RNase H cleaving region. The RNA strand of duplexes with ON3, ON5 and ON12 were cleaved more efficiently than the RNA strand of the DNA:RNA control duplex. There seems to be no correlation between the thermal stability between the duplexes and RNase H cleavage....

  13. The helicase and RNaseIIIa domains of Arabidopsis Dicer-Like1 modulate catalytic parameters during MicroRNA biogenesis

    KAUST Repository

    Liu, Chenggang

    2012-04-03

    Dicer-Like1 (DCL1), an RNaseIII endonuclease, and Hyponastic Leaves1 (HYL1), a double-stranded RNA-binding protein, are core components of the plant microRNA (miRNA) biogenesis machinery. hyl1 mutants accumulate low levels of miRNAs and display pleiotropic developmental phenotypes. We report the identification of five new hyl1 suppressor mutants, all of which are alleles of DCL1. These new alleles affect either the helicase or the RNaseIIIa domains of DCL1, highlighting the critical functions of these domains. Biochemical analysis of the DCL1 suppressor variants reveals that they process the primary transcript (pri-miRNA) more efficiently than wild-type DCL1, with both higher Kcat and lower Km values. The DCL1 variants largely rescue wild-type miRNA accumulation levels in vivo, but do not rescue the MIRNA processing precision defects of the hyl1 mutant. In vitro, the helicase domain confers ATP dependence on DCL1-catalyzed MIRNA processing, attenuates DCL1 cleavage activity, and is required for precise MIRNA processing of some substrates. © 2012 American Society of Plant Biologists.

  14. Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation

    Directory of Open Access Journals (Sweden)

    Yosuke Yamawaki

    2017-02-01

    Full Text Available Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL-cholesterol, and high-density lipoprotein (HDL-cholesterol. Prevention and control of obesity is complex, and requires a multifaceted approach. The elucidation of molecular mechanisms driving fat metabolism (adipogenesis and lipolysis aims at developing clinical treatments to control obesity. We recently reported a new regulatory mechanism in fat metabolism: a protein phosphatase binding protein, phospholipase C-related catalytically inactive protein (PRIP, regulates lipolysis in white adipocytes and heat production in brown adipocytes via phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation and increased energy expenditure, resulting in a lean phenotype. Here, we evaluate PRIP as a new therapeutic target for the control of obesity.

  15. Antibiotic stress-induced modulation of the endoribonucleolytic activity of RNase III and RNase G confers resistance to aminoglycoside antibiotics in Escherichia coli.

    Science.gov (United States)

    Song, Wooseok; Kim, Yong-Hak; Sim, Se-Hoon; Hwang, Soonhye; Lee, Jung-Hyun; Lee, Younghoon; Bae, Jeehyeon; Hwang, Jihwan; Lee, Kangseok

    2014-04-01

    Here, we report a resistance mechanism that is induced through the modulation of 16S ribosomal RNA (rRNA) processing on the exposure of Escherichia coli cells to aminoglycoside antibiotics. We observed decreased expression levels of RNase G associated with increased RNase III activity on rng mRNA in a subgroup of E. coli isolates that transiently acquired resistance to low levels of kanamycin or streptomycin. Analyses of 16S rRNA from the aminoglycoside-resistant E. coli cells, in addition to mutagenesis studies, demonstrated that the accumulation of 16S rRNA precursors containing 3-8 extra nucleotides at the 5' terminus, which results from incomplete processing by RNase G, is responsible for the observed aminoglycoside resistance. Chemical protection, mass spectrometry analysis and cell-free translation assays revealed that the ribosomes from rng-deleted E. coli have decreased binding capacity for, and diminished sensitivity to, streptomycin and neomycin, compared with wild-type cells. It was observed that the deletion of rng had similar effects in Salmonella enterica serovar Typhimurium strain SL1344. Our findings suggest that modulation of the endoribonucleolytic activity of RNase III and RNase G constitutes a previously uncharacterized regulatory pathway for adaptive resistance in E. coli and related gram-negative bacteria to aminoglycoside antibiotics.

  16. Tracking the elusive 5' exonuclease activity of Chlamydomonas reinhardtii RNase J.

    Science.gov (United States)

    Liponska, Anna; Jamalli, Ailar; Kuras, Richard; Suay, Loreto; Garbe, Enrico; Wollman, Francis-André; Laalami, Soumaya; Putzer, Harald

    2018-04-01

    Chlamydomonas RNase J is the first member of this enzyme family that has endo- but no intrinsic 5' exoribonucleolytic activity. This questions its proposed role in chloroplast mRNA maturation. RNA maturation and stability in the chloroplast are controlled by nuclear-encoded ribonucleases and RNA binding proteins. Notably, mRNA 5' end maturation is thought to be achieved by the combined action of a 5' exoribonuclease and specific pentatricopeptide repeat proteins (PPR) that block the progression of the nuclease. In Arabidopsis the 5' exo- and endoribonuclease RNase J has been implicated in this process. Here, we verified the chloroplast localization of the orthologous Chlamydomonas (Cr) RNase J and studied its activity, both in vitro and in vivo in a heterologous B. subtilis system. Our data show that Cr RNase J has endo- but no significant intrinsic 5' exonuclease activity that would be compatible with its proposed role in mRNA maturation. This is the first example of an RNase J ortholog that does not possess a 5' exonuclease activity. A yeast two-hybrid screen revealed a number of potential interaction partners but three of the most promising candidates tested, failed to induce the latent exonuclease activity of Cr RNase J. We still favor the hypothesis that Cr RNase J plays an important role in RNA metabolism, but our findings suggest that it rather acts as an endoribonuclease in the chloroplast.

  17. Multiple RNA processing defects and impaired chloroplast function in plants deficient in the organellar protein-only RNase P enzyme.

    Directory of Open Access Journals (Sweden)

    Wenbin Zhou

    Full Text Available Transfer RNA (tRNA precursors undergo endoribonucleolytic processing of their 5' and 3' ends. 5' cleavage of the precursor transcript is performed by ribonuclease P (RNase P. While in most organisms RNase P is a ribonucleoprotein that harbors a catalytically active RNA component, human mitochondria and the chloroplasts (plastids and mitochondria of seed plants possess protein-only RNase P enzymes (PRORPs. The plant organellar PRORP (PRORP1 has been characterized to some extent in vitro and by transient gene silencing, but the molecular, phenotypic and physiological consequences of its down-regulation in stable transgenic plants have not been assessed. Here we have addressed the function of the dually targeted organellar PRORP enzyme in vivo by generating stably transformed Arabidopsis plants in which expression of the PRORP1 gene was suppressed by RNA interference (RNAi. PRORP1 knock-down lines show defects in photosynthesis, while mitochondrial respiration is not appreciably affected. In both plastids and mitochondria, the effects of PRORP1 knock-down on the processing of individual tRNA species are highly variable. The drastic reduction in the levels of mature plastid tRNA-Phe(GAA and tRNA-Arg(ACG suggests that these two tRNA species limit plastid gene expression in the PRORP1 mutants and, hence, are causally responsible for the mutant phenotype.

  18. Downstream element determines RNase Y cleavage of the saePQRS operon in Staphylococcus aureus.

    Science.gov (United States)

    Marincola, Gabriella; Wolz, Christiane

    2017-06-02

    In gram-positive bacteria, RNase J1, RNase J2 and RNase Y are thought to be major contributors to mRNA degradation and maturation. In Staphylococcus aureus, RNase Y activity is restricted to regulating the mRNA decay of only certain transcripts. Here the saePQRS operon was used as a model to analyze RNase Y specificity in living cells. A RNase Y cleavage site is located in an intergenic region between saeP and saeQ. This cleavage resulted in rapid degradation of the upstream fragment and stabilization of the downstream fragment. Thereby, the expression ratio of the different components of the operon was shifted towards saeRS, emphasizing the regulatory role of RNase Y activity. To assess cleavage specificity different regions surrounding the sae CS were cloned upstream of truncated gfp, and processing was analyzed in vivo using probes up- and downstream of CS. RNase Y cleavage was not determined by the cleavage site sequence. Instead a 24-bp double-stranded recognition structure was identified that was required to initiate cleavage 6 nt upstream. The results indicate that RNase Y activity is determined by secondary structure recognition determinants, which guide cleavage from a distance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Evasion of antiviral innate immunity by Theiler's virus L* protein through direct inhibition of RNase L.

    Directory of Open Access Journals (Sweden)

    Frédéric Sorgeloos

    Full Text Available Theiler's virus is a neurotropic picornavirus responsible for chronic infections of the central nervous system. The establishment of a persistent infection and the subsequent demyelinating disease triggered by the virus depend on the expression of L*, a viral accessory protein encoded by an alternative open reading frame of the virus. We discovered that L* potently inhibits the interferon-inducible OAS/RNase L pathway. The antagonism of RNase L by L* was particularly prominent in macrophages where baseline oligoadenylate synthetase (OAS and RNase L expression levels are elevated, but was detectable in fibroblasts after IFN pretreatment. L* mutations significantly affected Theiler's virus replication in primary macrophages derived from wild-type but not from RNase L-deficient mice. L* counteracted the OAS/RNase L pathway through direct interaction with the ankyrin domain of RNase L, resulting in the inhibition of this enzyme. Interestingly, RNase L inhibition was species-specific as Theiler's virus L* protein blocked murine RNase L but not human RNase L or RNase L of other mammals or birds. Direct RNase L inhibition by L* and species specificity were confirmed in an in vitro assay performed with purified proteins. These results demonstrate a novel viral mechanism to elude the antiviral OAS/RNase L pathway. By targeting the effector enzyme of this antiviral pathway, L* potently inhibits RNase L, underscoring the importance of this enzyme in innate immunity against Theiler's virus.

  20. Global identification of new substrates for the yeast endoribonuclease, RNase mitochondrial RNA processing (MRP).

    Science.gov (United States)

    Aulds, Jason; Wierzbicki, Sara; McNairn, Adrian; Schmitt, Mark E

    2012-10-26

    RNase mitochondrial RNA processing (MRP) is an essential, evolutionarily conserved endoribonuclease composed of 10 different protein subunits and a single RNA. RNase MRP has established roles in multiple pathways including ribosome biogenesis, cell cycle regulation, and mitochondrial DNA replication. Although each of these functions is important to cell growth, additional functions may exist given the essential nature of the complex. To identify novel RNase MRP substrates, we utilized RNA immunoprecipitation and microarray chip analysis to identify RNA that physically associates with RNase MRP. We identified several new potential substrates for RNase MRP including a cell cycle-regulated transcript, CTS1; the yeast homolog of the mammalian p27(Kip1), SIC1; and the U2 RNA component of the spliceosome. In addition, we found RNase MRP to be involved in the regulation of the Ty1 transposon RNA. These results reinforce and broaden the role of RNase MRP in cell cycle regulation and help to identify new roles of this endoribonuclease.

  1. Global Identification of New Substrates for the Yeast Endoribonuclease, RNase Mitochondrial RNA Processing (MRP)*

    Science.gov (United States)

    Aulds, Jason; Wierzbicki, Sara; McNairn, Adrian; Schmitt, Mark E.

    2012-01-01

    RNase mitochondrial RNA processing (MRP) is an essential, evolutionarily conserved endoribonuclease composed of 10 different protein subunits and a single RNA. RNase MRP has established roles in multiple pathways including ribosome biogenesis, cell cycle regulation, and mitochondrial DNA replication. Although each of these functions is important to cell growth, additional functions may exist given the essential nature of the complex. To identify novel RNase MRP substrates, we utilized RNA immunoprecipitation and microarray chip analysis to identify RNA that physically associates with RNase MRP. We identified several new potential substrates for RNase MRP including a cell cycle-regulated transcript, CTS1; the yeast homolog of the mammalian p27Kip1, SIC1; and the U2 RNA component of the spliceosome. In addition, we found RNase MRP to be involved in the regulation of the Ty1 transposon RNA. These results reinforce and broaden the role of RNase MRP in cell cycle regulation and help to identify new roles of this endoribonuclease. PMID:22977255

  2. Biochemical Characterization of Mycobacterium smegmatis RnhC (MSMEG_4305), a Bifunctional Enzyme Composed of Autonomous N-Terminal Type I RNase H and C-Terminal Acid Phosphatase Domains.

    Science.gov (United States)

    Jacewicz, Agata; Shuman, Stewart

    2015-08-01

    C has a C-terminal acid phosphatase domain that is functionally autonomous of its N-terminal RNase H catalytic domain. RnhC homologs are prevalent in Actinobacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. The essential function of B. subtilis RNase III is to silence foreign toxin genes.

    Directory of Open Access Journals (Sweden)

    Sylvain Durand

    Full Text Available RNase III-related enzymes play key roles in cleaving double-stranded RNA in many biological systems. Among the best-known are RNase III itself, involved in ribosomal RNA maturation and mRNA turnover in bacteria, and Drosha and Dicer, which play critical roles in the production of micro (mi-RNAs and small interfering (si-RNAs in eukaryotes. Although RNase III has important cellular functions in bacteria, its gene is generally not essential, with the remarkable exception of that of Bacillus subtilis. Here we show that the essential role of RNase III in this organism is to protect it from the expression of toxin genes borne by two prophages, Skin and SPβ, through antisense RNA. Thus, while a growing number of organisms that use RNase III or its homologs as part of a viral defense mechanism, B. subtilis requires RNase III for viral accommodation to the point where the presence of the enzyme is essential for cell survival. We identify txpA and yonT as the two toxin-encoding mRNAs of Skin and SPβ that are sensitive to RNase III. We further explore the mechanism of RNase III-mediated decay of the txpA mRNA when paired to its antisense RNA RatA, both in vivo and in vitro.

  4. RNase-L regulates the stability of mitochondrial DNA-encoded mRNAs in mouse embryo fibroblasts

    International Nuclear Information System (INIS)

    Chandrasekaran, Krish; Mehrabian, Zara; Li Xiaoling; Hassel, Bret

    2004-01-01

    Accelerated decrease in the levels of mitochondrial DNA-encoded mRNA (mt-mRNA) occurs in neuronal cells exposed either to the excitatory amino acid, glutamate or to the sodium ionophore, monensin, suggesting a role of mitochondrial RNase(s) on the stability of mt-mRNAs. Here we report that in mouse embryo fibroblasts that are devoid of the interferon-regulated RNase, RNase-L, the monensin-induced decrease in the half-life of mt-mRNA was reduced. In monensin (250 nM)-treated RNase-L +/+ cells the average half-life of mt-mRNA, determined after termination of transcription with actinomycin D, was found to be 3 h, whereas in monensin-treated RNase-L -/- cells the half-life of mt-mRNA was >6 h. In contrast, the stability of nuclear DNA-encoded β-actin mRNA was unaffected. Induction of RNase-L expression in mouse 3T3 fibroblasts further decreased the monensin-induced reduction in mt-mRNA half-life to 1.5 h. The results indicate that the RNase-L-dependent decrease in mtDNA-encoded mRNA transcript levels occurs through a decrease in the half-life of mt-mRNA, and that RNase-L may play a role in the stability of mt-mRNA

  5. Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients.

    Directory of Open Access Journals (Sweden)

    Weiyan Huang

    Full Text Available Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5'-U/A-3' and 5'-C/A-3' dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10(-5 mg/ml- 10(-1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types.

  6. Site-Specific RNase A Activity Was Dramatically Reduced in Serum from Multiple Types of Cancer Patients

    Science.gov (United States)

    Huang, Weiyan; Zhao, Mei; Wei, Na; Wang, Xiaoxia; Cao, Huqing; Du, Quan; Liang, Zicai

    2014-01-01

    Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. PMID:24805924

  7. Influence of C-terminal tail deletion on structure and stability of hyperthermophile Sulfolobus tokodaii RNase HI.

    Science.gov (United States)

    Chen, Lin; Zhang, Ji-Long; Zheng, Qing-Chuan; Chu, Wen-Ting; Xue, Qiao; Zhang, Hong-Xing; Sun, Chia-Chung

    2013-06-01

    The C-terminus tail (G144-T149) of the hyperthermophile Sulfolobus tokodaii (Sto-RNase HI) plays an important role in this protein's hyperstabilization and may therefore be a good protein stability tag. Detailed understanding of the structural and dynamic effects of C-terminus tail deletion is required for gaining insights into the thermal stability mechanism of Sto-RNase HI. Focused on Sulfolobus tokodaii RNase HI (Sto-RNase HI) and its derivative lacking the C-terminal tail (ΔC6 Sto-RNase HI) (PDB codes: 2EHG and 3ALY), we applied molecular dynamics (MD) simulations at four different temperatures (300, 375, 475, and 500 K) to examine the effect of the C-terminal tail on the hyperstabilization of Sto-RNase HI and to investigate the unfolding process of Sto-RNase HI and ΔC6 Sto-RNase HI. The simulations suggest that the C-terminal tail has significant impact in hyperstabilization of Sto-RNase HI and the unfolding of these two proteins evolves along dissimilar pathways. Essential dynamics analysis indicates that the essential subspaces of the two proteins at different temperatures are non-overlapping within the trajectories and they exhibit different directions of motion. Our work can give important information to understand the three-state folding mechanism of Sto-RNase HI and to offer alternative strategies to improve the protein stability.

  8. Origin of allelic diversity in antirrhinum S locus RNases.

    Science.gov (United States)

    Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

    1996-01-01

    In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate. PMID:8672882

  9. Role of RNase MRP in viral RNA degradation and RNA recombination.

    Science.gov (United States)

    Jaag, Hannah M; Lu, Qiasheng; Schmitt, Mark E; Nagy, Peter D

    2011-01-01

    RNA degradation, together with RNA synthesis, controls the steady-state level of viral RNAs in infected cells. The endoribonucleolytic cleavage of viral RNA is important not only for viral RNA degradation but for RNA recombination as well, due to the participation of some RNA degradation products in the RNA recombination process. To identify host endoribonucleases involved in degradation of Tomato bushy stunt virus (TBSV) in a Saccharomyces cerevisiae model host, we tested eight known endoribonucleases. Here we report that downregulation of SNM1, encoding a component of the RNase MRP, and a temperature-sensitive mutation in the NME1 gene, coding for the RNA component of RNase MRP, lead to reduced production of the endoribonucleolytically cleaved TBSV RNA in yeast. We also show that the highly purified yeast RNase MRP cleaves the TBSV RNA in vitro, resulting in TBSV RNA degradation products similar in size to those observed in yeast cells. Knocking down the NME1 homolog in Nicotiana benthamiana also led to decreased production of the cleaved TBSV RNA, suggesting that in plants, RNase MRP is involved in TBSV RNA degradation. Altogether, this work suggests a role for the host endoribonuclease RNase MRP in viral RNA degradation and recombination.

  10. Insight into S-RNase-based self-incompatibility in Petunia: recent findings and future directions

    Directory of Open Access Journals (Sweden)

    Justin S Williams

    2015-02-01

    Full Text Available S-RNase-based self-incompatibility in Petunia is a self/non-self recognition system that allows the pistil to reject self-pollen to prevent inbreeding and to accept non-self pollen for outcrossing. Cloning of S-RNase in 1986 marked the beginning of nearly three decades of intensive research into the mechanism of this complex system. S-RNase was shown to be the sole female determinant in 1994, and the first male determinant, S-locus F-box protein1 (SLF1, was identified in 2004. It was discovered in 2010 that additional SLF proteins are involved in pollen specificity, and recently two S-haplotypes of P. inflata were found to possess 17 SLF genes based on pollen transcriptome analysis, further increasing the complexity of the system. Here, we first summarize the current understanding of how the interplay between SLF proteins and S-RNase in the pollen tube allows cross-compatible pollination, but results in self-incompatible pollination. We then discuss some of the aspects that are not yet elucidated, including uptake of S-RNase into the pollen tube, nature and assembly of SLF-containing complexes, the biochemical basis for differential interactions between SLF proteins and S-RNase, and fate of non-self S-RNases in the pollen tube.

  11. Effect of RNase E deficiency on translocon protein synthesis in an RNase E-inducible strain of enterohemorrhagic Escherichia coli O157:H7.

    Science.gov (United States)

    Lodato, Patricia B; Thuraisamy, Thujitha; Richards, Jamie; Belasco, Joel G

    2017-07-06

    Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that assembles a type III secretion system (T3SS) on its surface. The last portion of the T3SS, called the 'translocon', is composed of a filament and a pore complex that is inserted into the membrane of intestinal epithelial cells. The genes encoding the translocon (espADB) are part of the LEE4 operon. Their expression is regulated by a complex post-transcriptional mechanism that involves the processing of LEE4 mRNA by the essential endoribonuclease RNase E. Here, we report the construction of an EHEC strain (TEA028-rne) in which RNase E can be induced by adding IPTG to the culture medium. EHEC cells deficient in RNase E displayed an abnormal morphology and slower growth, in agreement with published observations in E. coli K-12. Under those conditions, EspA and EspB were produced at higher concentrations, and protein secretion still occurred. These results indicate that RNase E negatively regulates translocon protein synthesis and demonstrate the utility of E. coli strain TEA028-rne as a tool for investigating the influence of this ribonuclease on EHEC gene expression in vitro. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Influence of RNase E deficiency on the production of stx2-bearing phages and Shiga toxin in an RNase E-inducible strain of enterohaemorrhagic Escherichia coli (EHEC) O157:H7.

    Science.gov (United States)

    Thuraisamy, Thujitha; Lodato, Patricia B

    2018-05-01

    In enterohaemorrhagic Escherichia coli (EHEC), stx1 or stx2 genes encode Shiga toxin (Stx1 or Stx2, respectively) and are carried by prophages. The production and release of both stx phages and toxin occur upon initiation of the phage lytic cycle. Phages can further disseminate stx genes by infecting naïve bacteria in the intestine. Here, the effect of RNase E deficiency on these two virulence traits was investigated. Cultures of the EHEC strains TEA028-rne containing low versus normal RNase E levels or the parental strain (TEA028) were treated with mitomycin C (MMC) to induce the phage lytic cycle. Phages and Stx2 titres were quantified by the double-agar assay and the receptor ELISA technique, respectively. RNase E deficiency in MMC-treated cells significantly reduced the yield of infectious stx2 phages. Delayed cell lysis and the appearance of encapsidated phage DNA copies suggest a slow onset of the lytic cycle. However, these observations do not entirely explain the decrease of phage yields. stx1 phages were not detected under normal or deficient RNase E levels. After an initial delay, high levels of toxin were finally produced in MMC-treated cultures. RNase E scarcity reduces stx2 phage production but not toxin. Normal concentrations of RNase E are likely required for correct phage morphogenesis. Our future work will address the mechanism of RNase E action on phage morphogenesis.

  13. Next generation sequencing analysis reveals that the ribonucleases RNase II, RNase R and PNPase affect bacterial motility and biofilm formation in E. coli.

    Science.gov (United States)

    Pobre, Vânia; Arraiano, Cecília M

    2015-02-14

    The RNA steady-state levels in the cell are a balance between synthesis and degradation rates. Although transcription is important, RNA processing and turnover are also key factors in the regulation of gene expression. In Escherichia coli there are three main exoribonucleases (RNase II, RNase R and PNPase) involved in RNA degradation. Although there are many studies about these exoribonucleases not much is known about their global effect in the transcriptome. In order to study the effects of the exoribonucleases on the transcriptome, we sequenced the total RNA (RNA-Seq) from wild-type cells and from mutants for each of the exoribonucleases (∆rnb, ∆rnr and ∆pnp). We compared each of the mutant transcriptome with the wild-type to determine the global effects of the deletion of each exoribonucleases in exponential phase. We determined that the deletion of RNase II significantly affected 187 transcripts, while deletion of RNase R affects 202 transcripts and deletion of PNPase affected 226 transcripts. Surprisingly, many of the transcripts are actually down-regulated in the exoribonuclease mutants when compared to the wild-type control. The results obtained from the transcriptomic analysis pointed to the fact that these enzymes were changing the expression of genes related with flagellum assembly, motility and biofilm formation. The three exoribonucleases affected some stable RNAs, but PNPase was the main exoribonuclease affecting this class of RNAs. We confirmed by qPCR some fold-change values obtained from the RNA-Seq data, we also observed that all the exoribonuclease mutants were significantly less motile than the wild-type cells. Additionally, RNase II and RNase R mutants were shown to produce more biofilm than the wild-type control while the PNPase mutant did not form biofilms. In this work we demonstrate how deep sequencing can be used to discover new and relevant functions of the exoribonucleases. We were able to obtain valuable information about the

  14. RNase L mediated protection from virus induced demyelination.

    Directory of Open Access Journals (Sweden)

    Derek D C Ireland

    2009-10-01

    Full Text Available IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/- mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/- mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.

  15. Evolution of the RNase P RNA structural domain in Leptospira spp

    NARCIS (Netherlands)

    Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A.; Devendran, Ajay; Hartskeerl, Rudy A.; Raj, Stephen M. L.

    2014-01-01

    We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along

  16. Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutières syndrome.

    Science.gov (United States)

    Rice, Gillian I; Reijns, Martin A M; Coffin, Stephanie R; Forte, Gabriella M A; Anderson, Beverley H; Szynkiewicz, Marcin; Gornall, Hannah; Gent, David; Leitch, Andrea; Botella, Maria P; Fazzi, Elisa; Gener, Blanca; Lagae, Lieven; Olivieri, Ivana; Orcesi, Simona; Swoboda, Kathryn J; Perrino, Fred W; Jackson, Andrew P; Crow, Yanick J

    2013-08-01

    Aicardi-Goutières syndrome is an inflammatory disorder resulting from mutations in TREX1, RNASEH2A/2B/2C, SAMHD1, or ADAR1. Here, we provide molecular, biochemical, and cellular evidence for the pathogenicity of two synonymous variants in RNASEH2A. Firstly, the c.69G>A (p.Val23Val) mutation causes the formation of a splice donor site within exon 1, resulting in an out of frame deletion at the end of exon 1, leading to reduced RNase H2 protein levels. The second mutation, c.75C>T (p.Arg25Arg), also introduces a splice donor site within exon 1, and the internal deletion of 18 amino acids. The truncated protein still forms a heterotrimeric RNase H2 complex, but lacks catalytic activity. However, as a likely result of leaky splicing, a small amount of full-length active protein is apparently produced in an individual homozygous for this mutation. Recognition of the disease causing status of these variants allows for diagnostic testing in relevant families. © 2013 WILEY PERIODICALS, INC.

  17. RNase MRP and the RNA processing cascade in the eukaryotic ancestor.

    Science.gov (United States)

    Woodhams, Michael D; Stadler, Peter F; Penny, David; Collins, Lesley J

    2007-02-08

    Within eukaryotes there is a complex cascade of RNA-based macromolecules that process other RNA molecules, especially mRNA, tRNA and rRNA. An example is RNase MRP processing ribosomal RNA (rRNA) in ribosome biogenesis. One hypothesis is that this complexity was present early in eukaryotic evolution; an alternative is that an initial simpler network later gained complexity by gene duplication in lineages that led to animals, fungi and plants. Recently there has been a rapid increase in support for the complexity-early theory because the vast majority of these RNA-processing reactions are found throughout eukaryotes, and thus were likely to be present in the last common ancestor of living eukaryotes, herein called the Eukaryotic Ancestor. We present an overview of the RNA processing cascade in the Eukaryotic Ancestor and investigate in particular, RNase MRP which was previously thought to have evolved later in eukaryotes due to its apparent limited distribution in fungi and animals and plants. Recent publications, as well as our own genomic searches, find previously unknown RNase MRP RNAs, indicating that RNase MRP has a wide distribution in eukaryotes. Combining secondary structure and promoter region analysis of RNAs for RNase MRP, along with analysis of the target substrate (rRNA), allows us to discuss this distribution in the light of eukaryotic evolution. We conclude that RNase MRP can now be placed in the RNA-processing cascade of the Eukaryotic Ancestor, highlighting the complexity of RNA-processing in early eukaryotes. Promoter analyses of MRP-RNA suggest that regulation of the critical processes of rRNA cleavage can vary, showing that even these key cellular processes (for which we expect high conservation) show some species-specific variability. We present our consensus MRP-RNA secondary structure as a useful model for further searches.

  18. Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells

    Directory of Open Access Journals (Sweden)

    Sandra Jordaan

    2018-03-01

    Full Text Available Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC or a cytotoxic protein composing an immunotoxin (IT. Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP. However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell’s metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents.

  19. Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells.

    Science.gov (United States)

    Jordaan, Sandra; Akinrinmade, Olusiji A; Nachreiner, Thomas; Cremer, Christian; Naran, Krupa; Chetty, Shivan; Barth, Stefan

    2018-03-05

    Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell's metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents.

  20. Lucky number seven: RNase 7 can prevent Staphylococcus aureus skin colonization.

    Science.gov (United States)

    Cho, John S; Xuan, Caiyun; Miller, Lloyd S

    2010-12-01

    Staphylococcus aureus colonization is a major risk factor for infection. In this issue, Simanski et al. demonstrate that the antimicrobial peptide RNase 7 is essential for preventing S. aureus colonization in human skin. These findings suggest that therapeutic interventions aimed at targeting RNase 7 production in the skin may be a novel strategy to protect against S. aureus infections.

  1. Piv site-specific invertase requires a DEDD motif analogous to the catalytic center of the RuvC Holliday junction resolvases.

    Science.gov (United States)

    Buchner, John M; Robertson, Anne E; Poynter, David J; Denniston, Shelby S; Karls, Anna C

    2005-05-01

    Piv, a unique prokaryotic site-specific DNA invertase, is related to transposases of the insertion elements from the IS110/IS492 family and shows no similarity to the site-specific recombinases of the tyrosine- or serine-recombinase families. Piv tertiary structure is predicted to include the RNase H-like fold that typically encompasses the catalytic site of the recombinases or nucleases of the retroviral integrase superfamily, including transposases and RuvC-like Holliday junction resolvases. Analogous to the DDE and DEDD catalytic motifs of transposases and RuvC, respectively, four Piv acidic residues D9, E59, D101, and D104 appear to be positioned appropriately within the RNase H fold to coordinate two divalent metal cations. This suggests mechanistic similarity between site-specific inversion mediated by Piv and transposition or endonucleolytic reactions catalyzed by enzymes of the retroviral integrase superfamily. The role of the DEDD motif in Piv catalytic activity was addressed using Piv variants that are substituted individually or multiply at these acidic residues and assaying for in vivo inversion, intermolecular recombination, and DNA binding activities. The results indicate that all four residues of the DEDD motif are required for Piv catalytic activity. The DEDD residues are not essential for inv recombination site recognition and binding, but this acidic tetrad does appear to contribute to the stability of Piv-inv interactions. On the basis of these results, a working model for Piv-mediated inversion that includes resolution of a Holliday junction is presented.

  2. Genetic evidence that two independent S-loci control RNase-based self-incompatibility in diploid strawberry.

    Science.gov (United States)

    Bosković, Radovan I; Sargent, Daniel J; Tobutt, Kenneth R

    2010-03-01

    The self-incompatibility mechanism that reduces inbreeding in many plants of the Rosaceae is attributed to a multi-allelic S locus which, in the Prunoideae and Maloideae subfamilies, comprises two complementary genes, a stylar-expressed S-RNase and a pollen-expressed SFB. To elucidate incompatibility in the subfamily Rosoideae, stylar-specific RNases and self-(in)compatibility status were analysed in various diploid strawberries, especially Fragaria nubicola and F. viridis, both self-incompatible, and F. vesca, self-compatible, and in various progenies derived from them. Unexpectedly, two unlinked RNase loci, S and T, were found, encoding peptides distinct from Prunoideae and Maloideae S-RNases; the presence of a single active allele at either is sufficient to confer self-incompatibility. By contrast, in diploid Maloideae and Prunoideae a single locus encodes S-RNases that share several conserved regions and two active alleles are required for self-incompatibility. Our evidence implicates the S locus in unilateral inter-specific incompatibility and shows that S and T RNases can, remarkably, confer not only allele-specific rejection of cognate pollen but also unspecific rejection of Sn Tn pollen, where n indicates a null allele, consistent with the the presence of the pollen component, SFB, activating the cognitive function of these RNases. Comparison of relevant linkage groups between Fragaria and Prunus suggests that Prunus S-RNases, unique in having two introns, may have resulted from gene conversion in an ancestor of Prunus. In addition, it is shown that there is a non-S locus that is essential for self-incompatibility in diploid Fragaria.

  3. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase L(-/-)-MEFs, maintaining preadipocyte state while impairing their terminal differentiation. RNase L(-/-)-MEFs have decreased lipids storage capacity, insulin sensitivity and glucose uptake. Expression of ectopic...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  4. Identification of the gene encoding a type 1 RNase H with an N-terminal double-stranded RNA binding domain from a psychrotrophic bacterium.

    Science.gov (United States)

    Tadokoro, Takashi; Chon, Hyongi; Koga, Yuichi; Takano, Kazufumi; Kanaya, Shigenori

    2007-07-01

    The gene encoding a bacterial type 1 RNase H, termed RBD-RNase HI, was cloned from the psychrotrophic bacterium Shewanella sp. SIB1, overproduced in Escherichia coli, and the recombinant protein was purified and biochemically characterized. SIB1 RBD-RNase HI consists of 262 amino acid residues and shows amino acid sequence identities of 26% to SIB1 RNase HI, 17% to E. coli RNase HI, and 32% to human RNase H1. SIB1 RBD-RNase HI has a double-stranded RNA binding domain (RBD) at the N-terminus, which is commonly present at the N-termini of eukaryotic type 1 RNases H. Gel mobility shift assay indicated that this domain binds to an RNA/DNA hybrid in an isolated form, suggesting that this domain is involved in substrate binding. SIB1 RBD-RNase HI exhibited the enzymatic activity both in vitro and in vivo. Its optimum pH and metal ion requirement were similar to those of SIB1 RNase HI, E. coli RNase HI, and human RNase H1. The specific activity of SIB1 RBD-RNase HI was comparable to that of E. coli RNase HI and was much higher than those of SIB1 RNase HI and human RNase H1. SIB1 RBD-RNase HI showed poor cleavage-site specificity for oligomeric substrates. SIB1 RBD-RNase HI was less stable than E. coli RNase HI but was as stable as human RNase H1. Database searches indicate that several bacteria and archaea contain an RBD-RNase HI. This is the first report on the biochemical characterization of RBD-RNase HI.

  5. The human RNase MRP complex : composition, assembly and role in human disease

    NARCIS (Netherlands)

    Eenennaam, Hans van

    2002-01-01

    Not all RNA molecules in human cells are being translated into proteins. Some of them function in binding proteins, thereby forming so-called RNA-protein complexes. The RNase MRP complex is an example of such an RNA-protein complex. In this thesis two new protein components of the human RNase MRP

  6. RNase H2 Loss in Murine Astrocytes Results in Cellular Defects Reminiscent of Nucleic Acid-Mediated Autoinflammation

    Directory of Open Access Journals (Sweden)

    Kareen Bartsch

    2018-03-01

    Full Text Available Aicardi–Goutières syndrome (AGS is a rare early onset childhood encephalopathy caused by persistent neuroinflammation of autoimmune origin. AGS is a genetic disorder and >50% of affected individuals bear hypomorphic mutations in ribonuclease H2 (RNase H2. All available RNase H2 mouse models so far fail to mimic the prominent CNS involvement seen in AGS. To establish a mouse model recapitulating the human disease, we deleted RNase H2 specifically in the brain, the most severely affected organ in AGS. Although RNase H2ΔGFAP mice lacked the nuclease in astrocytes and a majority of neurons, no disease signs were apparent in these animals. We additionally confirmed these results in a second, neuron-specific RNase H2 knockout mouse line. However, when astrocytes were isolated from brains of RNase H2ΔGFAP mice and cultured under mitogenic conditions, they showed signs of DNA damage and premature senescence. Enhanced expression of interferon-stimulated genes (ISGs represents the most reliable AGS biomarker. Importantly, primary RNase H2ΔGFAP astrocytes displayed significantly increased ISG transcript levels, which we failed to detect in in vivo in brains of RNase H2ΔGFAP mice. Isolated astrocytes primed by DNA damage, including RNase H2-deficiency, exhibited a heightened innate immune response when exposed to bacterial or viral antigens. Taken together, we established a valid cellular AGS model that utilizes the very cell type responsible for disease pathology, the astrocyte, and phenocopies major molecular defects observed in AGS patient cells.

  7. No evidence for Fabaceae Gametophytic self-incompatibility being determined by Rosaceae, Solanaceae, and Plantaginaceae S-RNase lineage genes.

    Science.gov (United States)

    Aguiar, Bruno; Vieira, Jorge; Cunha, Ana E; Vieira, Cristina P

    2015-06-02

    Fabaceae species are important in agronomy and livestock nourishment. They have a long breeding history, and most cultivars have lost self-incompatibility (SI), a genetic barrier to self-fertilization. Nevertheless, to improve legume crop breeding, crosses with wild SI relatives of the cultivated varieties are often performed. Therefore, it is fundamental to characterize Fabaceae SI system(s). We address the hypothesis of Fabaceae gametophytic (G)SI being RNase based, by recruiting the same S-RNase lineage gene of Rosaceae, Solanaceae or Plantaginaceae SI species. We first identify SSK1 like genes (described only in species having RNase based GSI), in the Trifolium pratense, Medicago truncatula, Cicer arietinum, Glycine max, and Lupinus angustifolius genomes. Then, we characterize the S-lineage T2-RNase genes in these genomes. In T. pratense, M. truncatula, and C. arietinum we identify S-RNase lineage genes that in phylogenetic analyses cluster with Pyrinae S-RNases. In M. truncatula and C. arietinum genomes, where large scaffolds are available, these sequences are surrounded by F-box genes that in phylogenetic analyses also cluster with S-pollen genes. In T. pratense the S-RNase lineage genes show, however, expression in tissues not involved in GSI. Moreover, levels of diversity are lower than those observed for other S-RNase genes. The M. truncatula and C. arietinum S-RNase and S-pollen like genes phylogenetically related to Pyrinae S-genes, are also expressed in tissues other than those involved in GSI. To address if other T2-RNases could be determining Fabaceae GSI, here we obtained a style with stigma transcriptome of Cytisus striatus, a species that shows significant difference on the percentage of pollen growth in self and cross-pollinations. Expression and polymorphism analyses of the C. striatus S-RNase like genes revealed that none of these genes, is the S-pistil gene. We find no evidence for Fabaceae GSI being determined by Rosaceae, Solanaceae, and

  8. Overexpression and rapid purification of the orfE/rph gene product, RNase PH of Escherichia coli

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank; Andersen, J T; Poulsen, Peter

    1992-01-01

    acid residue protein which was recently identified as the phosphorolytic ribonuclease, RNase PH, that removes nucleotides from the 3' ends of tRNA precursors. In this paper we report the construction of a plasmid, which overexpresses the orfE and pyrE gene products substantially, as well....../min/mg, as characteristic for RNase PH. OrfE/RNase PH contains helix-turn-helix motifs resembling those in DNA-binding proteins, and it binds nonspecifically to DNA. On SDS gels, OrfE/RNase PH migrates as two distinct protein bands. This heterogeneity might be caused by post-translational modification other than...

  9. Alanine Counteracts the Destabilizing Effect that Urea has on RNase-A.

    Science.gov (United States)

    Chowhan, Rimpy K; Ali, Fasil; Bhat, Mohd Y; Rahman, Safikur; Singh, Laishram R; Ahmad, Faizan; Dar, Tanveer A

    2016-01-01

    It is generally believed that organisms use and accumulate methylamine osmolytes to prevent urea's damaging effect on protein stability and activity. However, urea-rich cells not only accumulate methylamines but also many other methylated and non-methylated compounds as well. But, so far it is not known whether osmolytes that are not accumulated in urea-rich cells could also confer urea-counteracting properties. We investigated the behavior of a non-methylamine osmolyte, alanine for its counteracting effect against urea denaturation of a model protein, ribonuclease A (RNase-A). We have measured structure and thermodynamic parameters (Tm, ΔHm, and ΔGD°) of RNase-A in the presence of alanine, urea and their combination. The results were also compared with the ability of glycine (osmolyte lacking one methyl group when compared with alanine) to counter urea's effect on protein stability. We observed that alanine but not glycine counteracts urea's harmful effect on RNase-A stability. The results indicated that alanine (in addition to methylamine osmolytes) may serve as an alternate urea-counteractant. Since glycine fails to protect RNase-A from urea's destabilizing effect, it seems that methylation to glycine might have some evolutionary significance to protect proteins against harmful effects of urea.

  10. R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters.

    Science.gov (United States)

    Chen, Liang; Chen, Jia-Yu; Zhang, Xuan; Gu, Ying; Xiao, Rui; Shao, Changwei; Tang, Peng; Qian, Hao; Luo, Daji; Li, Hairi; Zhou, Yu; Zhang, Dong-Er; Fu, Xiang-Dong

    2017-11-16

    R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-quadruplex in non-template DNA, corroborating with all biochemically established properties of R-loops. Transcription perturbation experiments further indicate that R-loop induction correlates to transcriptional pausing. Interestingly, we note that most mapped R-loops are each linked to a nearby free RNA end; by using a ribozyme to co-transcriptionally cleave nascent RNA, we demonstrate that such a free RNA end coupled with a G/C-skewed sequence is necessary and sufficient to induce R-loop. These findings provide a topological solution for RNA invasion into duplex DNA and suggest an order for R-loop initiation and elongation in an opposite direction to that previously proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Expressing foreign genes in the pistil: a comparison of S-RNase constructs in different Nicotiana backgrounds.

    Science.gov (United States)

    Murfett, J; McClure, B A

    1998-06-01

    Transgenic plant experiments have great potential for extending our understanding of the role of specific genes in controlling pollination. Often, the intent of such experiments is to over-express a gene and test for effects on pollination. We have examined the efficiency of six different S-RNase constructs in Nicotiana species and hybrids. Each construct contained the coding region, intron, and downstream sequences from the Nicotiana alata S(A2)-RNase gene. Among the six expression constructs, two utilized the cauliflower mosaic virus (CaMV) 35S promoter with duplicated enhancer, and four utilized promoters from genes expressed primarily in pistils. The latter included promoters from the tomato Chi2;1 and 9612 genes, a promoter from the N. alata S(A2)-RNase gene, and a promoter from the Brassica SLG-13 gene. Some or all of the constructs were tested in N. tabacum, N. plumbaginifolia, N. plumbaginifolia x SI N. alata S(C10)S(c10) hybrids, N. langsdorffii, and N. langsdorffii x SC N. alata hybrids. Stylar specific RNase activities and S(A2)-RNase transcript levels were determined in transformed plants. Constructs including the tomato Chi2;1 gene promoter or the Brassica SLG-13 promoter provided the highest levels of S(A2)-RNase expression. Transgene expression patterns were tightly regulated, the highest level of expression was observed in post-anthesis styles. Expression levels of the S(A2)-RNase transgenes was dependent on the genetic background of the host. Higher levels of S(A2)-RNase expression were observed in N. plumbaginifolia x SC N. alata hybrids than in N. plumbaginifolia.

  12. Studies of the aggregation of RNase Sa

    DEFF Research Database (Denmark)

    Khasa, Harshit; Kramer, Ryan; Maddux, Nathan

    2014-01-01

    Thirty-eight mutants of RNase Sa (ribonuclease from Streptomyces aureofaciens) were examined for their structure, thermal sensitivity, and tendency to aggregate. Although a biphasic correlation was seen between the effect of temperature on structure and the free energy of transfer changes in many...

  13. Two acid RNases from Dactylis glomerata seeds. Purification, properties and effect of polyamines and lectins on their activity

    Directory of Open Access Journals (Sweden)

    Janina Wiśniowska

    2014-01-01

    Full Text Available Two glycoproteidic acid RNases (RNase I and RNase II were obtained and purified from the seeds of Dactylis glomerata by extraction with acetate buffer, fractionation with ammonium sulfate, ion-exchange chromatography on DEAE-cellulose, DEAE-Sphadex, affinity chromatography on Con A-Sepharose and gel filtration on Bio-Gel P60. RNase I with a specific activity of 2582 U•mg-1 protein and an optimum pH of 4.9 and RNase II with a specific activity of 1928 U• mg-1 protein and optimum pH of 4.6, were isolated. They lacked nuclease, phosphodi- and monoesterase activities. Both forms of the enzyme hydrolyzed pyrimidine homopolymers with a preference for poly U and exhibited a low specificity for purine homopolymers (poly G and poly A. RNase I acted with a 3-fold higher hydrolytic activity on poly C homopolymer than RNase IL The hydrolytic activity of both enzymes was inhibited by Zn+2, Fe+2, Cu+2 ions when yeast RNA was the substrate. The amines spermine, spermidine and tyramine at a concentration of 0.1 mM increased the enzymatic activity of both RNases by 20 to 60% of the relative activity. The hydrolytic activity of RNases I and II was stimulated by the presence of lentil lectin (LL, soybean lectin (SBA and potato lectin (STA, and inhibited by the presence of concanavalin A. The 20-200% stimulation and 40-60% inhibition depended on the proportion, on a weight basis, of enzyme to lectin and were reversible in the presence of receptor sugars.

  14. Base substitutions at scissile bond sites are sufficient to alter RNA-binding and cleavage activity of RNase III.

    Science.gov (United States)

    Kim, Kyungsub; Sim, Se-Hoon; Jeon, Che Ok; Lee, Younghoon; Lee, Kangseok

    2011-02-01

    RNase III, a double-stranded RNA-specific endoribonuclease, degrades bdm mRNA via cleavage at specific sites. To better understand the mechanism of cleavage site selection by RNase III, we performed a genetic screen for sequences containing mutations at the bdm RNA cleavage sites that resulted in altered mRNA stability using a transcriptional bdm'-'cat fusion construct. While most of the isolated mutants showed the increased bdm'-'cat mRNA stability that resulted from the inability of RNase III to cleave the mutated sequences, one mutant sequence (wt-L) displayed in vivo RNA stability similar to that of the wild-type sequence. In vivo and in vitro analyses of the wt-L RNA substrate showed that it was cut only once on the RNA strand to the 5'-terminus by RNase III, while the binding constant of RNase III to this mutant substrate was moderately increased. A base substitution at the uncleaved RNase III cleavage site in wt-L mutant RNA found in another mutant lowered the RNA-binding affinity by 11-fold and abolished the hydrolysis of scissile bonds by RNase III. Our results show that base substitutions at sites forming the scissile bonds are sufficient to alter RNA cleavage as well as the binding activity of RNase III. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  15. Two tandem RNase III cleavage sites determine betT mRNA stability in response to osmotic stress in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Minji Sim

    Full Text Available While identifying genes regulated by ribonuclease III (RNase III in Escherichia coli, we observed that steady-state levels of betT mRNA, which encodes a transporter mediating the influx of choline, are dependent on cellular concentrations of RNase III. In the present study, we also observed that steady-state levels of betT mRNA are dependent on RNase III activity upon exposure to osmotic stress, indicating the presence of cis-acting elements controlled by RNase III in betT mRNA. Primer extension analyses of betT mRNA revealed two tandem RNase III cleavage sites in its stem-loop region, which were biochemically confirmed via in vitro cleavage assays. Analyses of cleavage sites suggested the stochastic selection of cleavage sites by RNase III, and mutational analyses indicated that RNase III cleavage at either site individually is insufficient for efficient betT mRNA degradation. In addition, both the half-life and abundance of betT mRNA were significantly increased in association with decreased RNase III activity under hyper-osmotic stress conditions. Our findings demonstrate that betT mRNA stability is controlled by RNase III at the post-transcriptional level under conditions of osmotic stress.

  16. Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

    Science.gov (United States)

    Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

    2017-05-31

    BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

  17. Inaction inertia

    NARCIS (Netherlands)

    van Putten, M.; Zeelenberg, M.; van Dijk, E.; Tykocinski, O.E.

    2013-01-01

    Inaction inertia occurs when bypassing an initial action opportunity has the effect of decreasing the likelihood that subsequent similar action opportunities will be taken. This overview of the inaction inertia literature demonstrates the impact of inaction inertia on decision making. Based on

  18. Equilibrium unfolding of A. niger RNase: pH dependence of chemical and thermal denaturation.

    Science.gov (United States)

    Kumar, Gundampati Ravi; Sharma, Anurag; Kumari, Moni; Jagannadham, Medicherla V; Debnath, Mira

    2011-08-01

    Equilibrium unfolding of A. niger RNase with chemical denaturants, for example GuHCl and urea, and thermal unfolding have been studied as a function of pH using fluorescence, far-UV, near-UV, and absorbance spectroscopy. Because of their ability to affect electrostatic interactions, pH and chemical denaturants have a marked effect on the stability, structure, and function of many globular proteins. ANS binding studies have been conducted to enable understanding of the folding mechanism of the protein in the presence of the denaturants. Spectroscopic studies by absorbance, fluorescence, and circular dichroism and use of K2D software revealed that the enzyme has α + β type secondary structure with approximately 29% α-helix, 24% β-sheet, and 47% random coil. Under neutral conditions the enzyme is stable in urea whereas GuHCl-induced equilibrium unfolding was cooperative. A. niger RNase has little ANS binding even under neutral conditions. Multiple intermediates were populated during the pH-induced unfolding of A. niger RNase. Urea and temperature-induced unfolding of A. niger RNase into the molten globule-like state is non-cooperative, in contrast to the cooperativity seen with the native protein, suggesting the presence of two parts/domains, in the molecular structure of A. niger RNase, with different stability that unfolds in steps. Interestingly, the GuHCl-induced unfolding of the A state (molten globule state) of A. niger RNase is unique, because a low concentration of denaturant not only induces structural change but also facilitates transition from one molten globule like state (A(MG1)) into another (I(MG2)).

  19. Phospholipase C-related catalytically inactive protein participates in the autophagic elimination of Staphylococcus aureus infecting mouse embryonic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Kae Harada-Hada

    Full Text Available Autophagy is an intrinsic host defense system that recognizes and eliminates invading bacterial pathogens. We have identified microtubule-associated protein 1 light chain 3 (LC3, a hallmark of autophagy, as a binding partner of phospholipase C-related catalytically inactive protein (PRIP that was originally identified as an inositol trisphosphate-binding protein. Here, we investigated the involvement of PRIP in the autophagic elimination of Staphylococcus aureus in infected mouse embryonic fibroblasts (MEFs. We observed significantly more LC3-positive autophagosome-like vacuoles enclosing an increased number of S. aureus cells in PRIP-deficient MEFs than control MEFs, 3 h and 4.5 h post infection, suggesting that S. aureus proliferates in LC3-positive autophagosome-like vacuoles in PRIP-deficient MEFs. We performed autophagic flux analysis using an mRFP-GFP-tagged LC3 plasmid and found that autophagosome maturation is significantly inhibited in PRIP-deficient MEFs. Furthermore, acidification of autophagosomes was significantly inhibited in PRIP-deficient MEFs compared to the wild-type MEFs, as determined by LysoTracker staining and time-lapse image analysis performed using mRFP-GFP-tagged LC3. Taken together, our data show that PRIP is required for the fusion of S. aureus-containing autophagosome-like vacuoles with lysosomes, indicating that PRIP is a novel modulator in the regulation of the innate immune system in non-professional phagocytic host cells.

  20. RNase-gold labelling in primary roots of Zea Mays L.: evaluation of a particulate marker

    International Nuclear Information System (INIS)

    Piche, Y.; Peterson, R.L.; Ackerley, C.A.; Rauser, W.E.

    1984-01-01

    RNase-gold complexes were applied to thin sections of glutaraldehyde-fixed and Spurr's resin-embedded corn root tips in order to assess the specificity of these gold complexes for RNA in meristematic cells. Numerous micrographs showed that among cellular compartments, nucleoli, nuclei and portions of the cytoplasm were densely labelled whereas cell walls and vacuoles were infrequently labelled. A number of controls used to test the specificity of the labelling showed that RNase-gold was bound to RNA in the cells. Quantitative evaluation of the labelling performed on the samples using morphometric and X-ray microanalysis confirmed the qualitative distribution of RNase-gold based on visual evidence. Minor discrepancies were apparent between morphometric and X-ray microanalysis results. These results show that corn root tissues fixed and embedded in this way retain RNA in a form which can be labelled effectively with RNase-colloidal gold complexes. (author)

  1. Extracellular Ribonuclease from Bacillus licheniformis (Balifase, a New Member of the N1/T1 RNase Superfamily

    Directory of Open Access Journals (Sweden)

    Yulia Sokurenko

    2016-01-01

    Full Text Available The N1/T1 RNase superfamily comprises enzymes with well-established antitumor effects, such as ribotoxins secreted by fungi, primarily by Aspergillus and Penicillium species, and bacterial RNase secreted by B. pumilus (binase and B. amyloliquefaciens (barnase. RNase is regarded as an alternative to classical chemotherapeutic agents due to its selective cytotoxicity towards tumor cells. New RNase with a high degree of structural similarity with binase (73% and barnase (74% was isolated and purified from Bacillus licheniformis (balifase, calculated molecular weight 12421.9 Da, pI 8.91. The protein sample with enzymatic activity of 1.5 × 106 units/A280 was obtained. The physicochemical properties of balifase are similar to those of barnase. However, in terms of its gene organization and promoter activity, balifase is closer to binase. The unique feature of balifase gene organization consists in the fact that genes of RNase and its inhibitor are located in one operon. Similarly to biosynthesis of binase, balifase synthesis is induced under phosphate starvation; however, in contrast to binase, balifase does not form dimers under natural conditions. We propose that the highest stability of balifase among analyzed RNase types allows the protein to retain its structure without oligomerization.

  2. RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory.

    Science.gov (United States)

    Sinkevicius, Kerstin W; Morrison, Thomas R; Kulkarni, Praveen; Cagliostro, Martha K Caffrey; Iriah, Sade; Malmberg, Samantha; Sabrick, Julia; Honeycutt, Jennifer A; Askew, Kim L; Trivedi, Malav; Ferris, Craig F

    2018-05-10

    RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity, and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests. While T1 and T2 weighted images of RNaseT2 knockout rats exhibited no evidence of cystic lesions, the prefrontal cortex and hippocampal complex were enlarged in knockout animals. Diffusion weighted imaging showed altered anisotropy and putative gray matter changes in the hippocampal complex of the RNaseT2 knockout rats. Immunohistochemistry for glial fibrillary acidic protein (GFAP) showed the presence of hippocampal neuroinflammation. Decreased levels of lysosome-associated membrane protein 2 (LAMP2) and elevated acid phosphatase and β-N-Acetylglucosaminidase (NAG) activities indicated that the RNASET2 knockout rats likely had altered lysosomal function and potential defects in autophagy. Object recognition tests confirmed the RNaseT2 knockout rats exhibited memory deficits. However, the Barnes maze, and balance beam and rotarod tests, indicated there were no differences in spatial memory or motor impairments, respectively. Overall, patients with RNASET2 deficiency exhibited a more severe neurodegeneration phenotype than was observed in the RNaseT2 knockout rats. However, the vulnerability of the knockout rat hippocampus as evidenced by neuroinflammation, altered lysosomal function, and cognitive defects indicates this is still a useful in vivo model to study RNASET2 function. © 2018. Published by The Company of Biologists Ltd.

  3. RNase MRP is required for entry of 35S precursor rRNA into the canonical processing pathway.

    Science.gov (United States)

    Lindahl, Lasse; Bommankanti, Ananth; Li, Xing; Hayden, Lauren; Jones, Adrienne; Khan, Miriam; Oni, Tolulope; Zengel, Janice M

    2009-07-01

    RNase MRP is a nucleolar RNA-protein enzyme that participates in the processing of rRNA during ribosome biogenesis. Previous experiments suggested that RNase MRP makes a nonessential cleavage in the first internal transcribed spacer. Here we report experiments with new temperature-sensitive RNase MRP mutants in Saccharomyces cerevisiae that show that the abundance of all early intermediates in the processing pathway is severely reduced upon inactivation of RNase MRP. Transcription of rRNA continues unabated as determined by RNA polymerase run-on transcription, but the precursor rRNA transcript does not accumulate, and appears to be unstable. Taken together, these observations suggest that inactivation of RNase MRP blocks cleavage at sites A0, A1, A2, and A3, which in turn, prevents precursor rRNA from entering the canonical processing pathway (35S > 20S + 27S > 18S + 25S + 5.8S rRNA). Nevertheless, at least some cleavage at the processing site in the second internal transcribed spacer takes place to form an unusual 24S intermediate, suggesting that cleavage at C2 is not blocked. Furthermore, the long form of 5.8S rRNA is made in the absence of RNase MRP activity, but only in the presence of Xrn1p (exonuclease 1), an enzyme not required for the canonical pathway. We conclude that RNase MRP is a key enzyme for initiating the canonical processing of precursor rRNA transcripts, but alternative pathway(s) might provide a backup for production of small amounts of rRNA.

  4. Short RNA guides cleavage by eukaryotic RNase III.

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    Bruno Lamontagne

    Full Text Available In eukaryotes, short RNAs guide a variety of enzymatic activities that range from RNA editing to translation repression. It is hypothesized that pre-existing proteins evolved to bind and use guide RNA during evolution. However, the capacity of modern proteins to adopt new RNA guides has never been demonstrated. Here we show that Rnt1p, the yeast orthologue of the bacterial dsRNA-specific RNase III, can bind short RNA transcripts and use them as guides for sequence-specific cleavage. Target cleavage occurred at a constant distance from the Rnt1p binding site, leaving the guide RNA intact for subsequent cleavage. Our results indicate that RNase III may trigger sequence-specific RNA degradation independent of the RNAi machinery, and they open the road for a new generation of precise RNA silencing tools that do not trigger a dsRNA-mediated immune response.

  5. The role of RNase H2 in processing ribonucleotides incorporated during DNA replication.

    Science.gov (United States)

    Williams, Jessica S; Gehle, Daniel B; Kunkel, Thomas A

    2017-05-01

    Saccharomyces cerevisiae RNase H2 resolves RNA-DNA hybrids formed during transcription and it incises DNA at single ribonucleotides incorporated during nuclear DNA replication. To distinguish between the roles of these two activities in maintenance of genome stability, here we investigate the phenotypes of a mutant of yeast RNase H2 (rnh201-RED; ribonucleotide excision defective) that retains activity on RNA-DNA hybrids but is unable to cleave single ribonucleotides that are stably incorporated into the genome. The rnh201-RED mutant was expressed in wild type yeast or in a strain that also encodes a mutant allele of DNA polymerase ε (pol2-M644G) that enhances ribonucleotide incorporation during DNA replication. Similar to a strain that completely lacks RNase H2 (rnh201Δ), the pol2-M644G rnh201-RED strain exhibits replication stress and checkpoint activation. Moreover, like its null mutant counterpart, the double mutant pol2-M644G rnh201-RED strain and the single mutant rnh201-RED strain delete 2-5 base pairs in repetitive sequences at a high rate that is topoisomerase 1-dependent. The results highlight an important role for RNase H2 in maintaining genome integrity by removing single ribonucleotides incorporated during DNA replication. Published by Elsevier B.V.

  6. Herpes Simplex Virus 1 DNA Polymerase RNase H Activity Acts in a 3'-to-5' Direction and Is Dependent on the 3'-to-5' Exonuclease Active Site.

    Science.gov (United States)

    Lawler, Jessica L; Mukherjee, Purba; Coen, Donald M

    2018-03-01

    The catalytic subunit (Pol) of herpes simplex virus 1 (HSV-1) DNA polymerase has been extensively studied both as a model for other family B DNA polymerases and for its differences from these enzymes as an antiviral target. Among the activities of HSV-1 Pol is an intrinsic RNase H activity that cleaves RNA from RNA-DNA hybrids. There has long been a controversy regarding whether this activity is due to the 3'-to-5' exonuclease of Pol or whether it is a separate activity, possibly acting on 5' RNA termini. To investigate this issue, we compared wild-type HSV-1 Pol and a 3'-to-5' exonuclease-deficient mutant, D368A Pol, for DNA polymerase activity, 3'-to-5' exonuclease activity, and RNase H activity in vitro Additionally, we assessed the RNase H activity using differentially end-labeled templates with 5' or 3' RNA termini. The mutant enzyme was at most modestly impaired for DNA polymerase activity but was drastically impaired for 3'-to-5' exonuclease activity, with no activity detected even at high enzyme-to-DNA substrate ratios. Importantly, the mutant showed no detectable ability to excise RNA with either a 3' or 5' terminus, while the wild-type HSV-1 Pol was able to cleave RNA from the annealed RNA-DNA hairpin template, but only detectably with a 3' RNA terminus in a 3'-to-5' direction and at a rate lower than that of the exonuclease activity. These results suggest that HSV-1 Pol does not have an RNase H separable from its 3'-to-5' exonuclease activity and that this activity prefers DNA degradation over degradation of RNA from RNA-DNA hybrids. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a member of the Herpesviridae family of DNA viruses, several of which cause morbidity and mortality in humans. Although the HSV-1 DNA polymerase has been studied for decades and is a crucial target for antivirals against HSV-1 infection, several of its functions remain to be elucidated. A hypothesis suggesting the existence of a 5'-to-3' RNase H activity intrinsic to this enzyme

  7. Single substitution in bacteriophage T4 RNase H alters the ratio between its exo- and endonuclease activities.

    Science.gov (United States)

    Kholod, Natalia; Sivogrivov, Dmitry; Latypov, Oleg; Mayorov, Sergey; Kuznitsyn, Rafail; Kajava, Andrey V; Shlyapnikov, Mikhail; Granovsky, Igor

    2015-11-01

    The article describes substitutions in bacteriophage T4 RNase H which provide so called das-effect. Phage T4 DNA arrest suppression (das) mutations have been described to be capable of partially suppressing the phage DNA arrest phenotype caused by a dysfunction in genes 46 and/or 47 (also known as Mre11/Rad50 complex). Genetic mapping of das13 (one of the das mutations) has shown it to be in the region of the rnh gene encoding RNase H. Here we report that Das13 mutant of RNase H has substitutions of valine 43 and leucine 242 with isoleucines. To investigate the influence of these mutations on RNase H nuclease properties we have designed a novel in vitro assay that allows us to separate and quantify exo- or endonuclease activities of flap endonuclease. The nuclease assay in vitro showed that V43I substitution increased the ratio between exonuclease/endonuclease activities of RNase H whereas L242I substitution did not affect the nuclease activity of RNase H in vitro. However, both mutations were necessary for the full das effect in vivo. Molecular modelling of the nuclease structure suggests that V43I substitution may lead to disposition of H4 helix, responsible for the interaction with the first base pairs of 5'end of branched DNA. These structural changes may affect unwinding of the first base pairs of gapped or nicked DNA generating a short flap and therefore may stabilize the DNA-enzyme complex. L242I substitution did not affect the structure of RNase H and its role in providing das-effect remains unclear. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. RNase H and replication of ColE1 DNA in Escherichia coli.

    OpenAIRE

    Naito, S; Uchida, H

    1986-01-01

    Amber mutations within the rnh (RNase H) gene of Escherichia coli K-12 were isolated by selecting for bacteria capable of replicating in a sup+ background replication-defective cer-6 mutant of the ColE1 replicon. The cer-6 mutation is an alteration of one base pair located 160 nucleotides upstream of the unique replication origin of this plasmid. Subsequently, we determined the DNA alterations present within these mutants. ColE1 DNA replicated in rnh(Am) recA cells, indicating that (i) RNase ...

  9. Crystallographic and Modeling Studies of RNase III Suggest a Mechanism for Double-Stranded RNA Cleavage | Center for Cancer Research

    Science.gov (United States)

    Background: Ribonuclease III belongs to the family of Mg2+-dependent endonucleases that show specificity for double-stranded RNA (dsRNA). RNase III is conserved in all known bacteria and eukaryotes and has 1–2 copies of a 9-residue consensus sequence, known as the RNase III signature motif. The bacterial RNase III proteins are the simplest, consisting of two domains: an

  10. Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.

    Science.gov (United States)

    Holmes, J Bradley; Akman, Gokhan; Wood, Stuart R; Sakhuja, Kiran; Cerritelli, Susana M; Moss, Chloe; Bowmaker, Mark R; Jacobs, Howard T; Crouch, Robert J; Holt, Ian J

    2015-07-28

    Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase γ in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication.

  11. Curcumin, a Natural Antioxidant, Acts as a Noncompetitive Inhibitor of Human RNase L in Presence of Its Cofactor 2-5A In Vitro

    Directory of Open Access Journals (Sweden)

    Ankush Gupta

    2014-01-01

    Full Text Available Ribonuclease L (RNase L is an antiviral endoribonuclease of the innate immune system, which is induced and activated by viral infections, interferons, and double stranded RNA (dsRNA in mammalian cells. Although, RNase L is generally protective against viral infections, abnormal RNase L expression and activity have been associated with a number of diseases. Here, we show that curcumin, a natural plant-derived anti-inflammatory active principle, inhibits RNase L activity; hence, it may be exploited for therapeutic interventions in case of pathological situations associated with excess activation of RNase L.

  12. Curcumin, a natural antioxidant, acts as a noncompetitive inhibitor of human RNase L in presence of its cofactor 2-5A in vitro.

    Science.gov (United States)

    Gupta, Ankush; Rath, Pramod C

    2014-01-01

    Ribonuclease L (RNase L) is an antiviral endoribonuclease of the innate immune system, which is induced and activated by viral infections, interferons, and double stranded RNA (dsRNA) in mammalian cells. Although, RNase L is generally protective against viral infections, abnormal RNase L expression and activity have been associated with a number of diseases. Here, we show that curcumin, a natural plant-derived anti-inflammatory active principle, inhibits RNase L activity; hence, it may be exploited for therapeutic interventions in case of pathological situations associated with excess activation of RNase L.

  13. Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery.

    Science.gov (United States)

    Donovan, Jesse; Rath, Sneha; Kolet-Mandrikov, David; Korennykh, Alexei

    2017-11-01

    Mammalian cells respond to double-stranded RNA (dsRNA) by activating a translation-inhibiting endoribonuclease, RNase L. Consensus in the field indicates that RNase L arrests protein synthesis by degrading ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs). However, here we provide evidence for a different and far more efficient mechanism. By sequencing abundant RNA fragments generated by RNase L in human cells, we identify site-specific cleavage of two groups of noncoding RNAs: Y-RNAs, whose function is poorly understood, and cytosolic tRNAs, which are essential for translation. Quantitative analysis of human RNA cleavage versus nascent protein synthesis in lung carcinoma cells shows that RNase L stops global translation when tRNAs, as well as rRNAs and mRNAs, are still intact. Therefore, RNase L does not have to degrade the translation machinery to stop protein synthesis. Our data point to a rapid mechanism that transforms a subtle RNA cleavage into a cell-wide translation arrest. © 2017 Donovan et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  14. Self-incompatibility in Petunia inflata: the relationship between a self-incompatibility locus F-box protein and its non-self S-RNases.

    Science.gov (United States)

    Sun, Penglin; Kao, Teh-hui

    2013-02-01

    The highly polymorphic S (for self-incompatibility) locus regulates self-incompatibility in Petunia inflata; the S-RNase regulates pistil specificity, and multiple S-locus F-box (SLF) genes regulate pollen specificity. The collaborative non-self recognition model predicts that, for any S-haplotype, an unknown number of SLFs collectively recognize all non-self S-RNases to mediate their ubiquitination and degradation. Using a gain-of-function assay, we examined the relationships between S2-SLF1 (for S2-allelic product of Type-1 SLF) and four S-RNases. The results suggest that S2-SLF1 interacts with S7- and S13-RNases, and the previously identified S1- and S3-RNases, but not with S5- or S11-RNase. An artificial microRNA expressed by the S2-SLF1 promoter, but not by the vegetative cell-specific promoter, Late Anther Tomato 52, suppressed expression of S2-SLF1 in S2 pollen, suggesting that SLF1 is specific to the generative cell. The S2 pollen with S2-SLF1 suppressed was compatible with S3-, S5-, S7-, S11-, and S13-carrying pistils, confirming that other SLF proteins are responsible for detoxifying S5- and S11-RNases and suggesting that S2-SLF1 is not the only SLF in S2 pollen that interacts with S3-, S7-, and S13-RNases. Petunia may have evolved at least two types of SLF proteins to detoxify any non-self S-RNase to minimize the deleterious effects of mutation in any SLF.

  15. Autonomously folding protein fragments reveal differences in the energy landscapes of homologous RNases H.

    Directory of Open Access Journals (Sweden)

    Laura E Rosen

    Full Text Available An important approach to understanding how a protein sequence encodes its energy landscape is to compare proteins with different sequences that fold to the same general native structure. In this work, we compare E. coli and T. thermophilus homologs of the protein RNase H. Using protein fragments, we create equilibrium mimics of two different potential partially-folded intermediates (I(core and I(core+1 hypothesized to be present on the energy landscapes of these two proteins. We observe that both T. thermophilus RNase H (ttRNH fragments are folded and have distinct stabilities, indicating that both regions are capable of autonomous folding and that both intermediates are present as local minima on the ttRNH energy landscape. In contrast, the two E. coli RNase H (ecRNH fragments have very similar stabilities, suggesting that the presence of additional residues in the I(core+1 fragment does not affect the folding or structure as compared to I(core. NMR experiments provide additional evidence that only the I(core intermediate is populated by ecRNH. This is one of the biggest differences that has been observed between the energy landscapes of these two proteins. Additionally, we used a FRET experiment in the background of full-length ttRNH to specifically monitor the formation of the I(core+1 intermediate. We determine that the ttRNH I(core+1 intermediate is likely the intermediate populated prior to the rate-limiting barrier to global folding, in contrast to E. coli RNase H for which I(core is the folding intermediate. This result provides new insight into the nature of the rate-limiting barrier for the folding of RNase H.

  16. Allelic diversity of S-RNase at the self-incompatibility locus in natural flowering cherry populations (Prunus lannesiana var. speciosa).

    Science.gov (United States)

    Kato, S; Mukai, Y

    2004-03-01

    In the Rosaceae family, which includes Prunus, gametophytic self-incompatibility (GSI) is controlled by a single multiallelic locus (S-locus), and the S-locus product expressed in the pistils is a glycoprotein with ribonuclease activity (S-RNase). Two populations of flowering cherry (Prunus lannesiana var. speciosa), located on Hachijo Island in Japan's Izu Islands, were sampled, and S-allele diversity was surveyed based on the sequence polymorphism of S-RNase. A total of seven S-alleles were cloned and sequenced. The S-RNases of flowering cherry showed high homology to those of Prunus cultivars (P. avium and P. dulcis). In the phylogenetic tree, the S-RNases of flowering cherry and other Prunus cultivars formed a distinct group, but they did not form species-specific subgroups. The nucleotide substitution pattern in S-RNases of flowering cherry showed no excess of nonsynonymous substitutions relative to synonymous substitutions. However, the S-RNases of flowering cherry had a higher Ka/Ks ratio than those of other Prunus cultivars, and a subtle heterogeneity in the nucleotide substitution rates was observed among the Prunus species. The S-genotype of each individual was determined by Southern blotting of restriction enzyme-digested genomic DNA, using cDNA for S-RNase as a probe. A total of 22 S-alleles were identified. All individuals examined were heterozygous, as expected under GSI. The allele frequencies were, contrary to the expectation under GSI, significantly unequal. The two populations studied showed a high degree of overlap, with 18 shared alleles. However, the allele frequencies differed considerably between the two populations.

  17. RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways.

    Science.gov (United States)

    Fang, Evandro Fei; Zhang, Chris Zhi Yi; Fong, Wing Ping; Ng, Tzi Bun

    2012-04-01

    Ribonucleases (RNases) are ubiquitously distributed nucleases that cleave RNA into smaller pieces. They are promising drugs for different cancers based on their concrete antitumor activities in vitro and in vivo. Here we report for the first time purification and characterization of a 14-kDa RNase, designated as RNase MC2, in the seeds of bitter gourd (Momordica charantia). RNase MC2 manifested potent RNA-cleavage activity toward baker's yeast tRNA, tumor cell rRNA, and an absolute specificity for uridine. RNase MC2 demonstrated both cytostatic and cytotoxic activities against MCF-7 breast cancer cells. Treatment of MCF-7 cells with RNase MC2 caused nuclear damage (karyorrhexis, chromatin condensation, and DNA fragmentation), ultimately resulting in early/late apoptosis. Further molecular studies unveiled that RNase MC2 induced differential activation of MAPKs (p38, JNK and ERK) and Akt. On the other hand, RNase MC2 exposure activated caspase-8, caspase-9, caspase-7, increased the production of Bak and cleaved PARP, which in turn contributed to the apoptotic response. In conclusion, RNase MC2 is a potential agent which can be exploited in the worldwide fight against breast cancer.

  18. Increased production of pyruvic acid by Escherichia coli RNase G mutants in combination with cra mutations.

    Science.gov (United States)

    Sakai, Taro; Nakamura, Naoko; Umitsuki, Genryou; Nagai, Kazuo; Wachi, Masaaki

    2007-08-01

    The Escherichia coli RNase G is known as an endoribonuclease responsible for the 5'-end maturation of 16S rRNA and degradation of several specific mRNAs such as adhE and eno mRNAs. In this study, we found that an RNase G mutant derived from the MC1061 strain did not grow on a glucose minimal medium. Genetic analysis revealed that simultaneous defects of cra and ilvIH, encoding a transcriptional regulator of glycolysis/gluconeogenesis and one of isozymes of acetohydroxy acid synthase, respectively, were required for this phenomenon to occur. The results of additional experiments presented here indicate that the RNase G mutation, in combination with cra mutation, caused the increased production of pyruvic acid from glucose, which was then preferentially converted to valine due to the ilvIH mutation, resulting in depletion of isoleucine. In fact, the rng cra double mutant produced increased amount of pyruvate in the medium. These results suggest that the RNase G mutation could be applied in the breeding of producer strains of pyruvate and its derivatives such as valine.

  19. An evaluation of the RNase H inhibitory effects of Vietnamese medicinal plant extracts and natural compounds.

    Science.gov (United States)

    Tai, Bui Huu; Nhut, Nguyen Duy; Nhiem, Nguyen Xuan; Quang, Tran Hong; Thanh Ngan, Nguyen Thi; Thuy Luyen, Bui Thi; Huong, Tran Thu; Wilson, Jennifer; Beutler, John A; Ban, Ninh Khac; Cuong, Nguyen Manh; Kim, Young Ho

    2011-10-01

    Acquired immune deficiency syndrome (AIDS) is a severe pandemic disease especially prevalent in poor and developing countries. Thus, developing specific, potent antiviral drugs that restrain infection by human immunodeficiency virus type 1 (HIV-1), a major cause of AIDS, remains an urgent priority. This study evaluated 32 extracts and 23 compounds from Vietnamese medicinal plants for their inhibitory effects against HIV-1 ribonuclease H (RNase H) and their role in reversing the cytopathic effects of HIV. The plants were air-dried and extracted in different solvent systems to produce plant extracts. Natural compounds were obtained as previously published. Samples were screened for RNase H inhibition followed by a cytopathic assay. Data were analyzed using the Microsoft Excel. At 50 μg/mL, 11 plant extracts and five compounds inhibited over 90% of RNase H enzymatic activity. Methanol extracts from Phyllanthus reticulatus and Aglaia aphanamixis leaves inhibited RNase H activity by 99 and 98%, respectively, whereas four extracts showed modest protection against the cytopathic effects of HIV. The screening results demonstrated that the butanol (BuOH) extract of Celastrus orbiculata leaves, methanol (MeOH) extracts of Glycosmis stenocarpa stems, Eurya ciliata leaves, and especially P. reticulatus leaves showed potential RNase H inhibition and protection against the viral cytopathic effects of HIV-1. Further chemical investigations should be carried out to find the active components of these extracts and compounds as potential anti-HIV drug candidates.

  20. Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

    Science.gov (United States)

    Kankanala, Jayakanth; Kirby, Karen A; Huber, Andrew D; Casey, Mary C; Wilson, Daniel J; Sarafianos, Stefan G; Wang, Zhengqiang

    2017-12-01

    Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have shown significant antiviral activities. We report herein the design, synthesis and biological evaluation of a novel N-hydroxy thienopyrimidine-2,3-dione chemotype (11) which potently and selectively inhibited RNase H with considerable potency against HIV-1 in cell culture. Current structure-activity-relationship (SAR) identified analogue 11d as a nanomolar inhibitor of RNase H (IC 50  = 0.04 μM) with decent antiviral potency (EC 50  = 7.4 μM) and no cytotoxicity (CC 50  > 100 μM). In extended biochemical assays compound 11d did not inhibit RT polymerase (pol) while inhibiting integrase strand transfer (INST) with 53 fold lower potency (IC 50  = 2.1 μM) than RNase H inhibition. Crystallographic and molecular modeling studies confirmed the RNase H active site binding mode. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Direct inhibition of RNAse T2 expression by the HTLV-1 viral protein Tax.

    Science.gov (United States)

    Polakowski, Nicholas; Han, Hongjin; Lemasson, Isabelle

    2011-08-01

    Adult T-cell leukemia (ATL) is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1) infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the ability of the viral protein to directly deregulate expression of specific cellular genes through interactions with numerous transcriptional regulators. To identify gene promoters where Tax is localized, we isolated Tax-DNA complexes from an HTLV-1-infected T-cell line through a chromatin immunoprecipitation (ChIP) assay and used the DNA to probe a CpG island microarray. A site within the RNASET2 gene was found to be occupied by Tax. Real-time PCR analysis confirmed this result, and transient expression of Tax in uninfected cells led to the recruitment of the viral protein to the promoter. This event correlated with a decrease in the level of RNase T2 mRNA and protein, suggesting that Tax represses expression of this gene. Loss of RNase T2 expression occurs in certain hematological malignancies and other forms of cancer, and RNase T2 was recently reported to function as a tumor suppressor. Consequently, a reduction in the level of RNase T2 by Tax may play a role in ATL development.

  2. Direct Inhibition of RNAse T2 Expression by the HTLV-1 Viral Protein Tax

    Directory of Open Access Journals (Sweden)

    Isabelle Lemasson

    2011-08-01

    Full Text Available Adult T-cell leukemia (ATL is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1 infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the ability of the viral protein to directly deregulate expression of specific cellular genes through interactions with numerous transcriptional regulators. To identify gene promoters where Tax is localized, we isolated Tax-DNA complexes from an HTLV-1-infected T-cell line through a chromatin immunoprecipitation (ChIP assay and used the DNA to probe a CpG island microarray. A site within the RNASET2 gene was found to be occupied by Tax. Real-time PCR analysis confirmed this result, and transient expression of Tax in uninfected cells led to the recruitment of the viral protein to the promoter. This event correlated with a decrease in the level of RNase T2 mRNA and protein, suggesting that Tax represses expression of this gene. Loss of RNase T2 expression occurs in certain hematological malignancies and other forms of cancer, and RNase T2 was recently reported to function as a tumor suppressor. Consequently, a reduction in the level of RNase T2 by Tax may play a role in ATL development.

  3. Partial Purification and Characterization of RNase P from Arabidopsis Thaliana Tissue

    National Research Council Canada - National Science Library

    2000-01-01

    ...) molecules to give mature 5, ends has been isolated from Arabidopsis thaliana tissue. The RNase P activity was isolated by ammonium sulfate precipitation of a tissue homogenate and further purified by anion exchange chromatography...

  4. The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for Viability of Thermococcus kodakarensis.

    Science.gov (United States)

    Burkhart, Brett W; Cubonova, Lubomira; Heider, Margaret R; Kelman, Zvi; Reeve, John N; Santangelo, Thomas J

    2017-07-01

    Many aspects of and factors required for DNA replication are conserved across all three domains of life, but there are some significant differences surrounding lagging-strand synthesis. In Archaea , a 5'-to-3' exonuclease, related to both bacterial RecJ and eukaryotic Cdc45, that associates with the replisome specifically through interactions with GINS was identified and designated GAN (for G INS- a ssociated n uclease). Despite the presence of a well-characterized flap endonuclease (Fen1), it was hypothesized that GAN might participate in primer removal during Okazaki fragment maturation, and as a Cdc45 homologue, GAN might also be a structural component of an archaeal CMG (Cdc45, MCM, and GINS) replication complex. We demonstrate here that, individually, either Fen1 or GAN can be deleted, with no discernible effects on viability and growth. However, deletion of both Fen1 and GAN was not possible, consistent with both enzymes catalyzing the same step in primer removal from Okazaki fragments in vivo RNase HII has also been proposed to participate in primer processing during Okazaki fragment maturation. Strains with both Fen1 and RNase HII deleted grew well. GAN activity is therefore sufficient for viability in the absence of both RNase HII and Fen1, but it was not possible to construct a strain with both RNase HII and GAN deleted. Fen1 alone is therefore insufficient for viability in the absence of both RNase HII and GAN. The ability to delete GAN demonstrates that GAN is not required for the activation or stability of the archaeal MCM replicative helicase. IMPORTANCE The mechanisms used to remove primer sequences from Okazaki fragments during lagging-strand DNA replication differ in the biological domains. Bacteria use the exonuclease activity of DNA polymerase I, whereas eukaryotes and archaea encode a flap endonuclease (Fen1) that cleaves displaced primer sequences. RNase HII and the GINS-associated exonuclease GAN have also been hypothesized to assist in primer

  5. Self-incompatibility of Prunus tenella and evidence that reproductively isolated species of Prunus have different SFB alleles coupled with an identical S-RNase allele.

    Science.gov (United States)

    Surbanovski, Nada; Tobutt, Kenneth R; Konstantinović, Miroslav; Maksimović, Vesna; Sargent, Daniel J; Stevanović, Vladimir; Bosković, Radovan I

    2007-05-01

    Many species of Prunus display an S-RNase-based gametophytic self-incompatibility (SI), controlled by a single highly polymorphic multigene complex termed the S-locus. This comprises tightly linked stylar- and pollen-expressed genes that determine the specificity of the SI response. We investigated SI of Prunus tenella, a wild species found in small, isolated populations on the Balkan peninsula, initially by pollination experiments and identifying stylar-expressed RNase alleles. Nine P. tenella S-RNase alleles (S(1)-S(9)) were cloned; their sequence analysis showed a very high ratio of non-synonymous to synonymous nucleotide substitutions (K(a)/K(s)) and revealed that S-RNase alleles of P. tenella, unlike those of Prunus dulcis, show positive selection in all regions except the conserved regions and that between C2 and RHV. Remarkably, S(8)-RNase, was found to be identical to S(1)-RNase from Prunus avium, a species that does not interbreed with P. tenella and, except for just one amino acid, to S(11) of P. dulcis. However, the corresponding introns and S-RNase-SFB intergenic regions showed considerable differences. Moreover, protein sequences of the pollen-expressed SFB alleles were not identical, harbouring 12 amino-acid replacements between those of P. tenella SFB(8) and P. avium SFB(1). Implications of this finding for hypotheses about the evolution of new S-specificities are discussed.

  6. The catalytic activity of several tungsten oxides for the oxidation of propene

    International Nuclear Information System (INIS)

    De Rossi, S.; Schiavello, M.; Rome Univ.; Iguchi, E.; Tilley, R.J.D.

    1976-01-01

    A study has been made of the catalytic oxidation of propene over the oxides WO 3 , WOsub(2,95), WOsub(2,90), WOsub(2,72) and Wo 2 , which were selected because they possess specific features of chemical and structural interest rather than for their catalytic ability. It was found that the oxides WOsub(2,95), WOsub(2,90) and WOsub(2,72) all selectively produce acrolein in small amounts. The oxides WO 3 and WO 2 were non-selective and rather inactive. The results are discussed in terms of a mechanism involving both variable valence in the crystal and the specific structural geometry of these compounds. (orig.) [de

  7. Structural and functional insights into the catalytic inactivity of the major fraction of buffalo milk xanthine oxidoreductase.

    Directory of Open Access Journals (Sweden)

    Kaustubh S Gadave

    Full Text Available BACKGROUND: Xanthine oxidoreductase (XOR existing in two interconvertible forms, xanthine dehydrogenase (XDH and xanthine oxidase (XO, catabolises xanthine to uric acid that is further broken down to antioxidative agent allantoin. XOR also produces free radicals serving as second messenger and microbicidal agent. Large variation in the XO activity has been observed among various species. Both hypo and hyper activity of XOR leads to pathophysiological conditions. Given the important nutritional role of buffalo milk in human health especially in south Asia, it is crucial to understand the functional properties of buffalo XOR and the underlying structural basis of variations in comparison to other species. METHODS AND FINDINGS: Buffalo XO activity of 0.75 U/mg was almost half of cattle XO activity. Enzymatic efficiency (k cat/K m of 0.11 sec(-1 µM(-1 of buffalo XO was 8-10 times smaller than that of cattle XO. Buffalo XOR also showed lower antibacterial activity than cattle XOR. A CD value (Δε430 nm of 46,000 M(-1 cm(-1 suggested occupancy of 77.4% at Fe/S I centre. Buffalo XOR contained 0.31 molybdenum atom/subunit of which 48% existed in active sulfo form. The active form of XO in buffalo was only 16% in comparison to ∼30% in cattle. Sequencing revealed 97.4% similarity between buffalo and cattle XOR. FAD domain was least conserved, while metal binding domains (Fe/S and Molybdenum were highly conserved. Homology modelling of buffalo XOR showed several variations occurring in clusters, especially close to FAD binding pocket which could affect NAD(+ entry in the FAD centre. The difference in XO activity seems to be originating from cofactor deficiency, especially molybdenum. CONCLUSION: A major fraction of buffalo milk XOR exists in a catalytically inactive form due to high content of demolybdo and desulfo forms. Lower Fe/S content and structural factors might be contributing to lower enzymatic efficiency of buffalo XOR in a minor way.

  8. Methylation of the S f locus in almond is associated with S-RNase loss of function.

    Science.gov (United States)

    Fernández i Martí, Angel; Gradziel, Thomas M; Socias i Company, Rafel

    2014-12-01

    Self-compatibility in almond (Prunus dulcis) is attributed to the presence of the S f haplotype, allelic to and dominant over the series of S-alleles controlling self-incompatibility. Some forms of the S f haplotype, however, are phenotypically self-incompatible even though their nucleotide sequences are identical. DNA from leaves and styles from genetically diverse almond samples was cloned and sequenced and then analyzed for changes affecting S f -RNase variants. Epigenetic changes in several cytosine residues were detected in a fragment of 4,700 bp of the 5' upstream region of all self-compatible samples of the S f -RNases, differentiating them from all self-incompatible samples of S f -RNases analyzed. This is the first report of DNA methylation in a Rosaceae species and appears to be strongly associated with inactivation of the S f allele. Results facilitate an understanding of the evolution of self-compatibility/self-incompatibility in almond and other Prunus species, and suggest novel approaches for future crop improvement.

  9. Some biological actions of PEG-conjugated RNase A oligomers

    Czech Academy of Sciences Publication Activity Database

    Poučková, P.; Škvor, J.; Gotte, G.; Vottariello, F.; Slavík, Tomáš; Matoušek, Josef; Laurents, D. V.; Libonati, M.; Souček, J.

    2006-01-01

    Roč. 53, č. 1 (2006), s. 79-85 ISSN 0028-2685 R&D Projects: GA ČR GA523/04/0755; GA MZd NR8233 Grant - others:Spanish Ministerio de Ciencia y Technologia BQU2003-05227 Institutional research plan: CEZ:AV0Z50450515 Keywords : RNase A oligomers * polyethylene glycol conjugates * anti-tumour activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.247, year: 2006

  10. Virtual Screening Models for Prediction of HIV-1 RT Associated RNase H Inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Kongsted, Jacob

    2013-01-01

    The increasing resistance to current therapeutic agents for HIV drug regiment remains a major problem for effective acquired immune deficiency syndrome (AIDS) therapy. Many potential inhibitors have today been developed which inhibits key cellular pathways in the HIV cycle. Inhibition of HIV-1...... databases. The methods used here include machine-learning algorithms (e.g. support vector machine, random forest and kappa nearest neighbor), shape similarity (rapid overlay of chemical structures), pharmacophore, molecular interaction fields-based fingerprints for ligands and protein (FLAP) and flexible...... for identifying structurally diverse and selective RNase H inhibitors from large chemical databases. In addition, pharmacophore models suggest that the inter-distance between hydrogen bond acceptors play a key role in inhibition of the RNase H domain through metal chelation....

  11. Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog

    Energy Technology Data Exchange (ETDEWEB)

    Volkov, Oleg A.; Kinch, Lisa; Ariagno, Carson; Deng, Xiaoyi; Zhong, Shihua; Grishin, Nick; Tomchick, Diana R.; Chen, Zhe; Phillips, Margaret A.

    2016-12-15

    Catalytically inactive enzyme paralogs occur in many genomes. Some regulate their active counterparts but the structural principles of this regulation remain largely unknown. We report X-ray structures ofTrypanosoma brucei S-adenosylmethionine decarboxylase alone and in functional complex with its catalytically dead paralogous partner, prozyme. We show monomericTbAdoMetDC is inactive because of autoinhibition by its N-terminal sequence. Heterodimerization with prozyme displaces this sequence from the active site through a complex mechanism involving acis-to-transproline isomerization, reorganization of a β-sheet, and insertion of the N-terminal α-helix into the heterodimer interface, leading to enzyme activation. We propose that the evolution of this intricate regulatory mechanism was facilitated by the acquisition of the dimerization domain, a single step that can in principle account for the divergence of regulatory schemes in the AdoMetDC enzyme family. These studies elucidate an allosteric mechanism in an enzyme and a plausible scheme by which such complex cooperativity evolved.

  12. GAMETOPHYTE DEFECTIVE 1, a putative subunit of RNases P/MRP, is essential for female gametogenesis and male competence in Arabidopsis.

    Science.gov (United States)

    Wang, Si-Qi; Shi, Dong-Qiao; Long, Yan-Ping; Liu, Jie; Yang, Wei-Cai

    2012-01-01

    RNA biogenesis, including biosynthesis and maturation of rRNA, tRNA and mRNA, is a fundamental process that is critical for cell growth, division and differentiation. Previous studies showed that mutations in components involved in RNA biogenesis resulted in abnormalities in gametophyte and leaf development in Arabidopsis. In eukaryotes, RNases P/MRP (RNase mitochondrial RNA processing) are important ribonucleases that are responsible for processing of tRNA, and transcription of small non-coding RNAs. Here we report that Gametophyte Defective 1 (GAF1), a gene encoding a predicted protein subunit of RNases P/MRP, AtRPP30, plays a role in female gametophyte development and male competence. Embryo sacs were arrested at stages ranging from FG1 to FG7 in gaf1 mutant, suggesting that the progression of the gametophytic division during female gametogenesis was impaired in gaf1 mutant. In contrast, pollen development was not affected in gaf1. However, the fitness of the mutant pollen tube was weaker than that of the wild-type, leading to reduced transmission through the male gametes. GAF1 is featured as a typical RPP30 domain protein and interacts physically with AtPOP5, a homologue of RNases P/MRP subunit POP5 of yeast. Together, our data suggest that components of the RNases P/MRP family, such as RPP30, play important roles in gametophyte development and function in plants.

  13. Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals.

    Science.gov (United States)

    Ngcapu, Sinaye; Theys, Kristof; Libin, Pieter; Marconi, Vincent C; Sunpath, Henry; Ndung'u, Thumbi; Gordon, Michelle L

    2017-11-08

    The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher's exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation.

  14. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

    Directory of Open Access Journals (Sweden)

    Alejandra eBernardini

    2015-10-01

    Full Text Available Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained S. maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457.. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

  15. RNase III-Binding-mRNAs Revealed Novel Complementary Transcripts in Streptomyces

    Czech Academy of Sciences Publication Activity Database

    Šetinová, D.; Šmídová, K.; Pohl, P.; Music, I.; Bobek, Jan

    2018-01-01

    Roč. 8, JAN 15 2018 (2018), č. článku 2693. ISSN 1664-302X R&D Projects: GA MŠk(CZ) LM2015055 Institutional support: RVO:61388971 Keywords : cis-antisense RNA * RNase III * Streptomyces Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.076, year: 2016

  16. Differential strengths of selection on S-RNases from Physalis and Solanum (Solanaceae

    Directory of Open Access Journals (Sweden)

    Kohn Joshua R

    2011-08-01

    Full Text Available Abstract Background The S-RNases of the Solanaceae are highly polymorphic self-incompatibility (S- alleles subject to strong balancing selection. Relatively recent diversification of S-alleles has occurred in the genus Physalis following a historical restriction of S-allele diversity. In contrast, the genus Solanum did not undergo a restriction of S-locus diversity and its S-alleles are generally much older. Because recovery from reduced S-locus diversity should involve increased selection, we employ a statistical framework to ask whether S-locus selection intensities are higher in Physalis than Solanum. Because different S-RNase lineages diversify in Physalis and Solanum, we also ask whether different sites are under selection in different lineages. Results Maximum-likelihood and Bayesian coalescent methods found higher intensities of selection and more sites under significant positive selection in the 48 Physalis S-RNase alleles than the 49 from Solanum. Highest posterior densities of dN/dS (ω estimates show that the strength of selection is greater for Physalis at 36 codons. A nested maximum likelihood method was more conservative, but still found 16 sites with greater selection in Physalis. Neither method found any codons under significantly greater selection in Solanum. A random effects likelihood method that examines data from both taxa jointly confirmed higher selection intensities in Physalis, but did not find different proportions of sites under selection in the two datasets. The greatest differences in strengths of selection were found in the most variable regions of the S-RNases, as expected if these regions encode self-recognition specificities. Clade-specific likelihood models indicated some codons were under greater selection in background Solanum lineages than in specific lineages of Physalis implying that selection on sites may differ among lineages. Conclusions Likelihood and Bayesian methods provide a statistical approach to

  17. Molecular mechanism of the S-RNase-based gametophytic self-incompatibility in fruit trees of Rosaceae.

    Science.gov (United States)

    Sassa, Hidenori

    2016-01-01

    Self-incompatibility (SI) is a major obstacle for stable fruit production in fruit trees of Rosaceae. SI of Rosaceae is controlled by the S locus on which at least two genes, pistil S and pollen S, are located. The product of the pistil S gene is a polymorphic and extracellular ribonuclease, called S-RNase, while that of the pollen S gene is a protein containing the F-box motif, SFB (S haplotype-specific F-box protein)/SFBB (S locus F-box brothers). Recent studies suggested that SI of Rosaceae includes two different systems, i.e., Prunus of tribe Amygdaleae exhibits a self-recognition system in which its SFB recognizes self-S-RNase, while tribe Pyreae (Pyrus and Malus) shows a non-self-recognition system in which many SFBB proteins are involved in SI, each recognizing subset of non-self-S-RNases. Further biochemical and biological characterization of the S locus genes, as well as other genes required for SI not located at the S locus, will help our understanding of the molecular mechanisms, origin, and evolution of SI of Rosaceae, and may provide the basis for breeding of self-compatible fruit tree cultivars.

  18. GAMETOPHYTE DEFECTIVE 1, a putative subunit of RNases P/MRP, is essential for female gametogenesis and male competence in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Si-Qi Wang

    Full Text Available RNA biogenesis, including biosynthesis and maturation of rRNA, tRNA and mRNA, is a fundamental process that is critical for cell growth, division and differentiation. Previous studies showed that mutations in components involved in RNA biogenesis resulted in abnormalities in gametophyte and leaf development in Arabidopsis. In eukaryotes, RNases P/MRP (RNase mitochondrial RNA processing are important ribonucleases that are responsible for processing of tRNA, and transcription of small non-coding RNAs. Here we report that Gametophyte Defective 1 (GAF1, a gene encoding a predicted protein subunit of RNases P/MRP, AtRPP30, plays a role in female gametophyte development and male competence. Embryo sacs were arrested at stages ranging from FG1 to FG7 in gaf1 mutant, suggesting that the progression of the gametophytic division during female gametogenesis was impaired in gaf1 mutant. In contrast, pollen development was not affected in gaf1. However, the fitness of the mutant pollen tube was weaker than that of the wild-type, leading to reduced transmission through the male gametes. GAF1 is featured as a typical RPP30 domain protein and interacts physically with AtPOP5, a homologue of RNases P/MRP subunit POP5 of yeast. Together, our data suggest that components of the RNases P/MRP family, such as RPP30, play important roles in gametophyte development and function in plants.

  19. The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca(2+) and Mg(2+) dependent-DNase activity and antifungal action on Moniliophthora perniciosa.

    Science.gov (United States)

    Pereira Menezes, Sara; de Andrade Silva, Edson Mario; Matos Lima, Eline; Oliveira de Sousa, Aurizângela; Silva Andrade, Bruno; Santos Lima Lemos, Livia; Peres Gramacho, Karina; da Silva Gesteira, Abelmon; Pirovani, Carlos Priminho; Micheli, Fabienne

    2014-06-11

    The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively.

  20. The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca2+ and Mg2+ dependent-DNase activity and antifungal action on Moniliophthora perniciosa

    Science.gov (United States)

    2014-01-01

    Background The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. Results TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. Conclusion To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively. PMID:24920373

  1. Evolutionary patterns at the RNase based gametophytic self - incompatibility system in two divergent Rosaceae groups (Maloideae and Prunus).

    Science.gov (United States)

    Vieira, Jorge; Ferreira, Pedro G; Aguiar, Bruno; Fonseca, Nuno A; Vieira, Cristina P

    2010-06-28

    Within Rosaceae, the RNase based gametophytic self-incompatibility (GSI) system has been studied at the molecular level in Maloideae and Prunus species that have been diverging for, at least, 32 million years. In order to understand RNase based GSI evolution within this family, comparative studies must be performed, using similar methodologies. It is here shown that many features are shared between the two species groups such as levels of recombination at the S-RNase (the S-pistil component) gene, and the rate at which new specificities arise. Nevertheless, important differences are found regarding the number of ancestral lineages and the degree of specificity sharing between closely related species. In Maloideae, about 17% of the amino acid positions at the S-RNase protein are found to be positively selected, and they occupy about 30% of the exposed protein surface. Positively selected amino acid sites are shown to be located on either side of the active site cleft, an observation that is compatible with current models of specificity determination. At positively selected amino acid sites, non-conservative changes are almost as frequent as conservative changes. There is no evidence that at these sites the most drastic amino acid changes may be more strongly selected. Many similarities are found between the GSI system of Prunus and Maloideae that are compatible with the single origin hypothesis for RNase based GSI. The presence of common features such as the location of positively selected amino acid sites and lysine residues that may be important for ubiquitylation, raise a number of issues that, in principle, can be experimentally addressed in Maloideae. Nevertheless, there are also many important differences between the two Rosaceae GSI systems. How such features changed during evolution remains a puzzling issue.

  2. Evolutionary patterns at the RNase based gametophytic self - incompatibility system in two divergent Rosaceae groups (Maloideae and Prunus

    Directory of Open Access Journals (Sweden)

    Fonseca Nuno A

    2010-06-01

    Full Text Available Abstract Background Within Rosaceae, the RNase based gametophytic self-incompatibility (GSI system has been studied at the molecular level in Maloideae and Prunus species that have been diverging for, at least, 32 million years. In order to understand RNase based GSI evolution within this family, comparative studies must be performed, using similar methodologies. Result It is here shown that many features are shared between the two species groups such as levels of recombination at the S-RNase (the S-pistil component gene, and the rate at which new specificities arise. Nevertheless, important differences are found regarding the number of ancestral lineages and the degree of specificity sharing between closely related species. In Maloideae, about 17% of the amino acid positions at the S-RNase protein are found to be positively selected, and they occupy about 30% of the exposed protein surface. Positively selected amino acid sites are shown to be located on either side of the active site cleft, an observation that is compatible with current models of specificity determination. At positively selected amino acid sites, non-conservative changes are almost as frequent as conservative changes. There is no evidence that at these sites the most drastic amino acid changes may be more strongly selected. Conclusions Many similarities are found between the GSI system of Prunus and Maloideae that are compatible with the single origin hypothesis for RNase based GSI. The presence of common features such as the location of positively selected amino acid sites and lysine residues that may be important for ubiquitylation, raise a number of issues that, in principle, can be experimentally addressed in Maloideae. Nevertheless, there are also many important differences between the two Rosaceae GSI systems. How such features changed during evolution remains a puzzling issue.

  3. Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI-treated patients.

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    André F A Santos

    Full Text Available BACKGROUND: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H is poorly understood. METHODS AND FINDINGS: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naïve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher's exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. CONCLUSIONS: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.

  4. RNase-assisted RNA chromatography

    Science.gov (United States)

    Michlewski, Gracjan; Cáceres, Javier F.

    2010-01-01

    RNA chromatography combined with mass spectrometry represents a widely used experimental approach to identify RNA-binding proteins that recognize specific RNA targets. An important drawback of most of these protocols is the high background due to direct or indirect nonspecific binding of cellular proteins to the beads. In many cases this can hamper the detection of individual proteins due to their low levels and/or comigration with contaminating proteins. Increasing the salt concentration during washing steps can reduce background, but at the cost of using less physiological salt concentrations and the likely loss of important RNA-binding proteins that are less stringently bound to a given RNA, as well as the disassembly of protein or ribonucleoprotein complexes. Here, we describe an improved RNA chromatography method that relies on the use of a cocktail of RNases in the elution step. This results in the release of proteins specifically associated with the RNA ligand and almost complete elimination of background noise, allowing a more sensitive and thorough detection of RNA-binding proteins recognizing a specific RNA transcript. PMID:20571124

  5. Conserved regions of ribonucleoprotein ribonuclease MRP are involved in interactions with its substrate.

    Science.gov (United States)

    Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2013-08-01

    Ribonuclease (RNase) MRP is a ubiquitous and essential site-specific eukaryotic endoribonuclease involved in the metabolism of a wide range of RNA molecules. RNase MRP is a ribonucleoprotein with a large catalytic RNA moiety that is closely related to the RNA component of RNase P, and multiple proteins, most of which are shared with RNase P. Here, we report the results of an ultraviolet-cross-linking analysis of interactions between a photoreactive RNase MRP substrate and the Saccharomyces cerevisiae RNase MRP holoenzyme. The results show that the substrate interacts with phylogenetically conserved RNA elements universally found in all enzymes of the RNase P/MRP family, as well as with a phylogenetically conserved RNA region that is unique to RNase MRP, and demonstrate that four RNase MRP protein components, all shared with RNase P, interact with the substrate. Implications for the structural organization of RNase MRP and the roles of its components are discussed.

  6. Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway.

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    Valéryane Dupuis-Maurin

    Full Text Available Deregulated expression of oncogenes or transcription factors such as specificity protein 1 (Sp1 is observed in many human cancers and plays a role in tumor maintenance. Paradoxically in untransformed cells, Sp1 overexpression induces late apoptosis but the early intrinsic response is poorly characterized. In the present work, we studied increased Sp1 level consequences in untransformed cells and showed that it turns on an early innate immune transcriptome. Sp1 overexpression does not activate known cellular stress pathways such as DNA damage response or endoplasmic reticulum stress, but induces the activation of the OAS-RNase L pathway and the generation of small self-RNAs, leading to the upregulation of genes of the antiviral RIG-I pathway at the transcriptional and translational levels. Finally, Sp1-induced intrinsic innate immune response leads to the production of the chemokine CXCL4 and to the recruitment of inflammatory cells in vitro and in vivo. Altogether our results showed that increased Sp1 level in untransformed cells constitutes a novel danger signal sensed by the OAS-RNase L axis leading to the activation of the RIG-I pathway. These results suggested that the OAS-RNase L-RIG-I pathway may be activated in sterile condition in absence of pathogen.

  7. Lack of S-RNase-Based Gametophytic Self-Incompatibility in Orchids Suggests That This System Evolved after the Monocot-Eudicot Split

    Directory of Open Access Journals (Sweden)

    Shan-Ce Niu

    2017-06-01

    Full Text Available Self-incompatibility (SI is found in approximately 40% of flowering plant species and at least 100 families. Although orchids belong to the largest angiosperm family, only 10% of orchid species present SI and have gametophytic SI (GSI. Furthermore, a majority (72% of Dendrobium species, which constitute one of the largest Orchidaceae genera, show SI and have GSI. However, nothing is known about the molecular mechanism of GSI. The S-determinants of GSI have been well characterized at the molecular level in Solanaceae, Rosaceae, and Plantaginaceae, which use an S-ribonuclease (S-RNase-based system. Here, we investigate the hypothesis that Orchidaceae uses a similar S-RNase to those described in Rosaceae, Solanaceae, and Plantaginaceae SI species. In this study, two SI species (Dendrobium longicornu and D. chrysanthum were identified using fluorescence microscopy. Then, the S-RNase- and SLF-interacting SKP1-like1 (SSK1-like genes present in their transcriptomes and the genomes of Phalaenopsis equestris, D. catenatum, Vanilla shenzhenica, and Apostasia shenzhenica were investigated. Sequence, phylogenetic, and tissue-specific expression analyses revealed that none of the genes identified was an S-determinant, suggesting that Orchidaceae might have a novel SI mechanism. The results also suggested that RNase-based GSI might have evolved after the split of monocotyledons (monocots and dicotyledons (dicots but before the split of Asteridae and Rosidae. This is also the first study to investigate S-RNase-based GSI in monocots. However, studies on gene identification, differential expression, and segregation analyses in controlled crosses are needed to further evaluate the genes with high expression levels in GSI tissues.

  8. Arabidopsis RNASE THREE LIKE2 Modulates the Expression of Protein-Coding Genes via 24-Nucleotide Small Interfering RNA-Directed DNA Methylation.

    Science.gov (United States)

    Elvira-Matelot, Emilie; Hachet, Mélanie; Shamandi, Nahid; Comella, Pascale; Sáez-Vásquez, Julio; Zytnicki, Matthias; Vaucheret, Hervé

    2016-02-01

    RNaseIII enzymes catalyze the cleavage of double-stranded RNA (dsRNA) and have diverse functions in RNA maturation. Arabidopsis thaliana RNASE THREE LIKE2 (RTL2), which carries one RNaseIII and two dsRNA binding (DRB) domains, is a unique Arabidopsis RNaseIII enzyme resembling the budding yeast small interfering RNA (siRNA)-producing Dcr1 enzyme. Here, we show that RTL2 modulates the production of a subset of small RNAs and that this activity depends on both its RNaseIII and DRB domains. However, the mode of action of RTL2 differs from that of Dcr1. Whereas Dcr1 directly cleaves dsRNAs into 23-nucleotide siRNAs, RTL2 likely cleaves dsRNAs into longer molecules, which are subsequently processed into small RNAs by the DICER-LIKE enzymes. Depending on the dsRNA considered, RTL2-mediated maturation either improves (RTL2-dependent loci) or reduces (RTL2-sensitive loci) the production of small RNAs. Because the vast majority of RTL2-regulated loci correspond to transposons and intergenic regions producing 24-nucleotide siRNAs that guide DNA methylation, RTL2 depletion modifies DNA methylation in these regions. Nevertheless, 13% of RTL2-regulated loci correspond to protein-coding genes. We show that changes in 24-nucleotide siRNA levels also affect DNA methylation levels at such loci and inversely correlate with mRNA steady state levels, thus implicating RTL2 in the regulation of protein-coding gene expression. © 2016 American Society of Plant Biologists. All rights reserved.

  9. Social background, bullying, and physical inactivity

    DEFF Research Database (Denmark)

    Henriksen, P W; Rayce, S B; Melkevik, O

    2016-01-01

    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...... 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...

  10. Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing.

    Science.gov (United States)

    Goldfarb, Katherine C; Cech, Thomas R

    2017-01-01

    MRP RNA is an abundant, essential noncoding RNA whose functions have been proposed in yeast but are incompletely understood in humans. Mutations in the genomic locus for MRP RNA cause pleiotropic human diseases, including cartilage hair hypoplasia (CHH). Here we applied CRISPR-Cas9 genome editing to disrupt the endogenous human MRP RNA locus, thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the majority of cells. The resulting accumulation of ribosomal RNA (rRNA) precursor-analyzed by RNA fluorescent in situ hybridization (FISH), Northern blots, and RNA sequencing-implicates MRP RNA in pre-rRNA processing. Amelioration of pre-rRNA imbalance is achieved through rescue of MRP RNA levels by ectopic expression. Furthermore, affinity-purified MRP ribonucleoprotein (RNP) from HeLa cells cleaves the human pre-rRNA in vitro at at least one site used in cells, while RNP isolated from cells with CRISPR-edited MRP loci loses this activity, and ectopic MRP RNA expression restores cleavage activity. Thus, a role for RNase MRP in human pre-rRNA processing is established. As demonstrated here, targeted CRISPR disruption is a valuable tool for functional studies of essential noncoding RNAs that are resistant to RNAi and RNase H-based degradation. © 2017 Goldfarb and Cech; Published by Cold Spring Harbor Laboratory Press.

  11. Pollen-expressed F-box gene family and mechanism of S-RNase-based gametophytic self-incompatibility (GSI) in Rosaceae.

    Science.gov (United States)

    Sassa, Hidenori; Kakui, Hiroyuki; Minamikawa, Mai

    2010-03-01

    Many species of Rosaceae, Solanaceae, and Plantaginaceae exhibit S-RNase-based self-incompatibility (SI) in which pistil-part specificity is controlled by S locus-encoded ribonuclease (S-RNase). Although recent findings revealed that S locus-encoded F-box protein, SLF/SFB, determines pollen-part specificity, how these pistil- and pollen-part S locus products interact in vivo and elicit the SI reaction is largely unclear. Furthermore, genetic studies suggested that pollen S function can differ among species. In Solanaceae and the rosaceous subfamily Maloideae (e.g., apple and pear), the coexistence of two different pollen S alleles in a pollen breaks down SI of the pollen, a phenomenon known as competitive interaction. However, competitive interaction seems not to occur in the subfamily Prunoideae (e.g., cherry and almond) of Rosaceae. Furthermore, the effect of the deletion of pollen S seems to vary among taxa. This review focuses on the potential differences in pollen-part function between subfamilies of Rosaceae, Maloideae, and Prunoideae, and discusses implications for the mechanistic divergence of the S-RNase-based SI.

  12. Suppression of NYVAC Infection in HeLa Cells Requires RNase L but Is Independent of Protein Kinase R Activity

    Science.gov (United States)

    Fernández-Escobar, Mercedes; Nájera, José Luis; Baldanta, Sara; Rodriguez, Dolores; Way, Michael; Esteban, Mariano

    2015-01-01

    Protein kinase R (PKR) and RNase L are host cell components that function to contain viral spread after infections. In this study, we analyzed the role of both proteins in the abortive infection of human HeLa cells with the poxvirus strain NYVAC, for which an inhibition of viral A27L and B5R gene expression is described. Specifically, the translation of these viral genes is independent of PKR activation, but their expression is dependent on the RNase L activity. PMID:26656695

  13. The economic cost of physical inactivity in China.

    Science.gov (United States)

    Zhang, Juan; Chaaban, Jad

    2013-01-01

    To estimate the total economic burden of physical inactivity in China. The costs of physical inactivity combine the medical and non-medical costs of five major Non Communicable Diseases (NCDs) associated with inactivity. The national data from the Chinese Behavioral Risk Factors Surveillance Surveys (2007) and the National Health Service Survey (2003) are used to compute population attributable risks (PARs) of inactivity for each major NCD. Costs specific to inactivity are obtained by multiplying each disease costs by the PAR for each NCD, by incorporating the inactivity effects through overweight and obesity. Physical inactivity contributes between 12% and 19% to the risks associated with the five major NCDs in China, namely coronary heart disease, stroke, hypertension, cancer, and type 2 diabetes. Physical inactivity is imposing a substantial economic burden on the country, as it is responsible alone for more than 15% of the medical and non-medical yearly costs of the main NCDs in the country. The high economic burden of physical inactivity implies the need to develop more programs and interventions that address this modifiable behavioral risk, in order to curb the rising NCDs epidemic in China. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and RDDP functions.

    Science.gov (United States)

    Corona, Angela; Onnis, Valentina; Deplano, Alessandro; Bianco, Giulia; Demurtas, Monica; Distinto, Simona; Cheng, Yung-Chi; Alcaro, Stefano; Esposito, Francesca; Tramontano, Enzo

    2017-08-31

    In the continuous effort to identify new HIV-1 inhibitors endowed with innovative mechanisms, the dual inhibition of different viral functions would provide a significant advantage against drug-resistant variants. The HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) is the only viral-encoded enzymatic activity that still lacks an efficient inhibitor. We synthesized a library of 3,5-diamino-N-aryl-1H-pyrazole-4-carbothioamide and 4-amino-5-benzoyl-N-phenyl-2-(substituted-amino)-1H-pyrrole-3-carbothioamide derivatives and tested them against RNase H activity. We identified the pyrazolecarbothioamide derivative A15, able to inhibit viral replication and both RNase H and RNA-dependent DNA polymerase (RDDP) RT-associated activities in the low micromolar range. Docking simulations hypothesized its binding to two RT pockets. Site-directed mutagenesis experiments showed that, with respect to wt RT, V108A substitution strongly reduced A15 IC50 values (12.6-fold for RNase H inhibition and 4.7-fold for RDDP), while substitution A502F caused a 9.0-fold increase in its IC50 value for RNase H, not affecting the RDDP inhibition, reinforcing the hypothesis of a dual-site inhibition. Moreover, A15 retained good inhibition potency against three non-nucleoside RT inhibitor (NNRTI)-resistant enzymes, confirming a mode of action unrelated to NNRTIs and suggesting its potential as a lead compound for development of new HIV-1 RT dual inhibitors active against drug-resistant viruses. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Health Risks of an Inactive Lifestyle

    Science.gov (United States)

    ... develop a hormonal imbalance What are the health risks of an inactive lifestyle? Having an inactive lifestyle ... By not getting regular exercise, you raise your risk of Obesity Heart diseases, including coronary artery disease ...

  16. Structural changes of human RNase L upon homodimerization investigated by Raman spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Kříž, M.; Snášel, Jan; Kopecký, V. Jr.; Páv, Ondřej; Rosenberg, Ivan; Štepánek, J.

    2012-01-01

    Roč. 1824, č. 9 (2012), s. 1039-1044 ISSN 1570-9639 R&D Projects: GA ČR GA202/09/0193; GA AV ČR KAN200520801 Grant - others:GA AV ČR(CZ) KJB101120805 Program:KJ Institutional support: RVO:61388963 Keywords : RNase L * Raman spectroscopy * DCDR spectroscopy * phosphonate oligoadenylate * ligand binding Subject RIV: BO - Biophysics Impact factor: 3.733, year: 2012

  17. Bovine brain ribonuclease is the functional homolog of human ribonuclease 1.

    Science.gov (United States)

    Eller, Chelcie H; Lomax, Jo E; Raines, Ronald T

    2014-09-19

    Mounting evidence suggests that human pancreatic ribonuclease (RNase 1) plays important roles in vivo, ranging from regulating blood clotting and inflammation to directly counteracting tumorigenic cells. Understanding these putative roles has been pursued with continual comparisons of human RNase 1 to bovine RNase A, an enzyme that appears to function primarily in the ruminant gut. Our results imply a different physiology for human RNase 1. We demonstrate distinct functional differences between human RNase 1 and bovine RNase A. Moreover, we characterize another RNase 1 homolog, bovine brain ribonuclease, and find pronounced similarities between that enzyme and human RNase 1. We report that human RNase 1 and bovine brain ribonuclease share high catalytic activity against double-stranded RNA substrates, a rare quality among ribonucleases. Both human RNase 1 and bovine brain RNase are readily endocytosed by mammalian cells, aided by tight interactions with cell surface glycans. Finally, we show that both human RNase 1 and bovine brain RNase are secreted from endothelial cells in a regulated manner, implying a potential role in vascular homeostasis. Our results suggest that brain ribonuclease, not RNase A, is the true bovine homolog of human RNase 1, and provide fundamental insight into the ancestral roles and functional adaptations of RNase 1 in mammals. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Socioeconomic Determinants of Physical Inactivity among Japanese Workers

    OpenAIRE

    Kumagai, Narimasa

    2012-01-01

    Background: Half of Japanese workers are physically inactive, but there are no studies on the relation between the leisure-time physical inactivity of Japanese workers and their socioeconomic status. The proportion of female workers who are physically inactive has been larger than that of male workers. Objectives: Using micro-data from nationwide surveys in Japan, this study explored the gender differences in socioeconomic determinants of leisure-time physical inactivity. Methods: We first es...

  19. Mapping of Mitochondrial RNA-Protein Interactions by Digital RNase Footprinting

    Directory of Open Access Journals (Sweden)

    Ganqiang Liu

    2013-11-01

    Full Text Available Human mitochondrial DNA is transcribed as long polycistronic transcripts that encompass each strand of the genome and are processed subsequently into mature mRNAs, tRNAs, and rRNAs, necessitating widespread posttranscriptional regulation. Here, we establish methods for massively parallel sequencing and analyses of RNase-accessible regions of human mitochondrial RNA and thereby identify specific regions within mitochondrial transcripts that are bound by proteins. This approach provides a range of insights into the contribution of RNA-binding proteins to the regulation of mitochondrial gene expression.

  20. Evolution of the RNase P RNA structural domain in Leptospira spp.

    Science.gov (United States)

    Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A; Devendran, Ajay; Hartskeerl, Rudy A; Raj, Stephen M L

    2014-12-01

    We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along with sequences determined from 8 reference strains were examined to fathom strain specific structural differences present in leptospiral RPR. Sequence variations in the RPR gene impacted on the configuration of loops, stems and bulges found in the RPR highlighting species and strain specific structural motifs. In vitro transcribed leptospiral RPR ribozymes are demonstrated to process pre-tRNA into mature tRNA in consonance with the positioning of Leptospira in the taxonomic domain of bacteria. RPR sequence datasets used to construct a phylogenetic tree exemplified the segregation of strains into their respective lineages with a (re)speciation of strain SH 9 to Leptospira borgpetersenii, strains Fiocruz LV 3954 and Fiocruz LV 4135 to Leptospira santarosai, strain CBC 613 to Leptospira kirschneri and strain HAI 1536 to Leptospira noguchii. Furthermore, it allowed characterization of an isolate P2653, presumptively characterized as either serovar Hebdomadis, Kremastos or Longnan to Leptospira weilii, serovar Longnan. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  1. 5-Hydroxypyrido[2,3-b]pyrazin-6(5H)-one derivatives as novel dual inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H and integrase.

    Science.gov (United States)

    Sun, Lin; Gao, Ping; Dong, Guanyu; Zhang, Xujie; Cheng, Xiqiang; Ding, Xiao; Wang, Xueshun; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Menéndez-Arias, Luis; Zhan, Peng; Liu, Xinyong

    2018-06-18

    We reported herein the design, synthesis and biological evaluation of a series of 5-hydroxypyrido[2,3-b]pyrazin-6(5H)-one derivatives as HIV-1 reverse transcriptase (RT) ribonuclease H (RNase H) inhibitors using a privileged structure-guided scaffold refining strategy. In view of the similarities between the pharmacophore model of RNase H and integrase (IN) inhibitors as well as their catalytic sites, we also performed IN inhibition assays. Notably, the majority of these derivatives inhibited RNase H and IN at micromolar concentrations. Among them, compound 7a exhibited similar inhibitory activity against RNase H and IN (IC 50 RNase H  = 1.77 μM, IC 50 IN  = 1.18 μM, ratio = 1.50). To the best of our knowledge, this is the first reported dual HIV-1 RNase H-IN inhibitor based on a 5-hydroxypyrido[2,3-b]pyrazin-6(5H)-one structure. Molecular modeling has been used to predict the binding mode of 7a in complex with the catalytic cores of HIV-1 RNase H and IN. Taken together these results strongly support the feasibility of developing HIV-1 dual inhibitors from analog-based optimization of divalent metal ion chelators. Recently, the identification of dual inhibitors proved to be a highly effective strategy for novel antivirals discovery. Therefore, these compounds appear to be useful leads that can be further modified to develop more valuable anti-HIV-1 molecules with suitable drug profiles. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  2. Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Quan, Chao; Khanova, Elena; Krasilnikov, Andrey S

    2010-02-17

    Ribonuclease (RNase) P is a site-specific endoribonuclease found in all kingdoms of life. Typical RNase P consists of a catalytic RNA component and a protein moiety. In the eukaryotes, the RNase P lineage has split into two, giving rise to a closely related enzyme, RNase MRP, which has similar components but has evolved to have different specificities. The eukaryotic RNases P/MRP have acquired an essential helix-loop-helix protein-binding RNA domain P3 that has an important function in eukaryotic enzymes and distinguishes them from bacterial and archaeal RNases P. Here, we present a crystal structure of the P3 RNA domain from Saccharomyces cerevisiae RNase MRP in a complex with RNase P/MRP proteins Pop6 and Pop7 solved to 2.7 A. The structure suggests similar structural organization of the P3 RNA domains in RNases P/MRP and possible functions of the P3 domains and proteins bound to them in the stabilization of the holoenzymes' structures as well as in interactions with substrates. It provides the first insight into the structural organization of the eukaryotic enzymes of the RNase P/MRP family.

  3. A Single RNaseIII Domain Protein from Entamoeba histolytica Has dsRNA Cleavage Activity and Can Help Mediate RNAi Gene Silencing in a Heterologous System.

    Science.gov (United States)

    Pompey, Justine M; Foda, Bardees; Singh, Upinder

    2015-01-01

    Dicer enzymes process double-stranded RNA (dsRNA) into small RNAs that target gene silencing through the RNA interference (RNAi) pathway. Dicer enzymes are complex, multi-domain RNaseIII proteins, however structural minimalism of this protein has recently emerged in parasitic and fungal systems. The most minimal Dicer, Saccharomyces castellii Dicer1, has a single RNaseIII domain and two double stranded RNA binding domains. In the protozoan parasite Entamoeba histolytica 27nt small RNAs are abundant and mediate silencing, yet no canonical Dicer enzyme has been identified. Although EhRNaseIII does not exhibit robust dsRNA cleavage in vitro, it can process dsRNA in the RNAi-negative background of Saccharomyces cerevisiae, and in conjunction with S. castellii Argonaute1 can partially reconstitute the RNAi pathway. Thus, although EhRNaseIII lacks the domain architecture of canonical or minimal Dicer enzymes, it has dsRNA processing activity that contributes to gene silencing via RNAi. Our data advance the understanding of small RNA biogenesis in Entamoeba as well as broaden the spectrum of non-canonical Dicer enzymes that contribute to the RNAi pathway.

  4. A Single RNaseIII Domain Protein from Entamoeba histolytica Has dsRNA Cleavage Activity and Can Help Mediate RNAi Gene Silencing in a Heterologous System.

    Directory of Open Access Journals (Sweden)

    Justine M Pompey

    Full Text Available Dicer enzymes process double-stranded RNA (dsRNA into small RNAs that target gene silencing through the RNA interference (RNAi pathway. Dicer enzymes are complex, multi-domain RNaseIII proteins, however structural minimalism of this protein has recently emerged in parasitic and fungal systems. The most minimal Dicer, Saccharomyces castellii Dicer1, has a single RNaseIII domain and two double stranded RNA binding domains. In the protozoan parasite Entamoeba histolytica 27nt small RNAs are abundant and mediate silencing, yet no canonical Dicer enzyme has been identified. Although EhRNaseIII does not exhibit robust dsRNA cleavage in vitro, it can process dsRNA in the RNAi-negative background of Saccharomyces cerevisiae, and in conjunction with S. castellii Argonaute1 can partially reconstitute the RNAi pathway. Thus, although EhRNaseIII lacks the domain architecture of canonical or minimal Dicer enzymes, it has dsRNA processing activity that contributes to gene silencing via RNAi. Our data advance the understanding of small RNA biogenesis in Entamoeba as well as broaden the spectrum of non-canonical Dicer enzymes that contribute to the RNAi pathway.

  5. Kinetics and Thermodynamics of DNA Processing by Wild Type DNA-Glycosylase Endo III and Its Catalytically Inactive Mutant Forms

    Directory of Open Access Journals (Sweden)

    Olga A. Kladova

    2018-03-01

    Full Text Available Endonuclease III (Endo III or Nth is one of the key enzymes responsible for initiating the base excision repair of oxidized or reduced pyrimidine bases in DNA. In this study, a thermodynamic analysis of structural rearrangements of the specific and nonspecific DNA-duplexes during their interaction with Endo III is performed based on stopped-flow kinetic data. 1,3-diaza-2-oxophenoxazine (tCO, a fluorescent analog of the natural nucleobase cytosine, is used to record multistep DNA binding and lesion recognition within a temperature range (5–37 °C. Standard Gibbs energy, enthalpy, and entropy of the specific steps are derived from kinetic data using Van’t Hoff plots. The data suggest that enthalpy-driven exothermic 5,6-dihydrouracil (DHU recognition and desolvation-accompanied entropy-driven adjustment of the enzyme–substrate complex into a catalytically active state play equally important parts in the overall process. The roles of catalytically significant amino acids Lys120 and Asp138 in the DNA lesion recognition and catalysis are identified. Lys120 participates not only in the catalytic steps but also in the processes of local duplex distortion, whereas substitution Asp138Ala leads to a complete loss of the ability of Endo III to distort a DNA double chain during enzyme–DNA complex formation.

  6. Physical inactivity and muscle oxidative capacity in humans

    DEFF Research Database (Denmark)

    Gram, Martin; Dahl, Rannvá; Dela, Flemming

    2014-01-01

    Physical inactivity is associated with a high prevalence of type 2 diabetes and is an independent predictor of mortality. It is possible that the detrimental effects of physical inactivity are mediated through a lack of adequate muscle oxidative capacity. This short review will cover the present...... literature on the effects of different models of inactivity on muscle oxidative capacity in humans. Effects of physical inactivity include decreased mitochondrial content, decreased activity of oxidative enzymes, changes in markers of oxidative stress and a decreased expression of genes and contents...... of proteins related to oxidative phosphorylation. With such a substantial down-regulation, it is likely that a range of adenosine triphosphate (ATP)-dependent pathways such as calcium signalling, respiratory capacity and apoptosis are affected by physical inactivity. However, this has not been investigated...

  7. The inaction effect in the psychology of regret.

    Science.gov (United States)

    Zeelenberg, Marcel; van de Bos, Kees; van Dijk, Eric; Pieters, Rik

    2002-03-01

    Previous research showed that decisions to act (i.e., actions) produce more regret than decisions not to act (i.e., inactions). This previous research focused on decisions made in isolation and ignored that decisions are often made in response to earlier outcomes. The authors show in 4 experiments that these prior outcomes may promote action and hence make inaction more abnormal. They manipulated information about a prior outcome. As hypothesized, when prior outcomes were positive or absent, people attributed more regret to action than to inaction. However, as predicted and counter to previous research, following negative prior outcomes, more regret was attributed to inaction, a finding that the authors label the inaction effect. Experiment 4, showing differential effects for regret and disappointment, demonstrates the need for emotion-specific predictions.

  8. Catalytic properties of lanthanide amide, imide and nitride formed by thermal degradation of liquid ammonia solutions of Eu and Yb metal

    International Nuclear Information System (INIS)

    Imamura, H.; Mizuno, K.; Ohishi, K.; Suda, E.; Kanda, K.; Sakata, Y.; Tsuchiya, S.

    1998-01-01

    The catalytic properties of lanthanide amide, imide and nitride prepared by the use of liquid ammonia solutions of lanthanide metals (Ln=Eu and Yb) were studied for catalytic hydrogenation. The reaction of Eu or Yb metal solutions in liquid ammonia with silica yielded SiO 2 -grafted lanthanide amide in the divalent state. The divalent amide showed catalytic activity for the selective hydrogenation of dienes and benzene. It was found that partial hydrogenation of benzene occurred with a very high selectivity for cyclohexene. Amides of calcium, strontium and barium were examined similarly in connection with catalytic studies on divalent amides. Imide and nitride, into which the lanthanide (Ln/AC) deposited by impregnation of active carbon (AC) with liquid ammonia solutions of lanthanide metals were converted thermally, were studied catalytically. It was concluded that imide or imide-like species generated during the thermal degradation of lanthanide amide to nitride were very active in the hydrogenation of ethene. Lanthanide nitride was virtually inactive, but the nitride highly dispersed on active carbon was activated when subjected to evacuation treatment above about 1000 K. (orig.)

  9. Physical inactivity and muscle oxidative capacity in humans.

    Science.gov (United States)

    Gram, Martin; Dahl, Rannvá; Dela, Flemming

    2014-01-01

    Physical inactivity is associated with a high prevalence of type 2 diabetes and is an independent predictor of mortality. It is possible that the detrimental effects of physical inactivity are mediated through a lack of adequate muscle oxidative capacity. This short review will cover the present literature on the effects of different models of inactivity on muscle oxidative capacity in humans. Effects of physical inactivity include decreased mitochondrial content, decreased activity of oxidative enzymes, changes in markers of oxidative stress and a decreased expression of genes and contents of proteins related to oxidative phosphorylation. With such a substantial down-regulation, it is likely that a range of adenosine triphosphate (ATP)-dependent pathways such as calcium signalling, respiratory capacity and apoptosis are affected by physical inactivity. However, this has not been investigated in humans, and further studies are required to substantiate this hypothesis, which could expand our knowledge of the potential link between lifestyle-related diseases and muscle oxidative capacity. Furthermore, even though a large body of literature reports the effect of physical training on muscle oxidative capacity, the adaptations that occur with physical inactivity may not always be opposite to that of physical training. Thus, it is concluded that studies on the effect of physical inactivity per se on muscle oxidative capacity in functional human skeletal muscle are warranted.

  10. Optimized bacterial expression and purification of the c-Src catalytic domain for solution NMR studies

    International Nuclear Information System (INIS)

    Piserchio, Andrea; Ghose, Ranajeet; Cowburn, David

    2009-01-01

    Progression of a host of human cancers is associated with elevated levels of expression and catalytic activity of the Src family of tyrosine kinases (SFKs), making them key therapeutic targets. Even with the availability of multiple crystal structures of active and inactive forms of the SFK catalytic domain (CD), a complete understanding of its catalytic regulation is unavailable. Also unavailable are atomic or near-atomic resolution information about their interactions, often weak or transient, with regulating phosphatases and downstream targets. Solution NMR, the biophysical method best suited to tackle this problem, was previously hindered by difficulties in bacterial expression and purification of sufficient quantities of soluble, properly folded protein for economically viable labeling with NMR-active isotopes. Through a choice of optimal constructs, co-expression with chaperones and optimization of the purification protocol, we have achieved the ability to bacterially produce large quantities of the isotopically-labeled CD of c-Src, the prototypical SFK, and of its activating Tyr-phosphorylated form. All constructs produce excellent spectra allowing solution NMR studies of this family in an efficient manner

  11. Inactive ingredient Search for Approved Drug Products

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final...

  12. On a accumulation of 131-I-RNase by ascites tumour cells of mice

    International Nuclear Information System (INIS)

    Sarrach, D.; Waldner, H.

    1976-01-01

    The accumulation of 131-I-labelled RNase by Ehrlich ascites tumour cells of mice was investigated in dependence on time, concentration, and pH. Kinetically a fast and a slow stage of reaction is distinguished. In both, the dependence on concentration is of the Langmuir type. Only the stage-I binding is reversibly diminished with increasing pH. Absorption due to electrostatic forces is suggested for this stae. (author)

  13. Tyrosyl-DNA Phosphodiesterase I Catalytic Mutants Reveal an Alternative Nucleophile That Can Catalyze Substrate Cleavage*

    Science.gov (United States)

    Comeaux, Evan Q.; Cuya, Selma M.; Kojima, Kyoko; Jafari, Nauzanene; Wanzeck, Keith C.; Mobley, James A.; Bjornsti, Mary-Ann; van Waardenburg, Robert C. A. M.

    2015-01-01

    Tyrosyl-DNA phosphodiesterase I (Tdp1) catalyzes the repair of 3′-DNA adducts, such as the 3′-phosphotyrosyl linkage of DNA topoisomerase I to DNA. Tdp1 contains two conserved catalytic histidines: a nucleophilic His (Hisnuc) that attacks DNA adducts to form a covalent 3′-phosphohistidyl intermediate and a general acid/base His (Hisgab), which resolves the Tdp1-DNA linkage. A Hisnuc to Ala mutant protein is reportedly inactive, whereas the autosomal recessive neurodegenerative disease SCAN1 has been attributed to the enhanced stability of the Tdp1-DNA intermediate induced by mutation of Hisgab to Arg. However, here we report that expression of the yeast HisnucAla (H182A) mutant actually induced topoisomerase I-dependent cytotoxicity and further enhanced the cytotoxicity of Tdp1 Hisgab mutants, including H432N and the SCAN1-related H432R. Moreover, the HisnucAla mutant was catalytically active in vitro, albeit at levels 85-fold less than that observed with wild type Tdp1. In contrast, the HisnucPhe mutant was catalytically inactive and suppressed Hisgab mutant-induced toxicity. These data suggest that the activity of another nucleophile when Hisnuc is replaced with residues containing a small side chain (Ala, Asn, and Gln), but not with a bulky side chain. Indeed, genetic, biochemical, and mass spectrometry analyses show that a highly conserved His, immediately N-terminal to Hisnuc, can act as a nucleophile to catalyze the formation of a covalent Tdp1-DNA intermediate. These findings suggest that the flexibility of Tdp1 active site residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl intermediates and provide the rationale for developing chemotherapeutics that stabilize the covalent Tdp1-DNA intermediate. PMID:25609251

  14. Vascular adaptation to physical inactivity in humans.

    NARCIS (Netherlands)

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

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

    Science.gov (United States)

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

    2018-01-01

    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.

  16. Mean field approximation for the kinetics of the selective catalytic reduction of NO by ammonia

    Energy Technology Data Exchange (ETDEWEB)

    Santos, M.; Bodanese, J.P. [Centro de Ensino Sao Jose, Universidade do Vale do Itajai (Brazil); S. Grandi, B.C. da [Departamento de Fisica, Universidade Federal de Santa Catarina, Florianopolis (Brazil)

    2007-04-15

    In this work we study a catalytic reaction model among three monomers in order to understand the chemical kinetics of the selective catalytic reduction of nitrogen oxide by ammonia (4NO+4NH{sub 3}+O{sub 2}{yields}4N{sub 2}+6H{sub 2}O). Our model takes into account the formation of the intermediate species in the global scheme of the reaction. In order to determine the dynamical behaviour of the model we used single site approximation method. In this approach we have observed that, depending on the values of the control parameters, the model presents an active or an inactive phase. In fact, the dynamical phase diagram of the model exhibits a first order line separating these two phases. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  17. Structural and functional basis for RNA cleavage by Ire1

    Directory of Open Access Journals (Sweden)

    Stroud Robert M

    2011-07-01

    Full Text Available Abstract Background The unfolded protein response (UPR controls the protein folding capacity of the endoplasmic reticulum (ER. Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis. Results This analysis and two new crystal structures suggest that Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general base pair contributing ≥ 7.6 kcal/mol and 1.4 kcal/mol to transition state stabilization, respectively, and asparagine N1057 and arginine R1056 for coordination of the scissile phosphate. Investigation of the stem-loop recognition revealed that additionally to the stem-loops derived from the classic Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave anticodon stem-loop (ASL of unmodified tRNAPhe, extending known substrate specificity of Ire1 RNase. Conclusions Our data define the catalytic center of Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently contains a separate catalytic apparatus for RNA cleavage, whereas two RNase subunits contribute to RNA stem-loop docking. Conservation of the key residues among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1 applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L.

  18. Shifting the Physical Inactivity Curve Worldwide by Closing the Gender Gap.

    Science.gov (United States)

    Mielke, Grégore I; da Silva, Inacio Crochemore M; Kolbe-Alexander, Tracy L; Brown, Wendy J

    2018-02-01

    The aims of this study were to (i) examine gender differences in physical inactivity in countries with different levels of Human Development Index (HDI); and (ii) assess whether small changes in the prevalence of inactivity in women could achieve the World Health Organization's (WHO) global inactivity target. Data on inactivity were extracted for 142 countries for the year 2010 from the WHO Data Repository. Data for HDI were obtained for the year 2010 from the United Nations Development Program. Absolute and relative gender differences were calculated for countries according to four HDI categories. The potential effects of increasing women's activity levels on achievement of the WHO physical inactivity target were computed. Overall inactivity prevalence was higher in women (27%) than in men (20%). Women were more inactive than men in all except eight countries. Absolute gender differences [median 7.5% (range -10.1 to 33.2)] did not vary by HDI category, but there was a small negative correlation between relative gender difference in inactivity and HDI (rho -0.19; p = 0.02), which was mostly influenced by three outlier countries with low HDI. A decrease in inactivity levels of 4.8% points among women across the world would achieve the WHO target of reducing global levels of inactivity by 10%. Gender differences in the prevalence of physical inactivity were highly variable, both within and across categories of HDI. Interventions which result in small changes in inactivity prevalence in women would achieve the 2025 WHO global target for inactivity, without any change to the prevalence in men.

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

    Science.gov (United States)

    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 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 neighborhood characteristics are needed to eliminate racial/ethnic disparities in adolescent inactivity.

  20. Obesity and Physical Inactivity in Rural America

    Science.gov (United States)

    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…

  1. Draft Whole-Genome Sequence of Bacillus altitudinis Strain B-388, a Producer of Extracellular RNase.

    Science.gov (United States)

    Shah Mahmud, Raihan; Ulyanova, Vera; Malanin, Sergey; Dudkina, Elena; Vershinina, Valentina; Ilinskaya, Olga

    2015-01-29

    Here, we present a draft genome sequence of Bacillus altitudinis strain B-388, including a putative plasmid. The strain was isolated from the intestine of Indian meal moth, a common pest of stored grains, and it is characterized by the production of extracellular RNase, similar to binase, which is of interest for comparative studies and biotechnology. Copyright © 2015 Shah Mahmud et al.

  2. Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.

    Science.gov (United States)

    Pinto Pereira, Snehal M; Li, Leah; Power, Chris

    2015-09-01

    Physical inactivity has a high prevalence and associated disease burden. A better understanding of influences on sustaining and changing inactive lifestyles is needed. We aimed to establish whether leisure time inactivity was stable in midadulthood and whether early life factors were associated with inactivity patterns. In the 1958 British birth cohort (n = 12,271), leisure time inactivity (frequency, less than once a week) assessed at 33 and 50 yr was categorized as "never inactive," "persistently inactive," "deteriorating," or "improving." Early life factors (birth to 16 yr) were categorized into three (physical, social, and behavioral) domains. Using multinomial logistic regression, we assessed associations with inactivity persistence and change of factors within each early life domain and the three domains combined with and without adjustment for adult factors. Inactivity prevalence was similar at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with age. In models adjusted for all domains simultaneously, factors associated with inactivity persistence versus never inactive were prepubertal stature (8% lower risk/height SD), poor hand control/coordination (17% higher risk/increase on four-point scale), cognition (16% lower/SD in ability) (physical); parental divorce (25% higher), class at birth (7% higher/reduction on four-point scale), minimal parental education (16% higher), household amenities (2% higher/increase in 19-point score (high = poor)) (social); and inactivity (22% higher/reduction in activity on four-point scale), low sports aptitude (47% higher), smoking (30% higher) (behavioral). All except stature, parental education, sports aptitude, and smoking were associated also with inactivity deterioration. Poor hand control/coordination was the only factor associated with improved status (13% lower/increase on four-point scale) versus persistently inactive. Adult leisure time inactivity is moderately stable. Early life factors are

  3. Variation in the Gender Gap in Inactive and Active Life Expectancy by the Definition of Inactivity Among Older Adults.

    Science.gov (United States)

    Malhotra, Rahul; Chan, Angelique; Ajay, Shweta; Ma, Stefan; Saito, Yasuhiko

    2016-10-01

    To assess variation in gender gap (female-male) in inactive life expectancy (IALE) and active life expectancy (ALE) by definition of inactivity. Inactivity, among older Singaporeans, was defined as follows: Scenario 1-health-related difficulty in activities of daily living (ADLs); Scenario 2-health-related difficulty in ADLs/instrumental ADLs (IADLs); Scenario 3-health-related difficulty in ADLs/IADLs or non-health-related non-performance of IADLs. Multistate life tables computed IALE and ALE at age 60, testing three hypotheses: In all scenarios, life expectancy, absolute and relative IALE, and absolute ALE are higher for females (Hypothesis 1 [H1]); gender gap in absolute and relative IALE expands, and in absolute ALE, it contracts in Scenario 2 versus 1 (Hypothesis 2 [H2]); gender gap in absolute and relative IALE decreases, and in absolute ALE, it increases in Scenario 3 versus 2 (Hypothesis 3 [H3]). H1 was supported in Scenarios 1 and 3 but not Scenario 2. Both H2 and H3 were supported. Definition of inactivity influences gender gap in IALE and ALE. © The Author(s) 2016.

  4. Regulation of 2-5A Dependent RNase at the Level of its Phosphorylation

    Science.gov (United States)

    1991-06-26

    extract as follows: 25 ul wheat germ extract 10 ul H2O 1 ul RNasin ribonuclease inhibitor (40 u/ml) 7 ul ImM amino acid mixture 1 ul IM...diacylglycerol (DAG) 2. TPA 3. Indolactam Figure 6. Chemical structure of: 1. H-7 (A kinase inhibitor) 2. okadaic acid (A phosphatase inhibitor) Figure 7...elevating agents: Forskolin and Cholera toxin Figure 17. Down-regulation of 2-5A-depRNase by Okadaic 77 acid : A phosphatase inhibitor Figure 18

  5. The rRNA methyltransferase Bud23 shows functional interaction with components of the SSU processome and RNase MRP.

    Science.gov (United States)

    Sardana, Richa; White, Joshua P; Johnson, Arlen W

    2013-06-01

    Bud23 is responsible for the conserved methylation of G1575 of 18S rRNA, in the P-site of the small subunit of the ribosome. bud23Δ mutants have severely reduced small subunit levels and show a general failure in cleavage at site A2 during rRNA processing. Site A2 is the primary cleavage site for separating the precursors of 18S and 25S rRNAs. Here, we have taken a genetic approach to identify the functional environment of BUD23. We found mutations in UTP2 and UTP14, encoding components of the SSU processome, as spontaneous suppressors of a bud23Δ mutant. The suppressors improved growth and subunit balance and restored cleavage at site A2. In a directed screen of 50 ribosomal trans-acting factors, we identified strong positive and negative genetic interactions with components of the SSU processome and strong negative interactions with components of RNase MRP. RNase MRP is responsible for cleavage at site A3 in pre-rRNA, an alternative cleavage site for separating the precursor rRNAs. The strong negative genetic interaction between RNase MRP mutants and bud23Δ is likely due to the combined defects in cleavage at A2 and A3. Our results suggest that Bud23 plays a role at the time of A2 cleavage, earlier than previously thought. The genetic interaction with the SSU processome suggests that Bud23 could be involved in triggering disassembly of the SSU processome, or of particular subcomplexes of the processome.

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

    Science.gov (United States)

    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...

  7. Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

    Energy Technology Data Exchange (ETDEWEB)

    Osterman, Ilya A.; Khabibullina, Nelli F.; Komarova, Ekaterina S.; Kasatsky, Pavel; Kartsev, Victor G.; Bogdanov, Alexey A.; Dontsova, Olga A.; Konevega, Andrey L.; Sergiev, Petr V.; Polikanov, Yury S. (InterBioScreen); (UIC); (MSU-Russia); (Kurchatov)

    2017-05-13

    The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.

  8. Long Term Inactive Well Program requirements : interim directive ID 97-08

    International Nuclear Information System (INIS)

    1997-01-01

    The Alberta Energy and Utilities Board and the petroleum industry have agreed that industry must take proactive measures to reduce the number of long term inactive wells in Alberta. This interim directive outlines the requirements of the Long Term Inactive Well Program, and provides a schedule for industry to reduce the number of inactive wells. EUB estimates that there are currently 35,000 inactive wells in Alberta, 10,000 of which have been inactive for more than 10 consecutive years. These wells pose a financial risk to the Abandonment Fund which was established to help fund the abandonment of orphan wells. The Long Term Inactive Well Program was created based on the recommendations of a joint government/industry committee, and will operate for five years. 5 tabs

  9. Characterization of ribonuclease III from Brucella.

    Science.gov (United States)

    Wu, Chang-Xian; Xu, Xian-Jin; Zheng, Ke; Liu, Fang; Yang, Xu-Dong; Chen, Chuang-Fu; Chen, Huan-Chun; Liu, Zheng-Fei

    2016-04-01

    Bacterial ribonuclease III (RNase III) is a highly conserved endonuclease, which plays pivotal roles in RNA maturation and decay pathways by cleaving double-stranded structure of RNAs. Here we cloned rncS gene from the genomic DNA of Brucella melitensis, and analyzed the cleavage properties of RNase III from Brucella. We identified Brucella-encoding small RNA (sRNA) by high-throughput sequencing and northern blot, and found that sRNA of Brucella and Homo miRNA precursor (pre-miRNA) can be bound and cleaved by B.melitensis ribonuclease III (Bm-RNase III). Cleavage activity of Bm-RNase III is bivalent metal cations- and alkaline buffer-dependent. We constructed several point mutations in Bm-RNase III, whose cleavage activity indicated that the 133th Glutamic acid residue was required for catalytic activity. Western blot revealed that Bm-RNase III was differently expressed in Brucella virulence strain 027 and vaccine strain M5-90. Collectively, our data suggest that Brucella RNase III can efficiently bind and cleave stem-loop structure of small RNA, and might participate in regulation of virulence in Brucella. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Effect of physical inactivity on major non-communicable diseases worldwide

    DEFF Research Database (Denmark)

    Lee, I-Min; Shiroma, Eric J; Lobelo, Felipe

    2012-01-01

    Strong evidence shows that physical inactivity increases the risk of many adverse health conditions, including major non-communicable diseases such as coronary heart disease, type 2 diabetes, and breast and colon cancers, and shortens life expectancy. Because much of the world's population...... is inactive, this link presents a major public health issue. We aimed to quantify the eff ect of physical inactivity on these major non-communicable diseases by estimating how much disease could be averted if inactive people were to become active and to estimate gain in life expectancy at the population level....

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

    Science.gov (United States)

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

    Science.gov (United States)

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

    2015-01-01

    To evaluate the physical inactivity-related inpatient costs of chronic non-communicable diseases. 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. 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. 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.

  13. Chronic recreational physical inactivity and epithelial ovarian cancer risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A

    2016-01-01

    . We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium 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......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......, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs 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...

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

    Directory of Open Access Journals (Sweden)

    Marija Stojkovic

    2016-12-01

    Full Text Available 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.

  15. Activation of the 2-5OAS/RNase L pathway in CVB1 or HAV/18f infected FRhK-4 cells does not require induction of OAS1 or OAS2 expression

    International Nuclear Information System (INIS)

    Kulka, Michael; Calvo, Mona S.; Ngo, Diana T.; Wales, Samantha Q.; Goswami, Biswendu B.

    2009-01-01

    The latent, constitutively expressed protein RNase L is activated in coxsackievirus and HAV strain 18f infected FRhK-4 cells. Endogenous oligoadenylate synthetase (OAS) from uninfected and virus infected cell extracts synthesizes active forms of the triphosphorylated 2-5A oligomer (the only known activator of RNase L) in vitro and endogenous 2-5A is detected in infected cell extracts. However, only the largest OAS isoform, OAS3, is readily detected throughout the time course of infection. While IFNβ treatment results in an increase in the level of all three OAS isoforms in FRhK-4 cells, IFNβ pretreatment does not affect the temporal onset or enhancement of RNase L activity nor inhibit virus replication. Our results indicate that CVB1 and HAV/18f activate the 2-5OAS/RNase L pathway in FRhK-4 cells during permissive infection through endogenous levels of OAS, but contrary to that reported for some picornaviruses, CVB1 and HAV/18f replication is insensitive to this activated antiviral pathway.

  16. Reactivity and Catalytic Activity of Hydrogen Atom Chemisorbed Silver Clusters.

    Science.gov (United States)

    Manzoor, Dar; Pal, Sourav

    2015-06-18

    Metal clusters of silver have attracted recent interest of researchers as a result of their potential in different catalytic applications and low cost. However, due to the completely filled d orbital and very high first ionization potential of the silver atom, the silver-based catalysts interact very weakly with the reacting molecules. In the current work, density functional theory calculations were carried out to investigate the effect of hydrogen atom chemisorption on the reactivity and catalytic properties of inert silver clusters. Our results affirm that the hydrogen atom chemisorption leads to enhancement in the binding energy of the adsorbed O2 molecule on the inert silver clusters. The increase in the binding energy is also characterized by the decrease in the Ag-O and increase in the O-O bond lengths in the case of the AgnH silver clusters. Pertinent to the increase in the O-O bond length, a significant red shift in the O-O stretching frequency is also noted in the case of the AgnH silver clusters. Moreover, the hydrogen atom chemisorbed silver clusters show low reaction barriers and high heat of formation of the final products for the environmentally important CO oxidation reaction as compared to the parent catalytically inactive clusters. The obtained results were compared with those of the corresponding gold and hydrogen atom chemisorbed gold clusters obtained at the same level of theory. It is expected the current computational study will provide key insights for future advances in the design of efficient nanosilver-based catalysts through the adsorption of a small atom or a ligand.

  17. LIFETIME PHYSICAL INACTIVITY IS ASSOCIATED WITH LUNG CANCER RISK AND MORTALITY.

    Science.gov (United States)

    Cannioto, Rikki; Etter, John Lewis; LaMonte, Michael J; Ray, Andrew D; Joseph, Janine M; Al Qassim, Emad; Eng, Kevin H; Moysich, Kirsten B

    2018-01-01

    Investigations of the independent associations of physical inactivity with cancer endpoints have been mounting in the epidemiological literature, in part due to the high prevalence of physical inactivity among cancer patients and to evidence that inactivity associates with carcinogenesis via pathways independent of obesity. Yet, physical inactivity is not currently recognized as a well-established risk or prognostic factor for lung cancer. As such, we examined the associations of lifetime physical inactivity with lung cancer risk and mortality in a hospital-based, case-control study. Materials and Methods: The analyses included data from 660 lung cancer patients and 1335 matched cancer-free controls. Multivariable logistic regression analyses were utilized to assess the association between lifetime physical inactivity and lung cancer risk, and Cox proportional hazards models were utilized to estimate the association between lifetime physical inactivity and mortality among lung cancer cases. Results: We observed a significant positive association between lifetime physical inactivity and lung cancer risk: [Odds ratio (OR)=2.23, 95% confidence interval (CI): 1.77-2.81]; the association remained significant among never smokers (OR=3.00, 95% CI:1.33-6.78) and non-smokers (OR=2.33, 95% CI: 1.79-3.02). We also observed a significant positive association between lifetime physical inactivity and lung cancer mortality [Hazard ratio (HR)=1.40, 95% CI: 1.14-1.71]; the association remained significant in non-smokers (HR=1.51, 95% CI: 1.16-1.95). These data add to the body of evidence suggesting that physical inactivity is an independent risk and prognostic factor for cancer. Additional research utilizing prospectively collected data is needed to substantiate the current findings.

  18. Inactive Publics: The Forgotten Publics in Public Relations.

    Science.gov (United States)

    Hallahan, Kirk

    2000-01-01

    Notes that recent public relations theory has largely ignored inactive publics, stakeholder groups that demonstrate low levels of knowledge and involvement in the organization or its products, services, candidates, or causes, but are important to an organization. Examines the nature of inactive publics and proposes a model that locates inactive…

  19. ClRTL1 Encodes a Chinese Fir RNase III–Like Protein Involved in Regulating Shoot Branching

    Directory of Open Access Journals (Sweden)

    Xia Li

    2015-10-01

    Full Text Available Identification of genes controlling shoot branching is crucial for improving plant architecture and increasing crop yield or biomass. A branching mutant of Chinese fir named “Dugansha” (Cunninghamia lanceolata var. dugan. has been isolated in our laboratory. We chose the cDNA-AFLP technique and an effective strategy to screen genes that potentially regulate shoot branching in Chinese fir using this mutant. An RNase III-like1 cDNA fragment named ClRTL1 was identified as a potential positive regulator. To investigate the function of ClRTL1 in regulating shoot branching, we cloned the full-length cDNA sequence from C. lanceolata (Lamb. Hook, deduced its secondary structure and function, and overexpressed the coding sequence in Arabidopsis. The ClRTL1 cDNA is 1045 bp and comprises an open reading frame of 705 bp. It encodes a protein of 235 amino acids. The deduced secondary structure of the ClRTL1 indicates that it is a mini-RNase III-like protein. The expression analysis and phenotypes of 35S: ClRTL1 in A. thaliana implies that ClRTL1 plays a role in promoting shoot branching in Chinese fir.

  20. Binding of Dumbbell Oligonucleotides to MoMuLV Reverse Transcriptase: Inhibitory Properties of RNase H Activity

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2010-01-01

    Full Text Available Dumbbell oligonucleotides with loops of various chemistry were synthesized. Incubation of dumbbell oligonucleotides containing phosphorothioate bonds or trimethylene phosphate linkages in loops with S1 nuclease did not result in significant cleavage under conditions which led to the degradation of dumbbell oligonucleotide containing phophodiester bonds in the loops. The binding of reverse transcriptase of Moloney Murine Leukemia Virus (MoMuLV was evaluated with all the five oligonucleotides. The protein binds to all the dumbbell oligonucleotides with similar affinity. The dissociation constants evaluated using PAGE band mobility shift assays were of the order of 10-7. The inhibitory properties of the retroviral RNase H activity was evaluated using 3H –UTP-labeled RNA:RNA-DNA hybrid. It was found that the best dumbbell oligonucleotide, inhibitor contained phosphorothioate residues in both the loops. Our value studies demonstrated that this particularly designed oligonucleotide displays an IC50 of 18 nM in its inhibition on the reverse transcriptase RNase H activity, a magnitude lower than that of first nucleotide reverse transcriptase of HIV-1, tenofovir, introduced by Gilead Science in the market.

  1. Detrimental effects of physical inactivity on neurogenesis

    Directory of Open Access Journals (Sweden)

    Trenton Lippert

    2016-01-01

    Full Text Available Patients diagnosed with neurological disorders exhibit a variety of physical and psychiatric symptoms, including muscle atrophy, general immobility, and depression. Patients who participate in physical rehabilitation at times show unexpected clinical improvement, which includes diminished depression and other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for central nervous system (CNS disorders, transplantation of exogenous stem cells, and enhancing the endogenous neurogenesis. The latter therapy utilizes a natural method of re-innervating the injured brain, which may mend neurological impairments. In this study, we examine how inactivity-induced atrophy, using the hindlimb suspension model, alters neurogenesis in rats. The hypothesis is that inactivity inhibits neurogenesis by decreasing circulation growth or trophic factors, such as vascular endothelial growth or neurotrophic factors. The restriction modifies neurogenesis and stem cell differentiation in the CNS, the stem cell microenvironment is examined by the trophic and growth factors, including stress-related proteins. Despite growing evidence revealing the benefits of "increased" exercise on neurogenesis, the opposing theory involving "physical inactivity," which simulates pathological states, continues to be neglected. This novel theory will allow us to explore the effects on neurogenesis by an intransigent stem cell microenvironment likely generated by inactivity. 5-bromo-2-deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid, and brain levels of trophic factors, growth factors, and stress-related proteins are suggested identifiers of neurogenesis, while evaluation of spontaneous movements will give insight into the psychomotor effects of inactivity. Investigations devised to show how in vivo stimulation, or lack thereof, affects the stem cell microenvironment are necessary to establish

  2. Isolation and characterization of multiple F-box genes linked to the S9- and S10-RNase in apple (Malus × domestica Borkh.).

    Science.gov (United States)

    Okada, Kazuma; Moriya, Shigeki; Haji, Takashi; Abe, Kazuyuki

    2013-06-01

    Using 11 consensus primer pairs designed from S-linked F-box genes of apple and Japanese pear, 10 new F-box genes (MdFBX21 to 30) were isolated from the apple cultivar 'Spartan' (S(9)S(10)). MdFBX21 to 23 and MdFBX24 to 30 were completely linked to the S(9) -RNase and S(10-)RNase, respectively, and showed pollen-specific expression and S-haplotype-specific polymorphisms. Therefore, these 10 F-box genes are good candidates for the pollen determinant of self-incompatibility in apple. Phylogenetic analysis and comparison of deduced amino acid sequences of MdFBX21 to 30 with those of 25 S-linked F-box genes previously isolated from apple showed that a deduced amino acid identity of greater than 88.0 % can be used as the tentative criterion to classify F-box genes into one type. Using this criterion, 31 of 35 F-box genes of apple were classified into 11 types (SFBB1-11). All types included F-box genes derived from S(3-) and S(9-)haplotypes, and seven types included F-box genes derived from S(3-), S(9-), and S(10-)haplotypes. Moreover, comparison of nucleotide sequences of S-RNases and multiple F-box genes among S(3-), S(9-), and S(10-)haplotypes suggested that F-box genes within each type showed high nucleotide identity regardless of the identity of the S-RNase. The large number of F-box genes as candidates for the pollen determinant and the high degree of conservation within each type are consistent with the collaborative non-self-recognition model reported for Petunia. These findings support that the collaborative non-self-recognition system also exists in apple.

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

    Science.gov (United States)

    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 physical inactivity at work prior to the event (OR = 12.99; P 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.

  4. Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein.

    Science.gov (United States)

    Shimodaira, Shingo; Asano, Yuki; Arai, Kenta; Iwaoka, Michio

    2017-10-24

    Selenoglutathione (GSeH) is a selenium analogue of naturally abundant glutathione (GSH). In this study, this water-soluble small tripeptide was synthesized in a high yield (up to 98%) as an oxidized diselenide form, i.e., GSeSeG (1), by liquid-phase peptide synthesis (LPPS). Obtained 1 was applied to the investigation of the glutathione peroxidase (GPx)-like catalytic cycle. The important intermediates, i.e., GSe - and GSeSG, besides GSeO 2 H were characterized by 77 Se NMR spectroscopy. Thiol exchange of GSeSG with various thiols, such as cysteine and dithiothreitol, was found to promote the conversion to GSe - significantly. In addition, disproportionation of GSeSR to 1 and RSSR, which would be initiated by heterolytic cleavage of the Se-S bond and catalyzed by the generated selenolate, was observed. On the basis of these redox behaviors, it was proposed that the heterolytic cleavage of the Se-S bond can be facilitated by the interaction between the Se atom and an amino or aromatic group, which is present at the GPx active site. On the other hand, when a catalytic amount of 1 was reacted with scrambled 4S species of RNase A in the presence of NADPH and glutathione reductase, native protein was efficiently regenerated, suggesting a potential use of 1 to repair misfolded proteins through reduction of the non-native SS bonds.

  5. Prevalence of physical inactivity in Iran: a systematic review.

    Science.gov (United States)

    Fakhrzadeh, Hossein; Djalalinia, Shirin; Mirarefin, Mojdeh; Arefirad, Tahereh; Asayesh, Hamid; Safiri, Saeid; Samami, Elham; Mansourian, Morteza; Shamsizadeh, Morteza; Qorbani, Mostafa

    2016-01-01

    Introduction: Physical inactivity is one of the most important risk factors for chronic diseases, including cardiovascular disease, cancer, and stroke. We aim to conduct a systematic review of the prevalence of physical inactivity in Iran. Methods: We searched international databases; ISI, PubMed/Medline, Scopus, and national databases Irandoc, Barakat knowledge network system, and Scientific Information Database (SID). We collected data for outcome measures of prevalence of physical inactivity by sex, age, province, and year. Quality assessment and data extraction has been conducted independently by two independent research experts. There were no limitations for time and language. Results: We analyzed data for prevalence of physical inactivity in Iranian population. According to our search strategy we found 254 records; of them 185 were from international databases and the remaining 69 were obtained from national databases after refining the data, 34 articles that met eligible criteria remained for data extraction. From them respectively; 9, 20, 2 and 3 studies were at national, provincial, regional and local levels. The estimates for inactivity ranged from approximately 30% to almost 70% and had considerable variation between sexes and studied sub-groups. Conclusion: In Iran, most of studies reported high prevalence of physical inactivity. Our findings reveal a heterogeneity of reported values, often from differences in study design, measurement tools and methods, different target groups and sub-population sampling. These data do not provide the possibility of aggregation of data for a comprehensive inference.

  6. Crystallization and preliminary X-ray diffraction analysis of the P3 RNA domain of yeast ribonuclease MRP in a complex with RNase P/MRP protein components Pop6 and Pop7

    International Nuclear Information System (INIS)

    Perederina, Anna; Esakova, Olga; Quan, Chao; Khanova, Elena; Krasilnikov, Andrey S.

    2009-01-01

    This article describes the first successful crystallization of components of eukaryotic ribonucleases P/MRP. Yeast RNase MRP RNA domain P3 was crystallized in a complex with the proteins Pop6 and Pop7; the crystals diffracted to 3.25 Å resolution. Eukaryotic ribonucleases P and MRP are closely related RNA-based enzymes which contain a catalytic RNA component and several protein subunits. The roles of the protein subunits in the structure and function of eukaryotic ribonucleases P and MRP are not clear. Crystals of a complex that included a circularly permuted 46-nucleotide-long P3 domain of the RNA component of Saccharomyces cerevisiae ribonuclease MRP and selenomethionine derivatives of the shared ribonuclease P/MRP protein components Pop6 (18.2 kDa) and Pop7 (15.8 kDa) were obtained using the sitting-drop vapour-diffusion method. The crystals belonged to space group P4 2 22 (unit-cell parameters a = b = 127.2, c = 76.8 Å, α = β = γ = 90°) and diffracted to 3.25 Å resolution

  7. Energy expenditure while playing active and inactive video games.

    Science.gov (United States)

    Leatherdale, Scott T; Woodruff, Sarah J; Manske, Stephen R

    2010-01-01

    To examine energy expenditure (EE) when playing active and inactive videogames (VG). Predicted EE was measured among 51 undergraduate students while playing active and inactive VG (Ontario, Canada). Predicted EE was significantly higher playing the active VG compared to the inactive VG according to heart rate monitor (97.4 kcal vs 64.7 kcal) and SenseWear armband (192.4 kcal vs 42.3 kcal) estimates. Active VG may be a viable intervention tool for increasing EE among students who would otherwise be spending time in sedentary screen-based behaviors.

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

    Science.gov (United States)

    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.

  9. A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation

    International Nuclear Information System (INIS)

    Littler, Dene R.; Walker, John R.; Davis, Tara; Wybenga-Groot, Leanne E.; Finerty, Patrick J. Jr; Newman, Elena; Mackenzie, Farell; Dhe-Paganon, Sirano

    2010-01-01

    A 1.9 Å resolution crystal structure of the isolated kinase domain from the α2 subunit of human AMPK, the first from a multicellular organism, is presented. The AMP-activated protein kinase (AMPK) is a highly conserved trimeric protein complex that is responsible for energy homeostasis in eukaryotic cells. Here, a 1.9 Å resolution crystal structure of the isolated kinase domain from the α2 subunit of human AMPK, the first from a multicellular organism, is presented. This human form adopts a catalytically inactive state with distorted ATP-binding and substrate-binding sites. The ATP site is affected by changes in the base of the activation loop, which has moved into an inhibited DFG-out conformation. The substrate-binding site is disturbed by changes within the AMPKα2 catalytic loop that further distort the enzyme from a catalytically active form. Similar structural rearrangements have been observed in a yeast AMPK homologue in response to the binding of its auto-inhibitory domain; restructuring of the kinase catalytic loop is therefore a conserved feature of the AMPK protein family and is likely to represent an inhibitory mechanism that is utilized during function

  10. A study of ribonuclease activity in venom of vietnam cobra

    Directory of Open Access Journals (Sweden)

    Thiet Van Nguyen

    2017-09-01

    Full Text Available Abstract Background Ribonuclease (RNase is one of the few toxic proteins that are present constantly in snake venoms of all types. However, to date this RNase is still poorly studied in comparison not only with other toxic proteins of snake venom, but also with the enzymes of RNase group. The objective of this paper was to investigate some properties of RNase from venom of Vietnam cobra Naja atra. Methods Kinetic methods and gel filtration chromatography were used to investigate RNase from venom of Vietnam cobra. Results RNase from venom of Vietnam cobra Naja atra has some characteristic properties. This RNase is a thermostable enzyme and has high conformational stability. This is the only acidic enzyme of the RNase A superfamily exhibiting a high catalytic activity in the pH range of 1–4, with pHopt = 2.58 ± 0.35. Its activity is considerably reduced with increasing ionic strength of reaction mixture. Venom proteins are separated by gel filtration into four peaks with ribonucleolytic activity, which is abnormally distributed among the isoforms: only a small part of the RNase activity is present in fractions of proteins with molecular weights of 12–15 kDa and more than 30 kDa, but most of the enzyme activity is detected in fractions of polypeptides, having molecular weights of less than 9 kDa, that is unexpected. Conclusions RNase from the venom of Vietnam cobra is a unique member of RNase A superfamily according to its acidic optimum pH (pHopt = 2.58 ± 0.35 and extremely low molecular weights of its major isoforms (approximately 8.95 kDa for RNase III and 5.93 kDa for RNase IV.

  11. The metabolite beta-aminoisobutyric acid and physical inactivity among hemodialysis patients.

    Science.gov (United States)

    Molfino, Alessio; Amabile, Maria Ida; Ammann, Thomas; Farcomeni, Alessio; Lionetto, Luana; Simmaco, Maurizio; Lai, Silvia; Laviano, Alessandro; Rossi Fanelli, Filippo; Chiappini, Maria Grazia; Muscaritoli, Maurizio

    2017-02-01

    Physical inactivity is frequent in patients on hemodialysis (HD), and represents a reliable predictor of morbidity and mortality. Beta-aminoisobutyric acid (BAIBA) is a contraction-induced myokine, the plasma levels of which increase with exercise and are inversely associated with metabolic risk factors. The aim of this study was to ascertain whether physical inactivity and clinical parameters relate to plasma BAIBA levels in this patient population. Adult patients on HD were included, and the presence of physical inactivity was assessed. BAIBA levels were measured in these patients and in healthy individuals. We assessed barriers to physical activity, including 23 items regarding psychophysical and financial barriers. Body composition was assessed by bioimpedance and muscle strength by handgrip dynamometer. Nonparametric tests and logistic regression analyses were performed. Forty-nine patients on HD were studied; 49% were physically active and 51% were inactive. Of the patients, 43 reported barriers to physical activity and 61% of inactive patients reported three or more barriers. BAIBA levels were lower in patients on HD with respect to controls (P HD patients as active and inactive, both groups showed significantly lower BAIBA levels versus controls (P = 0.0005, P HD showed increased BAIBA levels compared with diabetic patients (P HD endorsing the two most frequent barriers showed lower BAIBA levels than those not reporting these barriers (P = 0.006). Active patients showed higher intracellular water (%) (P = 0.008), and active and inactive patients showed significant correlation between total body muscle mass and handgrip strength (P = 0.04, P = 0.005, respectively). Physical inactivity is highly prevalent among patients on HD and BAIBA correlates with barriers to physical activity reported by inactive patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Engineering catalytic activity via ion beam bombardment of catalyst supports for vertically aligned carbon nanotube growth

    Science.gov (United States)

    Islam, A. E.; Nikolaev, P.; Amama, P. B.; Zakharov, D.; Sargent, G.; Saber, S.; Huffman, D.; Erford, M.; Semiatin, S. L.; Stach, E. A.; Maruyama, B.

    2015-09-01

    Carbon nanotube growth depends on the catalytic activity of metal nanoparticles on alumina or silica supports. The control on catalytic activity is generally achieved by variations in water concentration, carbon feed, and sample placement on a few types of alumina or silica catalyst supports obtained via thin film deposition. We have recently expanded the choice of catalyst supports by engineering inactive substrates like c-cut sapphire via ion beam bombardment. The deterministic control on the structure and chemistry of catalyst supports obtained by tuning the degree of beam-induced damage have enabled better regulation of the activity of Fe catalysts only in the ion beam bombarded areas and hence enabled controllable super growth of carbon nanotubes. A wide range of surface characterization techniques were used to monitor the catalytically active surface engineered via ion beam bombardment. The proposed method offers a versatile way to control carbon nanotube growth in patterned areas and also enhances the current understanding of the growth process. With the right choice of water concentration, carbon feed and sample placement, engineered catalyst supports may extend the carbon nanotube growth yield to a level that is even higher than the ones reported here, and thus offers promising applications of carbon nanotubes in electronics, heat exchanger, and energy storage.

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

    Science.gov (United States)

    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 G i 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. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    Olli Tikkanen

    Full Text Available 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.

  15. Exercise Responses after Inactivity

    Science.gov (United States)

    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.

  16. Educational differences in leisure-time physical inactivity: a descriptive and explanatory study.

    Science.gov (United States)

    Droomers, M; Schrijvers, C T; van de Mheen, H; Mackenbach, J P

    1998-12-01

    In this study we aim to explain educational differences in leisure-time physical inactivity in terms of psychosocial and material factors. Cross-sectional data were obtained from the baseline of the Dutch GLOBE study in 1991, including 2598 men and women, aged 15-74 years. Physical inactivity during leisure time was defined as not participating in any activity, such as sports, gardening, walking or cycling. Psychosocial factors included in the study were coping resources, personality, and stressors. Material factors were financial situation, employment status, and living conditions. Logistic regression models were used to calculate educational differences in physical inactivity. Physical inactivity was more prevalent in lower educational groups. Psychosocial factors related to physical inactivity were locus of control, parochialism, neuroticism, emotional social support, active problem focussing, optimistic and palliative coping styles. Material factors associated with physical inactivity were income, employment status and financial problems. All correlates of physical inactivity were unequally distributed over educational groups, except optimistic and palliative coping. Personality and coping style were the main contributors to the observed educational differences in physical inactivity. That is to say, parochialism, locus of control, neuroticism and active problem focussing explained about half of elevated odds ratios of physical inactivity in the lower educational groups. The material factors, equivalent income and employment status explained about 40% of the elevated odds ratios. Psychosocial and material correlates together reduced the odds ratios of lower educational groups by on average 75%. These results have practical consequences for the design of more effective interventions to promote physical activity. In particular, personality and coping style of risk groups, such as lower educational groups, should be taken into consideration at the future

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

    Science.gov (United States)

    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

  18. Average inactivity time model, associated orderings and reliability properties

    Science.gov (United States)

    Kayid, M.; Izadkhah, S.; Abouammoh, A. M.

    2018-02-01

    In this paper, we introduce and study a new model called 'average inactivity time model'. This new model is specifically applicable to handle the heterogeneity of the time of the failure of a system in which some inactive items exist. We provide some bounds for the mean average inactivity time of a lifespan unit. In addition, we discuss some dependence structures between the average variable and the mixing variable in the model when original random variable possesses some aging behaviors. Based on the conception of the new model, we introduce and study a new stochastic order. Finally, to illustrate the concept of the model, some interesting reliability problems are reserved.

  19. When Action-Inaction Framing Leads to Higher Escalation of Commitment: A New Inaction-Effect Perspective on the Sunk-Cost Fallacy.

    Science.gov (United States)

    Feldman, Gilad; Wong, Kin Fai Ellick

    2018-04-01

    Escalation of commitment to a failing course of action occurs in the presence of (a) sunk costs, (b) negative feedback that things are deviating from expectations, and (c) a decision between escalation and de-escalation. Most of the literature to date has focused on sunk costs, yet we offer a new perspective on the classic escalation-of-commitment phenomenon by focusing on the impact of negative feedback. On the basis of the inaction-effect bias, we theorized that negative feedback results in the tendency to take action, regardless of what that action may be. In four experiments, we demonstrated that people facing escalation-decision situations were indeed action oriented and that framing escalation as action and de-escalation as inaction resulted in a stronger tendency to escalate than framing de-escalation as action and escalation as inaction (mini-meta-analysis effect d = 0.37, 95% confidence interval = [0.21, 0.53]).

  20. Physical inactivity and obesity: relation to asthma and chronic obstructive pulmonary disease?

    Science.gov (United States)

    ten Hacken, Nick H T

    2009-12-01

    Physical inactivity and obesity are modifiable risk factors for many chronic diseases, including cardiovascular disease, diabetes mellitus, osteoporosis, osteoarthritis, and depression. Both physical inactivity and obesity are associated with low-grade systemic inflammation that may contribute to the inflammatory processes present in many chronic diseases. In asthma, almost no studies are available in which physical inactivity has been studied using performance-based instruments. In contrast, the association between obesity and a higher prevalence of asthma has often been suggested in a large number of studies. In chronic obstructive pulmonary disease (COPD) physical inactivity has been demonstrated in a few studies that used performance-based instruments; this was associated with the higher COPD Global Initiative on Obstructive Lung Disease (GOLD) stages and a higher degree of systemic inflammation, independent of body mass index. In contrast to physical inactivity, obesity in COPD is associated with the lower GOLD stages. Additionally, obesity is associated with the chronic obstructive phenotype and features of the metabolic syndrome. To elucidate the independent relation of physical inactivity and obesity with systemic inflammation, performance-based studies of physical inactivity in asthma and COPD are highly needed.

  1. Catalytic Mechanism of Nitrile Hydratase Proposed by Time-resolved X-ray Crystallography Using a Novel Substrate, tert-Butylisonitrile*S⃞

    Science.gov (United States)

    Hashimoto, Koichi; Suzuki, Hiroyuki; Taniguchi, Kayoko; Noguchi, Takumi; Yohda, Masafumi; Odaka, Masafumi

    2008-01-01

    Nitrile hydratases (NHases) have an unusual iron or cobalt catalytic center with two oxidized cysteine ligands, cysteine-sulfinic acid and cysteine-sulfenic acid, catalyzing the hydration of nitriles to amides. Recently, we found that the NHase of Rhodococcus erythropolis N771 exhibited an additional catalytic activity, converting tert-butylisonitrile (tBuNC) to tert-butylamine. Taking advantage of the slow reactivity of tBuNC and the photoreactivity of nitrosylated NHase, we present the first structural evidence for the catalytic mechanism of NHase with time-resolved x-ray crystallography. By monitoring the reaction with attenuated total reflectance-Fourier transform infrared spectroscopy, the product from the isonitrile carbon was identified as a CO molecule. Crystals of nitrosylated inactive NHase were soaked with tBuNC. The catalytic reaction was initiated by photo-induced denitrosylation and stopped by flash cooling. tBuNC was first trapped at the hydrophobic pocket above the iron center and then coordinated to the iron ion at 120 min. At 440 min, the electron density of tBuNC was significantly altered, and a new electron density was observed near the isonitrile carbon as well as the sulfenate oxygen of αCys114. These results demonstrate that the substrate was coordinated to the iron and then attacked by a solvent molecule activated by αCys114-SOH. PMID:18948265

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

    Science.gov (United States)

    Cadilhac, Dominique A; Cumming, Toby B; Sheppard, Lauren; Pearce, Dora C; Carter, Rob; Magnus, Anne

    2011-09-24

    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. 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. 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 opportunity cost savings in

  3. 80,000 Inactive Oil Wells: A Blessing or a Curse?

    Directory of Open Access Journals (Sweden)

    Lucija Muehlenbachs

    2017-02-01

    Full Text Available For a century, oil and gas wells have been Alberta’s economic pride. That there could be a hidden cost in maintaining these wells past their productive life is difficult to imagine, much less accept. The financial burden of abandoning a well officially is no doubt why Alberta producers delay doing so as long as possible. Turning a blind eye, they routinely keep non-producing wells in a state of “inactive” suspension and refuse to rule out the possibility that someday oil prices or technology, or both, will change significantly enough to make those wells profitable again. In most cases that will never happen, but the province plays along anyway: It enforces no limit on how long a well can be kept inactive before it must be reactivated or abandoned. While a convenience for well owners, there is no benefit to Albertans. They are exposed to the risk of thousands of inactive wells becoming a hazardous threat to public safety. The longer a well is inactive, the higher the likelihood that its owner may no longer be around to arrange and pay for its official abandonment, a process whereby wells are permanently sealed using regulated methods that insure they cause no environmental damage. Oil and gas producers come and go. Periodic price shocks, like the one that recently ravaged the sector, drive companies into insolvency. When the owner of an inactive well is no longer around to pay for its abandonment costs, the well becomes orphaned. Alberta’s permissive policies have led to a situation where there are now more than 80,000 inactive wells in the province. Some have been inactive for decades. If the possibility existed that they could eventually become economical, those wells might be considered a blessing. However, the simulations that model scenarios where prices are substantially higher or where production technology is significantly improved, clearly show that the vast majority of these wells will never be reactivated, no matter how

  4. Human development, occupational structure and physical inactivity among 47 low and middle income countries.

    Science.gov (United States)

    Atkinson, Kaitlin; Lowe, Samantha; Moore, Spencer

    2016-06-01

    This study aimed to (a) assess the relationship between a person's occupational category and their physical inactivity, and (b) analyze the association among country-level variables and physical inactivity. The World Health Survey (WHS) was administered in 2002-2003 among 47 low- and middle-income countries (n = 196,742). The International Physical Activity Questionnaire (IPAQ) was used to collect verbal reports of physical activity and convert responses into measures of physical inactivity. Economic development (GDP/c), degree of urbanization, and the Human Development Index (HDI) were used to measure country-level variables and physical inactivity. Multilevel logistic regression analysis was used to examine the association among country-level factors, individual occupational status, and physical inactivity. Overall, the worldwide prevalence of physical inactivity in 2002-2003 was 23.7%. Individuals working in the white-collar industry compared to agriculture were 84% more likely to be physically inactive (OR: 1.84, CI: 1.73-1.95). Among low- and middle-income countries increased HDI values were associated with decreased levels of physical inactivity (OR: 0.98, CI: 0.97-0.99). This study is one of the first to adjust for within-country differences, specifically occupation while analyzing physical inactivity. As countries experience economic development, changes are also seen in their occupational structure, which result in increased countrywide physical inactivity levels.

  5. Clustering of physical inactivity in leisure, work, commuting and household domains among Brazilian adults.

    Science.gov (United States)

    Del Duca, G F; Nahas, M V; de Sousa, T F; Mota, J; Hallal, P C; Peres, K G

    2013-06-01

    To identify the clustering of physical inactivity in leisure, work, commuting and household contexts, and the sociodemographic factors associated with the clustering of inactive behaviour in different domains among Brazilian adults. Cross-sectional population-based study. The study was performed in Florianopolis, capital of Santa Catarina, one of the southern states of Brazil, from September 2009 to January 2010. Adults aged 20-59 years were interviewed. Physical inactivity in each domain was defined as non-participation in specific physical activities, using a validated Brazilian questionnaire. Clustering of physical inactivity was identified by the ratio between observed prevalence and expected prevalence of 16 different combinations. Multinomial logistic regression was used in the analysis of sociodemographic factors associated with clustering of physical inactivity. Of the 1720 interviewees, the greatest differences between the observed and expected proportions were observed in simultaneous physical inactivity in the leisure and household domains for men, and physical inactivity in the leisure domain alone for women (59% and 88%, respectively); these differences were higher than expected if the behaviours were independent. Physical inactivity in two or more domains was observed more frequently in men and in individuals with a higher per-capita family income. Ageing was associated with physical inactivity in three or four domains. Physical inactivity was observed in different domains according to gender. Men and older individuals with a higher per-capita family income were more likely to exhibit physical inactivity when all domains were considered together. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1991-01-01

    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 the tube failure in some operating steam generators and heat exchangers. This paper presents a mathematical model for fluidelastic instability of loosely supported tubes exposed to nonuniform crossflow. the model incorporates all motion-dependent fluid forces based on the unsteady-flow theory. In the unstable region associated with a TSP-inactive mode, tube motion can be described by two linear models: TSP-inactive mode when tubes do not strike the TSP, and TSP-active mode when tubes do strike the TSP. The bilinear model (consisting of these linear models) presented here simulates the characteristics of fluidelastic instability of loosely supported tubes in stable and unstable regions associated with TSP-inactive modes. Analytical results obtained with the model are compared with published experimental data; they agree reasonably well. The prediction procedure presented for the fluidelastic instability response of loosely supported tubes is applicable to the stable and unstable regions of the TSP-inactive mode

  7. Pollen S-locus F-box proteins of Petunia involved in S-RNase-based self-incompatibility are themselves subject to ubiquitin-mediated degradation.

    Science.gov (United States)

    Sun, Penglin; Li, Shu; Lu, Dihong; Williams, Justin S; Kao, Teh-Hui

    2015-07-01

    Many flowering plants show self-incompatibility, an intra-specific reproductive barrier by which pistils reject self-pollen to prevent inbreeding and accept non-self pollen to promote out-crossing. In Petunia, the polymorphic S-locus determines self/non-self recognition. The locus contains a gene encoding an S-RNase, which controls pistil specificity, and multiple S-locus F-box (SLF) genes that collectively control pollen specificity. Each SLF is a component of an SCF (Skp1/Cullin/F-box) complex that is responsible for mediating degradation of non-self S-RNase(s), with which the SLF interacts, via the ubiquitin-26S proteasome pathway. A complete set of SLFs is required to detoxify all non-self S-RNases to allow cross-compatible pollination. Here, we show that SLF1 of Petunia inflata is itself subject to degradation via the ubiquitin-26S proteasome pathway, and identify an 18 amino acid sequence in the C-terminal region of S2 -SLF1 (SLF1 of S2 haplotype) that contains a degradation motif. Seven of the 18 amino acids are conserved among all 17 SLF proteins of S2 haplotype and S3 haplotype involved in pollen specificity, suggesting that all SLF proteins are probably subject to similar degradation. Deleting the 18 amino acid sequence from S2 -SLF1 stabilized the protein but abolished its function in self-incompatibility, suggesting that dynamic cycling of SLF proteins is an integral part of their function in self-incompatibility. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  8. Geographical Variations in the Environmental Determinants of Physical Inactivity among U.S. Adults.

    Science.gov (United States)

    An, Ruopeng; Li, Xinye; Jiang, Ning

    2017-10-31

    Physical inactivity is a major modifiable risk factor for morbidity, disability and premature mortality worldwide. This study assessed the geographical variations in the impact of environmental quality on physical inactivity among U.S. adults. Data on county-level prevalence of leisure-time physical inactivity came from the Behavioral Risk Factor Surveillance System. County environment was measured by the Environmental Quality Index (EQI), a comprehensive index of environmental conditions that affect human health. The overall EQI consists of five subdomains-air, water, land, social, and built environment. Geographically weighted regressions (GWRs) were performed to estimate and map county-specific impact of overall EQI and its five subdomains on physical inactivity prevalence. The prevalence of leisure-time physical inactivity among U.S. counties was 25% in 2005. On average, one standard deviation decrease in the overall EQI was associated with an increase in county-level prevalence of leisure-time physical inactivity by nearly 1%. However, substantial geographical variations in the estimated environmental determinants of physical inactivity were present. The estimated changes of county-level prevalence of leisure-time physical inactivity resulted from one standard deviation decrease of the overall EQI ranged from an increase of over 3% to a decrease of nearly 2% across U.S. counties. Analogous, the estimated changes of county-level prevalence of leisure-time physical inactivity resulted from one standard deviation decrease of the EQI air, water, land, social, and built environment subdomains ranged from an increase of 2.6%, 1.5%, 2.9%, 3.3%, and 1.7% to a decrease of 2.9%, 1.4%, 2.4%, 2.4%, and 0.8% across U.S. counties, respectively. Given the substantial heterogeneities in the environmental determinants of physical inactivity, locally customized physical activity interventions are warranted to address the most concerning area-specific environmental issue.

  9. Overexpression of the catalytically impaired Taspase1 T234V or Taspase1 D233A variants does not have a dominant negative effect in T(4;11 leukemia cells.

    Directory of Open Access Journals (Sweden)

    Carolin Bier

    Full Text Available BACKGROUND: The chromosomal translocation t(4;11(q21;q23 is associated with high-risk acute lymphoblastic leukemia of infants. The resulting AF4•MLL oncoprotein becomes activated by Taspase1 hydrolysis and is considered to promote oncogenic transcriptional activation. Hence, Taspase1's proteolytic activity is a critical step in AF4•MLL pathophysiology. The Taspase1 proenzyme is autoproteolytically processed in its subunits and is assumed to assemble into an αββα-heterodimer, the active protease. Therefore, we investigated here whether overexpression of catalytically inactive Taspase1 variants are able to interfere with the proteolytic activity of the wild type enzyme in AF4•MLL model systems. METHODOLOGY/FINDINGS: The consequences of overexpressing the catalytically dead Taspase1 mutant, Taspase1(T234V, or the highly attenuated variant, Taspase1(D233A, on Taspase1's processing of AF4•MLL and of other Taspase1 targets was analyzed in living cancer cells employing an optimized cell-based assay. Notably, even a nine-fold overexpression of the respective Taspase1 mutants neither inhibited Taspase1's cis- nor trans-cleavage activity in vivo. Likewise, enforced expression of the α- or β-subunits showed no trans-dominant effect against the ectopically or endogenously expressed enzyme. Notably, co-expression of the individual α- and β-subunits did not result in their assembly into an enzymatically active protease complex. Probing Taspase1 multimerization in living cells by a translocation-based protein interaction assay as well as by biochemical methods indicated that the inactive Taspase1 failed to assemble into stable heterocomplexes with the wild type enzyme. CONCLUSIONS: Collectively, our results demonstrate that inefficient heterodimerization appears to be the mechanism by which inactive Taspase1 variants fail to inhibit wild type Taspase1's activity in trans. Our work favours strategies targeting Taspase1's catalytic activity

  10. Effect of Early- and Adult-Life Socioeconomic Circumstances on Physical Inactivity.

    Science.gov (United States)

    Cheval, Boris; Sieber, Stefan; Guessous, Idris; Orsholits, Dan; Courvoisier, Delphine S; Kliegel, Matthias; Stringhini, Silvia; Swinnen, Stephan P; Burton-Jeangros, Claudine; Cullati, Stéphane; Boisgontier, Matthieu P

    2018-03-01

    This study aimed to investigate the associations between early- and adult-life socioeconomic circumstances and physical inactivity (level and evolution) in aging using large-scale longitudinal data. This study used the Survey of Health Ageing and Retirement in Europe, a 10-yr population-based cohort study with repeated measurements in five waves, every 2 yr between 2004 and 2013. Self-reported physical inactivity (waves 1, 2, 4, and 5), household income (waves 1, 2, 4, and 5), educational attainment (wave of the first measurement occasion), and early-life socioeconomic circumstance (wave 3) were collected in 22,846 individuals 50 to 95 yr of age. Risk of physical inactivity was increased for women with the most disadvantaged early-life socioeconomic circumstances (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.20-1.86). With aging, the risk of physical inactivity increased for both sexes and was strongest for those with the most disadvantaged early-life socioeconomic circumstances (OR, 1.04 (95% CI, 1.02-1.06) for women; OR, 1.02 (95% CI, 1.00-1.05) for men), with the former effect being more robust than the latter one. The association between early-life socioeconomic circumstances and physical inactivity was mediated by adult-life socioeconomic circumstances, with education being the strongest mediator. Early-life socioeconomic circumstances predicted high levels of physical inactivity at older ages, but this effect was mediated by socioeconomic indicators in adult life. This finding has implications for public health policies, which should continue to promote education to reduce physical inactivity in people at older ages and to ensure optimal healthy aging trajectories, especially among women with disadvantaged early-life socioeconomic circumstances.

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

    Science.gov (United States)

    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.

  12. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A

    2016-01-01

    physical activity and epithelial ovarian cancer (EOC) is less clear. Despite extensive research, including several epidemiological studies and 2 systematic reviews, insufficient and inconsistent evidence is available to support an independent association between recreational physical activity and risk......It is estimated that 5% of women in the United States and 10% to 50% of women worldwide are physically inactive. Previous studies have demonstrated that recreational physical activity is associated with decreased risks of developing breast, colon, and endometrial cancers. The association between...... of EOC. This is largely due to use of common methodology in most studies that overlooks recreational physical inactivity as an independent risk factor for EOC. The aim of this study was to determine whether self-reported, chronic, recreational physical inactivity is an independent risk factor...

  13. High-speed DNA-based rolling motors powered by RNase H

    Science.gov (United States)

    Yehl, Kevin; Mugler, Andrew; Vivek, Skanda; Liu, Yang; Zhang, Yun; Fan, Mengzhen; Weeks, Eric R.

    2016-01-01

    DNA-based machines that walk by converting chemical energy into controlled motion could be of use in applications such as next generation sensors, drug delivery platforms, and biological computing. Despite their exquisite programmability, DNA-based walkers are, however, challenging to work with due to their low fidelity and slow rates (~1 nm/min). Here, we report DNA-based machines that roll rather than walk, and consequently have a maximum speed and processivity that is three-orders of magnitude greater than conventional DNA motors. The motors are made from DNA-coated spherical particles that hybridise to a surface modified with complementary RNA; motion is achieved through the addition of RNase H, which selectively hydrolyses hybridised RNA. Spherical motors move in a self-avoiding manner, whereas anisotropic particles, such as dimerised particles or rod-shaped particles travel linearly without a track or external force. Finally, we demonstrate detection of single nucleotide polymorphism by measuring particle displacement using a smartphone camera. PMID:26619152

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

    Directory of Open Access Journals (Sweden)

    Cumming Toby B

    2011-09-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

    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

    2016-02-01

    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 (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 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 socioeconomic status. Special attention should be given to girls and to those who do not engage in any physical activity during the leisure time, so that they can adopt a more active lifestyle.

  16. Physical inactivity and associated factors among women from a municipality in southern Brazil.

    Science.gov (United States)

    Marcellino, Cristiano; Henn, Ruth Liane; Olinto, Maria Teresa; Bressan, Ana Weigert; Paniz, Vera Maria; Pattussi, Marcos Pascoal

    2014-05-01

    Physical inactivity is one of the most important modifiable risk factors that is raising the global burden of chronic diseases. This is a cross-sectional, population-based study of 790 women aged 20 years or older living in the urban area of a municipality in Southern Brazil. The level of physical activity was measured using the International Physical Activity Questionnaire, short form. Inactivity was defined as fewer than 150 min/wk-1 spent in moderate or vigorous physical activities. Prevalence ratios were calculated by robust Poisson regression. The prevalence of physical inactivity was 48.7% (95% CI, 43.3%-54.1%). After adjusting for confounders, we found a linear trend for increasing prevalence of physical inactivity with increasing body mass index (P = .008). Women who were married or in a domestic partnership were 29% less physically active than single women (P = .044). A borderline association was detected between the presence of minor psychiatric disorders (MPD) and physical inactivity (P = .058). There was a high prevalence of inactivity. Obese women, those married or in domestic partnerships and those with MPD were more likely to lead an inactive lifestyle. These results suggest that strategies are required for breaking down barriers to physical activity in this demographic group.

  17. Inhibition of the host proteasome facilitates papaya ringspot virus accumulation and proteosomal catalytic activity is modulated by viral factor HcPro.

    Directory of Open Access Journals (Sweden)

    Nandita Sahana

    Full Text Available The ubiquitin/26S proteasome system plays an essential role not only in maintaining protein turnover, but also in regulating many other plant responses, including plant-pathogen interactions. Previous studies highlighted different roles of the 20S proteasome in plant defense during virus infection, either indirectly through viral suppressor-mediated degradation of Argonaute proteins, affecting the RNA interference pathway, or directly through modulation of the proteolytic and RNase activity of the 20S proteasome, a component of the 20S proteasome, by viral proteins, affecting the levels of viral proteins and RNAs. Here we show that MG132, a cell permeable proteasomal inhibitor, caused an increase in papaya ringspot virus (PRSV accumulation in its natural host papaya (Carica papaya. We also show that the PRSV HcPro interacts with the papaya homologue of the Arabidopsis PAA (α1 subunit of the 20S proteasome, but not with the papaya homologue of Arabidopsis PAE (α5 subunit of the 20S proteasome, associated with the RNase activity, although the two 20S proteasome subunits interacted with each other. Mutated forms of PRSV HcPro showed that the conserved KITC54 motif in the N-terminal domain of HcPro was necessary for its binding to PAA. Co-agroinfiltration assays demonstrated that HcPro expression mimicked the action of MG132, and facilitated the accumulation of bothtotal ubiquitinated proteins and viral/non-viral exogenous RNA in Nicotiana benthamiana leaves. These effects were not observed by using an HcPro mutant (KITS54, which impaired the HcPro - PAA interaction. Thus, the PRSV HcPro interacts with a proteasomal subunit, inhibiting the action of the 20S proteasome, suggesting that HcPro might be crucial for modulating its catalytic activities in support of virus accumulation.

  18. TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities

    Directory of Open Access Journals (Sweden)

    Sara Montagner

    2016-05-01

    Full Text Available Summary: Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC in DNA to 5-hydroxymethylcytosine (5hmC. Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of downregulated genes. Impaired differentiation of Tet2-ablated cells could be relieved or further exacerbated by modulating the activity of other TET family members, and mechanistically it could be linked to the dysregulated expression of C/EBP family transcription factors. Conversely, the marked increase in proliferation induced by the loss of TET2 could be rescued exclusively by re-expression of wild-type or catalytically inactive TET2. Our data indicate that, in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression. : The impact of TET enzymes on gene expression and cell function is incompletely understood. Montagner et al. investigate the TET-mediated regulation of mast cell differentiation and function, uncover transcriptional pathways regulated by TET2, and identify both enzymatic activity-dependent and -independent functions of TET2. Keywords: differentiation, DNA hydroxymethylation, epigenetics, mast cells, proliferation, TET

  19. 10 CFR 40.2a - Coverage of inactive tailings sites.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Coverage of inactive tailings sites. 40.2a Section 40.2a... Coverage of inactive tailings sites. (a) Prior to the completion of the remedial action, the Commission..., if the site is covered by the remedial action program of title I of the Uranium Mill Tailings...

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

    Science.gov (United States)

    Kahan, David

    2015-01-01

    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. 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. 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)]. Physical inactivity prevalence in the Muslim world is higher than non-Muslim countries and the difference is primarily due to higher rates among Arabs.

  1. Light controllable catalytic activity of Au clusters decorated with photochromic molecules

    Science.gov (United States)

    Guo, Na; Meng Yam, Kah; Zhang, Chun

    2018-06-01

    By ab initio calculations, we show that when decorated with a photochromic molecule, the catalytic activity of an Au nanocluster can be reversibly controlled by light. The combination of a photochromic thiol-pentacarbonyl azobenzene (TPA) molecule and an Au8 cluster is chosen as a model catalyst. The TPA molecule has two configurations (trans and cis) that can be reversibly converted to each other upon photo-excitation. Our calculations show that when the TPA takes the trans configuration, the combined system (trans-Au8) is an excellent catalyst for CO oxidation. The reaction barrier of the catalyzed CO oxidation is less than 0.4 eV. While, the reaction barrier of CO oxidation catalyzed by cis-Au8 is very high (>2.7 eV), indicating that the catalyst is inactive. These results pave the way for a new class of light controllable nanoscale catalysts.

  2. Lifetime Traumatic Experiences and Leisure Physical Inactivity among Adolescent Boys.

    Science.gov (United States)

    Malinauskas, Romualdas; Malinauskiene, Vilija; Malinauskas, Mindaugas

    2018-03-01

    The aim of this study was to examine the associations between lifetime traumatic experiences and leisure physical inactivity among adolescent boys and to determine to what extent those associations are mediated by posttraumatic stress symptoms, unhealthy behaviors (smoking, alcohol use), the daily consumption of fresh fruit, and sense of coherence. A self-administered questionnaire combining 3 instruments measured leisure physical activity level (Godin and Shephard), symptoms of posttraumatic stress (IES-revised), lifetime traumatic experiences, sense of coherence (SOC-13, from Antonovsky), and behavioral and dietary patterns in a representative sample of eighth grade boys from a number of Kaunas, Lithuania, secondary schools (N = 885; response rate 88.6%). Fifty-six point eight percent of boys had experienced at least 1 lifetime traumatic event, with a 20.5% prevalence of PTS symptoms, and 5.4% were inactive during leisure time. In the logistic regression models, leisure physical inactivity was associated with lifetime traumatic experiences (adjusted OR = 2.33; 95% CI: 1.09-4.98). Sense of coherence and posttraumatic stress symptoms did not mediate those associations. Less-than-daily consumption of fresh fruit showed an independent effect, while smoking and weekly consumption of alcohol did not. Consistent associations between lifetime traumatic experiences and leisure physical inactivity among adolescent boys indicate that the presence of lifetime traumatic events should be taken into account when employing intervention and prevention programs on unhealthy lifestyles (physical inactivity, smoking, and alcohol).

  3. Elective Mutism Associated with Selective Inactivity.

    Science.gov (United States)

    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)

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

    Science.gov (United States)

    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

  5. Amplitude mediated chimera states with active and inactive oscillators

    Science.gov (United States)

    Mukherjee, Rupak; Sen, Abhijit

    2018-05-01

    The emergence and nature of amplitude mediated chimera states, spatio-temporal patterns of co-existing coherent and incoherent regions, are investigated for a globally coupled system of active and inactive Ginzburg-Landau oscillators. The existence domain of such states is found to shrink and shift in parametric space with the increase in the fraction of inactive oscillators. The role of inactive oscillators is found to be twofold—they get activated to form a separate region of coherent oscillations and, in addition, decrease the common collective frequency of the coherent regions by their presence. The dynamical origin of these effects is delineated through a bifurcation analysis of a reduced model system that is based on a mean field approximation. Our results may have practical implications for the robustness of such states in biological or physical systems where age related deterioration in the functionality of components can occur.

  6. Three Phase Bone Scintigraphy in Active and Inactive Osteomyelitis

    International Nuclear Information System (INIS)

    Yang, Woo Jin; Chung, Soo Kyo; Ha, Hyun Kwon; Bahk, Yong Whee

    1988-01-01

    To Appreciate the value of bone scintigraphy in determination of the bony infection, we performed three phase bone scintigraphy in 34 cases of osteomyelitis of extremities prospectively. They were clinically inactive in 11 and active in 23 cases. We confirmed the active osteomyelitis by operation or aspiration within one week after scintigraphy. Perfusion, blood pool and delayed images were analyzed respectively and compared with the plain roentgenograms. All 23 active lesions showed diffusely increased perfusion in affected limbs. The areas of the increased activities on blood pool images were larger than or similar to those on delayed images in 17 cases (73.9%) with active osteomyelitis and smaller in 6 cases (26.1%). 5 of the latter 6 cases showed definite soft tissue activities on blood pool images. In inactive cases bone scintigrams were completely normal in 4 cases. Two of those were normal on plain films and remaining two showed mild focal bony sclerosis. Among 7 inactive lesions, perfusion was normal in 2 cases, diffusely increased in 4 cases and diffusely decreased in 1 case. 6 of these 7 cases showed increased activities both on blood pool and delayed images and the areas of increased activities on blood pool images didn't exceed those on delayed images. Bony sclerosis was noted on plain films in those 7 inactive lesions and the extent of the sclerosis correlated well to delayed images. Large blood pool activity was characteristics of active osteomyelitis. Normal three phase bone scintigram may indicate the time to terminate the treatment, but increased activity on perfusion and blood pool scans is not absolute indication of active lesion if the extent of the lesion on the blood pool image is smaller than that on delayed image and if no definite soft tissue activity is noted on perfusion and blood pool images in clinically inactive patient.

  7. Physical inactivity and sedentary behavior: Overlooked risk factors in autoimmune rheumatic diseases?

    Science.gov (United States)

    Pinto, Ana Jéssica; Roschel, Hamilton; de Sá Pinto, Ana Lúcia; Lima, Fernanda Rodrigues; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Bonfá, Eloisa; Gualano, Bruno

    2017-07-01

    This review aims to (1) summarize the estimates of physical inactivity and sedentary behavior in autoimmune rheumatic diseases; (2) describe the relationship between physical (in)activity levels and disease-related outcomes; (3) contextualize the estimates and impact of physical inactivity and sedentary behavior in autoimmune diseases compared to other rheumatic diseases and chronic conditions; and (4) discuss scientific perspectives around this theme and potential clinical interventions to attenuate these preventable risk factors. We compiled evidence to show that estimates of physical inactivity and sedentary behavior in autoimmune rheumatic diseases are generally comparable to other rheumatic diseases as well as to other chronic conditions (e.g., type 2 diabetes, cardiovascular diseases, and obesity), in which a lack of physical activity and excess of sedentary behavior are well-known predictors of morbimortality. In addition, we also showed evidence that both physical inactivity and sedentary behavior may be associated with poor health-related outcomes (e.g., worse disease symptoms and low functionality) in autoimmune rheumatic diseases. Thus, putting into practice interventions to make the patients "sit less and move more", particularly light-intensity activities and/or breaking-up sedentary time, is a simple and prudent therapeutic approach to minimize physical inactivity and sedentary behavior, which are overlooked yet modifiable risk factors in the field of autoimmune rheumatic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Science.gov (United States)

    2010-07-01

    ..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED... discipline exist, may impose on a practitioner the following types of discipline: (1) Exclusion from practice...

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

    Science.gov (United States)

    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. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mark Brenneman

    2018-01-01

    Full Text Available Pleuropulmonary blastoma (PPB is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of PBB patients lack predisposing germline or mosaic mutations and have sporadic (rather than syndromic disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development.

  11. Examination of race disparities in physical inactivity among adults of similar social context.

    Science.gov (United States)

    Wilson-Frederick, Shondelle M; Thorpe, Roland J; Bell, Caryn N; Bleich, Sara N; Ford, Jean G; LaVeist, Thomas A

    2014-01-01

    The objective of the study was to determine whether race disparities in physical inactivity are present among urban low-income Blacks and Whites living in similar social context. This analysis included Black and White respondents ( > or = 18 years) from the Exploring Health Disparities in Integrated Communities-Southwest Baltimore (EHDIC-SWB; N=1350) Study and the National Health Interview Survey (NHIS; N = 67790). Respondents who reported no levels of moderate or vigorous physical activity, during leisure time, over a usual week were considered physically inactive. After controlling for confounders, Blacks had higher adjusted odds of physical inactivity compared to Whites in the national sample (odds ratio [OR] = 1.40; 95% confidence interval [CI] =1.30-1.51). In EHDIC-SWB, Blacks and Whites had a similar odds of physical inactivity (OR = 1.09; 95% CI .86-1.40). Social context contributes to our understanding of racial disparities in physical inactivity.

  12. Recreational physical inactivity and mortality in women with invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Cannioto, Rikki A.; LaMonte, Michael J.; Kelemen, Linda E

    2016-01-01

    Background: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity...... and mortality. Methods: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models...... to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years. Results: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR=1.34, 95% CI: 1.18-1.52) and without (HR=1.22, 95% CI: 1...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Thomas H A Haverkamp

    Full Text Available 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.

  15. Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

    Science.gov (United States)

    Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

    2015-02-01

    Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

  16. Prevalence and Correlates of Physical Inactivity in Community-Dwelling Older Adults in Ireland

    Science.gov (United States)

    Murtagh, Elaine M.; Murphy, Marie H.; Murphy, Niamh M.; Woods, Catherine; Nevill, Alan M.; Lane, Aoife

    2015-01-01

    The public health challenges associated with rapid population ageing are likely to be exacerbated by poor physical activity levels. The purpose of this study was to identify correlates of physical inactivity in a population-representative sample of older adults in Ireland. This paper reports a secondary analysis of data from 4892 adults aged 60+ from the Irish Longitudinal Study on Ageing (TILDA). TILDA includes an assessment of the mental and physical health, and social and financial circumstances of participants assessed in a home interview and self-completion questionnaire. Chi squared statistics and forced entry logistic regression were used to identify factors associated with physical inactivity. Females were over twice as likely to be inactive as their male counterparts (Odds Ratio 2.2). Increasing old age was associated with inactivity among males and females. Those who reported above secondary level education, no reported falls in the last year and no fear of falling were less likely to be physically inactive. While older adults who noted poor/fair self-reported health, that they did not look after grandchildren, did not own a car or did not attend a course were also more likely to be inactive than those who reported positively for these items. Gender displayed a strong but often contrasting influence on factors that affect physical activity among older adults. Among females, living alone or in a rural area, retirement, fair/poor emotional health and activity being limited by illness were all significantly associated with inactivity. While cohabiting, being employed and residing in an urban area were related to low levels of activity in males. Our findings identify specific groups of the older Irish population who may be at particular risk of physical inactivity and thereby the associated physiological and psychological hazards. These results can support the development of tailored interventions to promote healthy ageing. PMID:25671621

  17. Correlates of Leisure Time Physical Inactivity in a Scandinavian Population: A Basis for Interventions.

    Science.gov (United States)

    Bonn, Stephanie E; Alfredsson, Lars; Saevarsdottir, Saedis; Schelin, Maria E C

    2016-11-01

    Effective interventions are needed to increase physical activity in the general population. To target interventions, we need knowledge of insufficiently active groups in society. This study aims to identify demographic and health-related correlates of leisure-time physical inactivity in a general Scandinavian population. Study participants comprised 5734 control subjects, age 18 to 70 years, from 2 ongoing Swedish case-control studies. Participants self-reported their leisure-time physical activity level. The odds of being physically inactive were calculated using logistic regression. A total of 42% of participants were classified as physically inactive during leisure time. A lower prevalence of inactivity was associated with middle age, higher education, having previous experience of sports participation, following a low glycemic index/Mediterranean diet and having a light physical workload. A high prevalence of inactivity was associated with greater age, high body mass index, smoking, never drinking alcohol, having children, having a weak social network or lower levels of emotional support, and a low vegetable intake. Several factors were associated with leisure-time physical inactivity. Directing interventions to target groups defined by specific factors associated with physical inactivity could be an efficient way to increase activity and improve health in the general population.

  18. Accumulation of Domain-Specific Physical Inactivity and Presence of Hypertension in Brazilian Public Healthcare System.

    Science.gov (United States)

    Turi, Bruna Camilo; Codogno, Jamile S; Fernandes, Romulo A; Sui, Xuemei; Lavie, Carl J; Blair, Steven N; Monteiro, Henrique Luiz

    2015-11-01

    Hypertension is one of the most common noncommunicable diseases worldwide, and physical inactivity is a risk factor predisposing to its occurrence and complications. However, it is still unclear the association between physical inactivity domains and hypertension, especially in public healthcare systems. Thus, this study aimed to investigate the association between physical inactivity aggregation in different domains and prevalence of hypertension among users of Brazilian public health system. 963 participants composed the sample. Subjects were divided into quartiles groups according to 3 different domains of physical activity (occupational; physical exercises; and leisure-time and transportation). Hypertension was based on physician diagnosis. Physical inactivity in occupational domain was significantly associated with higher prevalence of hypertension (OR = 1.52 [1.05 to 2.21]). The same pattern occurred for physical inactivity in leisure-time (OR = 1.63 [1.11 to 2.39]) and aggregation of physical inactivity in 3 domains (OR = 2.46 [1.14 to 5.32]). However, the multivariate-adjusted model showed significant association between hypertension and physical inactivity in 3 domains (OR = 2.57 [1.14 to 5.79]). The results suggest an unequal prevalence of hypertension according to physical inactivity across different domains and increasing the promotion of physical activity in the healthcare system is needed.

  19. Steam reformer with catalytic combustor

    Science.gov (United States)

    Voecks, Gerald E. (Inventor)

    1990-01-01

    A steam reformer is disclosed having an annular steam reforming catalyst bed formed by concentric cylinders and having a catalytic combustor located at the center of the innermost cylinder. Fuel is fed into the interior of the catalytic combustor and air is directed at the top of the combustor, creating a catalytic reaction which provides sufficient heat so as to maintain the catalytic reaction in the steam reforming catalyst bed. Alternatively, air is fed into the interior of the catalytic combustor and a fuel mixture is directed at the top. The catalytic combustor provides enhanced radiant and convective heat transfer to the reformer catalyst bed.

  20. Estimating the burden of disease attributable to physical inactivity in South Africa in 2000.

    Science.gov (United States)

    Joubert, Jané; Norman, Rosana; Lambert, Estelle V; Groenewald, Pam; Schneider, Michelle; Bull, Fiona; Bradshaw, Debbie

    2007-08-01

    To quantify the burden of disease attributable to physical inactivity in persons 15 years or older, by age group and sex, in South Africa for 2000. The global comparative risk assessment (CRA) methodology of the World Health Organization was followed to estimate the disease burden attributable to physical inactivity. Levels of physical activity for South Africa were obtained from the World Health Survey 2003. A theoretical minimum risk exposure of zero, associated outcomes, relative risks, and revised burden of disease estimates were used to calculate population-attributable fractions and the burden attributed to physical inactivity. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. South Africa. Adults >or= 15 years. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, breast cancer, colon cancer, and type 2 diabetes mellitus. Overall in adults >or= 15 years in 2000, 30% of ischaemic heart disease, 27% of colon cancer, 22% of ischaemic stroke, 20% of type 2 diabetes, and 17% of breast cancer were attributable to physical inactivity. Physical inactivity was estimated to have caused 17,037 (95% uncertainty interval 11,394 - 20,407), or 3.3% (95% uncertainty interval 2.2 - 3.9%) of all deaths in 2000, and 176,252 (95% uncertainty interval 133,733 - 203,628) DALYs, or 1.1% (95% uncertainty interval 0.8 - 1.3%) of all DALYs in 2000. Compared with other regions and the global average, South African adults have a particularly high prevalence of physical inactivity. In terms of attributable deaths, physical inactivity ranked 9th compared with other risk factors, and 12th in terms of DALYs. There is a clear need to assess why South Africans are particularly inactive, and to ensure that physical activity/inactivity is addressed as a national health priority.

  1. Effect of physical inactivity on major noncommunicable diseases and life expectancy in Brazil.

    Science.gov (United States)

    de Rezende, Leandro Fornias Machado; Rabacow, Fabiana Maluf; Viscondi, Juliana Yukari Kodaira; Luiz, Olinda do Carmo; Matsudo, Victor Keihan Rodrigues; Lee, I-Min

    2015-03-01

    In Brazil, one-fifth of the population reports not doing any physical activity. This study aimed to assess the impact of physical inactivity on major noncommunicable diseases (NCDs), all-cause mortality and life expectancy in Brazil, by region and sociodemographic profile. We estimated the population attributable fraction (PAF) for physical inactivity associated with coronary heart disease, type 2 diabetes, breast cancer, colon cancer, and all-cause mortality. To calculate the PAF, we used the physical inactivity prevalence from the 2008 Brazilian Household Survey and relative risk data in the literature. In Brazil, physical inactivity is attributable to 3% to 5% of all major NCDs and 5.31% of all-cause mortality, ranging from 5.82% in the southeastern region to 2.83% in the southern region. Eliminating physical inactivity would increase the life expectancy by an average of 0.31 years. This reduction would affect mainly individuals with ≥ 15 years of schooling, male, Asian, elderly, residing in an urban area and earning ≥ 2 times the national minimum wage. In Brazil, physical inactivity has a major impact on NCDs and mortality, principally in the southeastern and central-west regions. Public policies and interventions promoting physical activity will significantly improve the health of the population.

  2. Physical inactivity of adults and 1-year health care expenditures in Brazil

    NARCIS (Netherlands)

    Codogno, J.S.; Turi, B.C.; Kemper, H.C.G.; Fernandes, R.A.; Christofaro, D.G.D.; Monteiro, H.L.

    2015-01-01

    Objectives: To analyze the association between physical inactivity in different domains and direct public healthcare expenditures in adults and to identify whether the clustering of physical inactivity in different domains would contribute to increased public healthcare. Methods: The sample composed

  3. Mutations reducing replication from R-loops suppress the defects of growth, chromosome segregation and DNA supercoiling in cells lacking topoisomerase I and RNase HI activity.

    Science.gov (United States)

    Usongo, Valentine; Martel, Makisha; Balleydier, Aurélien; Drolet, Marc

    2016-04-01

    R-loop formation occurs when the nascent RNA hybridizes with the template DNA strand behind the RNA polymerase. R-loops affect a wide range of cellular processes and their use as origins of replication was the first function attributed to them. In Escherichia coli, R-loop formation is promoted by the ATP-dependent negative supercoiling activity of gyrase (gyrA and gyrB) and is inhibited by topoisomerase (topo) I (topA) relaxing transcription-induced negative supercoiling. RNase HI (rnhA) degrades the RNA moiety of R-loops. The depletion of RNase HI activity in topA null mutants was previously shown to lead to extensive DNA relaxation, due to DNA gyrase inhibition, and to severe growth and chromosome segregation defects that were partially corrected by overproducing topo III (topB). Here, DNA gyrase assays in crude cell extracts showed that the ATP-dependent activity (supercoiling) of gyrase but not its ATP-independent activity (relaxation) was inhibited in topA null cells lacking RNase HI. To characterize the cellular event(s) triggered by the absence of RNase HI, we performed a genetic screen for suppressors of the growth defect of topA rnhA null cells. Suppressors affecting genes in replication (holC2::aph and dnaT18::aph) nucleotide metabolism (dcd49::aph), RNA degradation (rne59::aph) and fimbriae synthesis (fimD22::aph) were found to reduce replication from R-loops and to restore supercoiling, thus pointing to a correlation between R-loop-dependent replication in topA rnhA mutants and the inhibition of gyrase activity and growth. Interestingly, the position of fimD on the E. coli chromosome corresponds to the site of one of the five main putative origins of replication from R-loops in rnhA null cells recently identified by next-generation sequencing, thus suggesting that the fimD22::aph mutation inactivated one of these origins. Furthermore, we show that topo III overproduction is unable to complement the growth defect of topA rnhA null mutants at low

  4. Long-term sickness absence from work due to physical inactivity: A registry-based study.

    Science.gov (United States)

    Høgsbro, Cecilie; Davidsen, Michael; Sørensen, Jan

    2018-01-01

    The aim of this study was to explore the relationship between leisure-time physical inactivity and long-term sickness absence in a representative sample of individuals aged 16-54 years, within the labour market and in good health. It was hypothesised that physically inactive individuals have a higher risk of long-term sickness absence and longer duration of sickness absence. The study population was identified from the National Health and Morbidity Survey, 2010. Weekly data on long-term sickness absence were obtained from the National Register on Social Transfer Payments (the DREAM registry). The association of incidence and duration of long-term sickness absence with physical inactivity was explored using logistic and Poisson regression. Data were fitted to models with levels of physical activity, demographic, social and lifestyle characteristics as independent variables. A combined hurdle model was used to estimate the difference in mean number of absence weeks. Logistic regression showed that physically inactive individuals had a 27% higher incidence of long-term sickness absence compared with physically active individuals. The Poisson regression showed that long-term sickness absence was only slightly shorter (1 week less) for moderately active individuals compared with inactive individuals. The hurdle model estimated longer absence periods for inactive individuals (additional 2.5 weeks) in comparison with moderately and highly active individuals. The study showed that physically inactive individuals have a higher incidence of long-term absence and that physically inactive individuals have longer periods with sickness absence than moderately and highly active individuals. When adjustments for social and health behaviour were included, the estimated associations became statistically insignificant.

  5. Localization in the Nucleolus and Coiled Bodies of Protein Subunits of the Ribonucleoprotein Ribonuclease P

    Science.gov (United States)

    Jarrous, Nayef; Wolenski, Joseph S.; Wesolowski, Donna; Lee, Christopher; Altman, Sidney

    1999-01-01

    The precise location of the tRNA processing ribonucleoprotein ribonuclease P (RNase P) and the mechanism of its intranuclear distribution have not been completely delineated. We show that three protein subunits of human RNase P (Rpp), Rpp14, Rpp29 and Rpp38, are found in the nucleolus and that each can localize a reporter protein to nucleoli of cells in tissue culture. In contrast to Rpp38, which is uniformly distributed in nucleoli, Rpp14 and Rpp29 are confined to the dense fibrillar component. Rpp29 and Rpp38 possess functional, yet distinct domains required for subnucleolar localization. The subunit Rpp14 lacks such a domain and appears to be dependent on a piggyback process to reach the nucleolus. Biochemical analysis suggests that catalytically active RNase P exists in the nucleolus. We also provide evidence that Rpp29 and Rpp38 reside in coiled bodies, organelles that are implicated in the biogenesis of several other small nuclear ribonucleoproteins required for processing of precursor mRNA. Because some protein subunits of RNase P are shared by the ribosomal RNA processing ribonucleoprotein RNase MRP, these two evolutionary related holoenzymes may share common intranuclear localization and assembly pathways to coordinate the processing of tRNA and rRNA precursors. PMID:10444065

  6. Catalytic nanoporous membranes

    Science.gov (United States)

    Pellin, Michael J; Hryn, John N; Elam, Jeffrey W

    2013-08-27

    A nanoporous catalytic membrane which displays several unique features Including pores which can go through the entire thickness of the membrane. The membrane has a higher catalytic and product selectivity than conventional catalysts. Anodic aluminum oxide (AAO) membranes serve as the catalyst substrate. This substrate is then subjected to Atomic Layer Deposition (ALD), which allows the controlled narrowing of the pores from 40 nm to 10 nm in the substrate by deposition of a preparatory material. Subsequent deposition of a catalytic layer on the inner surfaces of the pores reduces pore sizes to less than 10 nm and allows for a higher degree of reaction selectivity. The small pore sizes allow control over which molecules enter the pores, and the flow-through feature can allow for partial oxidation of reactant species as opposed to complete oxidation. A nanoporous separation membrane, produced by ALD is also provided for use in gaseous and liquid separations. The membrane has a high flow rate of material with 100% selectivity. Also provided is a method for producing a catalytic membrane having flow-through pores and discreet catalytic clusters adhering to the inside surfaces of the pores.

  7. The pulsed migration of hydrocarbons across inactive faults

    Directory of Open Access Journals (Sweden)

    S. D. Harris

    1999-01-01

    Full Text Available Geological fault zones are usually assumed to influence hydrocarbon migration either as high permeability zones which allow enhanced along- or across-fault flow or as barriers to the flow. An additional important migration process inducing along- or across-fault migration can be associated with dynamic pressure gradients. Such pressure gradients can be created by earthquake activity and are suggested here to allow migration along or across inactive faults which 'feel' the quake-related pressure changes; i.e. the migration barriers can be removed on inactive faults when activity takes place on an adjacent fault. In other words, a seal is viewed as a temporary retardation barrier which leaks when a fault related fluid pressure event enhances the buoyancy force and allows the entry pressure to be exceeded. This is in contrast to the usual model where a seal leaks because an increase in hydrocarbon column height raises the buoyancy force above the entry pressure of the fault rock. Under the new model hydrocarbons may migrate across the inactive fault zone for some time period during the earthquake cycle. Numerical models of this process are presented to demonstrate the impact of this mechanism and its role in filling traps bounded by sealed faults.

  8. Physical inactivity displays a mediator role in the association of diabetes and poverty: A spatiotemporal analysis

    Directory of Open Access Journals (Sweden)

    Lung-Chang Chien

    2017-11-01

    Full Text Available Physical inactivity is one of the risk factors of diabetes. In addition, physical inactivity is attributed to urbanization-related factors, such as poverty, which is also one of the risk factors of diabetes. We hypothesized that physical inactivity is a mediator in the association between diabetes and poverty, and that spatial heterogeneity exists in these relationships. This study adopted a spatiotemporal modelling approach to conduct this mediator analysis. From 2004-2011, data were collected at the county level in 48 contiguous states (with a total of 3,109 counties from the Behavioral Risk Factor Surveillance System (BRFSS and American Community Survey. Poverty percentage significantly affected physical inactivity prevalence and diabetes prevalence in two separate models. Using a model with both physical inactivity and poverty percentages as independent variables, we verified that physical inactivity prevalence is a significant mediator. In this model, physical inactivity prevalence resulted in a significant positive association with diabetes prevalence, and the influence of poverty percentage on diabetes prevalence was significantly reduced (P=0.0009. An advanced spatiotemporal analysis revealed that 32.65% of counties having a significant positive association between diabetes prevalence and physical inactivity prevalence also had a significant positive association between physical inactivity prevalence and poverty percentage. Those counties were also likely located in the South and Southeast of USA. In summary, the findings of this study demonstrate the mediating effect of physical inactivity between diabetes and poverty. When implementing diabetes prevention in communities with higher poverty, appropriate strategies to reduce the cost burden of physical activity programmes should be considered.

  9. Physical inactivity displays a mediator role in the association of diabetes and poverty: A spatiotemporal analysis.

    Science.gov (United States)

    Chien, Lung-Chang; Li, Xiao; Staudt, Amanda

    2017-11-03

    Physical inactivity is one of the risk factors of diabetes. In addition, physical inactivity is attributed to urbanization-related factors, such as poverty, which is also one of the risk factors of diabetes. We hypothesized that physical inactivity is a mediator in the association between diabetes and poverty, and that spatial heterogeneity exists in these relationships. This study adopted a spatiotemporal modelling approach to conduct this mediator analysis. From 2004-2011, data were collected at the county level in 48 contiguous states (with a total of 3,109 counties) from the Behavioral Risk Factor Surveillance System (BRFSS) and American Community Survey. Poverty percentage significantly affected physical inactivity prevalence and diabetes prevalence in two separate models. Using a model with both physical inactivity and poverty percentages as independent variables, we verified that physical inactivity prevalence is a significant mediator. In this model, physical inactivity prevalence resulted in a significant positive association with diabetes prevalence, and the influence of poverty percentage on diabetes prevalence was significantly reduced (P=0.0009). An advanced spatiotemporal analysis revealed that 32.65% of counties having a significant positive association between diabetes prevalence and physical inactivity prevalence also had a significant positive association between physical inactivity prevalence and poverty percentage. Those counties were also likely located in the South and Southeast of USA. In summary, the findings of this study demonstrate the mediating effect of physical inactivity between diabetes and poverty. When implementing diabetes prevention in communities with higher poverty, appropriate strategies to reduce the cost burden of physical activity programmes should be considered.

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

    Science.gov (United States)

    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. Inactive Doses and Protein Concentration of Gamma Irradiated Yersinia Enterocolitica

    International Nuclear Information System (INIS)

    Irawan Sugoro; Sandra Hermanto

    2009-01-01

    Yersinia enterocolitica is one of bacteria which cause coliform mastitis in dairy cows. The bacteria could be inactivated by gamma irradiation as inactivated vaccine candidate. The experiment has been conducted to determine the inactive doses and the protein concentration of Yersinia enterocolitica Y3 which has been irradiated by gamma rays. The cells cultures were irradiated by gamma rays with doses of 0, 100, 200, 400, 600, 800, 1.000 and 1.500 Gy (doses rate was 1089,59 Gy/hours). The inactive dose was determined by the drop test method and the protein concentration of cells were determined by Lowry method. The results showed that the inactive doses occurred on 800 – 1500 Gy. The different irradiation doses of cell cultures showed the effect of gamma irradiation on the protein concentration that was random and has a significant effect on the protein concentration. (author)

  12. Hepatic steatosis development with four weeks of physical inactivity in previously active, hyperphagic OLETF rats.

    Science.gov (United States)

    Linden, Melissa A; Meers, Grace M; Ruebel, Meghan L; Jenkins, Nathan T; Booth, Frank W; Laughlin, M Harold; Ibdah, Jamal A; Thyfault, John P; Rector, R Scott

    2013-05-01

    Physical activity-induced prevention of hepatic steatosis is maintained during short-term (7-day) transitions to an inactive state; however, whether these protective effects are present under a longer duration of physical inactivity is largely unknown. Here, we sought to determine whether previous physical activity had protective effects on hepatic steatosis and metabolic health following 4 wk of physical inactivity. Four-week old, hyperphagic, male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly assigned to either a sedentary group for 16 wk (OLETF-SED), given access to running wheels for 16 wk with wheels locked 5 h (OLETF-WL5hr) or given access to running wheels for 12 wk with wheels locked 4 wk (OLETF-WL4wk) prior to death. Four weeks of physical inactivity caused hepatic steatosis development, but liver triglycerides remained 60% lower than OLETF-SED (P inactivity, whereas markers of fatty acid uptake and lipogenesis remained relatively suppressed following 4 wk of inactivity. In addition, 4 wk of inactivity caused a complete loss of activity-induced increases in serum IL-6 and reductions in regulated upon activation, normal T-cell expressed, and secreted (RANTES), and a partial loss in reductions in leptin, monocyte chemoattractant protein-1, and TNF-α. In conclusion, 4 wk of physical inactivity does not result in a complete loss in physical activity-induced benefits but does cause deterioration in the liver phenotype and overall metabolic health in hyperphagic OLETF rats.

  13. Time course of arterial vascular adaptations to inactivity and paralyses in humans.

    NARCIS (Netherlands)

    Groot, P.C.E. de; Kuppevelt, D. van; Pons, C.; Snoek, G.V.E.; Woude, L.H.V. van der; Hopman, M.T.E.

    2003-01-01

    PURPOSE: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

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

    Science.gov (United States)

    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 (pphysical 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

  15. Insights into the Prunus-Specific S-RNase-Based Self-Incompatibility System from a Genome-Wide Analysis of the Evolutionary Radiation of S Locus-Related F-box Genes.

    Science.gov (United States)

    Akagi, Takashi; Henry, Isabelle M; Morimoto, Takuya; Tao, Ryutaro

    2016-06-01

    Self-incompatibility (SI) is an important plant reproduction mechanism that facilitates the maintenance of genetic diversity within species. Three plant families, the Solanaceae, Rosaceae and Plantaginaceae, share an S-RNase-based gametophytic SI (GSI) system that involves a single S-RNase as the pistil S determinant and several F-box genes as pollen S determinants that act via non-self-recognition. Previous evidence has suggested a specific self-recognition mechanism in Prunus (Rosaceae), raising questions about the generality of the S-RNase-based GSI system. We investigated the evolution of the pollen S determinant by comparing the sequences of the Prunus S haplotype-specific F-box gene (SFB) with those of its orthologs in other angiosperm genomes. Our results indicate that the Prunus SFB does not cluster with the pollen S of other plants and diverged early after the establishment of the Eudicots. Our results further indicate multiple F-box gene duplication events, specifically in the Rosaceae family, and suggest that the Prunus SFB gene originated in a recent Prunus-specific gene duplication event. Transcriptomic and evolutionary analyses of the Prunus S paralogs are consistent with the establishment of a Prunus-specific SI system, and the possibility of subfunctionalization differentiating the newly generated SFB from the original pollen S determinant. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress.

    Science.gov (United States)

    Benoit, Stéphane L; Maier, Robert J

    2016-11-04

    Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H 2 O 2 ). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains ( katA H56A and katA Y339A ) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalase-deletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H 2 O 2 -dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new non-enzymatic protective mechanism of action for the ubiquitous enzyme. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Addressing physical inactivity in Omani adults: perceptions of public health managers.

    Science.gov (United States)

    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.

  18. Associations of unhealthy lifestyle factors with sexual inactivity and sexual dysfunctions in Denmark.

    Science.gov (United States)

    Christensen, Birgitte S; Grønbaek, Morten; Pedersen, Bo V; Graugaard, Christian; Frisch, Morten

    2011-07-01

    Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting. To examine associations between unhealthy lifestyle factors and sexual inactivity with a partner and four specific sexual dysfunctions in each sex. We used nationally representative survey data from 5,552 Danish men and women aged 16-97 years in 2005. Cross-sectional associations of lifestyle factors with sexual inactivity and sexual dysfunctions were estimated by logistic regression-derived, confounder-adjusted odds ratios (ORs). We calculated ORs for sexual inactivity with a partner and for sexual dysfunction and sexual difficulties overall in both sexes, for erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men, and for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women. Obesity (body mass index [BMI]≥30 kg/m(2) ) or a substantially increased waist circumference (men ≥102 cm; women ≥88 cm), physical inactivity, and, among women, tobacco smoking were each significantly associated with sexual inactivity in the last year. Among sexually active men, both underweight (BMI 21 alcoholic beverages/week), tobacco smoking, and use of hard drugs were each significantly positively associated with one or more sexual dysfunctions (ORs between 1.71 and 22.0). Among sexually active women, the only significant positive association between an unhealthy lifestyle factor and sexual dysfunction was between hashish use and anorgasmia (OR 2.85). In both sexes, several unhealthy lifestyle factors were associated with sexual inactivity with a partner in the last year. Additionally, among sexually active participants, men with unhealthy lifestyles were significantly more likely to experience sexual dysfunctions. Considering the importance of a good sex life, our findings may be useful in attempts to promote healthier

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

    Science.gov (United States)

    Chaligné, Ronan; Popova, Tatiana; Mendoza-Parra, Marco-Antonio; Saleem, Mohamed-Ashick M; Gentien, David; Ban, Kristen; Piolot, Tristan; Leroy, Olivier; Mariani, Odette; Gronemeyer, Hinrich; Vincent-Salomon, Anne; Stern, Marc-Henri; Heard, Edith

    2015-04-01

    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. © 2015 Chaligné et al.; Published by Cold Spring Harbor Laboratory Press.

  20. PHYSICAL (INACTIVITY AND WOMEN

    Directory of Open Access Journals (Sweden)

    Nina Đukanović

    2008-08-01

    Full Text Available Physical activity simply means movement of the body that uses energy. Physical inactivity is more common among women than men. In women physical activity reduces the risk of dying from coronary heart disease and stroke and of developing high blood pressure, diabetes mellitus, reduces blood cholesterol level, helps control weight and reduce body fat, helps control and prevention osteoporosis and artritis, reduces symptoms of anxiety and depression, reduces the risk for breast cancer. From health benefits, physical activity should be moderate or vigorous and add up to at the least 30 minutes a day.

  1. Non-thermal plasmas for non-catalytic and catalytic VOC abatement

    International Nuclear Information System (INIS)

    Vandenbroucke, Arne M.; Morent, Rino; De Geyter, Nathalie; Leys, Christophe

    2011-01-01

    Highlights: → We review the current status of catalytic and non-catalytic VOC abatement based on a vast number of research papers. → The underlying mechanisms of plasma-catalysis for VOC abatement are discussed. → Critical process parameters that determine the influent are discussed and compared. - Abstract: This paper reviews recent achievements and the current status of non-thermal plasma (NTP) technology for the abatement of volatile organic compounds (VOCs). Many reactor configurations have been developed to generate a NTP at atmospheric pressure. Therefore in this review article, the principles of generating NTPs are outlined. Further on, this paper is divided in two equally important parts: plasma-alone and plasma-catalytic systems. Combination of NTP with heterogeneous catalysis has attracted increased attention in order to overcome the weaknesses of plasma-alone systems. An overview is given of the present understanding of the mechanisms involved in plasma-catalytic processes. In both parts (plasma-alone systems and plasma-catalysis), literature on the abatement of VOCs is reviewed in close detail. Special attention is given to the influence of critical process parameters on the removal process.

  2. Physical inactivity affects skeletal muscle insulin signaling in a birth weight-dependent manner

    DEFF Research Database (Denmark)

    Mortensen, Brynjulf; Friedrichsen, Martin; Andersen, Nicoline Resen

    2014-01-01

    We investigated whether physical inactivity could unmask defects in insulin and AMPK signaling in low birth weight (LBW) subjects.......We investigated whether physical inactivity could unmask defects in insulin and AMPK signaling in low birth weight (LBW) subjects....

  3. A model for predicting Inactivity in the European Banking Sector

    Directory of Open Access Journals (Sweden)

    Themistokles Lazarides

    2015-08-01

    Full Text Available Purpose – The paper will addresses the issue of inactivity and will try to detect its causes using econometric models. The Banking sector of Europe has been under transformation or restructuring for almost half a century. Design/methodology/approach – Probit models and descriptive statistics have been used to create a system that predicts inactivity. The data was collected from Bankscope. Findings – The results of the econometric models show that from the six groups of indicators, four have been found to be statistically important (performance, size, ownership, corporate governance. These findings are consistent with the theory. Research limitations/implications – The limitation is that Bankscope does not provide any longitudinal data regarding ownership, management structure and there are some many missing values before 2007 for some of the financial ratios and data. Originality/value – The paper's value and innovation is that it has given a systemic approach to find indicators of inactivity.

  4. Physical inactivity, gender and culture in Arab countries: a systematic assessment of the literature.

    Science.gov (United States)

    Sharara, Eman; Akik, Chaza; Ghattas, Hala; Makhlouf Obermeyer, Carla

    2018-05-18

    Physical inactivity is associated with excess weight and adverse health outcomes. We synthesize the evidence on physical inactivity and its social determinants in Arab countries, with special attention to gender and cultural context. We searched MEDLINE, Popline, and SSCI for articles published between 2000 and 2016, assessing the prevalence of physical inactivity and its social determinants. We also included national survey reports on physical activity, and searched for analyses of the social context of physical activity. We found 172 articles meeting inclusion criteria. Standardized data are available from surveys by the World Health Organization for almost all countries, but journal articles show great variability in definitions, measurements and methodology. Prevalence of inactivity among adults and children/adolescents is high across countries, and is higher among women. Some determinants of physical inactivity in the region (age, gender, low education) are shared with other regions, but specific aspects of the cultural context of the region seem particularly discouraging of physical activity. We draw on social science studies to gain insights into why this is so. Physical inactivity among Arab adults and children/adolescents is high. Studies using harmonized approaches, rigorous analytic techniques and a deeper examination of context are needed to design appropriate interventions.

  5. Catalytic distillation process

    Science.gov (United States)

    Smith, L.A. Jr.

    1982-06-22

    A method is described for conducting chemical reactions and fractionation of the reaction mixture comprising feeding reactants to a distillation column reactor into a feed zone and concurrently contacting the reactants with a fixed bed catalytic packing to concurrently carry out the reaction and fractionate the reaction mixture. For example, a method for preparing methyl tertiary butyl ether in high purity from a mixed feed stream of isobutene and normal butene comprising feeding the mixed feed stream to a distillation column reactor into a feed zone at the lower end of a distillation reaction zone, and methanol into the upper end of said distillation reaction zone, which is packed with a properly supported cationic ion exchange resin, contacting the C[sub 4] feed and methanol with the catalytic distillation packing to react methanol and isobutene, and concurrently fractionating the ether from the column below the catalytic zone and removing normal butene overhead above the catalytic zone.

  6. Differential CT Attenuation of Metabolically Active and Inactive Adipose Tissues — Preliminary Findings

    Science.gov (United States)

    Hu, Houchun H.; Chung, Sandra A.; Nayak, Krishna S.; Jackson, Hollie A.; Gilsanz, Vicente

    2010-01-01

    This study investigates differences in CT Hounsfield units (HUs) between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. PET/CT data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified and standard uptake values (SUVs) and HUs were measured. HUs of active brown fat were more positive (p<0.001) than inactive fat (−62.4±5.3 versus −86.7±7.0) and the difference was observed in both males and females. PMID:21245691

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

    Science.gov (United States)

    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

  8. Human development, occupational structure and physical inactivity among 47 low and middle income countries

    OpenAIRE

    Atkinson, Kaitlin; Lowe, Samantha; Moore, Spencer

    2016-01-01

    This study aimed to (a) assess the relationship between a person's occupational category and their physical inactivity, and (b) analyze the association among country-level variables and physical inactivity. The World Health Survey (WHS) was administered in 2002?2003 among 47 low- and middle-income countries (n?=?196,742). The International Physical Activity Questionnaire (IPAQ) was used to collect verbal reports of physical activity and convert responses into measures of physical inactivity. ...

  9. Catalytic Combustion of Gasified Waste

    Energy Technology Data Exchange (ETDEWEB)

    Kusar, Henrik

    2003-09-01

    This thesis concerns catalytic combustion for gas turbine application using a low heating-value (LHV) gas, derived from gasified waste. The main research in catalytic combustion focuses on methane as fuel, but an increasing interest is directed towards catalytic combustion of LHV fuels. This thesis shows that it is possible to catalytically combust a LHV gas and to oxidize fuel-bound nitrogen (NH{sub 3}) directly into N{sub 2} without forming NO{sub x} The first part of the thesis gives a background to the system. It defines waste, shortly describes gasification and more thoroughly catalytic combustion. The second part of the present thesis, paper I, concerns the development and testing of potential catalysts for catalytic combustion of LHV gases. The objective of this work was to investigate the possibility to use a stable metal oxide instead of noble metals as ignition catalyst and at the same time reduce the formation of NO{sub x} In paper II pilot-scale tests were carried out to prove the potential of catalytic combustion using real gasified waste and to compare with the results obtained in laboratory scale using a synthetic gas simulating gasified waste. In paper III, selective catalytic oxidation for decreasing the NO{sub x} formation from fuel-bound nitrogen was examined using two different approaches: fuel-lean and fuel-rich conditions. Finally, the last part of the thesis deals with deactivation of catalysts. The various deactivation processes which may affect high-temperature catalytic combustion are reviewed in paper IV. In paper V the poisoning effect of low amounts of sulfur was studied; various metal oxides as well as supported palladium and platinum catalysts were used as catalysts for combustion of a synthetic gas. In conclusion, with the results obtained in this thesis it would be possible to compose a working catalytic system for gas turbine application using a LHV gas.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  12. The innate defense antimicrobial peptides hBD3 and RNase7 are induced in human umbilical vein endothelial cells by classical inflammatory cytokines but not Th17 cytokines.

    Science.gov (United States)

    Burgey, Christine; Kern, Winfried V; Römer, Winfried; Sakinc, Türkan; Rieg, Siegbert

    2015-05-01

    Antimicrobial peptides are multifunctional effector molecules of innate immunity. In this study we investigated whether endothelial cells actively contribute to innate defense mechanisms by expression of antimicrobial peptides. We therefore stimulated human umbilical vein endothelial cells (HUVEC) with inflammatory cytokines, Th17 cytokines, heat-inactivated bacteria, bacterial conditioned medium (BCM) of Staphylococcus aureus and Streptococcus sanguinis, and lipoteichoic acid (LTA). Stimulation with single cytokines induced discrete expression of human β-defensin 3 (hBD3) by IFN-γ or IL-1β and of ribonuclease 7 (RNase7) by TNF-α without any effects on LL-37 gene expression. Stronger hBD3 and RNase7 induction was observed after combined stimulation with IL-1β, TNF-α and IFN-γ and was confirmed by high hBD3 and RNase7 peptide levels in cell culture supernatants. In contrast, Th17 cytokines or stimulation with LTA did not result in AMP production. Moreover, only BCM of an invasive S. aureus bacteremia isolate induced hBD3 in HUVEC. We conclude that endothelial cells actively contribute to prevent dissemination of pathogens at the blood-tissue-barrier by production of AMPs that exhibit microbicidal and immunomodulatory functions. Further investigations should focus on tissue-specific AMP induction in different endothelial cell types, on pathogen-specific induction patterns and potentially involved pattern-recognition receptors of endothelial cells. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  13. Potent inhibition of mammalian ribonucleases by 3', 5'-pyrophosphate-linked nucleotides.

    Science.gov (United States)

    Russo, N; Shapiro, R

    1999-05-21

    Molecular modeling based on the crystal structure of the complex of bovine pancreatic RNase A with the inhibitor 5'-diphosphoadenosine 3'-phosphate (ppAp) (Leonidas, D. D., Shapiro, R., Irons, L. I., Russo, N., and Acharya, K. R. (1997) Biochemistry 36, 5578-5588) was used to design new inhibitors that extend into unoccupied regions of the enzyme active site. These compounds are dinucleotides that contain an unusual 3',5'-pyrophosphate linkage and were synthesized in solution by a combined chemical and enzymatic procedure. The most potent of them, 5'-phospho-2'-deoxyuridine 3'-pyrophosphate, P' --> 5'-ester with adenosine 3'-phosphate (pdUppAp), binds to RNase A with Ki values of 27 and 220 nM at pH 5.9 and 7, respectively. These values are 6-9-fold lower than those for ppAp and 50-fold lower than that for the transition state analogue, uridine vanadate. pdUppAp has broad specificity; it is an effective inhibitor of at least two other members of the pancreatic RNase superfamily, human RNase-2 (eosinophil-derived neurotoxin) and RNase-4, which share only 36-44% sequence identity with the pancreatic enzyme. The potency of pdUppAp and the other inhibitors described here depends critically on the extended internucleotide linkage; the pyrophosphate group enhances dinucleotide binding to the three RNases by 2.1-2.9 orders of magnitude, as compared with a monophosphate. These data give further insight into the organization of the catalytic centers of the various RNases. Moreover, the new class of inhibitors provides a useful means by which to probe the biological actions of these and other related enzymes.

  14. Barrier-beliefs about physical activity in active and inactive adults : an explorative study

    NARCIS (Netherlands)

    Bouma, Adrie

    2018-01-01

    Objectives: Perceived barriers are often a reason why people do not start physical activity or relapse to inactivity. From a psychological perspective, barriers can be seen as beliefs about what is obstructing people’s behavior. To understand inactivity and relapse from physical activity, this study

  15. Catalytic bioreactors and methods of using same

    Science.gov (United States)

    Worden, Robert Mark; Liu, Yangmu Chloe

    2017-07-25

    Various embodiments provide a bioreactor for producing a bioproduct comprising one or more catalytically active zones located in a housing and adapted to keep two incompatible gaseous reactants separated when in a gas phase, wherein each of the one or more catalytically active zones may comprise a catalytic component retainer and a catalytic component retained within and/or thereon. Each of the catalytically active zones may additionally or alternatively comprise a liquid medium located on either side of the catalytic component retainer. Catalytic component may include a microbial cell culture located within and/or on the catalytic component retainer, a suspended catalytic component suspended in the liquid medium, or a combination thereof. Methods of using various embodiments of the bioreactor to produce a bioproduct, such as isobutanol, are also provided.

  16. Characterization of TRZ1, a yeast homolog of the human candidate prostate cancer susceptibility gene ELAC2 encoding tRNase Z

    Directory of Open Access Journals (Sweden)

    Chen Yuan

    2005-05-01

    Full Text Available Abstract Background In humans, mutation of ELAC2 is associated with an increased risk of prostate cancer. ELAC2 has been shown to have tRNase Z activity and is associated with the γ-tubulin complex. Results In this work, we show that the yeast homolog of ELAC2, encoded by TRZ1 (tRNase Z 1, is involved genetically in RNA processing. The temperature sensitivity of a trz1 mutant can be rescued by multiple copies of REX2, which encodes a protein with RNA 3' processing activity, suggesting a role of Trz1p in RNA processing in vivo. Trz1p has two putative nucleotide triphosphate-binding motifs (P-loop and a conserved histidine motif. The histidine motif and the putative nucleotide binding motif at the C-domain are important for Trz1p function because mutant proteins bearing changes to the critical residues in these motifs are unable to rescue deletion of TRZ1. The growth defect exhibited by trz1 yeast is not complemented by the heterologous ELAC2, suggesting that Trz1p may have additional functions in yeast. Conclusion Our results provide genetic evidence that prostate cancer susceptibility gene ELAC2 may be involved in RNA processing, especially rRNA processing and mitochondrial function.

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

    Science.gov (United States)

    Cannioto, Rikki; LaMonte, Michael J; Risch, Harvey A; Hong, Chi-Chen; Sucheston-Campbell, Lara E; Eng, Kevin H; Brian Szender, J; Chang-Claude, Jenny; Schmalfeldt, Barbara; Klapdor, Ruediger; Gower, Emily; Minlikeeva, Albina N; Zirpoli, Gary R; 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; Leigh Pearce, Celeste; Pike, Malcolm C; Anne Rossing, Mary; 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

    2016-07-01

    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 to investigate the association between chronic recreational physical inactivity and EOC risk. 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 ORs 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. 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. 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. 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. Cancer Epidemiol Biomarkers Prev; 25(7); 1114-24. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress*♦

    Science.gov (United States)

    Benoit, Stéphane L.; Maier, Robert J.

    2016-01-01

    Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H2O2). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains (katAH56A and katAY339A) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalase-deletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H2O2-dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new non-enzymatic protective mechanism of action for the ubiquitous enzyme. PMID:27605666

  19. Career transitions of inactive nurses: a registration database analysis (1993-2006).

    Science.gov (United States)

    Alameddine, Mohamad; Baumann, Andrea; Onate, Kanecy; Deber, Raisa

    2011-02-01

    One important strategy to address nursing shortages is to tap into the pool of licensed nurses who are not currently working in nursing and induce them to return to the nursing labour market. However, there is a paucity of research examining their likelihood of return to the active labour market. Analyze the career transitions of nurses registered with the College of Nurses Ontario but not working in the province's nursing labour market to determine the proportion of these nurses rejoining the active nursing workforce and examine the variation by inactive sub-category and age group. Quantitative analysis of a linked longitudinal database for all those registered with the College of Nurses of Ontario for the years 1993-2006. Registration records of all 215,687 nurses registered at any time in those years were merged by their unique registration number. Each nurse was placed for each year into an employment category. Two groups of nurses were defined: active (registered, working in nursing in Ontario) and inactive (registered, not working in nursing in Ontario). Inactive nurses were then sub-categorized into five mutually exclusive sub-categories: 'not working and seeking nursing employment', 'working in non-nursing and seeking nursing employment', 'not working and not seeking nursing employment', 'working in non-nursing and not seeking nursing employment' and 'working outside Ontario'. One-year career movements of nurses were tracked by generating 13 year-to-year transition matrixes. In the short-term, inactive nurses seeking a nursing job had the highest average rate of return to the active workforce (27.3-30.8%), though they might become high risk of leaving the profession if they do not find employment in a timely manner. Inactive nurses not seeking nursing employment are a heterogeneous group, and include nurses on leave who are likely to subsequently rejoin the active workforce should appropriate opportunities arise. The proportion of nurses rejoining the

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

    Science.gov (United States)

    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.

  1. Catalytic process for tritium exchange reaction

    International Nuclear Information System (INIS)

    Hansoo Lee; Kang, H.S.; Paek, S.W.; Hongsuk Chung; Yang Geun Chung; Sook Kyung Lee

    2001-01-01

    The catalytic activities for a hydrogen isotope exchange were measured through the reaction of a vapor and gas mixture. The catalytic activity showed to be comparable with the published data. Since the gas velocity is relatively low, the deactivation was not found clearly during the 5-hour experiment. Hydrogen isotope transfer experiments were also conducted through the liquid phase catalytic exchange reaction column that consisted of a catalytic bed and a hydrophilic bed. The efficiencies of both the catalytic and hydrophilic beds were higher than 0.9, implying that the column performance was excellent. (author)

  2. Job strain as a risk factor for leisure-time physical inactivity

    DEFF Research Database (Denmark)

    Fransson, Eleonor I; Heikkilä, Katriina; Nyberg, Solja T

    2012-01-01

    Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14...... European cohort studies (baseline years from 1985-1988 to 2006-2008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50% women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 2-9 years....... In cross-sectional analyses, the odds for physical inactivity were 26% higher (odds ratio = 1.26, 95% confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21% higher (odds ratio = 1.21, 95% confidence interval: 1.11, 1.31) for those with passive jobs (low...

  3. Worldwide prevalence of physical inactivity and its association with human development index in 76 countries

    OpenAIRE

    Dumith, Samuel de Carvalho; Hallal, Pedro Rodrigues Curi; Reis, Rodrigo Siqueira; Kohl, Harold

    2011-01-01

    Objective. To describe the worldwide prevalence of physical inactivity and to analyze its association with development level of each country. Methods. Pooled analysis of three multicenter studies, conducted between 2002 and 2004, which investigated the prevalence of physical inactivity in 76 countries, and comprised almost 300,000 individuals aged 15 years or older. Each study used the International Physical Activity Questionnaire to assess physical inactivity. The level of development of ...

  4. Setting-related influences on physical inactivity of older adults in residential care settings: a review.

    Science.gov (United States)

    Douma, Johanna G; Volkers, Karin M; Engels, Gwenda; Sonneveld, Marieke H; Goossens, Richard H M; Scherder, Erik J A

    2017-04-28

    Despite the detrimental effects of physical inactivity for older adults, especially aged residents of residential care settings may spend much time in inactive behavior. This may be partly due to their poorer physical condition; however, there may also be other, setting-related factors that influence the amount of inactivity. The aim of this review was to review setting-related factors (including the social and physical environment) that may contribute to the amount of older adults' physical inactivity in a wide range of residential care settings (e.g., nursing homes, assisted care facilities). Five databases were systematically searched for eligible studies, using the key words 'inactivity', 'care facilities', and 'older adults', including their synonyms and MeSH terms. Additional studies were selected from references used in articles included from the search. Based on specific eligibility criteria, a total of 12 studies were included. Quality of the included studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Based on studies using different methodologies (e.g., interviews and observations), and of different quality (assessed quality range: 25-100%), we report several aspects related to the physical environment and caregivers. Factors of the physical environment that may be related to physical inactivity included, among others, the environment's compatibility with the abilities of a resident, the presence of equipment, the accessibility, security, comfort, and aesthetics of the environment/corridors, and possibly the presence of some specific areas. Caregiver-related factors included staffing levels, the available time, and the amount and type of care being provided. Inactivity levels in residential care settings may be reduced by improving several features of the physical environment and with the help of caregivers. Intervention studies could be performed in order to gain more insight into causal effects of improving setting-related factors on

  5. Contributions to the theory of catalytic titrations-III Neutralization catalytic titrations.

    Science.gov (United States)

    Gaál, F F; Abramović, B F

    1985-07-01

    Neutralization catalytic titrations of weak monoprotic adds and bases with both volumetric and coulometric addition of the titrant (strong base/acid) have been simulated by taking into account the equilibrium concentration of the catalyst during the titration. The influence of several factors on the shape of the simulated catalytic titration curve has been investigated and is discussed.

  6. Trends in social inequality in physical inactivity among Danish adolescents 1991-2014.

    Science.gov (United States)

    Johnsen, N F; Toftager, M; Melkevik, O; Holstein, B E; Rasmussen, M

    2017-12-01

    The aim of this study was to investigate social inequality in physical inactivity among adolescents from 1991 to 2014 and to describe any changes in inequality during this period. The analyses were based on data from the Danish part of the HBSC study, which consists of seven comparable cross-sectional studies of nationally representative samples of 11-15-year old adolescents. The available data consisted of weekly time (hours) spent on vigorous physical activity and parental occupation from 30,974 participants. In summary, 8.0% of the adolescents reported to be physically inactive, i.e. spend zero hours of vigorous leisure time physical activity per week. The proportion of physically inactive adolescents was 5.4% in high social class and 7.8% and 10.8%, respectively, in middle and low social class. The absolute social inequality measured as prevalence difference between low and high social class did not change systematically across the observation period from 1991 to 2014. Compared to high social class, OR (95% CI) for physical inactivity was 1.48 (1.32-1.65) in middle social class and 2.18 (1.92-2.47) in lower social class. This relative social inequality was similar in the seven data collection waves (p=0.971). Although the gap in physical inactivity between social classes does not seem to be widening in Danish adolescents, there are still considerable differences in the activity levels between high, middle and low social class adolescents. Consequently, there is a need for a targeted physical activity intervention among adolescents from low (and middle) social class.

  7. Patterns and Determinants of Physical Inactivity in Rural and Urban Areas in Peru: A Population-Based Study.

    Science.gov (United States)

    Miranda, J Jaime; Carrillo-Larco, Rodrigo M; Gilman, Robert H; Avilez, Jose L; Smeeth, Liam; Checkley, William; Bernabe-Ortiz, Antonio

    2016-06-01

    Physical inactivity and sedentary behaviors have been linked with impaired health outcomes. Establishing the physical inactivity profiles of a given population is needed to establish program targets and to contribute to international monitoring efforts. We report the prevalence of, and explore sociodemographical and built environment factors associated with physical inactivity in 4 resource-limited settings in Peru: rural Puno, urban Puno, Pampas de San Juan de Miraflores (urban), and Tumbes (semiurban). Cross-sectional analysis of the CRONICAS Cohort Study's baseline assessment. Outcomes of interest were physical inactivity of leisure time (physical activity (not reporting walking or cycling trips) domains of the IPAQ, as well as watching TV, as a proxy of sedentarism (≥2 hours per day). Exposures included demographic factors and perceptions about neighborhood's safety. Associations were explored using Poisson regression models with robust standard errors. Prevalence ratios (PR) and 95% confidence intervals (95% CI) are presented. Data from 3593 individuals were included: 48.5% males, mean age 55.1 (SD: 12.7) years. Physical inactivity was present at rates of 93.7% (95% CI 93.0%-94.5%) and 9.3% (95% CI 8.3%-10.2%) within the leisure time and transport domains, respectively. In addition, 41.7% (95% CI 40.1%-43.3%) of participants reported watching TV for more than 2 hours per day. Rates varied according to study settings (P physical inactivity relative to highly urban Lima. The pattern was different for transport-related physical inactivity: both Puno sites had around 75% to 50% lower prevalence of physical inactivity. Too much traffic was associated with higher levels of transport-related physical inactivity (PR = 1.24; 95% CI 1.01-1.54). Our study showed high levels of inactivity and marked contrasting patterns by rural/urban sites. These findings highlight the need to generate synergies to expand nationwide physical activity surveillance systems.

  8. Population attributable fraction of type 2 diabetes due to physical inactivity in adults: a systematic review.

    Science.gov (United States)

    Al Tunaiji, Hashel; Davis, Jennifer C; Mackey, Dawn C; Khan, Karim M

    2014-05-18

    Physical inactivity is a global pandemic. The population attributable fraction (PAF) of type 2 diabetes mellitus (T2DM) associated with physical inactivity ranges from 3% to 40%. The purpose of this systematic review was to determine the best estimate of PAF for T2DM attributable to physical inactivity and absence of sport participation or exercise for men and women. We conducted a systematic review that included a comprehensive search of MEDLINE, EMBASE, SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms adults and English. Two reviewers screened studies, extracted PAF related data and assessed the quality of the selected studies. We reconstructed 95% CIs for studies missing these data using a substitution method. Of the eight studies reporting PAF in T2DM, two studies included prospective cohort studies (3 total) and six were reviews. There were distinct variations in quality of defining and measuring physical inactivity, T2DM and adjusting for confounders. In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in men and 29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise ranged from 3% (95% CI: -11, 16) in men to 7% (95% CI: -9, 20) in women. The PAF of physical inactivity due to T2DM is substantial. Physical inactivity is a modifiable risk factor for T2DM. The contribution of physical inactivity to T2DM differs by sex; PAF also differs if physical inactivity is defined as the absence of 'sport' or absence of 'exercise'.

  9. Time trends in absolute and relative socioeconomic inequalities in leisure time physical inactivity in northern Sweden.

    Science.gov (United States)

    Szilcz, Máté; Mosquera, Paola A; Sebastián, Miguel San; Gustafsson, Per E

    2018-02-01

    The aim was to investigate the time trends in educational, occupational, and income-related inequalities in leisure time physical inactivity in 2006, 2010, and 2014 in northern Swedish women and men. This study was based on data obtained from the repeated cross-sectional Health on Equal Terms survey of 2006, 2010, and 2014. The analytical sample consisted of 20,667 (2006), 31,787 (2010), and 21,613 (2014) individuals, aged 16-84. Logistic regressions were used to model the probability of physical inactivity given a set of explanatory variables. Slope index of inequality (SII) and relative index of inequality (RII) were used as summary measures of the social gradient in physical inactivity. The linear trend in inequalities and difference between gender and years were estimated by interaction analyses. The year 2010 displayed the highest physical inactivity inequalities for all socioeconomic position indicators, but educational and occupational inequalities decreased in 2014. However, significant positive linear trends were found in absolute and relative income inequalities. Moreover, women had significantly higher RII of education in physical inactivity in 2014 and significantly higher SII and RII of income in physical inactivity in 2010, than did men in the same years. The recent reduction in educational and occupational inequalities following the high inequalities around the time of the great recession in 2010 suggests that the current policies might be fairly effective. However, to eventually alleviate inequities in physical inactivity, the focus of the researchers and policymakers should be directed toward the widening trends of income inequalities in physical inactivity.

  10. Catalytic distillation structure

    Science.gov (United States)

    Smith, L.A. Jr.

    1984-04-17

    Catalytic distillation structure is described for use in reaction distillation columns, and provides reaction sites and distillation structure consisting of a catalyst component and a resilient component intimately associated therewith. The resilient component has at least about 70 volume % open space and is present with the catalyst component in an amount such that the catalytic distillation structure consists of at least 10 volume % open space. 10 figs.

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

    Science.gov (United States)

    Chen, You; Zheng, Zhonghui; Yi, Jinyao; Yao, Shuqiao

    2014-07-22

    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. 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. 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 physically active than females (25.1% vs.14.6%; p 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 grade and decreased with socioeconomic status. Physical inactivity and sedentary behaviors were prevalent in Chinese adolescents. Further support, including parental guidance and the provision of

  12. Contaminant transport, revegetation, and trace element studies at inactive uranium mill tailings piles

    International Nuclear Information System (INIS)

    Dreesen, D.R.; Marple, M.L.; Kelley, N.E.

    1978-01-01

    The stabilization of inactive uranium mill tailings piles is presently under study. These studies have included investigations of stabilizing tailings by attempting to establish native vegetation without applying irrigation. Examination of processes which transport tailings or associated contaminants into the environment has been undertaken to better understand the containment provided by various stabilization methods. The uptake of toxic trace elements and radionuclides by vegetation has been examined as a mechanism of contaminant transport. The source terms of 222 Rn from inactive piles have been determined as well as the attenuation of radon flux provided by shallow soil covers. The possibility of shallow ground water contamination around an inactive pile has been examined to determine the significance of ground water transport as a mode of contaminant migration. The rationale in support of trace element studies related to uranium milling activities is presented including the enrichment, migration, and toxicities of trace elements often associated with uranium deposits. Some concepts for the stabilization of inactive piles are presented to extrapolate from research findings to practical applications. 25 references, 8 tables

  13. The effects of smoking and physical inactivity on advancing mortality in U.S. adults.

    Science.gov (United States)

    Borrell, Luisa N

    2014-06-01

    The aim of the study was to calculate the rate advancement period (RAP) by which deaths for all-cause and cardiovascular disease (CVD)-specific mortality is advanced by smoking and physical inactivity among U.S. adults aged 18 years or more who participated in the Third National Health and Nutrition Examination Survey and were followed to December 31, 2006. Mortality status was determined using the underlying cause of death. Cox regression was used to calculate the advanced time of deaths for all-cause and CVD-specific mortality among exposed adults relative to their nonexposed counterparts. Deaths for all-cause and CVD-specific mortality were advanced by 7.9 and 5.1 years among current smoker adults. For physically inactive adults, the RAPs for all-cause and CVD-specific mortality were 4.0 and 2.4 years, respectively. The joint effects of current smoking, physical inactivity, and obesity resulted in early all-cause and CVD-specific deaths of 14.2 and 12.2 years. For current smokers, physically inactive, and overweight adults, the RAPs for all-cause and CVD-specific deaths were 7.9 and 8.9 years, respectively. Our findings suggest that smoking and physical inactivity could significantly advance the time of death associated with all-cause and CVD-specific mortality by at least 2.4 years among U.S. adults. Moreover, the advancement death period for the joint effects of smoking, physical inactivity, and overweight or obesity could be at least 7.9 years. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Catalytic site identification—a web server to identify catalytic site structural matches throughout PDB

    Science.gov (United States)

    Kirshner, Daniel A.; Nilmeier, Jerome P.; Lightstone, Felice C.

    2013-01-01

    The catalytic site identification web server provides the innovative capability to find structural matches to a user-specified catalytic site among all Protein Data Bank proteins rapidly (in less than a minute). The server also can examine a user-specified protein structure or model to identify structural matches to a library of catalytic sites. Finally, the server provides a database of pre-calculated matches between all Protein Data Bank proteins and the library of catalytic sites. The database has been used to derive a set of hypothesized novel enzymatic function annotations. In all cases, matches and putative binding sites (protein structure and surfaces) can be visualized interactively online. The website can be accessed at http://catsid.llnl.gov. PMID:23680785

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

    Science.gov (United States)

    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. Are Australian immigrants at a risk of being physically inactive?

    Directory of Open Access Journals (Sweden)

    Gurrin Lyle

    2011-06-01

    Full Text Available Abstract Background We examined whether physical activity risk differed between migrant sub-groups and the Australian-born population. Methods Data were drawn from the Australian National Health Survey (2001 and each resident's country of birth was classified into one of 13 regions. Data were gathered on each resident's physical activity level in the fortnight preceding the survey. Multivariable logistic regression, adjusted for potential confounders examined the risk of physical inactivity of participants from each of the 13 regions compared to the Australian-born population. Results There was a greater prevalence of physical inactivity for female immigrants from most regions compared to male immigrants from a like region. Immigrants from South East Asia (OR 2.04% 95% CI 1.63, 2.56, Other Asia (OR 1.53 95% CI 1.10, 2.13, Other Oceania (1.81 95% CI 1.11, 2.95, the Middle East (OR 1.42 95% CI 0.97, 2.06 [note: border line significance] and Southern & Eastern Europe are at a significantly higher risk of being physically inactive compared to those born in Australian. In contrast, immigrants from New Zealand (OR 0.77 95% CI 0.62, 0.94, the UK & Ireland (OR 0.82 95% CI 0.73, 0.92, and other Africa (OR 0.69 95% CI 0.51, 0.94 are at a significantly lower risk of being physically inactive compared to the Australian born population. Conclusion Future research identifying potential barriers and facilitators to participation in physical activity will inform culturally sensitive physical activity programs that aim to encourage members of specific regional ethnic sub-groups to undertake physical activity.

  17. Prevalence and determinations of physical inactivity among public hospital employees in Shanghai, China: a cross-sectional study.

    Science.gov (United States)

    Li, Xinjian; Cheng, Minna; Zhang, Hao; Ke, Ting; Chen, Yisheng

    2015-03-01

    This study aims to explore the prevalence and determinations of physical inactivity among hospital employees in Shanghai, China. A cross-sectional study of 4612 employees aged 19 to 68 years was conducted through stratified cluster sampling from different classes of Shanghai hospitals in 2011. The total physical activity was evaluated using the metabolic equivalent according to the Global Physical Activity Questionnaire. Among the participants, 38.5%, 32.3%, and 64.6% of the employees are inactive at work, commuting, and taking leisure time, respectively. Up to 41.8% of the men and 37.8% of the women (P = 0.012) are physically inactive. When the age and educational level are adjusted, male doctors and medical technicians show a higher percentage of physical inactivity than male workers in logistics (P = 0.001). Among females, employees who are working in second- and third-class hospitals show a higher proportion of physical inactivity than those who are working in community health care centers. Logistic regression analyses show that the odds ratios (ORs) of leisure-time physical inactivity associated with the intensity of physical activity at work are 2.259, 2.897, and 4.266 for men (P physical inactivity in either sex (OR = 2.116 for men and 2.173 for women, P employees, particularly doctors and medical technicians, show a higher proportion of physical inactivity than other inhabitants in Shanghai. The time and intensity of activity at work and commuting are associated with leisure-time activities.

  18. Self-Esteem in People with Physical Disabilities: Differences between Active and Inactive Individuals

    Directory of Open Access Journals (Sweden)

    Nemček Dagmar

    2017-05-01

    Full Text Available The aim of the study was to determine the status of SE in people with physical disabilities (PwPD and compare SE scores between active and inactive individuals. The sample of PwPD (n = 186 was divided into two groups of those who are regularly participating in sport (active; n = 88 and those who are not participating in any sport in their leisure (inactive; n = 98. The Rosenberg Self-Esteem Scale (RSES was used as a primary research method. 10-item scale measures global self-worth by measuring positive and negative feelings about the self. Higher scores (from 10 to 40 points indicate higher SE. The Pearson chi-square test was used to determine the differences of 10 RSES items and total scores between active and inactive PwPD. We found that the mean score of RSES in PwPD was 28.83 points; active PwPD observed total score of RSES 30.01 points and group of inactive PwPD showed the lowest SE by achieving 27.76 points. Mean scores comparison of each RSES item between active and inactive PwPD revealed higher SE in the group of active PwPD. Significantly higher SE was presented by 4 from 10 RSES items and by total score in the group of active PwPD. The results of our study confirmed that actively living PwPD have significantly higher SE comparing those PwPD who are living sedentary life style.

  19. The association of lifetime physical inactivity with head and neck cancer: a hospital-based case-control analysis.

    Science.gov (United States)

    Platek, Alexis J; Cannioto, Rikki A; Etter, John Lewis; Kim, Jae; Joseph, Janine M; Gulati, Nicholas R; Schmitt, Kristina L; Callahan, Emily; Khachatryan, Edgar; Nagy, Ryan; Minlikeeva, Albina; Brian Szender, J; Singh, Anurag K; Danziger, Iris; Moysich, Kirsten B

    2017-10-01

    Despite mounting epidemiological evidence suggesting an inverse association between recreational physical activity and cancer risk, evidence associated with head and neck cancer is scant. We conducted a case-control analysis to examine the associations of lifetime physical inactivity with the risk of head and neck squamous cell carcinoma (HNSCC). We utilized data from the Patient Epidemiology Data System at Roswell Park Cancer Institute (RPCI). Participants included 246 patients with HNSCC and 504 cancer-free controls who received medical services at RPCI between 1990 and 1998. Participants were considered physically inactive if they did not participate in any regular, weekly recreational physical activity throughout their lifetime, prior to diagnosis. Multivariate logistic regression models were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) representing the association between lifetime physical inactivity and HNSCC risk. We observed a significant positive association between recreational physical inactivity and HNSCC risk (OR = 2.73, 95% CI 1.87-3.99, p physical inactivity associates with HNSCC independent of BMI. In addition, physical inactivity may be a modifiable risk factor among never smokers. These data add to the growing body of evidence suggesting that physical inactivity may be an independent risk factor for cancer.

  20. Gain-of-function mutations in the gene encoding the tyrosine phosphatase SHP2 induce hydrocephalus in a catalytically dependent manner.

    Science.gov (United States)

    Zheng, Hong; Yu, Wen-Mei; Waclaw, Ronald R; Kontaridis, Maria I; Neel, Benjamin G; Qu, Cheng-Kui

    2018-03-20

    Catalytically activating mutations in Ptpn11 , which encodes the protein tyrosine phosphatase SHP2, cause 50% of Noonan syndrome (NS) cases, whereas inactivating mutations in Ptpn11 are responsible for nearly all cases of the similar, but distinct, developmental disorder Noonan syndrome with multiple lentigines (NSML; formerly called LEOPARD syndrome). However, both types of disease mutations are gain-of-function mutations because they cause SHP2 to constitutively adopt an open conformation. We found that the catalytic activity of SHP2 was required for the pathogenic effects of gain-of-function, disease-associated mutations on the development of hydrocephalus in the mouse. Targeted pan-neuronal knockin of a Ptpn11 allele encoding the active SHP2 E76K mutant resulted in hydrocephalus due to aberrant development of ependymal cells and their cilia. These pathogenic effects of the E76K mutation were suppressed by the additional mutation C459S, which abolished the catalytic activity of SHP2. Moreover, ependymal cells in NSML mice bearing the inactive SHP2 mutant Y279C were also unaffected. Mechanistically, the SHP2 E76K mutant induced developmental defects in ependymal cells by enhancing dephosphorylation and inhibition of the transcription activator STAT3. Whereas STAT3 activity was reduced in Ptpn11 E76K/+ cells, the activities of the kinases ERK and AKT were enhanced, and neural cell-specific Stat3 knockout mice also manifested developmental defects in ependymal cells and cilia. These genetic and biochemical data demonstrate a catalytic-dependent role of SHP2 gain-of-function disease mutants in the pathogenesis of hydrocephalus. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Depressive symptoms are associated with physical inactivity in patients with type 2 diabetes. The DIAZOB Primary Care Diabetes study

    DEFF Research Database (Denmark)

    Koopmans, Berber; Pouwer, Francois; de Bie, Robert A

    2009-01-01

    through decreased physical activity. OBJECTIVE: To test whether type 2 diabetes patients with elevated depression scores are more often physically inactive. METHODS: 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. RESULTS: 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). CONCLUSIONS: Presence of depressive symptoms almost doubles the likelihood of physical inactivity...

  2. Associations of unhealthy lifestyle factors with sexual inactivity and sexual dysfunctions in Denmark

    DEFF Research Database (Denmark)

    Christensen, Birgitte S; Grønbaek, Morten; Pedersen, Bo V

    2011-01-01

    Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting.......Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting....

  3. Association of physical inactivity with hypertension and low educational level in people living with HIV / AIDS.

    Science.gov (United States)

    Silveira, Erika Aparecida; Santos, Annelisa Silva E Alves de Carvalho; Falco, Marianne de Oliveira; Cardoso, Rodrigo de Castro; Vitorino, Priscila Valverde de Oliveira

    2018-08-01

    The aim of this study was to determine the prevalence of physical inactivity and whether it is associated with sociodemographic, lifestyle, clinical, anthropometric, and body composition variables in people living with HIV/AIDS (PLWHA). This study makes use of data from a cohort of 288 adults aged ≥19 years, conducted between October 2009 and July 2011. The variables studied were sex, age, education, income, skin color, tobacco use, alcohol intake, body mass index, body fat percentage, waist circumference, and waist-hip ratio, length of HIV/AIDS diagnosis, use of antiretroviral therapy and length of its use, CD4, hypertension (HT) and diabetes mellitus. Physical inactivity was defined as a score below 600 metabolic equivalent minutes/week according to the International Physical Activity Questionnaire - Short Version. Poisson multiple regression was applied in the multivariate analysis with a significance level of 5%. The prevalence of physical inactivity was 44.1%. Education of ≤4 years of study (prevalence ratio [PR]: 1.71) and HT (PR: 1.49) were associated with physical inactivity. Physical inactivity was highly prevalent in PLWHA and associated with low educational level and HT. We highlight the simultaneous association between two cardiometabolic risk factors, HT and physical inactivity.

  4. Method of fabricating a catalytic structure

    Science.gov (United States)

    Rollins, Harry W [Idaho Falls, ID; Petkovic, Lucia M [Idaho Falls, ID; Ginosar, Daniel M [Idaho Falls, ID

    2009-09-22

    A precursor to a catalytic structure comprising zinc oxide and copper oxide. The zinc oxide has a sheet-like morphology or a spherical morphology and the copper oxide comprises particles of copper oxide. The copper oxide is reduced to copper, producing the catalytic structure. The catalytic structure is fabricated by a hydrothermal process. A reaction mixture comprising a zinc salt, a copper salt, a hydroxyl ion source, and a structure-directing agent is formed. The reaction mixture is heated under confined volume conditions to produce the precursor. The copper oxide in the precursor is reduced to copper. A method of hydrogenating a carbon oxide using the catalytic structure is also disclosed, as is a system that includes the catalytic structure.

  5. Activity, inactivity, and screen time in relation to weight and fatness over adolescence in girls.

    Science.gov (United States)

    Must, Aviva; Bandini, Linda G; Tybor, David J; Phillips, Sarah M; Naumova, Elena N; Dietz, William H

    2007-07-01

    The impact of activity and inactivity on relative weight and fatness change are best evaluated longitudinally. We examined the longitudinal relationship of physical activity, inactivity, and screen time with relative weight status and percentage body fat (%BF) and explored how it differed by parental overweight status. Non-obese pre-menarcheal girls (173), 8 to 12 years old, were followed until 4 years post-menarche. %BF, BMI z-score, and time spent sleeping, sitting, standing, walking, and in vigorous activity were assessed annually. We developed a physical activity index to reflect time and intensity of activity. Inactivity was defined as the sum of time spent sleeping, sitting, and standing. Screen time was defined as time spent viewing television, videotapes, or playing video games. Parental overweight was defined as at least one parent with BMI>25. In separate linear mixed effects models, activity, inactivity, and screen time were unrelated to BMI z-score longitudinally, with and without accounting for parental overweight. After controlling for parental overweight, activity was inversely related (phistory of overweight represent a target population of high priority for interventions around physical activity and inactivity.

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

    Science.gov (United States)

    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.

  7. Early adulthood determinants of mid-life leisure-time physical inactivity stability and change: Findings from a prospective birth cohort.

    Science.gov (United States)

    Pinto Pereira, Snehal M; Power, Chris

    2018-07-01

    Physical inactivity is highly prevalent. Knowledge is needed of influences on inactive lifestyles. We aimed to establish whether early adult factors predict subsequent inactivity patterns in mid-adulthood. Leisure-time inactivity (activity frequencyphysical status, mental function, social, family and neighbourhood circumstances with four 33-50y patterns (never inactive, persistently inactive, deteriorating or improving) using multinomial logistic regression with and without adjustment for childhood factors (e.g. social class). Inactivity prevalence was similar at 33y and 50y (∼31%), but 17% deteriorated and 18% improved with age. Factors associated with persistent vs never inactive were: limiting illness (relative risk ratio (RRR):1.21(1.04,1.42) per number of ages exposed (0,1 or 2 times across ages 23y and 33y), obesity (1.33(1.16,1.54) per number of ages exposed), height (0.93(0.89,0.98) per 5cm), depression (1.32(1.19,1.47) per number of ages exposed); education (1.28(1.20,1.38) per decrease on 5-point scale) and neighbourhood (1.59(1.37,1.86) in 'industrial/local authority housing areas' and 1.33(1.12,1.58) in 'growth/metropolitan inner areas' vs 'suburbs, service, rural or seaside areas'). Associations were broadly similar for inactivity deterioration. Industrial/local authority housing areas (0.75(0.61,0.91)) and longer obesity exposure (0.78(0.64,0.95)) were associated with lower RRRs for improvement. Number of children was associated with improvement, although associations varied by age. Associations remained after adjustment for childhood factors. Several early adult factors are associated with inactivity persistence and deterioration; fewer with improvement. Obesity duration and neighbourhood lived in during young adulthood had long-lasting associations with inactivity patterns in mid-life. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  8. Effect of support on the catalytic activity of manganese oxide catalyts for toluene combustion

    International Nuclear Information System (INIS)

    Pozan, Gulin Selda

    2012-01-01

    Highlights: ► α-Al 2 O 3 , obtained from Bohmite, as a support for enhancing of the activity. ► The support material for catalytic oxidation. ► The manganese state and oxygen species effect on the catalytic combustion reaction. - Abstract: The aim of this work was to study combustion of toluene (1000 ppm) over MnO 2 modified with different supports. α-Al 2 O 3 and γ-Al 2 O 3 obtained from Boehmite, γ-Al 2 O 3 (commercial), SiO 2 , TiO 2 and ZrO 2 were used as commercial support materials. In view of potential interest of this process, the influence of support material on the catalytic performance was discussed. The deposition of 9.5MnO 2 was performed by impregnation over support. The catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), temperature programmed reduction and oxidation (TPR/TPO) and thermogravimetric analysis (TGA). The catalytic tests were carried out at atmospheric pressure in a fixed-bed flow reactor. 9.5MnO 2 /α-Al 2 O 3 (B) (synthesized from Boehmite) catalyst exhibits the highest catalytic activity, over which the toluene conversion was up to 90% at a temperature of 289 °C. Considering all the characterization and reaction data reported in this study, it was concluded that the manganese state and oxygen species played an important role in the catalytic activity.

  9. A population-based survey on physical inactivity and leisure time physical activity among adults in Chiang Mai, Thailand, 2014.

    Science.gov (United States)

    Thanamee, Sanhapan; Pinyopornpanish, Kanokporn; Wattanapisit, Apichai; Suerungruang, Suparerk; Thaikla, Kanittha; Jiraporncharoen, Wichuda; Angkurawaranon, Chaisiri

    2017-01-01

    Reducing physical inactivity among the population is a challenge for many nations. Targeting leisure time physical activity (LTPA) may be useful in increasing overall physical activity as it is assumed it is associated with a higher degree of free choice and personal preference than physical activity at work and during travel. The study explored the prevalence of physical inactivity and focused on the overall level of energy expenditure and energy level spent during leisure time among those who were physically inactive and assessed the stages of change for LTPA among those who were physically inactive. A population-based survey was conducted in 2014 in Chiang Mai, Thailand using a stratified two-stage cluster sampling technique. The Global Physical Activity Questionnaire (GPAQ) was used to collect the data on physical activity. Sufficient levels of physical activity (PA) were defined as ≥150 min/week of moderate-intensity PA or ≥75 min/week of vigorous-intensity PA or ≥600 metabolic equivalent of task (MET)-minutes/week. Weighted analyses were used to estimate the prevalence of physical inactivity, the total energy expenditure and expenditure during LTPA as well as stages of change among the physically inactive population. A total of 1744 people (808 men and 936 women), aged 15 to 64 years, participated in the study. We estimated that a quarter (26%) of the population were physically inactive. Physical inactivity was more commonly found among women than men in most age groups. LTPA contributed a small proportion of overall PA. On average, physically inactive men spent 132.8 MET-minutes/week and inactive women spent 208.2 MET-minutes/week in overall PA which is well below the 600 MET-minutes/week recommend by the World Health Organization. Around 75% of physically inactive people had no intention of engaging in regular LTPA. About a quarter of the investigative population were physically inactive. Most physically inactive members of the population

  10. Decomposing socio-economic inequalities in leisure-time physical inactivity: the case of Spanish children.

    Science.gov (United States)

    Gonzalo-Almorox, Eduardo; Urbanos-Garrido, Rosa M

    2016-07-12

    Physical inactivity is associated with an increased risk of all-cause mortality and entails a substantial economic burden for health systems. Also, the analysis of inequality in lifestyles for young populations may contribute to reduce health inequalities during adulthood. This paper examines the income-related inequality regarding leisure-time physical inactivity in Spanish children. In this cross-sectional study based on the Spanish National Health Survey for 2011-12, concentration indices are estimated to measure socioeconomic inequalities in leisure-time physical inactivity. A decomposition analysis is performed to determine the factors that explain income-related inequalities. There is a significant socioeconomic gradient favouring the better-off associated with leisure-time physical inactivity amongst Spanish children, which is more pronounced in the case of girls. Income shows the highest contribution to total inequality, followed by education of the head of the household. The contribution of several factors (education, place of residence, age) significantly differs by gender. There is an important inequity in the distribution of leisure-time physical inactivity. Public policies aimed at promoting physical activity for children should prioritize the action into the most disadvantaged subgroups of the population. As the influence of determinants of health styles significantly differ by gender, this study points out the need of addressing the research on income-related inequalities in health habits from a gender perspective.

  11. Assessment of physical inactivity and perceived barriers to physical activity among health college students, south-western Saudi Arabia.

    Science.gov (United States)

    Awadalla, N J; Aboelyazed, A E; Hassanein, M A; Khalil, S N; Aftab, R; Gaballa, I I; Mahfouz, A A

    2014-10-20

    Physical inactivity is a public health problem in Saudi Arabia. A cross-sectional study was carried out to evaluate the pattern of physical activity, predictors of physical inactivity and perceived barriers to physical activity among health college students in King Khalid University. A total of 1257 students (426 males and 831 females) were recruited. The Arabic short form of the International Physical Activity Questionnaire was used. Overall, 58.0% of the students were physically inactive. Only 13.4% of the students performed vigorous physical activity, 14.8% moderate-intensity physical activity and 29.9% walking activities which met World Health Organization criteria of health-enhancing physical activities. The prevalence of inactive leisure time was 47.5%. The independent predictors of physical inactivity were non-membership of sports clubs and being a medical student. The top reported barrier to physical activity among inactive students was time limitations (51.3%). Overcoming perceived barriers may increase physical activity among students.

  12. From physical inactivity to immobilization: Dissecting the role of oxidative stress in skeletal muscle insulin resistance and atrophy.

    Science.gov (United States)

    Pierre, Nicolas; Appriou, Zephyra; Gratas-Delamarche, Arlette; Derbré, Frédéric

    2016-09-01

    In the literature, the terms physical inactivity and immobilization are largely used as synonyms. The present review emphasizes the need to establish a clear distinction between these two situations. Physical inactivity is a behavior characterized by a lack of physical activity, whereas immobilization is a deprivation of movement for medical purpose. In agreement with these definitions, appropriate models exist to study either physical inactivity or immobilization, leading thereby to distinct conclusions. In this review, we examine the involvement of oxidative stress in skeletal muscle insulin resistance and atrophy induced by, respectively, physical inactivity and immobilization. A large body of evidence demonstrates that immobilization-induced atrophy depends on the chronic overproduction of reactive oxygen and nitrogen species (RONS). On the other hand, the involvement of RONS in physical inactivity-induced insulin resistance has not been investigated. This observation outlines the need to elucidate the mechanism by which physical inactivity promotes insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Association between Natural Resources for OutdoorActivities and Physical Inactivity

    Data.gov (United States)

    U.S. Environmental Protection Agency — it includes available natural resources for outdoor activities, Physical inactivity and households income. This dataset is associated with the following publication:...

  14. New Method for Determination of Electrically Inactive Phosphorus in n-type Emitters

    OpenAIRE

    Steyer, Michael; Dastgheib-Shirazi, Amir; Hahn, Giso; Terheiden, Barbara

    2015-01-01

    The precise knowledge of the amount and the location in depth of inactive phosphorus in an n-type emitter is still a challenge. As a new approach, we determine the total amount of phosphorus (P dose) in the emitter stepwise in dependence of etching depth with the characterization tool ICP-OES. A comparison of the data with the electrically active P concentration profile measured by ECV allows to determine in which depths electrically inactive phosphorus is present. For a highly doped emitter,...

  15. 200 Area plateau inactive miscellaneous underground storage tanks locations

    International Nuclear Information System (INIS)

    Brevick, C.H.

    1997-01-01

    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

  16. Clustering of Physical Inactivity in Leisure, Work, Commuting, and Household Domains: Data From 47,477 Industrial Workers in Brazil.

    Science.gov (United States)

    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.

  17. Physical inactivity and associated factors among university students in 23 low-, middle- and high-income countries.

    Science.gov (United States)

    Pengpid, Supa; Peltzer, Karl; Kassean, Hemant Kumar; Tsala Tsala, Jacques Philippe; Sychareun, Vanphanom; Müller-Riemenschneider, Falk

    2015-07-01

    The aim of this study was to determine estimates of the prevalence and social correlates of physical inactivity among university students in 23 low-, middle- and high-income countries. The International Physical Activity Questionnaire was used to collect data from 17,928 undergraduate university students (mean age 20.8, SD = 2.8) from 24 universities in 23 countries. The prevalence of physical inactivity was 41.4 %, ranging from 21.9 % in Kyrgyzstan to 80.6 % in Pakistan. In multivariate logistic regression, older age (22-30 years), studying in a low- or lower middle-income country, skipping breakfast and lack of social support were associated with physical inactivity. In men, being underweight, being overweight or obese, not avoiding fat and cholesterol, not having severe depression symptoms, low beliefs in the health benefits of physical activity, low personal control and knowledge of exercise-heart link, and in women, not trying to eat fibre, low personal mastery and medium personal control were additionally associated with physical inactivity. Four in each ten students are physically inactive, calling for strategic interventions by relevant professionals in higher educational institutions.

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

    Science.gov (United States)

    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.

  19. Inaction inertia, regret, and valuation : A closer look

    NARCIS (Netherlands)

    Zeelenberg, Marcel; Nijstad, Bernard A.; van Putten, Marijke; van Dijk, Eric

    Inaction inertia is the phenomenon that one is not likely to act on an attractive opportunity after having bypassed an even more attractive opportunity. So far, all published work has assumed a causal role for the emotion regret in this effect. In a series of 5 experiments we found no support for

  20. Setting-related influences on physical inactivity of older adults in residential care settings : a review

    NARCIS (Netherlands)

    Douma, Johanna G.; Volkers, Karin M.; Engels, Gwenda; Sonneveld, Marieke H.; Goossens, Richard H. M.; Scherder, Erik J. A.

    2017-01-01

    Background: Despite the detrimental effects of physical inactivity for older adults, especially aged residents of residential care settings may spend much time in inactive behavior. This may be partly due to their poorer physical condition; however, there may also be other, setting-related factors

  1. Polynucleotide Phosphorylase, RNase E/G, and YbeY Are Involved in the Maturation of 4.5S RNA in Corynebacterium glutamicum.

    Science.gov (United States)

    Maeda, Tomoya; Tanaka, Yuya; Wachi, Masaaki; Inui, Masayuki

    2017-03-01

    Corynebacterium glutamicum has been applied for the industrial production of various metabolites, such as amino acids. To understand the biosynthesis of the membrane protein in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP is found in all three domains of life and plays an important role in the membrane insertion of proteins. SRP RNA is initially transcribed as precursor molecules; however, relatively little is known about its maturation. In C. glutamicum , SRP consists of the Ffh protein and 4.5S RNA lacking an Alu domain. In this study, we found that 3'-to-5' exoribonuclease, polynucleotide phosphorylase (PNPase), and two endo-type RNases, RNase E/G and YbeY, are involved in the 3' maturation of 4.5S RNA in C. glutamicum The mature form of 4.5S RNA was inefficiently formed in Δ rneG Δ pnp mutant cells, suggesting the existence of an alternative pathway for the 3' maturation of 4.5S RNA. Primer extension analysis also revealed that the 5' mature end of 4.5S RNA corresponds to that of the transcriptional start site. Immunoprecipitated Ffh protein contained immature 4.5S RNA in Δ pnp , Δ rneG , and Δ ybeY mutants, suggesting that 4.5S RNA precursors can interact with Ffh. These results imply that the maturation of 4.5S RNA can be performed in the 4.5S RNA-Ffh complex. IMPORTANCE Overproduction of a membrane protein, such as a transporter, is useful for engineering of strains of Corynebacterium glutamicum , which is a workhorse of amino acid production. To understand membrane protein biogenesis in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP contains the Ffh protein and SRP RNA and plays an important role in the membrane insertion of proteins. Although SRP RNA is highly conserved among the three domains of life, relatively little is known about its maturation. We show that PNPase, RNase E/G, and YbeY are involved in the 3' maturation of the SRP RNA (4.5S RNA) in

  2. Trends in social inequality in physical inactivity among Danish adolescents 1991–2014

    Directory of Open Access Journals (Sweden)

    N.F. Johnsen

    2017-12-01

    Full Text Available The aim of this study was to investigate social inequality in physical inactivity among adolescents from 1991 to 2014 and to describe any changes in inequality during this period. The analyses were based on data from the Danish part of the HBSC study, which consists of seven comparable cross-sectional studies of nationally representative samples of 11–15-year old adolescents. The available data consisted of weekly time (hours spent on vigorous physical activity and parental occupation from 30,974 participants. In summary, 8.0% of the adolescents reported to be physically inactive, i.e. spend zero hours of vigorous leisure time physical activity per week. The proportion of physically inactive adolescents was 5.4% in high social class and 7.8% and 10.8%, respectively, in middle and low social class. The absolute social inequality measured as prevalence difference between low and high social class did not change systematically across the observation period from 1991 to 2014. Compared to high social class, OR (95% CI for physical inactivity was 1.48 (1.32–1.65 in middle social class and 2.18 (1.92–2.47 in lower social class. This relative social inequality was similar in the seven data collection waves (p=0.971. Although the gap in physical inactivity between social classes does not seem to be widening in Danish adolescents, there are still considerable differences in the activity levels between high, middle and low social class adolescents. Consequently, there is a need for a targeted physical activity intervention among adolescents from low (and middle social class.

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

    Science.gov (United States)

    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.

  4. Early-life predictors of leisure-time physical inactivity in midadulthood: findings from a prospective British birth cohort.

    Science.gov (United States)

    Pinto Pereira, Snehal M; Li, Leah; Power, Chris

    2014-12-01

    Much adult physical inactivity research ignores early-life factors from which later influences may originate. In the 1958 British birth cohort (followed from 1958 to 2008), leisure-time inactivity, defined as activity frequency of less than once a week, was assessed at ages 33, 42, and 50 years (n = 12,776). Early-life factors (at ages 0-16 years) were categorized into 3 domains (i.e., physical, social, and behavioral). We assessed associations of adult inactivity 1) with factors within domains, 2) with the 3 domains combined, and 3) allowing for adult factors. At each age, approximately 32% of subjects were inactive. When domains were combined, factors associated with inactivity (e.g., at age 50 years) were prepubertal stature (5% lower odds per 1-standard deviation higher height), hand control/coordination problems (14% higher odds per 1-point increase on a 4-point scale), cognition (10% lower odds per 1-standard deviation greater ability), parental divorce (21% higher odds), institutional care (29% higher odds), parental social class at child's birth (9% higher odds per 1-point reduction on a 4-point scale), minimal parental education (13% higher odds), household amenities (2% higher odds per increase (representing poorer amenities) on a 19-point scale), inactivity (8% higher odds per 1-point reduction in activity on a 4-point scale), low sports aptitude (13% higher odds), and externalizing behaviors (i.e., conduct problems) (5% higher odds per 1-standard deviation higher score). Adjustment for adult covariates weakened associations slightly. Factors from early life were associated with adult leisure-time inactivity, allowing for early identification of groups vulnerable to inactivity. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Cosmopolitan Utilitarianism and the Problem of Local Inaction in a Globalized World

    Directory of Open Access Journals (Sweden)

    Fausto Corvino

    2015-10-01

    Full Text Available This article explores the problem of the public acceptability of political inaction as an extreme consequence of cosmopolitan utilitarianism. The case of political inaction as the utility-maximizing public policy option emerges more clearly in the globalized world, because of a misalignment between the electoral body and the persons that the government ought to consider while evaluating the consequences of a given policy. In this context, a situation can easily occur in which the only way to maximize utility in a global context is by renouncing action at the national or local level. However, the problem of inaction should not be interpreted simply as a by-product of globalization. Its origins can be traced to the basic structure of utilitarianism as a normative consequentialist theory. This drawback can even present itself at the local level in a less visible form. One example is that in which the performance of a supererogatory act in the exercise of public office leads to a reduction in overall utility. The aim of the article is to demonstrate that cosmopolitan utilitarianism can bind the decision maker to a series of inactions at the global and local levels that contradict his own mandate, generating a dangerous moral confusion in the implementation of public policies. This can seriously threaten the universal applicability of cosmopolitan utilitarianism as a normative political theory, especially in the age of globalization.

  6. Inactive vaccine derived from velogenic strain of local Newcastle disease virus .

    Directory of Open Access Journals (Sweden)

    Darminto

    1996-03-01

    Full Text Available The objective of this research is to evaluate an application of an inactive Newcastle disease (ND vaccine derived from velogenic strain of local Newcastle disease virus (NDV. In this research . the Ira strain of velogenic ND virus was grown in specific pathogen free (SPF eggs and then was inactivated by formalin at a final concentration of 1 :1,000 at 4°C. The inactive antigen was then emulsified with an oil adjuvant or aluminium hydroxide gel before being administered for vaccination in layers and compared to a commercial inactive ND vaccine . Results indicated that application of these inactivated ND vaccines for booster vaccination following vaccination with an active lentogenic ND virus in pullets nearly producing eggs, resulted in high antibody titre which persisted for considerable long period of time and capable of protecting layers from sick of ND and from reducing egg production . Hence, it could be concluded that the inactivated vaccine emulsified in either oil-adjuvant (lanolin-paraffin or aluminium hydroxide gel were considered to be highly immunogenic and capable of protecting layers from sick of ND and from reducing egg production

  7. Specific binding component of the 'inactive' stereoisomer (S,S)-[125I]IQNB to rat brain muscarinic receptors in vivo

    International Nuclear Information System (INIS)

    Boulay, Sheila F.; McRee, R. Carter; Cohen, Victor I.; Sood, Virendar K.; Zeeberg, Barry R.; Reba, Richard C.

    1996-01-01

    In vivo nonspecific binding can be estimated using the inactive stereoisomer of a receptor radioligand. However, the binding of the inactive stereoisomer may be partially specific. Specific binding of the inactive (S,S)-[ 125 I]IQNB was estimated from the inhibition induced by a competing nonradioactive ligand. This technique differed from the usual approach, since it was used to study the inactive rather than the active stereoisomer. The results indicate that there is substantial specific binding for (S,S)-[ 125 I]IQNB

  8. Application of inactive cycle stopping criteria for Monte Carlo Wielandt calculations

    International Nuclear Information System (INIS)

    Shim, H. J.; Kim, C. H.

    2009-01-01

    The Wielandt method is incorporated into Monte Carlo (MC) eigenvalue calculation as a way to speed up fission source convergence. To make the most of the MC Wielandt method, however, it is highly desirable to halt inactive cycle runs in a timely manner because it requires a much longer computational time to execute a single cycle MC run than the conventional MC eigenvalue calculations. This paper presents an algorithm to detect the onset of the active cycles and thereby to stop automatically the inactive cycle MC runs based on two anterior stopping criteria. The effectiveness of the algorithm is demonstrated by applying it to a slow convergence problem. (authors)

  9. Characterization of the conformational equilibrium between the two major substates of RNase A using NMR chemical shifts.

    Science.gov (United States)

    Camilloni, Carlo; Robustelli, Paul; De Simone, Alfonso; Cavalli, Andrea; Vendruscolo, Michele

    2012-03-07

    Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein. © 2012 American Chemical Society

  10. Heterogeneous catalytic materials solid state chemistry, surface chemistry and catalytic behaviour

    CERN Document Server

    Busca, Guido

    2014-01-01

    Heterogeneous Catalytic Materials discusses experimental methods and the latest developments in three areas of research: heterogeneous catalysis; surface chemistry; and the chemistry of catalysts. Catalytic materials are those solids that allow the chemical reaction to occur efficiently and cost-effectively. This book provides you with all necessary information to synthesize, characterize, and relate the properties of a catalyst to its behavior, enabling you to select the appropriate catalyst for the process and reactor system. Oxides (used both as catalysts and as supports for cata

  11. Kinetic and catalytic performance of a BI-porous composite material in catalytic cracking and isomerisation reactions

    KAUST Repository

    Al-Khattaf, S.

    2012-01-10

    Catalytic behaviour of pure zeolite ZSM-5 and a bi-porous composite material (BCM) were investigated in transformation of m-xylene, while zeolite HY and the bi-porous composite were used in the cracking of 1,3,5-triisopropylbenzene (TIPB). The micro/mesoporous material was used to understand the effect of the presence of mesopores on these reactions. Various characterisation techniques, that is, XRD, SEM, TGA, FT-IR and nitrogen sorption measurements were applied for complete characterisation of the catalysts. Catalytic tests using CREC riser simulator showed that the micro/mesoporous composite catalyst exhibited higher catalytic activity as compared with the conventional microporous ZSM-5 and HY zeolite for transformation of m-xylene and for the catalytic cracking of TIPB, respectively. The outstanding catalytic reactivity of m-xylene and TIPB molecules were mainly attributed to the easier access of active sites provided by the mesopores. Apparent activation energies for the disappearance of m-xylene and TIPB over all catalysts were found to decrease in the order: EBCM>EZSM-5 and EBCM>EHY, respectively. © 2012 Canadian Society for Chemical Engineering.

  12. Catalytic modification of cellulose and hemicellulose - Sugarefine

    Energy Technology Data Exchange (ETDEWEB)

    Repo, T. [Helsinki Univ. (Finland),Laboratory of Inorganic Chemistry], email: timo.repo@helsinki.fi

    2012-07-01

    The main goal of the project is to develop catalytic methods for the modification of lignocellulose-based saccharides in the biorefineries. The products of these reactions could be used for example as biofuel components, raw materials for the chemical industry, solvents and precursors for biopolymers. The catalyst development aims at creating efficient, selective and green catalytic methods for profitable use in biorefineries. The project is divided in three work packages: In WP1 (Catalytic dehydration of cellulose) the aim is at developing non-toxic, efficient methods for the catalytic dehydration of cellulose the target molecule being here 5-hydroxymethylfurfural (5-HMF). 5-HMF is an interesting platform chemical for the production of fuel additives, solvents and polymers. In WP2 (Catalytic reduction), the objective of the catalytic reduction studies is to produce commercially interesting monofunctional chemicals, such as 1-butanol or 2-methyltetrahydrofuran (2-MeTHF). In WP3 (Catalytic oxidation), the research focuses on developing a green and efficient oxidation method for producing acids. Whereas acetic and formic acids are bulk chemicals, diacids such as glucaric and xylaric acids are valuable specialty chemicals for detergent, polymer and food production.

  13. Back and neck pain prevalence and their association with physical inactivity domains in adolescents.

    Science.gov (United States)

    Scarabottolo, Catarina Covolo; Pinto, R Z; Oliveira, C B; Zanuto, E F; Cardoso, J R; Christofaro, D G D

    2017-09-01

    Back pain affects people of all ages. This may be associated with physical inactivity, and in the case of physical activity in different domains, the relationship with back pain is not clear in the literature. The aim of this study was to estimate the prevalence of low back and neck pain and investigate their association in different domains of physical inactivity. 1011 randomly selected students participated in this study. Neck and back pain were assessed using the Nordic questionnaire, whereas the Baecke Physical Activity questionnaire was used to measure physical activity domains. Separate Binary Logistic Regression models were performed to investigate the association of physical activity domains with neck or back pain. 17.4% of the students reported cervical pain, while 18.0% reported low back pain. Older adolescents had a higher prevalence of cervical pain (24.4%) than younger adolescents (11.9%) (p value pain, being 25.1% in older adolescents and 12.4% in younger (p value pain in the cervical region [OR 0.67 (0.44-0.99)] or back pain [OR 0.60 (0.40-0.91)]. Being inactive in occupational activities was associated with cervical pain [OR 1.49 (1.06-2.10)]. Being inactive in the sports environment presented a marginal relationship with pain in the cervical region [OR 1.41 (0.99-2.02)]. The prevalence of neck and low back pain was higher in older adolescents and physical inactivity in the sporting context and occupational activities could be a risk factor to increase the chances of back pain.

  14. Subjective neighborhood assessment and physical inactivity: An examination of neighborhood-level variance.

    Science.gov (United States)

    Prochaska, John D; Buschmann, Robert N; Jupiter, Daniel; Mutambudzi, Miriam; Peek, M Kristen

    2018-06-01

    Research suggests a linkage between perceptions of neighborhood quality and the likelihood of engaging in leisure-time physical activity. Often in these studies, intra-neighborhood variance is viewed as something to be controlled for statistically. However, we hypothesized that intra-neighborhood variance in perceptions of neighborhood quality may be contextually relevant. We examined the relationship between intra-neighborhood variance of subjective neighborhood quality and neighborhood-level reported physical inactivity across 48 neighborhoods within a medium-sized city, Texas City, Texas using survey data from 2706 residents collected between 2004 and 2006. Neighborhoods where the aggregated perception of neighborhood quality was poor also had a larger proportion of residents reporting being physically inactive. However, higher degrees of disagreement among residents within neighborhoods about their neighborhood quality was significantly associated with a lower proportion of residents reporting being physically inactive (p=0.001). Our results suggest that intra-neighborhood variability may be contextually relevant in studies seeking to better understand the relationship between neighborhood quality and behaviors sensitive to neighborhood environments, like physical activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Engineering reactors for catalytic reactions

    Indian Academy of Sciences (India)

    Extensive studies have been conducted to establish sound basis for design and engineering of reactors for practising such catalytic reactions and for realizing improvements in reactor performance. In this article, application of recent (and not so recent) developments in engineering reactors for catalytic reactions is ...

  16. Physical inactivity, abdominal obesity and risk of coronary heart disease in apparently healthy men and women

    NARCIS (Netherlands)

    Arsenault, B. J.; Rana, J. S.; Lemieux, I.; Després, J.-P.; Kastelein, J. J. P.; Boekholdt, S. M.; Wareham, N. J.; Khaw, K.-T.

    2010-01-01

    Objective: To test the hypothesis that for any given body mass index (BMI) category, active individuals would have a smaller waist circumference than inactive individuals. Our second objective was to examine the respective contribution of waist circumference and physical inactivity on coronary heart

  17. LLAMA: nuclear stellar properties of Swift-BAT AGN and matched inactive galaxies

    Science.gov (United States)

    Lin, Ming-Yi; Davies, R. I.; Hicks, E. K. S.; Burtscher, L.; Contursi, A.; Genzel, R.; Koss, M.; Lutz, D.; Maciejewski, W.; Müller-Sánchez, F.; Orban de Xivry, G.; Ricci, C.; Riffel, R.; Riffel, R. A.; Rosario, D.; Schartmann, M.; Schnorr-Müller, A.; Shimizu, T.; Sternberg, A.; Sturm, E.; Storchi-Bergmann, T.; Tacconi, L.; Veilleux, S.

    2018-02-01

    In a complete sample of local 14-195 keV selected active galactic nuclei (AGNs) and inactive galaxies, matched by their host galaxy properties, we study the spatially resolved stellar kinematics and luminosity distributions at near-infrared wavelengths on scales of 10-150 pc, using SINFONI on the VLT. In this paper, we present the first half of the sample, which comprises 13 galaxies, eight AGNs and five inactive galaxies. The stellar velocity fields show a disc-like rotating pattern, for which the kinematic position angle is in agreement with the photometric position angle obtained from large scale images. For this set of galaxies, the stellar surface brightness of the inactive galaxy sample is generally comparable to the matched sample of AGN, but extends to lower surface brightness. After removal of the bulge contribution, we find a nuclear stellar light excess with an extended nuclear disc structure, which exhibits a size-luminosity relation. While we expect the excess luminosity to be associated with a dynamically cooler young stellar population, we do not typically see a matching drop in dispersion. This may be because these galaxies have pseudo-bulges in which the intrinsic dispersion increases towards the centre. And although the young stars may have an impact in the observed kinematics, their fraction is too small to dominate over the bulge and compensate the increase in dispersion at small radii, so no dispersion drop is seen. Finally, we find no evidence for a difference in the stellar kinematics and nuclear stellar luminosity excess between these active and inactive galaxies.

  18. Self-reported physical inactivity and health complaints: a cross-sectional study of Lithuanian adolescent schoolgirls

    Directory of Open Access Journals (Sweden)

    Romualdas Malinauskas

    2015-05-01

    Full Text Available The study aimed to investigate the associations between physical inactivity and health complaints in relation to posttraumatic stress (PTS symptoms, behavioral and nutritional factors, and sense of coherence (SOC in eighth-grade girls enrolled in secondary schools in Kaunas, Lithuania. A random sample of girls (N = 862 was interviewed anonymously on health complaints, physical activity level, PTS symptoms, Antonovsky’s SOC scale, health behaviors, and dietary patterns. All health complaints were significantly associated with physical inactivity. Crude odds ratio (OR for physical inactivity and health complaints was 1.67 (95%CI: 1.09-2.56; after adjusting for PTS symptoms, the OR decreased to 1.57 (95%CI: 0.95-2.45; further adjustment for smoking, daily alcohol intake, daily consumption of fresh vegetables, and SOC decreased the OR to 1.25 (95%CI: 0.76-2.04. The effect of PTS symptoms and sense of coherence remained stable after all adjustments. The significant association between physical inactivity and health complaints was mediated by PTS symptoms.

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

    International Nuclear Information System (INIS)

    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

  20. Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Nóbrega Ana Carolina Mello

    2012-12-01

    Full Text Available Abstract Background Patients with Crohn’s disease (CD have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods Twenty-six patients with inactive Crohn’s disease, as defined by a Crohn’s Disease Activity Index (CDAI 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire to assess dyspeptic symptoms. Patients with scores ≥ 6 were considered to have dyspepsia. The control group was composed by 19 age- and sex-matched healthy volunteers. Results Patients with CD had a significantly longer t 1/2 and t lag (p Conclusion Delayed gastric emptying in inactive Crohn’s disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.

  1. Atomistic Details of the Associative Phosphodiester Cleavage in Human Ribonuclease H

    International Nuclear Information System (INIS)

    Elsasser, Brigitta M.; Fels, Gregor

    2010-01-01

    During translation of the genetic information of DNA into proteins, mRNA is synthesized by RNA polymerase and after the transcription process degraded by RNase H. The endoribonuclease RNase H is a member of the nucleotidyl-transferase (NT) superfamily and is known to hydrolyze the phosphodiester bonds of RNA which is hybridized to DNA. Retroviral RNase H is part of the viral reverse transcriptase enzyme that is indispensable for the proliferation of retroviruses, such as HIV. Inhibitors of this enzyme could therefore provide new drugs against diseases like AIDS. In our study we investigated the molecular mechanism of RNA cleavage by human RNase H using a comprehensive high level DFT/B3LYP QM/MM theoretical method for the calculation of the stationary points and nudged elastic band (NEB) and free energy calculations to identify the transition state structures, the rate limiting step and the reaction barrier. Our calculations reveal that the catalytic mechanism proceeds in two steps and that the nature of the nucleophile is a water molecule. In the first step, the water attack on the scissile phosphorous is followed by a proton transfer from the water to the O2P oxygen and a trigonal bipyramidal pentacoordinated phosphorane is formed. Subsequently, in the second step the proton is shuttled to the O30 oxygen to generate the product state. During the reaction mechanism two Mg2+ ions support the formation of a stable associated in-line SN2-type phosphorane intermediate. Our calculated energy barrier of 19.3 kcal mol*1 is in excellent agreement with experimental findings (20.5 kcal mol*1). These results may contribute to the clarification and understanding of the RNase H reaction mechanism and of further enzymes from the RNase family.

  2. Factors Associated with Physical Inactivity among Adult Urban Population of Puducherry, India: A Population Based Cross-sectional Study.

    Science.gov (United States)

    Newtonraj, Ariarathinam; Murugan, Natesan; Singh, Zile; Chauhan, Ramesh Chand; Velavan, Anandan; Mani, Manikandan

    2017-05-01

    Physical inactivity is the fourth leading cause of death worldwide. Increase in physical activity decreases the incidence of cardiovascular diseases, Type 2 diabetes, stroke, and improves psychological wellbeing. To study the level of physical inactivity among the adult population in an urban area of Puducherry in India and its associated risk factors. This cross-sectional study was conducted among 569 adult participants from an urban area of Pondicherry. The level of physical inactivity was measured by using WHO standard Global Physical Activity Questionnaire (GPAQ). Overall prevalence of physical inactivity in our study was 49.7% (CI: 45.6-53.8). Among the physically active people, contribution of physical activity by work was 77.4%, leisure time activities were 11.6% and transport time was 11%. Both men and women were equally inactive {Physically inactive among women was 50% (CI:44.1-55.9)} and {Physically inactive among men was 49.5% (CI:43.8-55.2)}. Prevalence of physical inactivity was increasing with increasing age. Non tobacco users were two times more active than tobacco users {Adjusted Odds Ratio: 2.183 (1.175- 4.057)}. Employed were more active as compared to retired {Adjusted Odds Ratio: 0.412 (0.171-0.991)}, students {Adjusted Odds Ratio: 0.456 (0.196-1.060)}, house wives {Adjusted Odds Ratio: 0.757 (0.509-1.127)} and unemployed {Adjusted Odds Ratio: 0.538 (0.271-1.068)}. Non alcoholics were only 0.34 times as active as alcoholics. Level of physical activity was found to be insufficient among adult urban population of Puducherry. Working adult population found to be active, that too due to their work pattern. There is a need to promote leisure time and travelling time physical activity.

  3. Trends in social inequality in physical inactivity among Danish adolescents 1991–2014

    DEFF Research Database (Denmark)

    Johnsen, N F; Toftager, Mette; Melkevik, Ole

    2017-01-01

    The aim of this study was to investigate social inequality in physical inactivity among adolescents from 1991 to 2014 and to describe any changes in inequality during this period. The analyses were based on data from the Danish part of the HBSC study, which consists of seven comparable cross...... hours of vigorous leisure time physical activity per week. The proportion of physically inactive adolescents was 5.4% in high social class and 7.8% and 10.8%, respectively, in middle and low social class. The absolute social inequality measured as prevalence difference between low and high social class...... did not change systematically across the observation period from 1991 to 2014. Compared to high social class, OR (95% CI) for physical inactivity was 1.48 (1.32–1.65) in middle social class and 2.18 (1.92–2.47) in lower social class. This relative social inequality was similar in the seven data...

  4. The Whole-Genome Sequence of Bacillus velezensis Strain SB1216 Isolated from the Great Salt Plains of Oklahoma Reveals the Presence of a Novel Extracellular RNase with Antitumor Activity

    OpenAIRE

    Marasini, Daya; Cornell, Carolyn R.; Oyewole, Opeoluwa; Sheaff, Robert J.; Fakhr, Mohamed K.

    2017-01-01

    ABSTRACT The whole-genome sequence of Bacillus velezensis strain SB1216, isolated from the Great Salt Plains of Oklahoma, showed the presence of a 3,814,720-bp circular chromosome and no plasmids. The presence of a novel 870-bp extracellular RNase gene is predicted to be responsible for this strain’s antitumor activity.

  5. Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

    Science.gov (United States)

    Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

    2013-01-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

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

    Science.gov (United States)

    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.

  7. Synthesis, spectroscopic characterization and catalytic oxidation ...

    Indian Academy of Sciences (India)

    were characterized by infrared, electronic, electron paramagnetic resonance ... The catalytic oxidation property of ruthenium(III) complexes were also ... cies at room temperature. ..... aldehyde part of Schiff base ligands, catalytic activ- ity of new ...

  8. Physical Inactivity Predicts Slow Gait Speed in an Elderly Multi-Ethnic Cohort Study: The Northern Manhattan Study.

    Science.gov (United States)

    Willey, Joshua Z; Moon, Yeseon P; Kulick, Erin R; Cheung, Ying Kuen; Wright, Clinton B; Sacco, Ralph L; Elkind, Mitchell S V

    2017-01-01

    Gait speed is associated with multiple adverse outcomes of aging. We hypothesized that physical inactivity would be prospectively inversely associated with gait speed independently of white matter hyperintensity volume and silent brain infarcts on MRI. Participants in the Northern Manhattan Study MRI sub-study had physical activity assessed when they were enrolled into the study. A mean of 5 years after the MRI, participants had gait speed measured via a timed 5-meter walk test. Physical inactivity was defined as reporting no leisure-time physical activity. Multi-variable logistic and quantile regression was performed to examine the associations between physical inactivity and future gait speed adjusted for confounders. Among 711 participants with MRI and gait speed measures (62% women, 71% Hispanic, mean age 74.1 ± 8.4), the mean gait speed was 1.02 ± 0.26 m/s. Physical inactivity was associated with a greater odds of gait speed in the lowest quartile (Physical inactivity is associated with slower gait speed independently of osteoarthritis, grip strength, and subclinical ischemic brain injury. Modifying sedentary behavior poses a target for interventions aimed at reducing decline in mobility. © 2017 S. Karger AG, Basel.

  9. WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity.

    Science.gov (United States)

    Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David

    2016-09-20

    The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.

  10. Depressive symptoms, physical inactivity and risk of cardiovascular mortality in older adults: the Cardiovascular Health Study

    Science.gov (United States)

    Win, Sithu; Parakh, Kapil; Eze-Nliam, Chete M; Gottdiener, John S; Kop, Willem J

    2011-01-01

    Background Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality. Methods A cohort of 5888 individuals (mean 72.8±5.6 years, 58% female, 16% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables. Results At baseline, 20% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8%), of which 1176 (20.1%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all pphysical inactivity had greater cardiovascular mortality than those with either individually (pPhysical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26% after adjustment. This was similar for persons with (25%) and without (23%) established coronary heart disease. Conclusions Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status. PMID:21339320

  11. The Whole-Genome Sequence of Bacillus velezensis Strain SB1216 Isolated from the Great Salt Plains of Oklahoma Reveals the Presence of a Novel Extracellular RNase with Antitumor Activity.

    Science.gov (United States)

    Marasini, Daya; Cornell, Carolyn R; Oyewole, Opeoluwa; Sheaff, Robert J; Fakhr, Mohamed K

    2017-11-22

    The whole-genome sequence of Bacillus velezensis strain SB1216, isolated from the Great Salt Plains of Oklahoma, showed the presence of a 3,814,720-bp circular chromosome and no plasmids. The presence of a novel 870-bp extracellular RNase gene is predicted to be responsible for this strain's antitumor activity. Copyright © 2017 Marasini et al.

  12. Automatic Detection of Inactive Solar Cell Cracks in Electroluminescence Images

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso

    2017-01-01

    We propose an algorithm for automatic determination of the electroluminescence (EL) signal threshold level corresponding to inactive solar cell cracks, resulting from their disconnection from the electrical circuit of the cell. The method enables automatic quantification of the cell crack size...

  13. Characterization of RNase MRP RNA and novel snoRNAs from Giardia intestinalis and Trichomonas vaginalis

    Science.gov (United States)

    2011-01-01

    Background Eukaryotic cells possess a complex network of RNA machineries which function in RNA-processing and cellular regulation which includes transcription, translation, silencing, editing and epigenetic control. Studies of model organisms have shown that many ncRNAs of the RNA-infrastructure are highly conserved, but little is known from non-model protists. In this study we have conducted a genome-scale survey of medium-length ncRNAs from the protozoan parasites Giardia intestinalis and Trichomonas vaginalis. Results We have identified the previously 'missing' Giardia RNase MRP RNA, which is a key ribozyme involved in pre-rRNA processing. We have also uncovered 18 new H/ACA box snoRNAs, expanding our knowledge of the H/ACA family of snoRNAs. Conclusions Results indicate that Giardia intestinalis and Trichomonas vaginalis, like their distant multicellular relatives, contain a rich infrastructure of RNA-based processing. From here we can investigate the evolution of RNA processing networks in eukaryotes. PMID:22053856

  14. Characterization of RNase MRP RNA and novel snoRNAs from Giardia intestinalis and Trichomonas vaginalis

    Directory of Open Access Journals (Sweden)

    Chen Xiaowei S

    2011-11-01

    Full Text Available Abstract Background Eukaryotic cells possess a complex network of RNA machineries which function in RNA-processing and cellular regulation which includes transcription, translation, silencing, editing and epigenetic control. Studies of model organisms have shown that many ncRNAs of the RNA-infrastructure are highly conserved, but little is known from non-model protists. In this study we have conducted a genome-scale survey of medium-length ncRNAs from the protozoan parasites Giardia intestinalis and Trichomonas vaginalis. Results We have identified the previously 'missing' Giardia RNase MRP RNA, which is a key ribozyme involved in pre-rRNA processing. We have also uncovered 18 new H/ACA box snoRNAs, expanding our knowledge of the H/ACA family of snoRNAs. Conclusions Results indicate that Giardia intestinalis and Trichomonas vaginalis, like their distant multicellular relatives, contain a rich infrastructure of RNA-based processing. From here we can investigate the evolution of RNA processing networks in eukaryotes.

  15. Catalytic exhaust control

    Energy Technology Data Exchange (ETDEWEB)

    Heinemann, H

    1973-09-01

    Recent achievements and problems in the development of exhaust control devices in the USA are reviewed. To meet the 1976 emission standards, catalytic systems for the oxidation of carbon monoxide and hydrocarbons and for the reduction of nitrogen oxides to nitrogen and water are needed. While oxidizing catalysts using platinum, palladium, copper, vanadium, and chromium appplied on alumina or ceramic materials are more or less effective in emission control, there are no catalytic devices for the reduction of nitrogen oxides with the required useful life of 25,000 to 50,000 miles as yet available. In the case of platinum catalysts on monolithic supports, the operating temperature of 650 to 750/sup 0/C as required for the oxidation process may cause inactivation of the catalysts and fusion of the support material. The oxidation of CO and hydrocarbons is inhibited by high concentrations of CO, nitric oxide, and hydrocarbons. The use of catalytic converters requires the use of lead-free or low-lead gasoline. The nitrogen oxides conversion efficiency is considerably influenced by the oxygen-to-CO ratio of the exhaust gas, which makes limitation of this ratio necessary.

  16. The economic burden of physical inactivity: a systematic review and critical appraisal.

    Science.gov (United States)

    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

  17. Implications of an assessment of potential organic contamination of ground water at an inactive uranium mill

    International Nuclear Information System (INIS)

    Price, J.B.

    1986-01-01

    Laws and regulations concerning remedial actions at inactive uranium mills explicitly recognize radiological and nonradiological hazards and may implicitly recognize the potential presence of hazardous wastes at these mill sites. Ground-water studies at the sites have placed an increasing emphasis on screening for priority pollutants. The Grand Junction, Colorado, mill site was deemed to have a high potential for the presence of organic compounds in ground water, and was chosen as a prototype for assessing the presence of organic compounds in ground water at inactive sites. Lessons learned from the assessment of organics at the Grand Junction site were used to develop a screening procedure for other inactive mill sites

  18. Catalytic Wittig and aza-Wittig reactions

    Directory of Open Access Journals (Sweden)

    Zhiqi Lao

    2016-11-01

    Full Text Available This review surveys the literature regarding the development of catalytic versions of the Wittig and aza-Wittig reactions. The first section summarizes how arsenic and tellurium-based catalytic Wittig-type reaction systems were developed first due to the relatively easy reduction of the oxides involved. This is followed by a presentation of the current state of the art regarding phosphine-catalyzed Wittig reactions. The second section covers the field of related catalytic aza-Wittig reactions that are catalyzed by both phosphine oxides and phosphines.

  19. Efficient catalytic combustion in integrated micropellistors

    International Nuclear Information System (INIS)

    Bársony, I; Ádám, M; Fürjes, P; Dücső, Cs; Lucklum, R; Hirschfelder, M; Kulinyi, S

    2009-01-01

    This paper analyses two of the key issues of the development of catalytic combustion-type sensors: the selection and production of active catalytic particles on the micropellistor surface as well as the realization of a reliable thermal conduction between heater element and catalytic surface, for the sensing of temperature increase produced by the combustion. The report also demonstrates that chemical sensor product development by a MEMS process is a continuous struggle for elimination of all uncertainties influencing reliability and sensitivity of the final product

  20. Prevalence, social and health correlates of physical inactivity among ...

    African Journals Online (AJOL)

    Individuals who had high social capital (OR: 0.69, CI: 0.60, 0.79) were less likely to be physically inactive than those with low social capital. Several sociodemographic (older age, female, higher education and urban residence) and health risk (such as overweight, weak grip strength, functional disability, and low fruit and ...

  1. Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up.

    Science.gov (United States)

    Piirtola, Maarit; Kaprio, Jaakko; Kujala, Urho M; Heikkilä, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Ropponen, Annina

    2016-08-04

    Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models. Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations. Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow

  2. Adsorbent catalytic nanoparticles and methods of using the same

    Energy Technology Data Exchange (ETDEWEB)

    Slowing, Igor Ivan; Kandel, Kapil

    2017-01-31

    The present invention provides an adsorbent catalytic nanoparticle including a mesoporous silica nanoparticle having at least one adsorbent functional group bound thereto. The adsorbent catalytic nanoparticle also includes at least one catalytic material. In various embodiments, the present invention provides methods of using and making the adsorbent catalytic nanoparticles. In some examples, the adsorbent catalytic nanoparticles can be used to selectively remove fatty acids from feedstocks for biodiesel, and to hydrotreat the separated fatty acids.

  3. Urban-Rural Differences in Overweight Status and Physical Inactivity among US Children Aged 10-17 Years

    Science.gov (United States)

    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…

  4. Catalytic pyrolysis of hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Vail' eva, N A; Buyanov, R A

    1979-01-01

    Catalytic pyrolysis of petroleum fractions (undecane) was performed with the object of clarifying such questions as the mechanism of action of the catalyst, the concepts of activity and selectivity of the catalyst, the role of transport processes, the temperature ranges and limitations of the catalytic process, the effect of the catalyst on secondary processes, and others. Catalysts such as quartz, MgO, Al/sub 2/O/sub 3/, were used. Analysis of the experimental findings and the fact that the distribution of products is independent of the nature of the surface, demonstrate that the pyrolysis of hydrocarbons in the presence of catalysts is based on the heterogeneous-homogeneous radical-chain mechanism of action, and that the role of the catalysts reduces to increasing the concentration of free radicals. The concept of selectivity cannot be applied to catalysts here, since they do not affect the mechanism of the unfolding of the process of pyrolysis and their role consists solely in initiating the process. In catalytic pyrolysis the concepts of kinetic and diffusive domains of unfolding of the catalytic reaction do not apply, and only the outer surface of the catalyst is engaged, whereas the inner surface merely promotes deletorious secondary processes reducing the selectivity of the process and the activity of the catalyst. 6 references, 2 figures.

  5. Predictors of physical inactivity in men and women with type 2 diabetes from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study.

    Science.gov (United States)

    McCarthy, Margaret M; Davey, Janice; Wackers, Frans J Th; Chyun, Deborah A

    2014-01-01

    The purpose of this secondary analysis was to determine changes in physical inactivity from baseline to 5 years and to identify factors associated with and predictive of physical inactivity among individuals with type 2 diabetes enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. DIAD was a prospective randomized screening trial that assessed the prevalence of silent ischemia in asymptomatic patients with type 2 diabetes. Subjects were recruited from diabetes and primary care practices at 14 centers throughout the United States and Canada. This is a secondary data analysis of the physical activity data (type and hours/week) collected. No intervention was conducted. In all subjects, physical inactivity rose from 24% at baseline to 33% at 5 years (S = 28.93; P physical inactivity as well as in factors predictive of physical inactivity at 5 years. Important factors associated at both time points included lower level of education, current employment, presence of peripheral and autonomic neuropathy, and indicators of overweight/obesity. Baseline physical inactivity was strongly predictive of physical inactivity at 5 years (odds ratio, 3.27; 95% confidence interval, 2.36-4.54; P physical inactivity. © 2014 The Author(s).

  6. Automatic Detection of Inactive Solar Cell Cracks in Electroluminescence Images

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso

    2017-01-01

    We propose an algorithm for automatic determination of the electroluminescence (EL) signal threshold level corresponding to inactive solar cell cracks, resulting from their disconnection from the electrical circuit of the cell. The method enables automatic quantification of the cell crack size an...

  7. Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study.

    Science.gov (United States)

    Etter, John Lewis; Cannioto, Rikki; Soh, Kah Teong; Alquassim, Emad; Almohanna, Hani; Dunbar, Zachary; Joseph, Janine M; Balderman, Sophia; Hernandez-Ilizaliturri, Francisco; Moysich, Kirsten B

    2018-03-27

    Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest. Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk. We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15-3.15) and NHL (OR = 1.35, 95% CI: 1.01-1.82). The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Leisure-time physical inactivity and association with body mass index: a Finnish Twin Study with a 35-year follow-up.

    Science.gov (United States)

    Piirtola, Maarit; Kaprio, Jaakko; Waller, Katja; Heikkilä, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Kujala, Urho M; Ropponen, Annina

    2017-02-01

    We investigated the stability and change of leisure-time physical inactivity in adult men and women during a 35-year follow-up. We also analysed the impact of long-term physical inactivity on the development of body mass index (BMI). : In this population-based cohort study, 5254 Finnish twin individuals (59% women) participated in four surveys in 1975, 1981, 1990 and 2011. Mean age at baseline was 23.9 years. Individual long-term leisure-time physical activity (LTPA) was categorized into seven classes varying from 'persistently inactive' to 'persistently active'. We used the multivariate multilevel mixed-effects linear regression model and paired-sample t-test in the analyses. Co-twin control design was used for examining within-pair associations. : Of men 11%, and of women 8%, were persistently inactive. Among both sexes, the mean BMI slope trajectories were steeper among the persistently inactive and those who became inactive than among those who were persistently active. Overall, the inactive participants gained 1.4 kg/m 2 [95% confidence interval (CI) 1.2 to 1.7] more in weight than did the active participants from 1975 to 2011. Among twin pairs discordant for LTPA, the corresponding difference was 1.4 kg/m 2 (95% CI 0.83 to 2.0) in dizygotic pairs and 0.68 kg/m 2 (95% CI 0.05 to1.3) in monozygotic pairs. Over a 35-year time span from young adulthood, persistently inactive participants and those who had become inactive had greater weight increases than those who were persistently active. This association was also found in twin-pair analyses, although attenuated in monozygotic pairs. This may support the importance of LTPA in weight management, although further causal inference is required. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  9. Experience during the monitoring of inactive scrap for the detection of inadvertent presence of radioactivity

    International Nuclear Information System (INIS)

    Sharma, Ranjit; Anoj Kumar; Vikas; Singh, Rajvir; Patra, R.P.; Vikas Kumar; Pradeepkumar, K.S.

    2012-01-01

    The paper describes about the experience gained during the radiation monitoring of inactive scrap generated at various nuclear facilities. This type surveillance is carried out to prevent the spread of radioactivity in public domain and also as requirement by regulatory authorities. The inspection and certification of scrap material from nuclear facilities is a regulatory requirement to ensure that no radioactive material reaches public domain. This paper describes the methodology and experience in detection of radioactivity at inactive Scrap monitoring facility. Inactive scraps (metallic and non metallic) generated from various nuclear facilities of BARC, Trombay is dispatched to Trombay Village Store (TVS) for temporary storage before auction to the public. The monitoring at the facility includes visual inspection and radiation measurement before loading the scrap in the truck. An online PC based monitoring system and portable monitoring instruments in the range (nSv/h-µSv/h) are used to carry out radiation monitoring of inactive scrap loaded in a vehicle. Radioactive source of high activity with potential for serious environmental hazard has not been detected, but few cases of presence of radioactive/contaminated material (MS plate/equipments with low level of 137 Cs contamination) have been detected and identified using portable gamma spectrometer. Implementation of strict regulatory measures and radiation monitoring at nuclear facilities can minimize the probability of radioactive material reaching the public domain. The methodology followed for monitoring of inactive scrap is found to be effective even for detection of presence of radioactivity in scrap if any. (author)

  10. Model and Reduction of Inactive Times in a Maintenance Workshop Following a Diagnostic Error

    Directory of Open Access Journals (Sweden)

    T. Beda

    2011-04-01

    Full Text Available The majority of maintenance workshops in manufacturing factories are hierarchical. This arrangement permits quick response in advent of a breakdown. Reaction of the maintenance workshop is done by evaluating the characteristics of the breakdown. In effect, a diagnostic error at a given level of the process of decision making delays the restoration of normal operating state. The consequences are not just financial loses, but loss in customers’ satisfaction as well. The goal of this paper is to model the inactive time of a maintenance workshop in case that an unpredicted catalectic breakdown has occurred and a diagnostic error has also occurred at a certain level of decision-making, during the treatment process of the breakdown. We show that the expression for the inactive times obtained, is depended only on the characteristics of the workshop. Next, we propose a method to reduce the inactive times.

  11. Radioimmunoassay of inactive creatine kinase B protein in human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Burnam, M H; Shell, W E [California Univ., Los Angeles (USA). School of Medicine

    1981-08-27

    The authors describe a rapid, sensitive radioimmunoassay for enzymatically inactive creatine kinase B protein (CK-Bi) in plasma. /sup 125/I-CK-Bi of high specific activity and good stability was prepared by oxidant-based iodination. A 12-minute first antibody incubation was used. Bound and free antigen were separated by a second antibody system. Large excesses of purified CK-MM from human skeletal muscle did not react in the assay. Cross reactivity to CK-MB purified from the plasma of patients with acute myocardial infarction was negligible. The 95th percentile of plasma CK-Bi in 150 adults was 145 ..mu..g equivalents/ml. Within-assay and between-assay precision ranged from 5% to 9% and 6% to 10%, respectively. Evidence is presented indicating that the assay measures inactive creatine kinase B protein, a protein not measured by current assay systems dependent on biological activity.

  12. Radioimmunoassay of inactive creatine kinase B protein in human plasma

    International Nuclear Information System (INIS)

    Burnam, M.H.; Shell, W.E.

    1981-01-01

    The authors describe a rapid, sensitive radioimmunoassay for enzymatically inactive creatine kinase B protein (CK-Bi) in plasma. 125 I-CK-Bi of high specific activity and good stability was prepared by oxidant-based iodination. A 12-minute first antibody incubation was used. Bound and free antigen were separated by a second antibody system. Large excesses of purified CK-MM from human skeletal muscle did not react in the assay. Cross reactivity to CK-MB purified from the plasma of patients with acute myocardial infarction was negligible. The 95th percentile of plasma CK-Bi in 150 adults was 145 μg equivalents/ml. Within-assay and between-assay precision ranged from 5% to 9% and 6% to 10%, respectively. Evidence is presented indicating that the assay measures inactive creatine kinase B protein, a protein not measured by current assay systems dependent on biological activity. (Auth.)

  13. Emerging health problems among women: Inactivity, obesity, and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Yi-Ju Tsai

    2014-02-01

    Full Text Available The increase in obesity and metabolic syndrome has been documented worldwide. However, few studies have investigated the risk of inactivity, obesity, and metabolic syndrome specifically in women. Hormone balance plays a crucial role in regulating metabolism and helps to maintain optimal health. It is likely that the sex difference in obesity may be due to the variation in hormone concentration throughout a woman's life, which predisposes them to weight gain. This paper reviews previous literature and discusses factors that influence the risk of adiposity-related health consequences among women for three critical biological transitions throughout a woman's life: puberty, menopause, and pregnancy. To improve quality of life and metabolic health for women, interventions are needed to target women at different transition stages and provide tailored health education programs. Interventions should raise awareness of physical inactivity, obesity, and metabolic syndrome, and promote healthy behavioral change in women.

  14. The Body Image Of Physically Active And Inactive Women

    Directory of Open Access Journals (Sweden)

    Guszkowska Monika

    2015-06-01

    Full Text Available Introduction. The aim of the study was to compare the image of the body, the level of its acceptance and satisfaction with it, as well as anxiety about one’s physical appearance and overall self-esteem in a group of adult women who did fitness exercise and those who were physically inactive.

  15. Guanidinium chloride induction of partial unfolding in amide proton exchange in RNase A.

    Science.gov (United States)

    Mayo, S L; Baldwin, R L

    1993-11-05

    Amide (NH) proton exchange rates were measured in 0.0 to 0.7 M guanidinium chloride (GdmCl) for 23 slowly exchanging peptide NH protons of ribonuclease A (RNase A) at pH* 5.5 (uncorrected pH measured in D2O), 34 degrees C. The purpose was to find out whether GdmCl induces exchange through binding to exchange intermediates that are partly or wholly unfolded. It was predicted that, when the logarithm of the exchange rate is plotted as a function of the molarity of GdmCl, the slope should be a measure of the amount of buried surface area exposed to GdmCl in the exchange intermediate. The results indicate that these concentrations of GdmCl do induce exchange by means of a partial unfolding mechanism for all 23 protons; this implies that exchange reactions can be used to study the unfolding and stability of local regions. Of the 23 protons, nine also show a second mechanism of exchange at lower concentrations of GdmCl, a mechanism that is nearly independent of GdmCl concentration and is termed "limited structural fluctuation."

  16. Topical thermal therapy with hot packs suppresses physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF.

    Science.gov (United States)

    Nakagawa, Tatsuki; Hiraga, Shin-Ichiro; Mizumura, Kazue; Hori, Kiyomi; Ozaki, Noriyuki; Koeda, Tomoko

    2017-10-12

    We focused on the analgesic effect of hot packs for mechanical hyperalgesia in physically inactive rats. Male Wistar rats were randomly divided into four groups: control, physical inactivity (PI), PI + sham treatment (PI + sham), and PI + hot pack treatment (PI + hot pack) groups. Physical inactivity rats wore casts on both hind limbs in full plantar flexed position for 4 weeks. Hot pack treatment was performed for 20 min a day, 5 days a week. Although mechanical hyperalgesia and the up-regulation of NGF in the plantar skin and gastrocnemius muscle were observed in the PI and the PI + sham groups, these changes were significantly suppressed in the PI + hot pack group. The present results clearly demonstrated that hot pack treatment was effective in reducing physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF in plantar skin and gastrocnemius muscle.

  17. Catalytic cracking models developed for predictive control purposes

    Directory of Open Access Journals (Sweden)

    Dag Ljungqvist

    1993-04-01

    Full Text Available The paper deals with state-space modeling issues in the context of model-predictive control, with application to catalytic cracking. Emphasis is placed on model establishment, verification and online adjustment. Both the Fluid Catalytic Cracking (FCC and the Residual Catalytic Cracking (RCC units are discussed. Catalytic cracking units involve complex interactive processes which are difficult to operate and control in an economically optimal way. The strong nonlinearities of the FCC process mean that the control calculation should be based on a nonlinear model with the relevant constraints included. However, the model can be simple compared to the complexity of the catalytic cracking plant. Model validity is ensured by a robust online model adjustment strategy. Model-predictive control schemes based on linear convolution models have been successfully applied to the supervisory dynamic control of catalytic cracking units, and the control can be further improved by the SSPC scheme.

  18. The association of lifetime physical inactivity with bladder and renal cancer risk: A hospital-based case-control analysis.

    Science.gov (United States)

    Cannioto, Rikki; Etter, John Lewis; Guterman, Lauren Beryl; Joseph, Janine M; Gulati, Nicholas R; Schmitt, Kristina L; LaMonte, Michael J; Nagy, Ryan; Minlikeeva, Albina; Szender, James Brian; Moysich, Kirsten B

    2017-08-01

    Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk. In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk. In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively. In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effect of inlet cone pipe angle in catalytic converter

    Science.gov (United States)

    Amira Zainal, Nurul; Farhain Azmi, Ezzatul; Arifin Samad, Mohd

    2018-03-01

    The catalytic converter shows significant consequence to improve the performance of the vehicle start from it launched into production. Nowadays, the geometric design of the catalytic converter has become critical to avoid the behavior of backpressure in the exhaust system. The backpressure essentially reduced the performance of vehicles and increased the fuel consumption gradually. Consequently, this study aims to design various models of catalytic converter and optimize the volume of fluid flow inside the catalytic converter by changing the inlet cone pipe angles. Three different geometry angles of the inlet cone pipe of the catalytic converter were assessed. The model is simulated in Solidworks software to determine the optimum geometric design of the catalytic converter. The result showed that by decreasing the divergence angle of inlet cone pipe will upsurge the performance of the catalytic converter.

  20. Characteristics of the activity-affect association in inactive people: an ambulatory assessment study in daily life.

    Directory of Open Access Journals (Sweden)

    Birte eVon Haaren

    2013-04-01

    Full Text Available Acute and regular exercise as well as physical activity is related to wellbeing and positive affect. Recent studies have shown that even daily, unstructured physical activities increase positive affect. However, the attempt to achieve adherence to physical activity 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 physical activity in daily life. Therefore the present study investigated whether the association between physical activity 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 yrs ± 1.7 using the method of ambulatory assessment. Affect was assessed via electronic diary and physical activity was measured with accelerometers. Participants had to rate affect every two hours 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 minutes 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 physical activity in daily life. Analyzing the physical activity-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

  1. Level trend analysis summary report for Oak Ridge National Laboratory inactive liquid low-level waste tanks

    International Nuclear Information System (INIS)

    1994-09-01

    Oak Ridge National Laboratory facilities have produced liquid low-level waste (LLLW) that is radioactive and/or hazardous. Storage tanks have been used to collect and store these wastes. Most of the collection system, including the tanks, is located below the ground surface. Many of the systems have been removed from service (i.e., are not inactive) but contain residual amounts of waste liquid and sludges. A plan of action has been developed by DOE to ensure that environmental impacts from the waste remaining in the inactive tanks system are minimized. The Federal Facility Agreement (FFA) does not require any type of testing or monitoring for the inactive LLLW tanks that are removed from service but does require waste characterization of tanks contents, risk characterization of tanks removed from service, and remediation of the inactive tanks and their contents. This report is form information only and is not required by the FFA. It includes a description of the methodology and results of level trend analyses for the Category D tanks listed in the FFA that currently belong to the Environmental Restoration Program

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

    Science.gov (United States)

    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…

  3. Catalytic burners in larger boiler appliances

    Energy Technology Data Exchange (ETDEWEB)

    Silversand, Fredrik; Persson, Mikael (Catator AB, Lund (Sweden))

    2009-02-15

    This project focuses on the scale up of a Catator's catalytic burner technology to enable retrofit installation in existing boilers and the design of new innovative combinations of catalytic burners and boilers. Different design approaches are discussed and evaluated in the report and suggestions are made concerning scale-up. Preliminary test data, extracted from a large boiler installation are discussed together with an accurate analysis of technical possibilities following an optimization of the boiler design to benefit from the advantages of catalytic combustion. The experimental work was conducted in close collaboration with ICI Caldaie (ICI), located in Verona, Italy. ICI is a leading European boiler manufacturer in the effect segment ranging from about 20 kWt to several MWt. The study shows that it is possibly to scale up the burner technology and to maintain low emissions. The boilers used in the study were designed around conventional combustion and were consequently not optimized for implementation of catalytic burners. From previous experiences it stands clear that the furnace volume can be dramatically decreased when applying catalytic combustion. In flame combustion, this volume is normally dimensioned to avoid flame impingement on cold surfaces and to facilitate completion of the gas-phase reactions. The emissions of nitrogen oxides can be reduced by decreasing the residence time in the furnace. Even with the over-dimensioned furnace used in this study, we easily reached emission values close to 35 mg/kWh. The emissions of carbon monoxide and unburned hydrocarbons were negligible (less than 5 ppmv). It is possible to decrease the emissions of nitrogen oxides further by designing the furnace/boiler around the catalytic burner, as suggested in the report. Simultaneously, the size of the boiler installation can be reduced greatly, which also will result in material savings, i.e. the production cost can be reduced. It is suggested to optimize the

  4. From inactive to regular jogger

    DEFF Research Database (Denmark)

    Lund-Cramer, Pernille; Brinkmann Løite, Vibeke; Bredahl, Thomas Viskum Gjelstrup

    study was conducted using individual semi-structured interviews on how a successful long-term behavior change had been achieved. Ten informants were purposely selected from participants in the DANO-RUN research project (7 men, 3 women, average age 41.5). Interviews were performed on the basis of Theory...... of Planned Behavior (TPB) and The Transtheoretical Model (TTM). Coding and analysis of interviews were performed using NVivo 10 software. Results TPB: During the behavior change process, the intention to jogging shifted from a focus on weight loss and improved fitness to both physical health, psychological......Title From inactive to regular jogger - a qualitative study of achieved behavioral change among recreational joggers Authors Pernille Lund-Cramer & Vibeke Brinkmann Løite Purpose Despite extensive knowledge of barriers to physical activity, most interventions promoting physical activity have proven...

  5. Concentric catalytic combustor

    Science.gov (United States)

    Bruck, Gerald J [Oviedo, FL; Laster, Walter R [Oviedo, FL

    2009-03-24

    A catalytic combustor (28) includes a tubular pressure boundary element (90) having a longitudinal flow axis (e.g., 56) separating a first portion (94) of a first fluid flow (e.g., 24) from a second portion (95) of the first fluid flow. The pressure boundary element includes a wall (96) having a plurality of separate longitudinally oriented flow paths (98) annularly disposed within the wall and conducting respective portions (100, 101) of a second fluid flow (e.g., 26) therethrough. A catalytic material (32) is disposed on a surface (e.g., 102, 103) of the pressure boundary element exposed to at least one of the first and second portions of the first fluid flow.

  6. Effect of support on the catalytic activity of manganese oxide catalyts for toluene combustion.

    Science.gov (United States)

    Pozan, Gulin Selda

    2012-06-30

    The aim of this work was to study combustion of toluene (1000ppm) over MnO(2) modified with different supports. α-Al(2)O(3) and γ-Al(2)O(3) obtained from Boehmite, γ-Al(2)O(3) (commercial), SiO(2), TiO(2) and ZrO(2) were used as commercial support materials. In view of potential interest of this process, the influence of support material on the catalytic performance was discussed. The deposition of 9.5MnO(2) was performed by impregnation over support. The catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), temperature programmed reduction and oxidation (TPR/TPO) and thermogravimetric analysis (TGA). The catalytic tests were carried out at atmospheric pressure in a fixed-bed flow reactor. 9.5MnO(2)/α-Al(2)O(3)(B) (synthesized from Boehmite) catalyst exhibits the highest catalytic activity, over which the toluene conversion was up to 90% at a temperature of 289°C. Considering all the characterization and reaction data reported in this study, it was concluded that the manganese state and oxygen species played an important role in the catalytic activity. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Relation between body mass index, physical inactivity and use of prescription drugs: the Doetinchem Cohort Study.

    Science.gov (United States)

    Milder, I E J; Klungel, O H; Mantel-Teeuwisse, A K; Verschuren, W M M; Bemelmans, W J E

    2010-06-01

    Obesity and physical inactivity are associated with several diseases such as diabetes, cardiovascular diseases, musculoskeletal complaints, osteoporosis, certain types of cancer and depression. However, few data are available on the specific types of medication associated with obesity and physical inactivity. The aim of this study was to determine the independent association of body mass index (BMI) and physical inactivity with use of specific classes of prescription drugs, and the interaction between BMI and physical inactivity. The Doetinchem Cohort Study is a population-based longitudinal study. We analyzed cross-sectional data of 1703 men and 1841 women, examined between 1998 and 2002, for whom drug-dispending data were available from the PHARMO database. Drugs were coded according to the WHO Anatomical Therapeutic Chemical (ATC) classification system. Body weight was measured during the physical examination. Physical activity was assessed using an extensive questionnaire. Persons were defined as a user of a certain drug class if they filed at least one prescription in the year around (+/-6 months) the examination. Compared with normal weight persons (BMI 18.5-25 kg m(-2)), obese persons (BMI>30 kg m(-2)) had a higher use of prescription drugs of several drug classes, especially cardiovascular drugs (OR (95% CI): 3.83 (2.61-5.64) in men and 2.80 (2.03-3.86) in women) and diabetes drugs (OR (95% CI): 5.72 (2.32-14.14) in men and 3.92 (1.80-8.54) in women). In women, physical inactivity was also associated with higher use of certain drug classes, such as drugs for blood and blood-forming organs (OR (95% CI): 2.11 (1.22-3.65)) and musculoskeletal drugs (OR (95% CI): 2.07 (1.45-2.97)), whereas in men this was not the case. We found no interaction between BMI and physical inactivity with respect to use of prescription drugs. In both men and women, obesity was associated with a higher use of several types of prescription drugs, whereas physical inactivity was only

  8. 40 CFR 61.151 - Standard for inactive waste disposal sites for asbestos mills and manufacturing and fabricating...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Standard for inactive waste disposal sites for asbestos mills and manufacturing and fabricating operations. 61.151 Section 61.151 Protection... inactive waste disposal sites for asbestos mills and manufacturing and fabricating operations. Each owner...

  9. Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up

    Directory of Open Access Journals (Sweden)

    Maarit Piirtola

    2016-08-01

    Full Text Available Abstract Background Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. Methods This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945–1957 (59 % women, of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %. The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR with 95 % Confidence Intervals (CI were calculated using logistic and conditional (fixed-effects regression models. Results Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99 in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00 and OR 0.94 (95 % CI 0.91, 0.98, respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding of education on inactivity. However, the point estimates were lower than in the individual

  10. Catalytic models developed through social work

    DEFF Research Database (Denmark)

    Jensen, Mogens

    2015-01-01

    of adolescents placed in out-of-home care and is characterised using three situated cases as empirical data. Afterwards the concept of catalytic processes is briefly presented and then applied in an analysis of pedagogical treatment in the three cases. The result is a different conceptualisation of the social......The article develops the concept of catalytic processes in relation to social work with adolescents in an attempt to both reach a more nuanced understanding of social work and at the same time to develop the concept of catalytic processes in psychology. The social work is pedagogical treatment...

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

    Science.gov (United States)

    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. Validity and reliability of a physical activity/inactivity questionnaire in ...

    African Journals Online (AJOL)

    Objective. We sought to determine the validity and reliability of a self-report physical activity questionnaire (PAQ) measuring physical activity/inactivity in South African schoolgirls of different ethnic origins. Methods. Construct validity of the PAQ was tested against physical activity energy expenditure estimated from an ...

  13. Ferredoxin-thioredoxin reductase: a catalytically active dithiol group links photoreduced ferredoxin to thioredoxin functional in photosynthetic enzyme regulation

    Energy Technology Data Exchange (ETDEWEB)

    Droux, M.; Miginiac-Maslow, M.; Jacquot, J.P.; Gadal, P.; Crawford, N.A.; Kosower, N.S.; Buchanan, B.B.

    1987-07-01

    The mechanism by which the ferredoxin-thioredoxin system activates the target enzyme, NADP-malate dehydrogenase, was investigated by analyzing the sulfhydryl status of individual protein components with (/sup 14/C)iodoacetate and monobromobimane. The data indicate that ferredoxin-thioredoxin reductase (FTR)--an iron-sulfur enzyme present in oxygenic photosynthetic organisms--is the first member of a thiol chain that links light to enzyme regulation. FTR possesses a catalytically active dithiol group localized on the 13 kDa (similar) subunit, that occurs in all species investigated and accepts reducing equivalents from photoreduced ferredoxin and transfers them stoichiometrically to the disulfide form of thioredoxin m. The reduced thioredoxin m, in turn, reduces NADP-malate dehydrogenase, thereby converting it from an inactive (S-S) to an active (SH) form. The means by which FTR is able to combine electrons (from photoreduced ferredoxin) with protons (from the medium) to reduce its active disulfide group remains to be determined.

  14. Ferredoxin-thioredoxin reductase: a catalytically active dithiol group links photoreduced ferredoxin to thioredoxin functional in photosynthetic enzyme regulation

    International Nuclear Information System (INIS)

    Droux, M.; Miginiac-Maslow, M.; Jacquot, J.P.; Gadal, P.; Crawford, N.A.; Kosower, N.S.; Buchanan, B.B.

    1987-01-01

    The mechanism by which the ferredoxin-thioredoxin system activates the target enzyme, NADP-malate dehydrogenase, was investigated by analyzing the sulfhydryl status of individual protein components with [ 14 C]iodoacetate and monobromobimane. The data indicate that ferredoxin-thioredoxin reductase (FTR)--an iron-sulfur enzyme present in oxygenic photosynthetic organisms--is the first member of a thiol chain that links light to enzyme regulation. FTR possesses a catalytically active dithiol group localized on the 13 kDa (similar) subunit, that occurs in all species investigated and accepts reducing equivalents from photoreduced ferredoxin and transfers them stoichiometrically to the disulfide form of thioredoxin m. The reduced thioredoxin m, in turn, reduces NADP-malate dehydrogenase, thereby converting it from an inactive (S-S) to an active (SH) form. The means by which FTR is able to combine electrons (from photoreduced ferredoxin) with protons (from the medium) to reduce its active disulfide group remains to be determined

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

    International Nuclear Information System (INIS)

    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

  16. Catalytically favorable surface patterns in Pt-Au nanoclusters

    KAUST Repository

    Mokkath, Junais Habeeb

    2013-01-01

    Motivated by recent experimental demonstrations of novel PtAu nanoparticles with highly enhanced catalytic properties, we present a systematic theoretical study that explores principal catalytic indicators as a function of the particle size and composition. We find that Pt electronic states in the vicinity of the Fermi level combined with a modified electron distribution in the nanoparticle due to Pt-to-Au charge transfer are the origin of the outstanding catalytic properties. From our model we deduce the catalytically favorable surface patterns that induce ensemble and ligand effects. © The Royal Society of Chemistry 2013.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

    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

  18. Turning goals into results: the power of catalytic mechanisms.

    Science.gov (United States)

    Collins, J

    1999-01-01

    Most executives have a big, hairy, audacious goal. They write vision statements, formalize procedures, and develop complicated incentive programs--all in pursuit of that goal. In other words, with the best of intentions, they install layers of stultifying bureaucracy. But it doesn't have to be that way. In this article, Jim Collins introduces the catalytic mechanism, a simple yet powerful managerial tool that helps translate lofty aspirations into concrete reality. Catalytic mechanisms are the crucial link between objectives and performance; they are a galvanizing, nonbureaucratic means to turn one into the other. What's the difference between catalytic mechanisms and most traditional managerial controls? Catalytic mechanisms share five characteristics. First, they produce desired results in unpredictable ways. Second, they distribute power for the benefit of the overall system, often to the discomfort of those who traditionally hold power. Third, catalytic mechanisms have teeth. Fourth, they eject "viruses"--those people who don't share the company's core values. Finally, they produce an ongoing effect. Catalytic mechanisms are just as effective for reaching individual goals as they are for corporate ones. To illustrate how catalytic mechanisms work, the author draws on examples of individuals and organizations that have relied on such mechanisms to achieve their goals. The same catalytic mechanism that works in one organization, however, will not necessarily work in another. Catalytic mechanisms must be tailored to specific goals and situations. To help readers get started, the author offers some general principles that support the process of building catalytic mechanisms effectively.

  19. Atomically Precise Metal Nanoclusters for Catalytic Application

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Rongchao [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    2016-11-18

    The central goal of this project is to explore the catalytic application of atomically precise gold nanoclusters. By solving the total structures of ligand-protected nanoclusters, we aim to correlate the catalytic properties of metal nanoclusters with their atomic/electronic structures. Such correlation unravel some fundamental aspects of nanocatalysis, such as the nature of particle size effect, origin of catalytic selectivity, particle-support interactions, the identification of catalytically active centers, etc. The well-defined nanocluster catalysts mediate the knowledge gap between single crystal model catalysts and real-world conventional nanocatalysts. These nanoclusters also hold great promise in catalyzing certain types of reactions with extraordinarily high selectivity. These aims are in line with the overall goals of the catalytic science and technology of DOE and advance the BES mission “to support fundamental research to understand, predict, and ultimately control matter and energy at the level of electrons, atoms, and molecules”. Our group has successfully prepared different sized, robust gold nanoclusters protected by thiolates, such as Au25(SR)18, Au28(SR)20, Au38(SR)24, Au99(SR)42, Au144(SR)60, etc. Some of these nanoclusters have been crystallographically characterized through X-ray crystallography. These ultrasmall nanoclusters (< 2 nm diameter) exhibit discrete electronic structures due to quantum size effect, as opposed to quasicontinuous band structure of conventional metal nanoparticles or bulk metals. The available atomic structures (metal core plus surface ligands) of nanoclusters serve as the basis for structure-property correlations. We have investigated the unique catalytic properties of nanoclusters (i.e. not observed in conventional nanogold catalysts) and revealed the structure-selectivity relationships. Highlights of our

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

    Science.gov (United States)

    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…

  1. Physical inactivity prevalence and trends among Mexican adults: results from the National Health and Nutrition Survey (ENSANUT) 2006 and 2012.

    Science.gov (United States)

    Medina, Catalina; Janssen, Ian; Campos, Ismael; Barquera, Simón

    2013-11-11

    Lifestyles such as unhealthy diets and the lack of physical activity have been contributed to the increased prevalence of obesity. In 2012, the world health organization published the first global recommendation for physical activity and health. People who do not meet at least 150 minutes of moderate-to-vigorous physical activity are considered to be physically inactive. The prevalence of physical inactivity worldwide is 31%, however there is insufficient data from prevalence and trends of physical inactivity in Mexican population. The purposes of this study are to describe the physical inactivity prevalence and recent trends in Mexican adults and to examine the association between physical inactivity with biologic and sociodemographic characteristics. Representative samples of 17,183 and 10,729 adults (aged 20 to 69 years) who participated in the National Health and Nutrition Survey (ENSANUT) in 2006 and 2012, respectively. Moderate-to-vigorous physical activity (MVPA) was assessed using the short form version of the International Physical Activity Questionnaire (IPAQ), which was administered in face-to-face interviews. Self-reported IPAQ MVPA levels were adjusted using an equation derived from a previous validation study. Participants were considered inactive if they engaged in <150-minutes/week of moderate physical activity or <75 minutes/week of vigorous physical activity according to WHO classification criteria. The prevalence of physical inactivity was significantly higher in 2012 (19.4%, 95% CI: 18.1, 20.7) than in 2006 (13.4%, 95% CI: 12.5, 14.5). Adults in the obese category, 60-69 age group, and those in the highest socioeconomic status tertile were more likely to be physically inactive. The proportion of the Mexican adult population who do not meet the minimum WHO physical activity criteria has increased by 6% points between 2006 and 2012. Given the increasing prevalence of obesity, the aging of the population, and the shift in socioeconomic status in

  2. Administration of additional inactive iodide during radioiodine therapy for Graves' disease. Who might benefit?

    International Nuclear Information System (INIS)

    Dietlein, M.; Moka, D.; Reinholz, U.; Schmidt, M.; Schomaecker, K.; Schicha, H.; Wellner, U.

    2007-01-01

    Aim: Graves' hyperthyroidism and antithyroid drugs empty the intrathyroid stores of hormones and iodine. The consequence is rapid 131 I turnover and impending failure of radioiodine therapy. Can administration of additional inactive iodide improve 131I kinetics? Patients, methods: Fifteen consecutive patients, in whom the 48 h post-therapeutically calculated thyroid dose was between 150 and 249 Gy due to an unexpectedly short half-life, received 3 x 200 μg inactive potassium-iodide ( 127 I) daily for 3 days (Group A), while 17 consecutive patients with a thyroid dose of = 250 Gy (Group B) served as the non-iodide group. 48 hours after 131 I administration (M1) and 4 or 5 days later (M2) the following parameters were compared: effective 131 I half-life, thyroid dose, total T3, total T4, 131 I-activity in the T3- and T4-RIAs. Results: In Group A, the effective 131 I half-life M1 before iodine (3.81 ± 0.93 days) was significantly (p 131 I half-life M2 (4.65 ± 0.79 days). Effective 131 I half-life M1 correlated with the benefit from inactive 127 I (r = -0.79): Administration of 127 I was beneficial in patients with an effective 131 I half-life M1 of 131 I activity of T3 and T4 showed lower specific 131 I activity after addition of inactive iodine compared with patients from the same group with a lower initial specific 131 I activity of T3 and T4 and compared with the patient group B who was given no additional inactive iodide. This correlation was mathematically described and reflected in the flatter gradient in Group A (y = 0.5195x + 0.8727 for 131 I T3 and y = 1.0827x - 0.4444 for 131 I T4) and steeper gradient for Group B (y = 0.6998x + 0.5417 for 131 I T3 and y = 1.3191x - 0.2901 for 131 I T4). Radioiodine therapy was successful in all 15 patients from Group A. Conclusion: The administration of 600 μg inactive iodide for three days during radioiodine therapy in patients with Graves' hyperthyroidism and an unexpectedly short half-life of <3 or 4 days was a safe

  3. On the mechanism of sulfite activation of chloroplast thylakoid ATPase and the relation of ADP tightly bound at a catalytic site to the binding change mechanism

    International Nuclear Information System (INIS)

    Du, Z.; Boyer, P.D.

    1990-01-01

    Washed chloroplast thylakoid membranes upon exposure to [ 3 H]ADP retain in tightly bound [ 3 H]ADP on a catalytic site of the ATP synthase. The presence of sufficient endogenous or added Mg 2+ results in an enzyme with essentially no ATPase activity. Sulfite activates the ATPase, and many molecules of ATP per synthase can be hydrolyzed before most of the bound [ 3 H]ADP is released, a result interpreted as indicating that the ADP is not bound at a site participating in catalysis by the sulfite-activated enzyme. The authors present evidence that this is not the case. The Mg 2+ - and ADP-inhibited enzyme when exposed to MgATP and 20-100 mM sulfite shows a lag of about 1 min at 22 degree C and of about 15 s at 37 degree C before reaching the same steady-state rate as attained with light-activated ATPase that has not been inhibited by Mg 2+ and ADP. The lag is not eliminated if the enzyme is exposed to sulfite prior to MgATP addition, indicating that ATPase turnover is necessary for the activation. The release of most of the bound [ 3 H]ADP parallels the onset of ATPase activity, although some [ 3 H]ADP is not released even with prolonged catalytic turnover and may be on poorly active or inactive enzyme or at noncatalytic sites. The results are consistent with most of the tightly bound [ 3 H]ADP being at a catalytic site and being replaced as this Mg 2+ - and ADP-inhibited site regains equivalent participation with other catalytic sites on the activated enzyme. The sulfite activation can be explained by sulfite combination at a P i binding site of the enzyme-ADP-Mg 2+ complex to give a form more readily activated by ATP binding at an alternative site

  4. Kinetic Parameters of Non-Isothermal Thermogravimetric Non-Catalytic and Catalytic Pyrolysis of Empty Fruit Bunch with Alumina by Kissinger and Ozawa Methods

    Science.gov (United States)

    Rahayu Mohamed, Alina; Li, Nurfahani; Sohaimi, Khairunissa Syairah Ahmad; Izzati Iberahim, Nur; Munirah Rohaizad, Nor; Hamzah, Rosniza

    2018-03-01

    The non-isothermal thermogravimetric non-catalytic and catalytic empty fruit bunch (EFB) pyrolysis with alumina were performed at different heating rates of 10, 15, 20, 25, 30 and 40 K/min under nitrogen atmosphere at a flow rate of 100 ml/min under dynamic conditions from 301 K to 1273 K. The activation energy were calculated based on Kissinger and Ozawa methods. Both reactions followed first order reactions. By Kissinger method, the activation energy and Ln A values for non-catalytic and catalytic EFB pyrolysis with alumina were 188.69 kJ mol-1 and 201.67 kJ/mol respectively. By Ozawa method, the activation energy values for non-catalytic and catalytic EFB pyrolysis with alumina were 189.13 kJ/mol and 201.44 kJ/mol respectively. The presence of catalyst increased the activation energy values for EFB pyrolysis as calculated by Kissinger and Ozawa methods.

  5. Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells.

    Science.gov (United States)

    Knoepp, Stewart M; Chahal, Manpreet S; Xie, Yuhuan; Zhang, Zhihong; Brauner, Daniel J; Hallman, Mark A; Robinson, Stephanie A; Han, Shujie; Imai, Masaki; Tomlinson, Stephen; Meier, Kathryn E

    2008-09-01

    The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 confers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are unchanged in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt; inactive PLD2 has no effect. Expression of active PLD2 is associated with increased spreading and elongation of cells on tissue culture plastic, whereas inactive PLD2 inhibits cell spreading. Inactive PLD2 also inhibits cell adhesion, migration, and serum-induced invasion. Cells expressing active PLD2 form metastases in syngeneic mice, as do the parental cells; cells expressing inactive PLD2 form fewer metastases than parental cells. In summary, active PLD2 enhances FAK phosphorylation, Akt activation, and cell invasion in EL4 lymphoma cells, whereas inactive PLD2 exerts inhibitory effects on adhesion, migration, invasion, and tumor formation. Overall, expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis.

  6. A Mononuclear Non-Heme Manganese(IV)-Oxo Complex Binding Redox-Inactive Metal Ions

    Energy Technology Data Exchange (ETDEWEB)

    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 [Ewha; (Purdue); (Osaka)

    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.

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

    Directory of Open Access Journals (Sweden)

    Belhumeur Pierre

    2008-11-01

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

  8. Impact of poor sleep quality and physical inactivity on cognitive function in community-dwelling older adults.

    Science.gov (United States)

    Nakakubo, Sho; Makizako, Hyuma; Doi, Takehiko; Tsutsumimoto, Kota; Lee, Sangyoon; Lee, Sungchul; Hotta, Ryo; Bae, Seongryu; Suzuki, Takao; Shimada, Hiroyuki

    2017-11-01

    The purpose of the present study was to examine whether the combination of subjective sleep quality and physical activity is associated with cognitive performance among community-dwelling older adults. Cross-sectional data on 5381 older adults who participated in part of the National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes were analyzed. We assessed general cognitive impairment using the Mini-Mental State Examination, and also assessed story memory, attention, executive function and processing speed using the National Center for Geriatrics and Gerontology Functional Assessment Tool. Physical activity was assessed using two questionnaires, and participants were categorized as active or inactive. Sleep quality was assessed using the Pittsburgh Sleep Quality Index, and participants were categorized as having poor (PS) or good sleep quality (GS). Participants in the inactive + PS group had worse performances than those in the active + GS group in all cognitive measures (Mini-Mental State Examination: P = 0.008, story memory: P = 0.007, other cognitive measures: P performances than those in the inactive + GS and active + PS groups in the trail-making test, part B, and the symbol digit substitution test (P performances than in the active + GS in the trail-making test, part B, and the symbol digit substitution test (P = 0.002 and P = 0.001, respectively). Inactivity and poor sleep quality were associated with poor cognitive performance among community-dwelling older adults. The combination of poor sleep quality and physical inactivity also worsened cognitive performance. Geriatr Gerontol Int 2017; 17: 1823-1828. © 2017 Japan Geriatrics Society.

  9. Catalytic Stereoinversion of L-Alanine to Deuterated D-Alanine.

    Science.gov (United States)

    Moozeh, Kimia; So, Soon Mog; Chin, Jik

    2015-08-03

    A combination of an achiral pyridoxal analogue and a chiral base has been developed for catalytic deuteration of L-alanine with inversion of stereochemistry to give deuterated D-alanine under mild conditions (neutral pD and 25 °C) without the use of any protecting groups. This system can also be used for catalytic deuteration of D-alanine with retention of stereochemistry to give deuterated D-alanine. Thus a racemic mixture of alanine can be catalytically deuterated to give an enantiomeric excess of deuterated D-alanine. While catalytic deracemization of alanine is forbidden by the second law of thermodynamics, this system can be used for catalytic deracemization of alanine with deuteration. Such green and biomimetic approach to catalytic stereocontrol provides insights into efficient amino acid transformations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Seepage studies through hydraulic structures and their foundations by inactive and radio tracers

    International Nuclear Information System (INIS)

    Ansari, Azher; Mahajan, N.M.; Kamble, M.D.

    1977-01-01

    In the last ten years extensive efforts have been made by the Central Water and Power Research Station, Pune to study seepage by means of inactive and radiotracers. Various inactive tracers like electrolytes and organic dyes and radiotracers like 82 Br and 3 H in the form of tritiated water have been used for location of source of seepage. Different techniques like borehole dilution, in situ detection at various observation points and analysis of water samples in liquid scintillation spectrometer in the laboratory have been employed to suit the field conditions. Some typical studies at river valley projects indicating the techniques are enumerated. (author)

  11. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Science.gov (United States)

    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...

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

    Science.gov (United States)

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

    2015-01-01

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

  13. A Review on Catalytic Membranes Production and Applications

    Directory of Open Access Journals (Sweden)

    Heba Abdallah

    2017-05-01

    Full Text Available The development of the chemical industry regarding reducing the production cost and obtaining a high-quality product with low environmental impact became the essential requirements of the world in these days. The catalytic membrane is considered as one of the new alternative solutions of catalysts problems in the industries, where the reaction and separation can be amalgamated in one unit. The catalytic membrane has numerous advantages such as breaking the thermodynamic equilibrium limitation, increasing conversion rate, reducing the recycle and separation costs. But the limitation or most disadvantages of catalytic membranes related to the high capital costs for fabrication or the fact that manufacturing process is still under development. This review article summarizes the most recent advances and research activities related to preparation, characterization, and applications of catalytic membranes. In this article, various types of catalytic membranes are displayed with different applications and explained the positive impacts of using catalytic membranes in various reactions. Copyright © 2017 BCREC Group. All rights reserved. Received: 1st April 2016; Revised: 14th February 2017; Accepted: 22nd February 2017 How to Cite: Abdallah, H. (2017. A Review on Catalytic Membranes Production and Applications. Bulletin of Chemical Reaction Engineering & Catalysis, 12 (2: 136-156 (doi:10.9767/bcrec.12.2.462.136-156 Permalink/DOI: http://dx.doi.org/10.9767/bcrec.12.2.462.136-156

  14. Identification of species of viridans group streptococci in clinical blood culture isolates by sequence analysis of the RNase P RNA gene, rnpB.

    Science.gov (United States)

    Westling, Katarina; Julander, Inger; Ljungman, Per; Vondracek, Martin; Wretlind, Bengt; Jalal, Shah

    2008-03-01

    Viridans group streptococci (VGS) cause severe diseases such as infective endocarditis and septicaemia. Genetically, VGS species are very close to each other and it is difficult to identify them to species level with conventional methods. The aims of the present study were to use sequence analysis of the RNase P RNA gene (rnpB) to identify VGS species in clinical blood culture isolates, and to compare the results with the API 20 Strep system that is based on phenotypical characteristics. Strains from patients with septicaemia or endocarditis were analysed with PCR amplification and sequence analysis of the rnpB gene. Clinical data were registered as well. One hundred and thirty two VGS clinical blood culture isolates from patients with septicaemia (n=95) or infective endocarditis (n=36) were analysed; all but one were identified by rnpB. Streptococcus oralis, Streptococcus sanguinis and Streptococcus gordonii strains were most common in the patients with infective endocarditis. In the isolates from patients with haematological diseases, Streptococcus mitis and S. oralis dominated. In addition in 76 of the isolates it was possible to compare the results from rnpB analysis and the API 20 Strep system. In 39/76 (51%) of the isolates the results were concordant to species level; in 55 isolates there were no results from API 20 Strep. Sequence analysis of the RNase P RNA gene (rnpB) showed that almost all isolates could be identified. This could be of importance for evaluation of the portal of entry in patients with septicaemia or infective endocarditis.

  15. Is sedentary behaviour just physical inactivity by another name?

    OpenAIRE

    van der Ploeg, Hidde P.; Hillsdon, Melvyn

    2017-01-01

    The relationship between sedentary behaviour and physical activity and their role in the development of health conditions is an ongoing topic of research. This debate paper presents arguments in favour and against the statement: “Is sedentary behaviour just physical inactivity by another name?” The paper finishes with recommendations for future research in the field of sedentary behaviour, physical activity and public health.

  16. An Inactive Geminin Mutant That Binds Cdt1

    Directory of Open Access Journals (Sweden)

    Marissa Suchyta

    2015-05-01

    Full Text Available The initiation of DNA replication is tightly regulated in order to ensure that the genome duplicates only once per cell cycle. In vertebrate cells, the unstable regulatory protein Geminin prevents a second round of DNA replication by inhibiting the essential replication factor Cdt1. Cdt1 recruits mini-chromosome maintenance complex (MCM2-7, the replication helicase, into the pre-replication complex (pre-RC at origins of DNA replication. The mechanism by which Geminin inhibits MCM2-7 loading by Cdt1 is incompletely understood. The conventional model is that Geminin sterically hinders a direct physical interaction between Cdt1 and MCM2-7. Here, we describe an inactive missense mutant of Geminin, GemininAWA, which binds to Cdt1 with normal affinity yet is completely inactive as a replication inhibitor even when added in vast excess. In fact, GemininAWA can compete with GemininWT for binding to Cdt1 and prevent it from inhibiting DNA replication. GemininAWA does not inhibit the loading of MCM2-7 onto DNA in vivo, and in the presence of GemininAWA, nuclear DNA is massively over-replicated within a single S phase. We conclude that Geminin does not inhibit MCM loading by simple steric interference with a Cdt1-MCM2-7 interaction but instead works by a non-steric mechanism, possibly by inhibiting the histone acetyltransferase HBO1.

  17. Motor proficiency and physical fitness in active and inactive girls ...

    African Journals Online (AJOL)

    In modern day society physical activity levels diminish rapidly among girls and may be a direct consequence of girls experiencing motor difficulties. Therefore the aim of the study was to compare motor proficiency levels and physical fitness levels among active and inactive girls (N=97), aged 12 to 13 years. The BOTMP ...

  18. Optimization of Inactive Material Content in Lithium Iron Phosphate Electrodes for High Power Applications

    International Nuclear Information System (INIS)

    Ha, Seonbaek; Ramani, Vijay K.; Lu, Wenquan; Prakash, Jai

    2016-01-01

    The electrochemical performance of lithium iron phosphate (LiFePO 4 ) electrodes has been studied to find the optimum content of inactive materials (carbon black + polyvinylidene difluoride [PVDF] polymer binder) and to better understand electrode performance with variation in electrode composition. Trade-offs between inactive material content and electrochemical performance have been characterized in terms of electrical resistance, rate-capability, area-specific impedance (ASI), pulse-power characterization, and energy density calculations. The ASI and electrical conductivity were found to correlate well with ohmic polarization. The results showed that a 80:10:10 (active material: binder: carbon agents) electrode had a higher pulse-power density and energy density at rates above 1C as compared to 90:5:5, 86:7:7 and 70:15:15 formulations, while the 70:15:15 electrode had the highest electrical conductivity of 0.79 S cm −1 . A CB/PVDF ratio of ca. 1.22 was found to be the optimum formulation of inactive material when the LiFePO 4 composition was 80 wt%.

  19. On the Structural Context and Identification of Enzyme Catalytic Residues

    Directory of Open Access Journals (Sweden)

    Yu-Tung Chien

    2013-01-01

    Full Text Available Enzymes play important roles in most of the biological processes. Although only a small fraction of residues are directly involved in catalytic reactions, these catalytic residues are the most crucial parts in enzymes. The study of the fundamental and unique features of catalytic residues benefits the understanding of enzyme functions and catalytic mechanisms. In this work, we analyze the structural context of catalytic residues based on theoretical and experimental structure flexibility. The results show that catalytic residues have distinct structural features and context. Their neighboring residues, whether sequence or structure neighbors within specific range, are usually structurally more rigid than those of noncatalytic residues. The structural context feature is combined with support vector machine to identify catalytic residues from enzyme structure. The prediction results are better or comparable to those of recent structure-based prediction methods.

  20. Prevalence and time trends in diabetes and physical inactivity among adult West African populations: the epidemic has arrived.

    Science.gov (United States)

    Abubakari, A R; Lauder, W; Jones, M C; Kirk, A; Agyemang, C; Bhopal, R S

    2009-09-01

    To determine the prevalence and distribution of, and trends in, physical inactivity and diabetes in adult West African populations. Systematic review and meta-analysis. Literature searches were conducted using four electronic databases. Journal hand searches and examination of citations of relevant articles were also undertaken. To be included, studies had to be population based, use clearly defined criteria for measuring diabetes and physical inactivity, present data that allowed calculation of the prevalence of diabetes or physical inactivity, and sample adult participants. Studies retrieved were appraised critically. Meta-analysis was performed using the DerSimonian-Laird random effect model. Twenty-one reports were retrieved for diabetes and 15 reports were retrieved for physical in/activity. Most studies (10 for diabetes and six for physical activity) were conducted solely among urban populations. The prevalence of diabetes in West Africa was approximately 4.0% [95% confidence interval (CI) 2.0-9.0] in urban adults and 2.6% (95%CI 1.5-4.4) in rural adults, and was similar in men and women [prevalence ratio (PR) 1.36, 95%CI 0.96-1.92]. Cumulative time trend analyses suggested an increase in the prevalence of diabetes among adults in urban West Africa, from approximately 3.0% (95%CI 1.0-7.0) to 4.0% (95%CI 2.0-9.0) in the past 10 years. The prevalence of inactivity in West Africa was 13% (95%CI 9.0-18.0). An association was found between physical inactivity and being older (> or = 50 years) (PR 1.82, 95%CI 1.36-2.44), female gender (PR 1.62, 95%CI 1.41-1.87) and urban residence (PR 2.04, 95%CI 1.58-2.63). Diabetes and physical inactivity are important public health issues in urban West Africa, with similar prevalences to wealthy industrialized countries. There is an urgent need for policy makers, politicians and health promotion experts to put measures in place to encourage active lifestyles and control diabetes in urban West Africa.

  1. An efficient algorithm for removal of inactive blocks in reservoir simulation

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Kassem, J.H.; Ertekin, T. (Pennsylvania State Univ., PA (United States))

    1992-02-01

    In the efficient simulation of reservoirs having irregular boundaries one is confronted with two problems: the removal of inactive blocks at the matrix level and the development and application of a variable band-width solver. A simple algorithm is presented that provides effective solutions to these two problems. The algorithm is demonstrated for both the natural ordering and D4 ordering schemes. It can be easily incorporated in existing simulators and results in significant savings in CPU and matrix storage requirements. The removal of the inactive blocks at the matrix level plays a major role in effecting these savings whereas the application of a variable band-width solver plays an enhancing role only. The value of this algorithm lies in the fact that it takes advantage of irregular reservoir boundaries that are invariably encountered in almost all practical applications of reservoir simulation. 11 refs., 3 figs., 3 tabs.

  2. Catalytic activity of Au nanoparticles

    DEFF Research Database (Denmark)

    Larsen, Britt Hvolbæk; Janssens, Ton V.W.; Clausen, Bjerne

    2007-01-01

    Au is usually viewed as an inert metal, but surprisingly it has been found that Au nanoparticles less than 3–5 nm in diameter are catalytically active for several chemical reactions. We discuss the origin of this effect, focusing on the way in which the chemical activity of Au may change with par......Au is usually viewed as an inert metal, but surprisingly it has been found that Au nanoparticles less than 3–5 nm in diameter are catalytically active for several chemical reactions. We discuss the origin of this effect, focusing on the way in which the chemical activity of Au may change...... with particle size. We find that the fraction of low-coordinated Au atoms scales approximately with the catalytic activity, suggesting that atoms on the corners and edges of Au nanoparticles are the active sites. This effect is explained using density functional calculations....

  3. Analysis of S-RNase alleles of almond (Prunus dulcis): characterization of new sequences, resolution of synonyms and evidence of intragenic recombination.

    Science.gov (United States)

    Ortega, Encarnación; Bosković, Radovan I; Sargent, Daniel J; Tobutt, Kenneth R

    2006-11-01

    Cross-compatibility relationships in almond are controlled by a gametophytically expressed incompatibility system partly mediated by stylar RNases, of which 29 have been reported. To resolve possible synonyms and to provide data for phylogenetic analysis, 21 almond S-RNase alleles were cloned and sequenced from SP (signal peptide region) or C1 (first conserved region) to C5, except for the S29 allele, which could be cloned only from SP to C1. Nineteen sequences (S4, S6, S11-S22, S25-S29)) were potentially new whereas S10 and S24 had previously been published but with different labels. The sequences for S16 and S17 were identical to that for S1, published previously; likewise, S15 was identical to S5. In addition, S4 and S20 were identical, as were S13 and S19. A revised version of the standard table of almond incompatibility genotypes is presented. Several alleles had AT or GA tandem repeats in their introns. Sequences of the 23 distinct newly cloned or already published alleles were aligned. Sliding windows analysis of Ka/Ks identified regions where positive selection may operate; in contrast to the Maloideae, most of the region from the beginning of C3 to the beginning of RC4 appeared not to be under positive selection. Phylogenetic analysis indicated four pairs of alleles had "bootstrap" support > 80%: S5/S10, S4/S8, S11/S24, and S3/S6. Various motifs up to 19 residues long occurred in at least two alleles, and their distributions were consistent with intragenic recombination, as were separate phylogenetic analyses of the 5' and 3' sections. Sequence comparison of phylogenetically related alleles indicated the significance of the region between RC4 and C5 in defining specificity.

  4. Targeting Micrornas With Small Molecules: A Novel Approach to Treating Breast Cancer

    Science.gov (United States)

    2010-10-01

    DNAzyme, or deoxyribozyme, is a catalytic DNA that site-specifically cleaves the target RNA Watson – Crick base pairing to a complementary target...conserved antiparallel RNA A-helix fold among the selected pre- miRNA targets (Fig. 1a). Furthermore, 3D characteristics including Watson - Crick base pairs... Watson – Crick binding, leading to RNAse-H- mediated cleavage of the mRNA of the target gene. The ASOs also inhibit transcription, splicing, and

  5. The Relationship Between Neighborhood Socioeconomic Characteristics and Physical Inactivity Among Adolescents Living in Boston, Massachusetts

    Science.gov (United States)

    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

  6. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Charlotte Proudhon

    2016-06-01

    Full Text Available V(DJ recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control.

  7. Engineering Metallic Nanoparticles for Enhancing and Probing Catalytic Reactions.

    Science.gov (United States)

    Collins, Gillian; Holmes, Justin D

    2016-07-01

    Recent developments in tailoring the structural and chemical properties of colloidal metal nanoparticles (NPs) have led to significant enhancements in catalyst performance. Controllable colloidal synthesis has also allowed tailor-made NPs to serve as mechanistic probes for catalytic processes. The innovative use of colloidal NPs to gain fundamental insights into catalytic function will be highlighted across a variety of catalytic and electrocatalytic applications. The engineering of future heterogenous catalysts is also moving beyond size, shape and composition considerations. Advancements in understanding structure-property relationships have enabled incorporation of complex features such as tuning surface strain to influence the behavior of catalytic NPs. Exploiting plasmonic properties and altering colloidal surface chemistry through functionalization are also emerging as important areas for rational design of catalytic NPs. This news article will highlight the key developments and challenges to the future design of catalytic NPs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A retraining program for inactive physicians.

    Science.gov (United States)

    Brown, M; Sakai, F J; Selzer, A

    1969-11-01

    During the past two years a pilot project was conducted in which 19 inactive physicians were retrained in preparation for resumption of active practice. The initial program consisted of a flexible training program of six months to one year patterned after conventional internship-residency concepts. During the second year the program was modified by providing an initial condensed indoctrination period of two months' duration especially designed for this purpose, followed by a preceptorship type of training. The project was considered successful in permitting trainees to enter some form of active medical work, or to enroll in formal specialty training. The observations made by the faculty of the program and its accomplishments are discussed in the light of the effort expended and the cost of the project.

  9. Hydrocarbon conversion with an attenuated superactive multimetallic catalytic composite

    International Nuclear Information System (INIS)

    Antos, G.J.

    1981-01-01

    Hydrocarbons are converted by contacting them at hydrocarbon conversion conditions with a novel attenuated superactive multimetallic catalytic composite comprising a combination of a catalytically effective amount of a pyrolyzed rhenium carbonyl component with a porous carrier material containing a uniform dispersion of catalytically effective amounts of a platinum group component, which is maintained in the elemental metallic state during the incorporation and pyrolysis of the rhenium carbonyl component, and of an iron component. In a highly preferred embodiment, this novel catalytic composite also contains a catalytically effective amount of a halogen component. The platinum group component, pyrolyzed rhenium carbonyl component, iron component and optional halogen component are preferably present in the multimetallic catalytic composite in amounts, calculated on an elemental basis, corresponding to about 0.01 to about 2 wt. % platinum group metal, about 0.01 to about 5 wt. % rhenium, about 0.005 to about 4 wt. % iron and about 0.1 to about 5 wt. % halogen. A key feature associated with the preparation of the subject catalytic composite is reaction of a rhenium carbonyl complex with a porous carrier material containing a uniform dispersion of an iron component and of a platinum group component maintained in the elemental state, whereby the interaction of the rhenium moiety with the platinum group moiety is maximized due to the platinophilic (i.e., platinum-seeking) propensities of the carbon monoxide ligands associated with the rhenium reagent. A specific example of the type of hydrocarbon conversion process disclosed herein is a process for the catalytic reforming of a low octane gasoline fraction wherein the gasoline fraction and a hydrogen stream are contacted with the attenuated superactive multimetallic catalytic composite at reforming conditions

  10. Catalytic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bindley, W T.R.

    1931-04-18

    An apparatus is described for the catalytic treatment of liquids, semi-liquids, and gases comprising a vessel into which the liquid, semi-liquid, or gas to be treated is introduced through a common inlet to a chamber within the vessel whence it passes to contact with a catalyst through radially arranged channels or passages to a common outlet chamber.

  11. Effect of moderate versus high intensity interval exercise training on vascular function in inactive latin-american adults: a randomized clinical trial

    OpenAIRE

    Hernández Quiñonez, Paula Andrea

    2016-01-01

    Exercise training is effective for improving cardiometabolic health and physical fitness in inactive adults. However, limited research has been conducted on the optimal exercise training intensity for this population. We investigate the effect of moderate versus high intensity interval exercise training on vascular function and physical fitness in physically inactive adults. Twenty inactive adults were randomly allocated to receive either moderate intensity training (MCT group) or high intens...

  12. Leisure-time physical inactivity and psychological distress in female-dominated occupations in Lithuania.

    Science.gov (United States)

    Malinauskiene, Vilija; Malinauskas, Romualdas; Malinauskas, Mindaugas

    2017-12-27

    Poor mental health, manifesting as psychological distress, has become a leading problem recently; therefore, determining associated factors is important, especially in female-dominated occupations, as women are more prone to psychological distress than men, in part due to demands of both professional and domestic tasks. The objective of the present study was to investigate associations between leisure-time physical inactivity and psychological distress, accounting for the possible relation of psychosocial factors at work (job demands, job control, social support at work, workplace bullying) and life events in representative samples of family physicians, internal medicine department nurses and secondary-school teachers in Lithuania. In total, 323 family physicians, 748 internal medicine department nurses and 517 secondary-school teachers were interviewed during 2012-2014 in Lithuania. Godin leisure-time exercise, Goldberg General Health, Job content, and Negative acts questionnaires were administered. Logistic regression was used. A high proportion of family physicians, nurses and teachers were physically inactive during leisure. Leisure-time physical inactivity was strongly associated with psychological distress, adjusting for age, workplace bullying, job demands, job control, social support at work and traumatic life events in all three female-dominated occupations. Efforts to increase leisure-time physical activity level in medical occupations could be beneficial.

  13. Catalytic cleavage activities of 10–23 DNAzyme analogs functionalized with an amino group in its catalytic core

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2012-02-01

    Full Text Available Functionalization of the catalytic loop of 10–23 DNAzyme with an amino group was performed by incorporation of 7-(3-aminopropyl-8-aza-7-deaza-2′-deoxyadenosine in different single positions. Among the nine modified positions in the catalytic loop, A9 is the unique position with positive contribution by such modification. These results indicated that more efficient deoxyribozymes remain to be explored by introduction of exogenous functional groups in an appropriate position in the catalytic loop of 10–23 DNAzyme, such as the combination of 7-functional group substituted 8-aza-7-deaza-2′-deoxyadenosine analogs and A9 position.

  14. An initial study of the behaviour under repository conditions of inactive components of nuclear wastes

    International Nuclear Information System (INIS)

    Biddle, P.; Rees, J.H.

    1988-02-01

    This review extends the appreciation of repository behaviour to include the inactive components of wastes and their degradation products. These materials include a wide range of metals and organics, sludges and decommissioning wastes. The effect of degradation products on the solubility of long-lived radionuclides and any active daughters and their sorption on surfaces of the repository are assessed. Research requirements are identified that may help to improve significantly the assessment of the effects of inactive materials. Data required to improve the quality of inventory data on nuclear wastes are listed. (author)

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

    Science.gov (United States)

    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...

  16. The relationship between coping, health competence and patient participation among patients with inactive inflammatory bowel disease.

    Science.gov (United States)

    Gandhi, Seema; Jedel, S; Hood, M M; Mutlu, E; Swanson, G; Keshavarzian, A

    2014-05-01

    Coping is an integral part of adjustment for patients with Inflammatory Bowel Disease but has not been well described in the literature. This study explored the relationship between coping, perceived health competence, patient preference for involvement in their treatment, depression and quality of life, particularly among patients with inactive disease (in remission). Subjects (n=70) with active and inactive IBD completed questionnaires, including the Inflammatory Bowel Disease Quality of Life Questionnaire, Beck Depression Inventory, Perceived Health Competence Scale and the Coping Inventory for Stressful Situations. The Harvey Bradshaw Index measured disease activity. Patients with inactive IBD demonstrated significantly more interest in participating in their treatment (pperceived health competence (p=.001), less depressive symptoms (pperceived control of their health, and exhibit less depression symptoms. Our findings may increase awareness of the importance of identifying coping strategies for IBD patients, including those in remission. © 2013.

  17. Hypoxia Aggravates Inactivity-Related Muscle Wasting

    Directory of Open Access Journals (Sweden)

    Tadej Debevec

    2018-05-01

    Full Text Available Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i bed rest in normoxia (NBR; PiO2 = 133.1 ± 0.3 mmHg, (ii bed rest in normobaric hypoxia (HBR; PiO2 = 90.0 ± 0.4 mmHg and ambulatory confinement in normobaric hypoxia (HAmb; PiO2 = 90.0 ± 0.4 mmHg. Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P < 0.001 was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027. Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47. Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017 and calf (-3.3%, SE 0.7%, P < 0.001 muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P < 0.05. Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

  18. An Aptamer Bio-barCode (ABC) assay using SPR, RNase H, and probes with RNA and gold-nanorods for anti-cancer drug screening.

    Science.gov (United States)

    Loo, Jacky Fong-Chuen; Yang, Chengbin; Tsang, Hing Lun; Lau, Pui Man; Yong, Ken-Tye; Ho, Ho Pui; Kong, Siu Kai

    2017-10-07

    With modifications to an ultra-sensitive bio-barcode (BBC) assay, we have developed a next generation aptamer-based bio-barcode (ABC) assay to detect cytochrome-c (Cyto-c), a cell death marker released from cancer cells, for anti-cancer drug screening. An aptamer is a short single-stranded DNA selected from a synthetic DNA library that is capable of binding to its target with high affinity and specificity based on its unique DNA sequence and 3D structure after folding. Similar to the BBC assay, Cyto-c is captured by a micro-magnetic particle (MMP) coated with capturing antibodies (Ab) and an aptamer specifically against Cyto-c to form sandwich structures ([MMP-Ab]-[Cyto-c]-[Aptamer]). After washing and melting, our aptamers, acting as a DNA bio-barcode, are released from the sandwiches and hybridized with the probes specially designed for RNase H for surface plasmon resonance (SPR) sensing. In an aptamer-probe duplex, RNase H digests the RNA in the probe and releases the intact aptamer for another round of hybridization and digestion. With signal enhancement effects from gold-nanorods (Au-NRs) on probes for SPR sensing, the detection limit was found to be 1 nM for the aptamer and 80 pM for Cyto-c. Without the time-consuming DNA amplification steps by PCR, the detection process of this new ABC assay can be completed within three hours. As a proof-of-concept, phenylarsine oxide was found to be a potent agent to kill liver cancer cells with multi-drug resistance at the nano-molar level. This approach thus provides a fast, sensitive and robust tool for anti-cancer drug screening.

  19. Inactive Mineral Filler as a Stiffness Modulus Regulator in Foamed Bitumen-Modified Recycled Base Layers

    Science.gov (United States)

    Buczyński, Przemyslaw; Iwański, Marek

    2017-10-01

    The article presents the results of a cold recycled mix test with a foam bitumen including the addition of the inactive mineral filler as a dust of basalt. Basalt dust was derived from dedusting system by extraction of aggregates in the mine. Assessment of the impact of a basalt dust on the properties of a recycled base layer was carried out in terms of the amount of mineral filler (basalt) in the composition of the mineral mixture. This experiment involved a dosing of mineral filler in range from 5 to 20% with steps of 7.5% in the mineral mixture composition. The foamed bitumen was performed at optimum foaming process settings (ie. bitumen temperature, air pressure) and at 2.5% of the water content. The amount of a hydraulic binder as a Portland cement was 2.0%. The evaluation of rheological properties allowed to determine whether the addition of inactive mineral fillers can act as a stiffness modulus controller in the recycled base layer. The analysis of the rheological properties of a recycled base layer in terms of the amount of inactive fillers was performed in accordance with given standard EN 12697-26 Annex D. The study was carried out according to the direct tension-compression test methodology on cylindrical samples. The sample was subjected to the oscillatory sinusoidal strain ε0 < 25με. Studies carried out at a specific temperature set-points: - 7°C, 5°C, 13°C, 25°C and 40°C and at the frequency 0.1 Hz, 0.3 Hz, 1 Hz, 3 Hz, 10 Hz and 20 Hz. The obtained results allow to conclude that the use of an inactive filler can reduce the stiffness of an appropriate designed mixes of the cold recycled foundation. In addition, the analysis of the relation E‧-E″ showed a similar behaviour of a recycled base, regardless of the amount of inactive fillers in the mix composition, at high temperatures/high frequency of induced load.

  20. Cytochrome oxidase assembly does not require catalytically active cytochrome C.

    Science.gov (United States)

    Barrientos, Antoni; Pierre, Danielle; Lee, Johnson; Tzagoloff, Alexander

    2003-03-14

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen. COX assembly requires the coming together of nuclear- and mitochondrial-encoded subunits and the assistance of a large number of nuclear gene products acting at different stages of maturation of the enzyme. In Saccharomyces cerevisiae, expression of cytochrome c, encoded by CYC1 and CYC7, is required not only for electron transfer but also for COX assembly through a still unknown mechanism. We have attempted to distinguish between a functional and structural requirement of cytochrome c in COX assembly. A cyc1/cyc7 double null mutant strain was transformed with the cyc1-166 mutant gene (Schweingruber, M. E., Stewart, J. W., and Sherman, F. (1979) J. Biol. Chem. 254, 4132-4143) that expresses stable but catalytically inactive iso-1-cytochrome c. The COX content of the cyc1/cyc7 double mutant strain harboring non-functional iso-1-cytochrome c has been characterized spectrally, functionally, and immunochemically. The results of these studies demonstrate that cytochrome c plays a structural rather than functional role in assembly of cytochrome c oxidase. In addition to its requirement for COX assembly, cytochrome c also affects turnover of the enzyme. Mutants containing wild type apocytochrome c in mitochondria lack COX, suggesting that only the folded and mature protein is able to promote COX assembly.

  1. Progress in catalytic naphtha reforming process: A review

    International Nuclear Information System (INIS)

    Rahimpour, Mohammad Reza; Jafari, Mitra; Iranshahi, Davood

    2013-01-01

    Catalytic naphtha reforming process is a vital process for refineries due to the production of high-octane components, which is intensely demanded in our modern life. The significance of this industrial process induced researchers to investigate different aspects of catalytic naphtha reforming process intensively. Some of the investigators try to improve this process by representing more effective catalysts, while others try to elucidate its kinetic and deactivation mechanisms and design more efficient reactor setups. The amount of these established papers is so much that may confuse some of the researchers who want to find collective information about catalytic naphtha reforming process. In the present paper, the published studies from 1949 until now are categorized into three main groups including finding suitable catalyst, revealing appropriate kinetic and deactivation model, and suggesting efficient reactor configuration and mode of operation. These studies are reviewed separately, and a suitable reference is provided for those who want to have access to generalized information about catalytic naphtha reforming process. Finally, various suggestions for revamping the catalytic naphtha reforming process have been proposed as a guideline for further investigations

  2. Effect of inactive yeast cell wall on growth performance, survival rate and immune parameters in Pacific White Shrimp (Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Rutchanee Chotikachinda

    2008-10-01

    Full Text Available Effects of dietary inactive yeast cell wall on growth performance, survival rate, and immune parameters in pacific white shrimp (Litopenaeus vannamei was investigated. Three dosages of inactive yeast cell wall (0, 1, and 2 g kg-1 were tested in three replicate groups of juvenile shrimps with an average initial weight of 7.15±0.05 g for four weeks. There was no significant difference in final weight, survival rate, specific growth rate, feed conversion ratio, feed intake, protein efficiency ratio, and apparent net protein utilization of each treatments. However, different levels of inactive yeast cell wall showed an effect on certain immune parameters (p<0.05. Total hemocyte counts, granular hemocyte count, and bacterial clearance were better in shrimp fed diets supplemented with 1 and 2 g kg-1 inactive yeast cell wall as compared with thecontrol group.

  3. Catalytically favorable surface patterns in Pt-Au nanoclusters

    KAUST Repository

    Mokkath, Junais Habeeb; Schwingenschlö gl, Udo

    2013-01-01

    Motivated by recent experimental demonstrations of novel PtAu nanoparticles with highly enhanced catalytic properties, we present a systematic theoretical study that explores principal catalytic indicators as a function of the particle size

  4. Catalytic Aminohalogenation of Alkenes and Alkynes.

    Science.gov (United States)

    Chemler, Sherry R; Bovino, Michael T

    2013-06-07

    Catalytic aminohalogenation methods enable the regio- and stereoselective vicinal difunctionalization of alkynes, allenes and alkenes with amine and halogen moieties. A range of protocols and reaction mechanisms including organometallic, Lewis base, Lewis acid and Brønsted acid catalysis have been disclosed, enabling the regio- and stereoselective synthesis of halogen-functionalized acyclic amines and nitrogen heterocycles. Recent advances including aminofluorination and catalytic enantioselective aminohalogenation reactions are summarized in this review.

  5. Development of closure criteria for inactive radioactive waste disposal sites at Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Kocher, D.C.

    1989-01-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended, specifies that cleanup of inactive waste disposal sites at Department of Energy (DOE) facilities shall at least attain legally applicable or relevant and appropriate requirements (ARARs) for cleanup or control of environmental contamination. This paper discusses potential ARARs for cleanup of inactive radioactive waste disposal sites and proposes a set of closure criteria for such sites at Oak Ridge National Laboratory (ORNL). The most important potential ARARs include Federal standards for radiation protection of the public, radioactivity in drinking water, and near-surface land disposal of radioactive wastes. On the basis of these standards, we propose that cleanup and closure of inactive radioactive waste disposal sites at ORNL shall achieve (1) limits on annual effective dose equivalent for off-site individuals and inadvertent intruders that conform to the DOE's performance objectives for new low-level waste disposal facilities and (2) to the extent reasonably achievable, limits on radionuclide concentrations in ground water and surface waters in accordance with Federal drinking water standards and ground-water protection requirements

  6. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-06-07

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-11-27

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

  8. Design of a randomized-controlled trial on low-intensity aerobic wheelchair exercise for inactive persons with chronic spinal cord injury

    NARCIS (Netherlands)

    van der Scheer, Jan W.; de Groot, Sonja; Postema, Klaas; Veeger, DirkJan H. E. J.; van der Woude, Lucas H. V.

    Purpose: To investigate effects and working mechanisms of low-intensity aerobic wheelchair exercise on fitness, (upper-body) health and active lifestyle in inactive persons with chronic spinal cord injury (SCI). Methods: A multicenter randomized-controlled trial (RCT) in 40 inactive manual

  9. Physical Inactivity from Adolescence to Young Adulthood: The Relevance of Various Dimensions of Inequality in a Swedish Longitudinal Sample

    Science.gov (United States)

    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.,…

  10. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  11. Childhood and contemporaneous correlates of adolescent leisure time physical inactivity: a longitudinal study.

    Science.gov (United States)

    Richards, Rosalina; Poulton, Richie; Reeder, Anthony I; Williams, Sheila

    2009-03-01

    Although concurrent influences on adolescent physical activity are well documented, longitudinal studies offer additional insights about early life antecedents of participation. The aim of this study was to examine associations between childhood and contemporaneous factors and patterns of physical activity participation during adolescence. Physical activity participation at ages 15 and 18 was assessed among members of the Dunedin Multidisciplinary Health and Development Study cohort using the interview-based Minnesota Leisure Time Physical Activity Questionnaire. Logistic regression was used to examine associations between childhood factors (socioeconomic status, family "active-recreation" orientation, home activities, motor ability, intelligence, and psychiatric disorder), contemporaneous factors (parental health, body mass index, predicted VO(2 max), general health, television viewing, smoking, and alcohol use) and "persistent inactivity," "declining participation," or "persistent activity" during adolescence. In multivariate models, persistent inactivity during adolescence was associated with lower childhood family active-recreation orientation, and poorer cardiorespiratory fitness and general health during adolescence. Declining participation was more likely among those who reported fewer activities at home during childhood. Persistent activity was associated with better cardiorespiratory fitness and watching less television during adolescence. This study found that childhood and contemporaneous factors were associated with persistent inactivity, persistent activity and declining participation during adolescence. The findings highlight several factors from the family and home environment of potential importance in early intervention programs to support adolescent participation in physical activity.

  12. Ambient fine particulate matter air pollution and leisure-time physical inactivity among US adults.

    Science.gov (United States)

    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.

  13. Administration of additional inactive iodide during radioiodine therapy for Graves' disease. Who might benefit?

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Moka, D.; Reinholz, U.; Schmidt, M.; Schomaecker, K.; Schicha, H.; Wellner, U. [Koeln Univ. (Germany). Dept. of Nuclear Medicine

    2007-07-01

    Aim: Graves' hyperthyroidism and antithyroid drugs empty the intrathyroid stores of hormones and iodine. The consequence is rapid {sup 131}I turnover and impending failure of radioiodine therapy. Can administration of additional inactive iodide improve 131I kinetics? Patients, methods: Fifteen consecutive patients, in whom the 48 h post-therapeutically calculated thyroid dose was between 150 and 249 Gy due to an unexpectedly short half-life, received 3 x 200 {mu}g inactive potassium-iodide ({sup 127}I) daily for 3 days (Group A), while 17 consecutive patients with a thyroid dose of = 250 Gy (Group B) served as the non-iodide group. 48 hours after {sup 131}I administration (M1) and 4 or 5 days later (M2) the following parameters were compared: effective {sup 131}I half-life, thyroid dose, total T3, total T4, {sup 131}I-activity in the T3- and T4-RIAs. Results: In Group A, the effective {sup 131}I half-life M1 before iodine (3.81 {+-} 0.93 days) was significantly (p <0.01) shorter than the effective {sup 131}I half-life M2 (4.65 {+-} 0.79 days). Effective {sup 131}I half-life M1 correlated with the benefit from inactive {sup 127}I (r = -0.79): Administration of {sup 127}I was beneficial in patients with an effective {sup 131}I half-life M1 of <3 or 4 days. Patients from Group A with high initial specific {sup 131}I activity of T3 and T4 showed lower specific {sup 131}I activity after addition of inactive iodine compared with patients from the same group with a lower initial specific {sup 131}I activity of T3 and T4 and compared with the patient group B who was given no additional inactive iodide. This correlation was mathematically described and reflected in the flatter gradient in Group A (y = 0.5195x + 0.8727 for {sup 131}I T3 and y = 1.0827x - 0.4444 for {sup 131}I T4) and steeper gradient for Group B (y = 0.6998x + 0.5417 for {sup 131}I T3 and y = 1.3191x - 0.2901 for {sup 131}I T4). Radioiodine therapy was successful in all 15 patients from Group A

  14. Novel Metal Nanomaterials and Their Catalytic Applications

    Directory of Open Access Journals (Sweden)

    Jiaqing Wang

    2015-09-01

    Full Text Available In the rapidly developing areas of nanotechnology, nano-scale materials as heterogeneous catalysts in the synthesis of organic molecules have gotten more and more attention. In this review, we will summarize the synthesis of several new types of noble metal nanostructures (FePt@Cu nanowires, Pt@Fe2O3 nanowires and bimetallic Pt@Ir nanocomplexes; Pt-Au heterostructures, Au-Pt bimetallic nanocomplexes and Pt/Pd bimetallic nanodendrites; Au nanowires, CuO@Ag nanowires and a series of Pd nanocatalysts and their new catalytic applications in our group, to establish heterogeneous catalytic system in “green” environments. Further study shows that these materials have a higher catalytic activity and selectivity than previously reported nanocrystal catalysts in organic reactions, or show a superior electro-catalytic activity for the oxidation of methanol. The whole process might have a great impact to resolve the energy crisis and the environmental crisis that were caused by traditional chemical engineering. Furthermore, we hope that this article will provide a reference point for the noble metal nanomaterials’ development that leads to new opportunities in nanocatalysis.

  15. Cardiovascular risk in active, insufficiently active and inactive users of public parks

    Directory of Open Access Journals (Sweden)

    Gustavo Fernades de Oliveira

    2008-07-01

    Full Text Available http://dx.doi.org/10.5007/1980-0037.2008v10n2p170 Physical activity has been recommended for heart disease prevention and rehabilitation. However, when performed incorrectly, which is more common when practiced without supervision and in public places, the risk of cardiovascular events increases. The objective of this study was to compare cardiovascular risk factors among users of São Paulo´s public parks with differing levels of physical activity – active, insuffi ciently active, and inactive. The evaluation consisted of a questionnaire about cardiovascular diseases, symptoms and risk factors; physical activity practice; and anthropometric and arterial blood pressure measurements. There was no difference between the groups in terms of the prevalence of cardiovascular disease or controllable risk factors. However, inactive people had a higher prevalence of cardiovascular symptoms (35%. With regard to uncontrollable cardiovascular risk factors, there was a higher prevalence of the gender/age factor among active (50% and insuffi ciently active (45% subjects, and heredity was more prevalent among inactive people (35%. There was no difference in obesity or blood pressure between the groups. The study also showed that active and insuffi ciently active subjects have a better knowledge of their health status, and a higher prevalence of being prescribed physical activity by physicians. The results demonstrate that most of the people who exercise in public parks are elderly and are at a moderate to high cardiovascular risk from this practice, which suggests that a physical education professional should be present.

  16. Catalytic Organic Transformations Mediated by Actinide Complexes

    Directory of Open Access Journals (Sweden)

    Isabell S. R. Karmel

    2015-10-01

    Full Text Available This review article presents the development of organoactinides and actinide coordination complexes as catalysts for homogeneous organic transformations. This chapter introduces the basic principles of actinide catalysis and deals with the historic development of actinide complexes in catalytic processes. The application of organoactinides in homogeneous catalysis is exemplified in the hydroelementation reactions, such as the hydroamination, hydrosilylation, hydroalkoxylation and hydrothiolation of alkynes. Additionally, the use of actinide coordination complexes for the catalytic polymerization of α-olefins and the ring opening polymerization of cyclic esters is presented. The last part of this review article highlights novel catalytic transformations mediated by actinide compounds and gives an outlook to the further potential of this field.

  17. Modeling and simulation of heterogeneous catalytic processes

    CERN Document Server

    Dixon, Anthony

    2014-01-01

    Heterogeneous catalysis and mathematical modeling are essential components of the continuing search for better utilization of raw materials and energy, with reduced impact on the environment. Numerical modeling of chemical systems has progressed rapidly due to increases in computer power, and is used extensively for analysis, design and development of catalytic reactors and processes. This book presents reviews of the state-of-the-art in modeling of heterogeneous catalytic reactors and processes. Reviews by leading authorities in the respective areas Up-to-date reviews of latest techniques in modeling of catalytic processes Mix of US and European authors, as well as academic/industrial/research institute perspectives Connections between computation and experimental methods in some of the chapters.

  18. Atypical protein disulfide isomerases (PDI: Comparison of the molecular and catalytic properties of poplar PDI-A and PDI-M with PDI-L1A.

    Directory of Open Access Journals (Sweden)

    Benjamin Selles

    Full Text Available Protein disulfide isomerases are overwhelmingly multi-modular redox catalysts able to perform the formation, reduction or isomerisation of disulfide bonds. We present here the biochemical characterization of three different poplar PDI isoforms. PDI-A is characterized by a single catalytic Trx module, the so-called a domain, whereas PDI-L1a and PDI-M display an a-b-b'-a' and a°-a-b organisation respectively. Their activities have been tested in vitro using purified recombinant proteins and a series of model substrates as insulin, NADPH thioredoxin reductase, NADP malate dehydrogenase (NADP-MDH, peroxiredoxins or RNase A. We demonstrated that PDI-A exhibited none of the usually reported activities, although the cysteines of the WCKHC active site signature are able to form a disulfide with a redox midpoint potential of -170 mV at pH 7.0. The fact that it is able to bind a [Fe2S2] cluster upon Escherichia coli expression and anaerobic purification might indicate that it does not have a function in dithiol-disulfide exchange reactions. The two other proteins were able to catalyze oxidation or reduction reactions, PDI-L1a being more efficient in most cases, except that it was unable to activate the non-physiological substrate NADP-MDH, in contrast to PDI-M. To further evaluate the contribution of the catalytic domains of PDI-M, the dicysteinic motifs have been independently mutated in each a domain. The results indicated that the two a domains seem interconnected and that the a° module preferentially catalyzed oxidation reactions whereas the a module catalyzed reduction reactions, in line with the respective redox potentials of -170 mV and -190 mV at pH 7.0. Overall, these in vitro results illustrate that the number and position of a and b domains influence the redox properties and substrate recognition (both electron donors and acceptors of PDI which contributes to understand why this protein family expanded along evolution.

  19. Catalytic gasification of oil-shales

    Energy Technology Data Exchange (ETDEWEB)

    Lapidus, A.; Avakyan, T. [I.M. Gubkin Russian State Univ. of Oil and Gas, Moscow (Russian Federation); Strizhakova, Yu. [Samara State Univ. (Russian Federation)

    2012-07-01

    Nowadays, the problem of complex usage of solid fossil fuels as raw materials for obtaining of motor fuels and chemical products is becoming increasingly important. A one of possible solutions of the problem is their gasification with further processing of gaseous and liquid products. In this work we have investigated the process of thermal and catalytic gasification of Baltic and Kashpir oil-shales. We have shown that, as compared with non-catalytic process, using of nickel catalyst in the reaction increases the yield of gas, as well as hydrogen content in it, and decreases the amount of liquid products. (orig.)

  20. Population-attributable causes of cancer in Korea: obesity and physical inactivity.

    Science.gov (United States)

    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.

  1. Anthropometric measurements of students athletes in relation to physically inactive students

    Directory of Open Access Journals (Sweden)

    Namik Trtak

    2012-04-01

    Full Text Available Introduction: Anthropometry is a method of anthropology that refers to the measuring and testing the human body and to the relationship between the size of its individual parts.The task of anthropometry is as accurately as possible quantitatively characterize the morphological features of the human body.Measurements are made due to the anthropometric points which can be: fixed (standard on the site of prominence and virtual (change due to the bodyposition. Goals of research: To evaluate the impact of basketball on the growth and development of seventeen years old adolescents and prevention of deformities of the spinal column and chest.Methods: The study included 40 respondents. Criteria for inclusion: male respondents aged 17 years who played basketball for more than one year, male respondents aged 17 years who are physically inactive. Criteria for exclusion: female respondents, respondents who played basketball for less than one year, respondents who are engaged in some other sport professionally or recreationally, respondents younger and olderthan 17 years. In the study,there were made measurements of thorax scope in the axillary and mamilar level, measurements of body weight and height and measurements of Body mass index.Results of research: Out of 40 respondents 20 are basketball players and 20 physically inactive. Compared to the average value between the two groups of respondents certain differences were observed, which aremost noticeable in body weight (basketball players had more weigh about, 5 kg on average and height (basketball players are taller, about 7 cm on average. During the anthropometric measurements of thoraxdeformities of the spinal column have been observed which affect the deformation of the thorax. Of the 20 players one has a deformity of the spinal column, and out of the same number of physically inactive studentseven 12 have deformed spine.Conclusion: Basketball has a positive effect on the proper growth and development

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

    Science.gov (United States)

    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…

  3. Kinetic catalytic studies of scorpion's hemocyanin

    International Nuclear Information System (INIS)

    Queinnec, E.; Vuillaume, M.; Gardes-Albert, M.; Ferradini, C.; Ducancel, F.

    1991-01-01

    Hemocyanins are copper proteins which function as oxygen carriers in the haemolymph of Molluscs and Arthropods. They possess enzymatic properties: peroxidatic and catalatic activities, although they have neither iron nor porphyrin ring at the active site. The kinetics of the catalytic reaction is described. The reaction of superoxide anion with hemocyanin has been studied using pulse radiolysis at pH 9. The catalytic rate constant is 3.5 X 10 7 mol -1 .l.s -1 [fr

  4. Levels and correlates of physical activity, inactivity and body mass index among Saudi women working in office jobs in Riyadh city.

    Science.gov (United States)

    Albawardi, Nada M; Jradi, Hoda; Al-Hazzaa, Hazzaa M

    2016-06-20

    Physical inactivity is among the leading risk factors for non-communicable diseases. Saudi Arabia has just begun to address physical inactivity as recent studies have shown an alarming prevalence of insufficiently physically active adults. Saudi women are identified as among the most overweight/obese and least active worldwide. With an increase in the number of women in office based jobs, the risk of physical inactivity is likely to increase. Identifying the level and correlates for high BMI and physical inactivity in Saudi women will help to plan more effective public health strategies. The aim of this study is to assess the level of physical activity, inactivity and body mass index among Saudi women working in office based jobs in Riyadh city and identify the correlates for overweight, obesity and low physical activity. A cross- sectional study was conducted on 420 Saudi women aged 18 to 58 years working in office based jobs in eight worksites in Riyadh, Saudi Arabia. Body mass index was determined using weight and height measurements and physical activity was assessed based on a validated self-administered questionnaire. The majority of the subjects were overweight or obese (58.3 %). Overweight/obesity was associated with increased age, lower income and with those working in the public versus private sector. More than half of the sample (52.1 %) were insufficiently physically active. Participants working seven or more hours per day and those working in private versus public sector were significantly associated with low physical activity. This study identified Saudi women working in office based jobs as a high risk group for overweight, obesity and physical inactivity. As sedentary jobs may compound the risk for obesity and physical inactivity, this may support the use of workplace health programs to reduce sitting time and promote physical activity as a viable public health initiative.

  5. The prevalence and correlates of physical inactivity among adults in Ho Chi Minh City

    Directory of Open Access Journals (Sweden)

    Phongsavan Philayrath

    2008-06-01

    Full Text Available Abstract Background Socioeconomic changes have led to profound changes in individuals' lifestyles, including the adoption of unhealthy food consumption patterns, prevalent tobacco use, alcohol abuse and physical inactivity, especially in large cities like Ho Chi Minh City (HCMC. The Stepwise Approach to Surveillance of Non-communicable Disease Risk Factors survey was conducted to identify physical activity patterns and factors associated with 'insufficient' levels of physical activity for health in adults in HCMC. Methods A cross-sectional survey was conducted in 2005 among 1906 adults aged 25–64 years using a probability proportional to size cluster sampling method to estimate the prevalence of non-communicable disease risk factors including physical inactivity. Data on socioeconomic status, health behaviours, and time spent in physical activity during work, commuting and leisure time were collected. Physical activity was measured using the validated Global Physical Activity Questionnaire (GPAQ. Responders were classified as 'sufficiently active' or 'insufficiently active' using the GPAQ protocol. Correlates of insufficient physical activity were identified using multivariable logistic regression. Results A high proportion of adults were physically inactive, with only 56.2% (95% CI = 52.1–60.4 aged 25–64 years in HCMC achieving the minimum recommendation of 'doing 30 minutes moderate-intensity physical activity for at least 5 days per week'. The main contributors to total physical activity among adults were from working and active commuting. Leisure-time physical activity represented a very small proportion (9.4% of individuals' total activity level. Some differences in the pattern of physical activity between men and women were noted, with insufficient activity levels decreasing with age among women, but not among men. Physical inactivity was positively associated with high income (OR = 1.77, 95% CI = 1.05–2.97 and high household

  6. On the mechanism of sulfite activation of chloroplast thylakoid ATPase and the relation of ADP tightly bound at a catalytic site to the binding change mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Du, Z.; Boyer, P.D. (Univ. of California, Los Angeles (USA))

    1990-01-16

    Washed chloroplast thylakoid membranes upon exposure to ({sup 3}H)ADP retain in tightly bound ({sup 3}H)ADP on a catalytic site of the ATP synthase. The presence of sufficient endogenous or added Mg{sup 2+} results in an enzyme with essentially no ATPase activity. Sulfite activates the ATPase, and many molecules of ATP per synthase can be hydrolyzed before most of the bound ({sup 3}H)ADP is released, a result interpreted as indicating that the ADP is not bound at a site participating in catalysis by the sulfite-activated enzyme. The authors present evidence that this is not the case. The Mg{sup 2+}- and ADP-inhibited enzyme when exposed to MgATP and 20-100 mM sulfite shows a lag of about 1 min at 22{degree}C and of about 15 s at 37{degree}C before reaching the same steady-state rate as attained with light-activated ATPase that has not been inhibited by Mg{sup 2+} and ADP. The lag is not eliminated if the enzyme is exposed to sulfite prior to MgATP addition, indicating that ATPase turnover is necessary for the activation. The release of most of the bound ({sup 3}H)ADP parallels the onset of ATPase activity, although some ({sup 3}H)ADP is not released even with prolonged catalytic turnover and may be on poorly active or inactive enzyme or at noncatalytic sites. The results are consistent with most of the tightly bound ({sup 3}H)ADP being at a catalytic site and being replaced as this Mg{sup 2+}- and ADP-inhibited site regains equivalent participation with other catalytic sites on the activated enzyme. The sulfite activation can be explained by sulfite combination at a P{sub i} binding site of the enzyme-ADP-Mg{sup 2+} complex to give a form more readily activated by ATP binding at an alternative site.

  7. Tunable preparation of ruthenium nanoparticles with superior size-dependent catalytic hydrogenation properties

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuan; Luo, Yaodong; Yang, Xuan; Yang, Yaxin; Song, Qijun, E-mail: qsong@jiangnan.edu.cn

    2017-06-15

    Highlights: • A facile and efficient strategy is firstly developed for the synthesis of Ru NPs. • Ru NPs are stable and uniform with the controllable sizes from 2.6 to 51.5 nm. • Ru NPs exhibit size-dependent and superior catalytic hydrogenation activity. - Abstract: Ruthenium (Ru) featured with an unusual catalytic behavior is of great significance in several heterogeneous and electro-catalytic reactions. The preparation of tractable Ru nanocatalysts and the building of highly active catalytic system at ambient temperature remains a grand challenge. Herein, a facile strategy is developed for the controllable preparation of Ru nanoparticles (NPs) with the sizes ranging from 2.6 to 51.5 nm. Ru NPs show superior size-dependent catalytic performance with the best kinetic rate constant as high as −1.52 min{sup −1}, which could far surpass the other traditional noble metals. Ru NPs exert exceedingly efficient low-temperature catalytic activity and good recyclability in the catalytic reduction of nitroaromatic compounds (NACs) and azo dyes. The developed catalytic system provides a distinguishing insight for the artificial preparation of Ru NPs with desired sizes, and allows for the development of rational design rules for exploring catalysts with superior catalytic performances, potentially broadening the applications of metallic NP-enabled catalytic analysis.

  8. Peripheral aneurysm rupture in a patient with inactive systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Engelke, Christoph; Sabharwal, Tarun; Reidy, John F. [Department of Radiology, Guy' s and St. Thomas' Hospital Trust, St. Thomas' Street, London SE1 9RT (United Kingdom); Mohan, Aarthi R. [Department of Chest Medicine, Guy' s and St. Thomas' Hospital Trust, St. Thomas' Street, London SE1 9RT (United Kingdom)

    2002-12-01

    We describe a patient with inactive systemic lupus erythematosus (SLE) presenting with sudden haemothorax, due to a ruptured internal mammary artery (IMA) aneurysm 7 years after the corticosteroid treatment was terminated. The unusual imaging findings and the treatment with embolization are discussed with a view to the role of a regular vascular screening in this patient group. (orig.)

  9. Orion EFT-1 Catalytic Tile Experiment Overview and Flight Measurements

    Science.gov (United States)

    Salazar, Giovanni; Amar, Adam; Hyatt, Andrew; Rezin, Marc D.

    2016-01-01

    This paper describes the design and results of a surface catalysis flight experiment flown on the Orion Multipurpose Crew Vehicle during Exploration Flight Test 1 (EFT1). Similar to previous Space Shuttle catalytic tile experiments, the present test consisted of a highly catalytic coating applied to an instrumented TPS tile. However, the present catalytic tile experiment contained significantly more instrumentation in order to better resolve the heating overshoot caused by the change in surface catalytic efficiency at the interface between two distinct materials. In addition to collecting data with unprecedented spatial resolution of the "overshoot" phenomenon, the experiment was also designed to prove if such a catalytic overshoot would be seen in turbulent flow in high enthalpy regimes. A detailed discussion of the results obtained during EFT1 is presented, as well as the challenges associated with data interpretation of this experiment. Results of material testing carried out in support of this flight experiment are also shown. Finally, an inverse heat conduction technique is employed to reconstruct the flight environments at locations upstream and along the catalytic coating. The data and analysis presented in this work will greatly contribute to our understanding of the catalytic "overshoot" phenomenon, and have a significant impact on the design of future spacecraft.

  10. COURAGE AND FEAR IN THE CONTEXT OF OPPOSITION OF HUMAN ACTIVITY AND INACTIVITY: EXISTENTIAL ASPECT

    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko

    2013-12-01

    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposi-tion of human activity and inactivity that may lead to a profound understanding of the essence, causes and existen-tial aspects of human activity and inactivity. The implementation of the objective assumes the solution of the follow-ing tasks: analysis of philosophical interpretation of fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inac-tivity through the opposition of fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of hu-man activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authen-tic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific nov-elty. For the first time the analysis of the fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the fundamental existential character of the fear and courage opposition and its es-sential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being. If classical philosophy placed emphasis on courage and associated fear with human mind and conscious decision, non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental mean

  11. COURAGE AND FEAR IN THE CONTEXT OF OPPOSITION OF HUMAN ACTIVITY AND INACTIVITY: EXISTENTIAL ASPECT

    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko

    2013-12-01

    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposition of human activity and inactivity that may lead to a profound understanding of the essence, causes and existential aspects of human activity and inactivity. The implementation of the objective assumes the solution of the following tasks: analysis of philosophical interpretation of  fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inactivity through the opposition of  fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of human activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authentic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific novelty. For the first time the analysis of the  fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the  fundamental existential character of the fear and courage opposition and its essential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being.  If classical philosophy placed emphasis on courage and associated fear with  human mind and conscious decision,  non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental meaning

  12. Comparison of fractions of inactive modules between Run1 and Run2

    CERN Document Server

    Motohashi, Kazuki; The ATLAS collaboration

    2015-01-01

    Fraction of inactive modules for each component of the ATLAS pixel detector at the end of Run 1 and the beginning of Run 2. A similar plot which uses a result of functionality tests during LS1 can be found in ATL-INDET-SLIDE-2014-388.

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

    Science.gov (United States)

    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…

  14. Unemployment, Employment and Inactivity in Denmark: An Analysis of Event History Data

    DEFF Research Database (Denmark)

    Lauzadyté, Agné

    disadvantaged. These give the evidence that the "Flexicurity"model makes the weakest individuals disadvantaged in the Danish labour market. And finally, I find that those, who survived in a job one year, tend to remain employed, while persons, longer than one year inactive, face much higher risk...

  15. Childhood attention-deficit/hyperactivity disorder symptoms are risk factors for obesity and physical inactivity in adolescence.

    Science.gov (United States)

    Khalife, Natasha; Kantomaa, Marko; Glover, Vivette; Tammelin, Tuija; Laitinen, Jaana; Ebeling, Hanna; Hurtig, Tuula; Jarvelin, Marjo-Riitta; Rodriguez, Alina

    2014-04-01

    To prospectively investigate the association and directionality between attention-deficit/hyperactivity disorder (ADHD) symptoms and obesity from childhood to adolescence in the general population. We examined whether obesogenic behaviors, namely, physical inactivity and binge eating, underlie the potential ADHD symptom-obesity association. We explored whether childhood conduct disorder (CD) symptoms are related to adolescent obesity/physical inactivity. At 7 to 8 years (n = 8,106), teachers reported ADHD and CD symptoms, and parents reported body mass index (BMI) and physically active play. At 16 years (n = 6,934), parents reported ADHD symptoms; adolescents reported physical activity (transformed to metabolic equivalent of task [MET] hours per week) and binge eating; BMI and waist-hip ratio (WHR) were measured via clinical examination. Obesity was defined using the International Obesity Task Force (IOTF) cut-offs for BMI and the 95th percentile cut-off for WHR. Childhood ADHD symptoms significantly predicted adolescent obesity, rather than the opposite. Inattention-hyperactivity symptoms at 8 years were associated with indices of obesity at 16 years (obese BMI: odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.10-3.33; 95th percentile WHR: OR = 1.71, 95% CI = 1.05-2.78), adjusted for gender, baseline BMI, physical activity, family structure change, and maternal education. Child CD symptoms associated with indices of adolescent obesity. Reduced physically active play in childhood predicted adolescent inattention (OR = 1.61, 95% CI = 1.16-2.24). Childhood ADHD and CD symptoms were linked with physical inactivity in adolescence (inattention-hyperactivity; OR = 1.60, 95% CI = 1.20-2.13), but not binge eating. Physical inactivity mediated the associations. Children with ADHD or CD symptoms are at increased risk for becoming obese and physically inactive adolescents. Physical activity may be beneficial for both behavior problems and obesity

  16. Networks of high mutual information define the structural proximity of catalytic sites: implications for catalytic residue identification.

    Directory of Open Access Journals (Sweden)

    Cristina Marino Buslje

    Full Text Available Identification of catalytic residues (CR is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI, and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls, combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution.

  17. Networks of high mutual information define the structural proximity of catalytic sites: implications for catalytic residue identification.

    Science.gov (United States)

    Marino Buslje, Cristina; Teppa, Elin; Di Doménico, Tomas; Delfino, José María; Nielsen, Morten

    2010-11-04

    Identification of catalytic residues (CR) is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI), and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA) database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL) conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI) was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC) was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls), combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution.

  18. Heterogeneous catalytic degradation of polyacrylamide solution | Hu ...

    African Journals Online (AJOL)

    Modified with trace metal elements, the catalytic activity of Fe2O3/Al2O3 could be changed greatly. Among various trace metal elements, Fe2O3/Al2O3 catalysts modified with Co and Cu showed great increase on catalytic activity. International Journal of Engineering, Science and Technology, Vol. 2, No. 7, 2010, pp. 110- ...

  19. Catalytic Subunit 1 of Protein Phosphatase 2A Is a Subunit of the STRIPAK Complex and Governs Fungal Sexual Development

    Directory of Open Access Journals (Sweden)

    Anna Beier

    2016-06-01

    Full Text Available The generation of complex three-dimensional structures is a key developmental step for most eukaryotic organisms. The details of the molecular machinery controlling this step remain to be determined. An excellent model system to study this general process is the generation of three-dimensional fruiting bodies in filamentous fungi like Sordaria macrospora. Fruiting body development is controlled by subunits of the highly conserved striatin-interacting phosphatase and kinase (STRIPAK complex, which has been described in organisms ranging from yeasts to humans. The highly conserved heterotrimeric protein phosphatase PP2A is a subunit of STRIPAK. Here, catalytic subunit 1 of PP2A was functionally characterized. The Δpp2Ac1 strain is sterile, unable to undergo hyphal fusion, and devoid of ascogonial septation. Further, PP2Ac1, together with STRIPAK subunit PRO22, governs vegetative and stress-related growth. We revealed in vitro catalytic activity of wild-type PP2Ac1, and our in vivo analysis showed that inactive PP2Ac1 blocks the complementation of the sterile deletion strain. Tandem affinity purification, followed by mass spectrometry and yeast two-hybrid analysis, verified that PP2Ac1 is a subunit of STRIPAK. Further, these data indicate links between the STRIPAK complex and other developmental signaling pathways, implying the presence of a large interconnected signaling network that controls eukaryotic developmental processes. The insights gained in our study can be transferred to higher eukaryotes and will be important for understanding eukaryotic cellular development in general.

  20. SHORT COMMUNICATION CATALYTIC KINETIC ...

    African Journals Online (AJOL)

    IV) catalyzes the discoloring reaction of DBS-arsenazo oxidized by potassium bromate, a new catalytic kinetic spectrophotometric method for the determination of trace titanium (IV) was developed. The linear range of the determination of ...